deamino-arginine-vasopressin and Hemorrhage

Intranasal, subcutaneous, or intravenous desmopressin can be utilized to release von Willebrand Factor and Factor VIII into circulation, enhance platelet adhesion and shorten bleeding time. Due to these properties, desmopressin can be effective in controlling bleeding in mild hemophilia A, certain subtypes of von Willebrand disease and in acute bleeding from uremia, end stage renal disease, and liver disease. Its use, however, can be complicated by hyponatremia and rarely arterial thrombotic events. While desmopressin has also been used as a prophylactic blood sparing agent in orthopedic, renal, and hepatic procedures, clinical studies have shown limited benefit in these settings. The purpose of this article is to review the evidence for desmopressin in primary hematologic disorders, discuss its mechanism of action and evaluate its utility as a hemostatic and blood sparing product in various bleeding conditions.

Topics: Deamino Arginine Vasopressin; Hemorrhage; Hemostasis; Hemostatics; Humans; von Willebrand Diseases; von Willebrand Factor

Vascular surgery may be followed by internal bleeding due to inadequate surgical haemostasis, abnormal clotting, or surgical complications. Bleeding ranges from minor, with no transfusion requirement, to massive, requiring multiple blood product transfusions. There are a number of drugs, given systemically or applied locally, which may reduce the need for blood transfusion.. To assess the effectiveness and safety of anti-fibrinolytic and haemostatic drugs and agents in reducing bleeding and the need for blood transfusion in people undergoing major vascular surgery or vascular procedures with a risk of moderate or severe (> 500 mL) blood loss.. We searched: Cochrane Central Register of Controlled Trials; MEDLINE; Embase; CINAHL, and Transfusion Evidence Library. We also searched the WHO ICTRP and ClinicalTrials.gov trial registries for ongoing and unpublished trials. Searches used a combination of MeSH and free text terms from database inception to 31 March 2022, without restriction on language or publication status.. We included randomised controlled trials (RCTs) in adults of drug treatments to reduce bleeding due to major vascular surgery or vascular procedures with a risk of moderate or severe blood loss, which used placebo, usual care or another drug regimen as control.. We used standard Cochrane methods. Our primary outcomes were units of red cells transfused and all-cause mortality. Our secondary outcomes included risk of receiving an allogeneic blood product, risk of reoperation or repeat procedure due to bleeding, risk of a thromboembolic event, risk of a serious adverse event and length of hospital stay. We used GRADE to assess certainty of evidence.. We included 22 RCTs with 3393 participants analysed, of which one RCT with 69 participants was reported only in abstract form, with no usable data. Seven RCTs evaluated systemic drug treatments (three aprotinin, two desmopressin, two tranexamic acid) and 15 RCTs evaluated topical drug treatments (drug-containing bioabsorbable dressings or glues), including fibrin, thrombin, collagen, gelatin, synthetic sealants and one investigational new agent. Most trials were conducted in high-income countries and the majority of the trials only included participants undergoing elective surgery. We also identified two ongoing RCTs. We were unable to perform the planned network meta-analysis due to the sparse reporting of outcomes relevant to this review. Systemic drug treatments We identified seven trials of three systemic drugs: aprotinin, desmopressin and tranexamic acid, all with placebo controls. The trials of aprotinin and desmopressin were small with very low-certainty evidence for all of our outcomes. Tranexamic acid versus placebo was the systemic drug comparison with the largest number of participants (2 trials; 1460 participants), both at low risk of bias. The largest of these included a total of 9535 individuals undergoing a number of different higher risk surgeries and reported limited information on the vascular subgroup (1399 participants). Neither trial reported the number of units of red cells transfused per participant up to 30 days. Three outcomes were associated with very low-certainty evidence due to the very wide confidence intervals (CIs) resulting from small study sizes and low number of events. These were: all-cause mortality up to 30 days; number of participants requiring an allogeneic blood transfusion up to 30 days; and risk of requiring a repeat procedure or operation due to bleeding. Tranexamic acid may have no effect on the risk of thromboembolic events up to 30 days (risk ratio (RR) 1.10, 95% CI 0.88 to 1.36; 1 trial, 1360 participants; low-certainty evidence due to imprecision). There is one large ongoing trial (8320 participants) comparing tranexamic acid versus placebo in people undergoing non-cardiac surgery who are at high risk of requiring a red cell transfusion. This aims to complete recruitment in April 2023. This trial has primary outcomes of proportion of participants transfused with red blood cells and incidence of venous thromboembolism (DVT or PE). Topical drug treatments Most trials of topical drug treatments were at high ri. Because of a lack of data, we are uncertain whether any systemic or topical treatments used to reduce bleeding due to major vascular surgery have an effect on: all-cause mortality up to 30 days; risk of requiring a repeat procedure or operation due to bleeding; number of red cells transfused per participant up to 30 days or the number of participants requiring an allogeneic blood transfusion up to 30 days. There may be no effect of tranexamic acid on the risk of thromboembolic events up to 30 days, this is important as there has been concern that this risk may be increased. Trials with sample size targets of thousands of participants and clinically relevant outcomes are needed, and we look forward to seeing the results of the ongoing trials in the future.

Topics: Adult; Aprotinin; Blood Transfusion; Deamino Arginine Vasopressin; Fibrin Tissue Adhesive; Hemorrhage; Humans; Network Meta-Analysis; Tranexamic Acid

Kidney biopsy is the gold standard for diagnosing kidney disease but may result in bleeding, especially in uraemia. DDAVP (1-deamino-8-d-arginine vasopressin) may reduce uraemic bleeding but guidelines on its use are lacking.. To evaluate whether DDAVP reduced bleeding complications after percutaneous kidney biopsies.. We searched CENTRAL, PubMed, Embase, LILACS, WHO Trials Registry and ClinicalTrials.gov until May 2019 for randomised controlled trials (RCT), quasi-RCT and prospective cohort studies that compared DDAVP with placebo or no intervention, prior to native or allograft kidney biopsy. The primary outcome was post-biopsy bleeding. Secondary outcome was adverse events related to DDAVP.. Currently available prospective data are insufficient to support the routine use of DDAVP prior to percutaneous kidney biopsies hence high quality trials are required.

Topics: Biopsy; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Kidney

Unclassified bleeding disorders account for 2.6% of all new bleeding disorder registrations in the UK. The management of the bleeding phenotype associated with these disorders is poorly described. Systematic review and meta-analysis to determine the bleeding rates associated with tranexamic acid, desmopressin, platelet transfusion, plasma transfusion and recombinant activated factor VII, for patients with unclassified bleeding disorders undergoing surgery, childbirth or with menorrhagia. We searched for randomized controlled trials in MEDLINE, Embase, The Cochrane Central Register of Controlled Trials, PubMed, ISI Web of Science and the Transfusion Evidence Library from inception to 24 February 2020. Wherever appropriate, data were pooled using the metaprop function of STATA. Two studies with 157 participants with unclassified bleeding disorders were identified. The pooled risk of minor bleeding for patients undergoing surgery treated with peri-operative tranexamic acid was 11% (95% confidence interval 3--20%; n = 52; I2 = 0%); the risk for desmopressin and tranexamic acid in combination was 3% (95% confidence interval 0--7%; n = 71; I2 = 0%). There were no instances of major bleeding. In one procedure, 1 of 71 (1.4%), treated with a combination of desmopressin and tranexamic acid, the patient had a line-related deep vein thrombosis. There were too few patients treated to prevent postpartum haemorrhage or for menorrhagia to draw conclusions. The GRADE quality of evidence was very low suggesting considerable uncertainty over the results. However, both tranexamic acid, and the combination of tranexamic and desmopressin have high rates of haemostatic efficacy and have few adverse events.. PROSPERO CRD42020169727.

Topics: Antifibrinolytic Agents; Blood Component Transfusion; Deamino Arginine Vasopressin; Disease Management; Female; Hemorrhage; Hemorrhagic Disorders; Hemostatics; Humans; Menorrhagia; Postoperative Hemorrhage; Postpartum Hemorrhage; Pregnancy; Tranexamic Acid

The deficiency or abnormal activity of von Willebrand factor, a multi-adhesive protein which binds platelets to exposed subendothelium and carries factor VIII in circulation, is responsible for von Willebrand disease, the most frequent inherited bleeding disorder. Clinical symptoms are characterized by mucous membrane and soft tissue bleeding, bleeding after surgery and rarely joint and gastrointestinal bleeding. Intriguingly, also factor VIII, the protein deficient in hemophilia A, may be variably reduced because VWF stabilizes it into circulation. Treatment strategies are well designed for patients with levels of VWF activity <30 U/dL, while the diagnosis and the magnitude of risk may be difficult to be assessed accurately for subjects with levels between 30 and 50 U/dL. Three types of the disorder have been identified according to partial (type 1) or severe VWF quantitative deficiency (type 3) while patients who present variable abnormality of VWF structure are categorized as type 2. The aim of treatment is to correct either the abnormal/reduced von Willebrand factor and the associated deficiency of factor VIII, when present. Desmopressin is able to transiently correct the deficiency of FVIII and VWF for up to 8-12 h in a significant proportion of patients with type 1 von Willebrand disease and factor VIII and von Willebrand factor levels ≥10 U/dL. When desmopressin is not usual (mainly in patients with type 2 and 3 VWD) or correction is required cannot be used for an extended time (e.g., major surgery), von Willebrand factor-containing concentrates, with or without FVIII, must be used.

Topics: Deamino Arginine Vasopressin; Factor VIII; Hemophilia A; Hemorrhage; Humans; von Willebrand Disease, Type 1; von Willebrand Diseases; von Willebrand Factor

The goal of treating Von Willebrand Disease (VWD) is to replace deficient or dysfunctional Von Willebrand Factor (VWF) protein. However, the choice of treatment has to be considered carefully in view of patient factors and the unique properties of replacement products. Tailoring a treatment plan to an individual patient's bleeding challenge is an intricate process. This review describes personalization of treatment selection for desmopressin (DDAVP), VWF replacement concentrates, including the newly available recombinant VWF (rVWF) and prophylaxis as a treatment approach in VWD.

Topics: Deamino Arginine Vasopressin; Hemorrhage; Humans; Precision Medicine; von Willebrand Diseases; von Willebrand Factor

Von Willebrand disease (VWD) is the most common inherited bleeding disorder with an estimated prevalence of ~1% and clinically relevant bleeding symptoms in approximately 1:10,000 individuals. VWD is caused by a deficiency and/or defect of von Willebrand factor (VWF). The most common symptoms are mucocutaneous bleeding, hematomas, and bleeding after trauma or surgery. For decades, treatment to prevent or treat bleeding has consisted of desmopressin in milder cases and of replacement therapy with plasma-derived concentrates containing VWF and Factor VIII (FVIII) in more severe cases. Both are usually combined with supportive therapy, e.g. antifibrinolytic agents, and maximal hemostatic measures. Several developments such as the first recombinant VWF concentrate, which has been recently licensed for VWD, will make a more "personalized" approach to VWD management possible. As research on new treatment strategies for established therapies, such as population pharmacokinetic-guided dosing of clotting factor concentrates, and novel treatment modalities such as aptamers and gene therapy are ongoing, it is likely that the horizon to tailor therapy to the individual patients' needs will be extended, thus, further improving the already high standard of care in VWD in most high-resource countries.

Topics: Antifibrinolytic Agents; Aptamers, Nucleotide; Deamino Arginine Vasopressin; Factor VIII; Genetic Therapy; Hemorrhage; Hemostatic Techniques; Humans; Interleukin-11; von Willebrand Diseases; von Willebrand Factor

Von Willebrand Disease (VWD) is the most common human inherited bleeding disorder due to a defect of Von Willebrand Factor (VWF), which a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels < 50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50IU/dL). Von willebrand factor is a complex multimeric protein with two functions: it forms a bridge between the platelets and areas of vascular damage and it binds to and stabilizes factor VIII, which is necessary for the clotting cascade. By taking a clinical history of bleeding (mucocutaneous bleeding symptoms suggestive of a primary haemostatic disorder, a quantitative or qualitative abnormality of VWF is possible) it is important to think about VWD and to make the appropriate diagnosis. If the VWD is suspected diagnostic tests should include an activated partial thromboplastin time, bleeding time, factor VIII: C Ristocetin cofactor and vWF antigen. Additional testing of ristocetin induced plattlet adhesion (RIPA) the multimeric structure and collagen binding test and genanalysis allow diagnosing the different types of von. Willebrand Disease. The treatment of choice in mild forms is the synthetic agent desmopressin. In patients with severe type 1, type 2B, 2N and type 3 or in people who do not response to desmopressin, the appropriate treatment is a factor VIII concentrate that is rich of VWF. We report a case of infant in 27-month-old boy who had been referred due to haemorrhagic shock. His birth histories, his familie's social history and developmental milestones were unremarkable. He was born at full term with no antenatal or perinatal complications. Prior to the symptoms, the child was on a normal diet and was thriving appropriately. The child presented one days before his admission trauma to the inner face of the lower lip that caused an external acute bleeding loss. The laboratory data showed unfortunately, the most severe form of Von Willebrand's Disease; Type 3. The management was based on erythrocyte and fresh-frozen plasma (FFP) transfusions with administration of factor VII with good evolution.

Topics: Child, Preschool; Deamino Arginine Vasopressin; Erythrocyte Transfusion; Factor VIII; Hemorrhage; Humans; Male; Partial Thromboplastin Time; Plasma; Severity of Illness Index; von Willebrand Diseases; von Willebrand Factor

Von Willebrand disease (VWD) is the most common genetic bleeding disorder. VWD is caused by a deficiency or dysfunction of von Willebrand factor (VWF), a plasma protein that mediates the initial adhesion of platelets at sites of vascular injury and binds and stabilises coagulation factor VIII (FVIII) in the blood. Prophylaxis of surgical bleeding in patients with VWD requires consideration of the individual situation, including the type of procedure and the bleeding rate, before decisions about treatment type, dose, duration and adjunctive therapy with antifibrinolytics or antithrombotic prophylaxis can be made. Although desmopressin (DDAVP)-stimulated release of endogenous VWD is an effective treatment strategy in many patients, plasma concentrates containing VWF are the preferred option for most patients undergoing surgical procedures. Recommendations for the management of surgery in patients with VWD are summarised, including the severity of VWD and the type of the surgical procedure.

Topics: Clinical Decision-Making; Deamino Arginine Vasopressin; Disease Management; Factor VIII; Hemorrhage; Humans; Premedication; Surgical Procedures, Operative; Thrombosis; Treatment Outcome; von Willebrand Diseases; von Willebrand Factor

Essentials The optimal management of patients with platelet dysfunction undergoing surgery is unclear. This meta-analysis compared perioperative administration of desmopressin to placebo. Desmopressin reduced red cell transfusions, blood loss and risk of re-operation due to bleeding. There were too few events to determine if there was a change in the risk of thrombotic events.. Background Platelet dysfunction, including that caused by antiplatelet agents, increases the risk of perioperative bleeding. The optimal management of patients with platelet dysfunction undergoing surgery is unclear. Objectives To assess whether desmopressin reduces perioperative allogeneic red cell transfusion and bleeding in patients with platelet dysfunction. Patients/Methods We searched for randomized controlled trials in The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, the Transfusion Evidence Library and the ISI Web of Science to 7th July 2016. Data were pooled using mean difference (MD), relative risks or Peto odds ratios (pOR) using a random-effects model. Results Ten trials with 596 participants were identified, all in the setting of cardiac surgery. Platelet dysfunction was due to antiplatelet agents in six trials and cardiopulmonary bypass in four trials. Patients treated with desmopressin were transfused with fewer red cells (MD, -0.65 units; 95% Confidence Interval [CI], -1.16 to -0.13 units), lost less blood (MD, -253.93 mL; 95% CI, -408.01 to -99.85 mL) and had a lower risk of re-operation due to bleeding (pOR, 0.39; 95% CI, 0.18-0.84). The GRADE quality of evidence was very low to moderate, suggesting considerable uncertainty over the results Conclusions Desmopressin may be a useful agent to reduce bleeding and transfusion requirements for people with platelet dysfunction or with a history of recent antiplatelet drug administration undergoing cardiac surgery.

Topics: Blood Loss, Surgical; Blood Platelet Disorders; Blood Platelets; Blood Transfusion; Deamino Arginine Vasopressin; Erythrocyte Transfusion; Hemorrhage; Hemostatics; Humans; Platelet Aggregation Inhibitors; Platelet Transfusion; Randomized Controlled Trials as Topic; Thrombosis; Treatment Outcome

Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPN) comprise a heterogeneous group of chronic hematologic malignancies. The quality of life, morbidity, and mortality of patients with MPN are primarily affected by disease-related symptoms, thromboembolic and hemorrhagic complications, and progression to myelofibrosis and acute leukemia. Major bleeding represents a common and important complication in MPN, and the incidence of such bleeding events will become even more relevant in the future due to the increasing disease prevalence and survival of MPN patients. This review discusses the causes, differential diagnoses, prevention, and management of bleeding episodes in patients with MPN, aiming at defining updated standards of care in these often challenging situations.

Topics: Anticoagulants; Antineoplastic Agents; Blood Coagulation Factors; Blood Loss, Surgical; Blood Transfusion; Blood Vessels; Clinical Trials as Topic; Contraindications; Deamino Arginine Vasopressin; Disease Management; Elective Surgical Procedures; Hemorrhage; Hemostatic Techniques; Humans; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Liver; Multicenter Studies as Topic; Myeloproliferative Disorders; Platelet Aggregation Inhibitors; Platelet Function Tests; Platelet Transfusion; Postoperative Hemorrhage; Thrombophilia; Tranexamic Acid; von Willebrand Diseases; von Willebrand Factor

People with thrombocytopenia due to bone marrow failure are vulnerable to bleeding. Platelet transfusions have limited efficacy in this setting and alternative agents that could replace, or reduce platelet transfusion, and are effective at reducing bleeding are needed.. To compare the relative efficacy of different interventions for patients with thrombocytopenia due to chronic bone marrow failure and to derive a hierarchy of potential alternative treatments to platelet transfusions.. We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (the Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 27 April 2016.. We included randomised controlled trials in people with thrombocytopenia due to chronic bone marrow failure who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII (rFVIIa), desmopressin (DDAVP), recombinant factor XIII (rFXIII), recombinant interleukin (rIL)6 or rIL11, or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard of care or platelet transfusion). We excluded people undergoing intensive chemotherapy or stem cell transfusion.. Two review authors independently screened search results, extracted data and assessed trial quality. We estimated summary risk ratios (RR) for dichotomous outcomes. We planned to use summary mean differences (MD) for continuous outcomes. All summary measures are presented with 95% confidence intervals (CI).We could not perform a network meta-analysis because the included studies had important differences in the baseline severity of disease for the participants and in the number of participants undergoing chemotherapy. This raised important concerns about the plausibility of the transitivity assumption in the final dataset and we could not evaluate transitivity statistically because of the small number of trials per comparison. Therefore, we could only perform direct pairwise meta-analyses of included interventions.We employed a random-effects model for all analyses. We assessed statistical heterogeneity using the I. We identified seven completed trials (472 participants), and four ongoing trials (recruiting 837 participants) which are due to be completed by December 2020. Of the seven completed trials, five trials (456 participants) compared a TPO mimetic versus placebo (four romiplostim trials, and one eltrombopag trial), one trial (eight participants) compared DDAVP with placebo and one trial (eight participants) compared tranexamic acid with placebo. In the DDAVP trial, the only outcome reported was the bleeding time. In the tranexamic acid trial there were methodological flaws and bleeding definitions were subject to significant bias. Consequently, these trials could not be incorporated into the quantitative synthesis. No randomised trial of artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII, rIL6 or rIL11 was identified.We assessed all five trials of TPO mimetics included in this review to be at high risk of bias because the trials were funded by the manufacturers of the TPO mimetics and the authors had financial stakes in the sponsoring companies.The GRADE quality of the evidence was very low to moderate across the different outcomes.There was insufficient evidence to detect a difference in the number of participants with at least one bleeding episode between TPO mimetics and placebo (RR 0.86, 95% CI 0.56 to 1.31, four trials, 206 participants, low-quality evidence).There was insufficient evidence to detect a difference in the risk of a life-threatening bleed between those treated with a TPO mimetic and placebo (RR 0.31, 95% CI 0.04 to 2.26, one trial, 39 participants, low-quality evidence).There was insufficient evidence to detect a difference in the risk of all-cause mortality between those treated with a TPO mimetic and placebo (RR 0.74, 95%CI 0.52 to 1.05, five trials, 456 participants, very low-quality evidence).There was a significant reduction in the number of participants receiving any platelet transfusion between those treated with TPO mimetics and placebo (RR 0.76, 95% CI 0.61 to 0.95, four trials, 206 participants, moderate-quality evidence).There was no evidence for a difference in the incidence of transfusion reactions between those treated with TPO mimetics and placebo (pOR 0.06, 95% CI 0.00 to 3.44, one trial, 98 participants, very low-quality evidence).There was no evidence for a difference in thromboembolic events between TPO mimetics and placebo (RR 1.41, 95%CI 0.39 to 5.01, five trials, 456 participa. There is insufficient evidence at present for thrombopoietin (TPO) mimetics for the prevention of bleeding for people with thrombocytopenia due to chronic bone marrow failure. There is no randomised controlled trial evidence for artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII or rIL6 or rIL11, antifibrinolytics or DDAVP in this setting.

Topics: Benzoates; Bone Marrow Diseases; Chronic Disease; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Hydrazines; Platelet Transfusion; Pyrazoles; Randomized Controlled Trials as Topic; Receptors, Fc; Recombinant Fusion Proteins; Thrombocytopenia; Thrombopoietin; Tranexamic Acid

von Willebrand disease (VWD) is the commonest inherited bleeding disorder and results from either a quantitative or qualitative deficiency in the plasma glycoprotein von Willebrand factor (VWF). Recent large cohort studies have significantly enhanced our understanding of the molecular mechanisms involved in the pathogenesis of VWD. In contrast, however, there have been relatively few advances in the therapeutic options available for the treatment of bleeding in patients with VWD. Established treatment options include tranexamic acid, 1-deamino-8-d-arginine vasopressin (DDAVP), and plasma-derived VWF concentrates. In addition, a recombinant VWF has also recently been developed. In this review, we focus on how recent insights into the clinical and molecular aspects underpinning VWD are already beginning to influence treatment in the clinic. For example, a number of different bleeding assessment tools (BATs) have been developed to objectively assess bleeding symptoms in patients with VWD. Interestingly, however, these BAT scores may also have an important role to play in predicting bleeding risk in VWD. Furthermore, recent studies have demonstrated that enhanced VWF clearance plays a critical role in the etiology of both type 1 and type 2 VWD. These findings have direct translational relevance with respect to the use of DDAVP in patients with VWD. As understanding of the mechanisms involved in VWD pathogenesis continues to advance, novel treatment options are likely to emerge. Critically, however, large adequately powered and stratified clinical trials will be required to address the outstanding questions that remain regarding VWD treatment optimization.

Topics: Deamino Arginine Vasopressin; Hemorrhage; Humans; Tranexamic Acid; von Willebrand Diseases; von Willebrand Factor

Topics: Age Factors; Algorithms; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Male; Menorrhagia; von Willebrand Diseases; von Willebrand Factor

Treatment of mucosal bleeding (epistaxis, gastrointestinal bleeding, and menorrhagia) and joint bleeding remains problematic in clinically severe von Willebrand disease (VWD). Patients are often unresponsive to treatment (e.g. desmopressin or antifibrinolytic therapy) and may require von Willebrand factor (VWF) replacement therapy. There are little data on the use of prophylaxis in VWD, and none have been applied in a prospective, treatment escalation design.. Evaluate the effect of escalating dose prophylaxis in severe VWD.. Patients eligible for enrollment in this prospective study included those with type 1 VWD with VW factor activity-ristocetin cofactor ratio ≤ 20% and unresponsive to desmopressin, patients with type 2 VWD not responsive to desmopressin and all subjects with type 2B and type 3 VWD. Entry criteria were strictly defined, as were therapy escalation parameters and clinical data collection.. Eleven subjects completed the study. Six had type 2A, and five had type 3 VWD. Six patients presented with epistaxis, three with GI bleeding, and two with joint bleeding. Seven had dose escalation above the first level. Among the 10 subjects with evaluable bleeding log data, use of prophylaxis decreased the median annualized bleeding rate from 25 to 6.1 (95% confidence interval of the rate difference: -51.6 to -1.7), and the median annualized bleeding rate was even lower (4.0; 95% confidence interval: -57.5 to -5.3) when the subjects reached their final dosing level.. This is the first prospective study to demonstrate that prophylaxis with VW factor concentrates is highly effective in reducing mucosal and joint bleeding rates in clinically severe VWD.

Topics: Blood Loss, Surgical; Blood Transfusion; Clinical Trials as Topic; Deamino Arginine Vasopressin; Drug Administration Schedule; Factor VIII; Female; Hemarthrosis; Hemorrhage; Hospitalization; Humans; Male; Menorrhagia; Multicenter Studies as Topic; Postoperative Hemorrhage; Prospective Studies; Recombinant Proteins; Retrospective Studies; von Willebrand Diseases; von Willebrand Factor

Bleeding disorders, including haemophilia, von Willebrand disease, and platelet function abnormalities pose a substantial, ongoing management challenge. Patients with these disorders not only require treatment during bleeding events but also need effective management strategies to prepare for events ranging from minor dental procedures to major surgery and childbirth. Moreover, women with bleeding disorders often require ongoing treatment to prevent menorrhagia during childbearing years. Desmopressin (DDAVP), a synthetic derivative of the antidiuretic hormone l-arginine vasopressin, has become a well-established tool for the management of patients with bleeding disorders in a variety of clinical settings. However, despite the widespread use of DDAVP, the available clinical evidence on its efficacy and safety in these settings is limited, and there has not been a recent comprehensive review of its role in the clinical management of patients with bleeding disorders. As such, this article provides a review of the mechanism of action and pharmacokinetic properties of DDAVP, followed by a concise summary of the available evidence for its use in the treatment and prevention of bleeding.

Topics: Blood Coagulation Disorders, Inherited; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostatics; Humans; Male; Surgical Procedures, Operative; Treatment Outcome

Type 2B von Willebrand disease (VWD) accounts for fewer than 5% of all VWD patients. In this disease, mutations in the A1 domain result in increased von Willebrand factor (VWF) binding to platelet GPIbα receptors, causing increased platelet clearance and preferential loss of high molecular weight VWF multimers. Diagnosis is complicated because of significant clinical variations even among patients with identical mutations. Platelet transfusion often provides suboptimal results since transfused platelets may be aggregated by the patients' abnormal VWF. Desmopressin may cause a transient decrease in platelet count that could lead to an increased risk of bleeding. Replacement therapy with factor VIII/VWF concentrates is the most effective approach to prevention and treatment of bleeding in type 2B VWD.

Topics: Blood Platelets; Deamino Arginine Vasopressin; Diagnosis, Differential; Drug Combinations; Factor VIII; Hemorrhage; Humans; Mutation; Platelet Glycoprotein GPIb-IX Complex; von Willebrand Disease, Type 2; von Willebrand Factor

Topics: Child; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; von Willebrand Diseases

The complex nature of haemostasis in patients with liver disease can result in bleeding and/or thrombosis. These opposing outcomes, which have multiple contributing factors, can pose diagnostic and therapeutic dilemmas for physicians. With the high rate of haemorrhagic complications in patients with cirrhosis, we examine the various procoagulants available for use in this population. In this Review, we describe the clinical and current rationale for using each of the currently available procoagulants-vitamin K, fresh frozen plasma (FFP), cryoprecipitate, platelets, recombinant factor VIIa (rFVIIa), antifibrinolytics, prothrombin concentrate complexes (PCC), desmopressin and red blood cells. By examining the evidence and use of these agents in liver disease, we provide a framework for targeted, goal-directed therapy with procoagulants.

Topics: Antifibrinolytic Agents; Coagulants; Deamino Arginine Vasopressin; Erythrocyte Transfusion; Factor VIIa; Factor VIII; Fibrinogen; Hemorrhage; Humans; Liver Diseases; Plasma; Recombinant Proteins; Vitamin K

The article represents a review of recent data about the therapy of von Willebrand disease in children and adolescents (hereditary as well as acquired forms of the disease). The treatment of bleeding events in these patients, the indications in different subtypes, and the future lines of research are mentioned.

Topics: Adolescent; Blood Loss, Surgical; Child; Deamino Arginine Vasopressin; Disease Progression; Factor VIII; Hemorrhage; Humans; Immunosuppressive Agents; Platelet Adhesiveness; Prognosis; von Willebrand Diseases; von Willebrand Factor

Desmopressin is a synthetic vasopressin analog that increases the plasma levels of coagulation factor VIII, von Willebrand factor, and tissue plasminogen activator. This hemostatic agent, which can be administered either parenterally or intranasally, has been approved for use in the prevention and treatment of hemorrhagic events during surgery in patients with hemophilia A, in cases of prolonged idiopathic bleeding, and for complications associated with platelet antiaggregant therapy. This case report describes cardiac toxicity associated with desmopressin administered according to the recommended indications: a 55-year-old woman diagnosed with Wegener's granulomatosis (WG) was treated with desmopressin to improve hemostasis and shorten bleeding time before a planned renal biopsy. She developed cardiac arrest within 60 minutes of the desmopressin injection. Cardiopulmonary resuscitation began immediately and was successful, although the patient subsequently died of WG-associated complications. Desmopressin administration thus appears, in some cases, to be associated with a high risk of thrombotic events, possibly by stimulating the rapid release of endothelial factors such as an abnormal multimeric form of von Willebrand factor, which might cause platelet aggregation. Clinicians should be aware of the possible occurrence of this little-known but potentially serious cardiac event associated with desmopressin administration and be prepared to initiate cardiopulmonary resuscitation immediately if needed.

Topics: Biopolymers; Biopsy; Bleeding Time; Deamino Arginine Vasopressin; Disease Progression; Endothelium, Vascular; Fatal Outcome; Female; Granulomatosis with Polyangiitis; Heart Arrest; Hemorrhage; Hemostatics; Humans; Immunosuppressive Agents; Kidney; Middle Aged; Myocardial Infarction; Thromboembolism; Thrombolytic Therapy; von Willebrand Factor

During the past 25 years, our knowledge concerning the pathogenesis, diagnostic strategies, and treatment of von Willebrand disease (VWD) has increased significantly. Following the immunological differentiation of factor VIII (FVIII) and von Willebrand factor (VWF) in the 1970s and the cloning of the FVIII and VWF genes in the mid-1980s, substantial progress has been made in our understanding of this, the most common inherited bleeding disorder. We now recognize that VWD represents a range of genetic diseases all with the clinical endpoint of increased mucocutaneous bleeding. The molecular pathology of Type 2 and 3 VWD is now comprehensively documented and involves rare sequence variants at the VWF locus. In contrast, the genetic causation of Type 1 disease remains incompletely defined and in many cases appears to involve genetic determinants in addition to or instead of VWF. The diagnostic triad of a personal history of excessive mucocutaneous bleeding, laboratory tests for VWF that are consistent with VWD, and a family history of the condition remain the keystone to VWD identification. In the laboratory, measurement of VWF antigen and function continue to be the most important diagnostic studies, and while our understanding of the molecular genetic pathology of VWD has advanced considerably in the past decade, genetic testing as a component of diagnosis is limited to certain distinct subtypes of the disorder. Treatment of VWD has been relatively unchanged for the past decade and continues to involve either stimulation of the release of intrinsic VWF with desmopressin or the infusion of VWF concentrates.

Topics: Cloning, Molecular; Deamino Arginine Vasopressin; Factor VIII; Genetic Testing; Hemorrhage; Hemostatics; Humans; von Willebrand Diseases; von Willebrand Factor

Congenital abnormalities of platelet function disorder (PFD) are associated with the heightened risk for bleeding. Typically, patients with PFDs have mucocutaneous bleeding of variable severity and excessive hemorrhage after surgery or trauma. The diagnostic laboratory assessment appropriate for the evaluation of suspected inherited PFD should be based on a two-step diagnostic strategy: the first step, based on screening tests, helps raising a diagnostic hypothesis, which should then be tested in the second step, which is based on the use of specific tests. The first step should include: complete blood cell count, examination of the peripheral blood smear, and assessment of platelet aggregation. Although light transmission aggregometry (LTA) is the most widely used platelet function test, it is relatively insensitive to defects of platelet secretion; for this reason, laboratory tests that measure platelet aggregation and secretion simultaneously, such as lumi-aggregometry, should be preferred to traditional LTA. The second step includes specific tests (e.g., flow cytometry, Western blotting, DNA analysis). Platelet transfusions should be used only to treat severe bleeding episodes. Recombinant Factor VIIa can be used in patients with severe bleeding episodes who do not respond to platelet transfusion because of alloimmunization. Fibrinolytic inhibitors or the vasopressin analogue desmopressin (DDAVP) should be used in all other circumstances.

Topics: Blood Cell Count; Blood Platelet Disorders; Blood Platelets; Blotting, Western; Deamino Arginine Vasopressin; Factor VIIa; Flow Cytometry; Hemorrhage; Hemostatics; Humans; Platelet Aggregation; Platelet Function Tests; Platelet Transfusion; Recombinant Proteins; Sequence Analysis, DNA

Type 1 von Willebrand disease and mild platelet function defects are among the most common disorders seen by pediatric hematologists. The management and prevention of bleeding in these patients can be challenging, as there are limited published data to guide clinical practice, and a complete lack of randomized clinical trials. Desmopressin (DDAVP) and antifibrinolytics are the mainstays of treatment in these patients, yet the optimal dosing and timing of these agents to prevent or resolve bleeding, while minimizing adverse side effects, is sometimes unclear. DDAVP-induced hyponatremia is a particularly under-recognized complication in children with bleeding disorders who undergo surgery. Clinicians need to be aware of local measures that are equally important in treating problems such as epistaxis and surgical bleeding. This review will discuss the published literature and provide practical suggestions regarding four common management issues in the care of children and adolescents with mild bleeding disorders: epistaxis, heavy menstrual bleeding, dental extractions, and tonsillectomy.

Topics: Adolescent; Child; Deamino Arginine Vasopressin; Disease Management; Hemorrhage; Hemostatics; Humans; von Willebrand Disease, Type 1

Strategies to reduce blood loss and the need for transfusions in surgery include enhancement of coagulation, inhibition of fibrinolysis, and an improved decision algorithm for transfusion based on bedside monitoring of global hemostasis. The synthetic antifibrinolytic drug tranexamic acid has emerged as an effective alternative in this respect for orthopedic and cardiac surgery. Although it seems less effective than aprotinin, it has not been associated with the increased risk of mortality of the latter. Thromboelastography to monitor the global hemostatic capacity and to guide the appropriate use of blood components in cardiac surgery is also effective in reducing the need for transfusion. Patients on antithrombotic drug therapy may need reversal before surgery to avoid excessive blood loss, or intraoperatively in cases of unexpected bleeding. Available options are protamine for unfractionated or low-molecular-weight heparin, recombinant activated factor VII for fondaparinux, prothrombin complex concentrate for vitamin K antagonists and possibly for oral factor Xa inhibitors, dialysis and possibly activated prothrombin complex concentrate for oral thrombin inhibitors, desmopressin for aspirin and possibly for thienopyridines, and platelet transfusions for the latter.

Topics: Administration, Oral; Antifibrinolytic Agents; Deamino Arginine Vasopressin; Factor Xa Inhibitors; Fibrinogen; Fibrinolysis; Fibrinolytic Agents; Hematology; Hemorrhage; Hemostasis; Heparin; Heparin, Low-Molecular-Weight; Humans; Models, Biological; Orthopedics; Protamines; Recombinant Proteins; Thrombelastography; Tranexamic Acid; Vitamin K

Recent multicenter studies have clarified the molecular basis underlying the different von Willebrand disease (VWD) types, all of which are caused by the deficiency and/or abnormality of von Willebrand factor (VWF). These studies have suggested a unifying pathophysiologic concept. The diagnosis of VWD, remains difficult because its clinical and laboratory phenotype is very heterogeneous and may overlap with normal subjects. Stringent criteria are therefore required for a clinically useful diagnosis. In this paper, we delineate a practical approach to the diagnosis and treatment of VWD. Our approach is based on the critical importance of a standardized bleeding history that has been condensed into a final bleeding score and a few widely available laboratory tests, such as VWF ristocetin cofactor activity, VWF antigen and factor VIII. This approach would help identify those subjects who will probably benefit from a diagnosis of VWD. The next step involves performing a trial infusion with desmopressin in all patients who fail to exhibit an enhanced responsiveness to ristocetin. On the basis of these results and through a series of illustrative examples, the clinician will be able to select the best approach for the optimal management of VWD, according to the patient's characteristics and clinical circumstances.

Topics: Adolescent; Adult; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostatics; Humans; Male; Middle Aged; Multicenter Studies as Topic; Ristocetin; von Willebrand Diseases; von Willebrand Factor

Autosomal dominant von Willebrand disease (VWD) type 1/2E is a quantitative/qualitative defect in the von Willebrand factor (VWF) caused by heterozygous cysteine and non-cysteine mutations in the D3 domain of the VWF gene and results in a secretion-multimerization-clearance defect in mutant VWF with the loss of large VWF multimers not due to proteolysis. The multimers of patients with dominant VWD type 1/2E due to mutations in the D3 domain show an aberrant triplet structure with lack of outer bands but with pronounced inner bands of the triplet structure combined with a relative decrease in large multimers reflecting heterozygosity for multimerization defects. There is a good response to desmopressin (DDAVP) followed by rapid clearance of VWF:antigen (Ag), factor VIII coagulant activity (FVIII:C) and VWF:ristocetin cofactor activity (RCo) as the main cause of VWD type 1 or 2 with typical 2E multimeric pattern (VWD type 1/2E). Cysteine mutations in the D3 domains (C1130, C1149 and C1190) show pronounced features of VWD 1/2E with the relative loss of large and relative increase in small VWF multimers with abnormal triplet structure in heterozygotes. Such abnormalities are less pronounced in patients with a milder form of VWD type 1 due to non-cysteine mutations W1144G, T1156M and W1120S in the D3 domain. VWD type 1 Vicenza is caused by the R1205H mutation in the D3 domain and characterized by equally low levels of FVIII:C, VWF:Ag and VWF:RCo. The response to DDAVP in VWD Vicenza is good for FVIII:C, VWF:Ag and VWF:RCo, which is followed by a rapid clearance in less than a few hours of FVIII:C and VWF parameters. The ratios for FVIII:C/VWF:Ag, VWF:RCo/Ag and VWF:CB/Ag remain normal before and after DDAVP indicating that VWD Vicenza clearly differs from VWD type 1, 1/2E and 2M. A new set of missense mutations in D4, B1-B3 and C1-C2 domains has been discovered as the cause of a mild VWD type 1 secretion defect with normal VWF multimers or smeary VWF multimeric pattern. Cysteine mutations in exons 38, 40, 42 and 43 (D4, B1-B3 and C1 domain), show smeary patterns (either smf or sm), with the presence of large VWF multimers and a laboratory phenotype of mild VWD type 1 with variable penetrance of bleeding manifestations. Recent studies showed that the ratio of VWF propeptide (pp) to VWF:Ag can be used to predict a shorter than normal half-life for VWF:Ag. There is a strong inverse correlation between rapid clearance of VWF:Ag after DDAVP and increased VWFpp/Ag r

Topics: Bleeding Time; Deamino Arginine Vasopressin; Diagnosis, Differential; Female; Genes, Dominant; Genotype; Hemorrhage; Humans; Male; Models, Molecular; Mutation, Missense; Pedigree; Penetrance; Phenotype; Point Mutation; Protein Precursors; Protein Processing, Post-Translational; Protein Structure, Quaternary; Protein Structure, Tertiary; von Willebrand Diseases; von Willebrand Factor

Pertinent findings in patients with von Willebrand disease (VWD) type 2A include prolonged bleeding time (BT), consistently low von Willebrand factor (VWF):ristocetin cofactor activity (RCo)/antigen concentration (Ag) and VWF:collagen binding (CB)/Ag ratios, absence of high, and (depending on severity) intermediate and large VWF multimers, the presence of pronounced triplet structure of individual bands and increased VWF degradation products due to increased proteolysis caused by mutations in the A2 domain of VWF. Two categories of VWD type 2A can be distinguished: group I with severe and group II with mild VWD. A minority of VWD type 2A have mild VWD characterized by near normal to prolonged BT, normal factor VIII coagulant activity and VWF:Ag, low VWF:RCo and VWF:CB, a normal ristocetin-induced platelet aggregation and complete but transient correction of BT and functional VWF parameters to normal levels for only a few hours due to short half-lives for VWF:RCo and CWF:CB. Such transient complete responses to desmopressin (DDAVP) lasting only a few hours may facilitate treatment and prophylaxis of minor bleedings, but may not be able to prevent bleeding during minor and major surgery. Most VWD type 2A patients have pronounced VWD with very low VWF:RCo, prolonged BT, PFA-100 closure times >250 s, and response to DDAVP is only transient, minor, poor or absent, with no correction of the BT despite some increase in VWF:RCo, thus being candidates for factor VIII-VWF concentrate substitution for the acute and prophylactic treatment of bleeding symptoms.

Topics: ADAM Proteins; ADAMTS13 Protein; Adult; Aged; Bleeding Time; Blood Protein Electrophoresis; Collagen; Deamino Arginine Vasopressin; Exons; Female; Hemorrhage; Humans; Male; Middle Aged; Molecular Weight; Mutation, Missense; Platelet Aggregation; Pregnancy; Pregnancy Complications, Hematologic; Protein Structure, Quaternary; Protein Structure, Tertiary; von Willebrand Diseases; von Willebrand Factor

Acquired von Willebrand disease (aVWD) occurs in association with a variety of underlying disorders, most frequently in lymphoproliferative and myeloproliferative disorders, other malignancies, and cardiovascular disease. aVWD is a complex and heterogeneous defect with a multifactorial etiology and the pathophysiologic mechanisms remain unclear in many cases. Assays for anti-factor VIII (FVIII)/von Willebrand factor (VWF) activities often yield negative results although antibodies may be present in autoimmune disease and some lymphoproliferative disorders. Functional assays of VWF in patients' plasma and particularly in heart valve disease, VWF multimer analysis are important for aVWD diagnosis. In patients with normal partial thromboplastin times and normal VWF activity, the diagnosis of aVWD is based on clinical suspicion and a careful bleeding history, which should prompt the clinician to initiate further laboratory investigations. Management of bleeding in aVWD relies mainly on desmopressin, FVIII/VWF concentrates and high-dose intravenous immunoglobulin. The half-life of VWF may be very short, and in bleeding episodes high doses of FVIII/VWF concentrates at short intervals may be necessary even when high-dose intravenous immunoglobulin was applied before. Since the optimal treatment strategy has not yet been defined for aVWD of different etiology, controlled multicenter trials aiming at the development of standardized treatment protocols are urgently needed.

Topics: Antibody Specificity; Autoantibodies; Autoantigens; Autoimmune Diseases; Deamino Arginine Vasopressin; Heart Diseases; Hemorrhage; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lymphoproliferative Disorders; Neoplasms; von Willebrand Diseases; von Willebrand Factor

Easy bruising and bleeding are prominent features of some heritable disorders of connective tissue (HDCT), resulting from fragility of capillaries and the perivascular connective tissue rather than clotting or platelet dysfunction. The bleeding tendency is most prominent in the Ehlers-Danlos syndrome (EDS), a heterogeneous group of HDCT sharing clinical manifestations of fragility in skin, ligaments, blood vessels and internal organs. Most EDS-subtypes are caused by mutations in genes encoding fibrillar collagens type I, III or V, or genes encoding enzymes involved in the posttranslational modification of collagens. In the vascular subtype of EDS, caused by defects in type III collagen, fragility of vessel walls can lead to life-threatening bleeding and premature death. Bleeding tendency is also a common feature in other EDS-subtypes, leading to bruising either spontaneously or after minimal trauma. This paper reviews the clinical aspects of bleeding and bruising in different HDCT and covers diagnostic and therapeutic aspects relevant to bleeding in these disorders.

Topics: Collagen Type III; Connective Tissue Diseases; Deamino Arginine Vasopressin; Ehlers-Danlos Syndrome; Extracellular Matrix; Hemorrhage; Hemostasis; Hemostatics; Humans

Factor XI (FXI) deficiency is a rare inherited coagulation disorder characterized by infrequent spontaneous bleeding, but increased risk of hemorrhagic complications especially after trauma or surgery. Treatment options for FXI-deficient patients include virus-inactivated fresh frozen plasma, plasma-derived FXI concentrates, and activated recombinant FVII. Inhibitors of fibrinolysis, such as tranexamic acid, and desmopressin (DDAVP) have also been used in these patients, especially in mild cases. The current knowledge on the use of the latter agent in this congenital bleeding condition is systematically reviewed here. Although limited, the available literature data suggest the potential role of DDAVP for either treatment of bleeding episodes or the prevention of postoperative bleeding in patients with milder FXI defects. However, these findings need to be supported by further trials on large population of patients.

Topics: Deamino Arginine Vasopressin; Factor XI Deficiency; Hemorrhage; Hemostatics; Humans; Postoperative Complications

The wide clinical spectrum of von Willebrand disease (VWD), its complex pathophysiology and its classification into distinct quantitative (type 1 or type 3) and qualitative (type 2) types with further subtle distinctions have prevented most clinicians from establishing a straightforward approach to diagnosing and treating this inherited bleeding disorder. The results of studies involving large cohorts of patients with a wide range of bleeding manifestations and variable von Willebrand factor (VWF) reduction have recently become available. These data have allowed the proposal of minimal criteria for a clinically useful diagnosis and for differentiating patients with mild VWD from subjects with borderline or only slightly reduced VWF levels who will not benefit from a specific diagnosis. These criteria are based on measurement of VWF ristocetin cofactor (VWF:RCo), VWF antigen (VWF:Ag), factor VIII and a standardized bleeding score (BS). Demonstration of the inheritance of the disorder could help to classify patients for whom insufficient hemostatic challenges may produce a falsely reassuring BS (like in children). Using this approach, mild VWD appears to be mostly composed of type 1 cases. Complemented by the results of desmopressin trial infusion, these parameters form the basis for a clinically oriented classification of all forms of VWD and may be useful for selecting the best treatment according to the severity of the disease. Although few molecular data have revealed practical utility, there is no doubt that the clarification of the molecular pathophysiology of VWD has allowed the unification of this complex disorder into a simple conceptual framework. This framework underlies the proposed utilization of simple phenotypic markers for optimizing treatments in individual patients.

Topics: Adult; Child; Deamino Arginine Vasopressin; Disease Management; Factor VIII; Female; Hemorrhage; Humans; Male; Mutation; Patient Selection; Phenotype; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic; Severity of Illness Index; von Willebrand Diseases; von Willebrand Factor

In mild/moderate haemophilia A (MHA) patients, many factor VIII (FVIII) gene defects, mainly missense mutations, have been identified and greatly improved the understanding of the structure and function of FVIII molecule. Characterization of the molecular mechanisms involved in MHA has helped to identify regions critical for proper FVIII biosynthesis, thrombin activation, intramolecular stability as well as binding regions for important intermolecular interactions with von Willebrand factor, factor IXa and the phospholipid surface. Some missense mutations were also recognized as contributing factors to inhibitor development in MHA, in parallel to acquired factors such as inflammatory state or intensity of treatment. Treatment of MHA with inhibitor patients raises questions on how best to stop or prevent bleeding episodes and eradicate the inhibitor. Longitudinal data collection is currently being conducted in France and Belgium to enhance our knowledge in this field and to further help make treatment decision. The description of mutations in MHA finally contributed to the identification of epitopes involved in the immune response to FVIII. In some patients, the epitope specificity of inhibitor antibodies recognizing normal exogenous FVIII alone and not patient ('self') FVIII was described. This distinguished epitope specificity could also be demonstrated at the T-cell clonal level. One might expect that these molecular studies will have a major impact on development of new FVIII products in the future.

Topics: Antibodies; Deamino Arginine Vasopressin; Epitopes; Factor IXa; Factor VIII; Genotype; Hemophilia A; Hemorrhage; Hemostatics; Humans; Immune Tolerance; Mutation, Missense; Thrombin

Hemorrhage in trauma is a significant challenge, accounting for 30% to 40% of all fatalities, second only to central nervous system injury as a cause of death. However, hemorrhagic death is the leading preventable cause of mortality in combat casualties and typically occurs within 6 to 24 hrs of injury. In cases of severe hemorrhage, massive transfusion may be required to replace more than the entire blood volume. Early prediction of massive transfusion requirements, using clinical and laboratory parameters, combined with aggressive management of hemorrhage by surgical and nonsurgical means, has significant potential to reduce early mortality.. Although the classification of massive transfusion varies, the most frequently used definition is ten or more units of blood in 24 hrs. Transfusion of red blood cells is intended to restore blood volume, tissue perfusion, and oxygen-carrying capacity; platelets, plasma, and cryoprecipitate are intended to facilitate hemostasis through prevention or treatment of coagulopathy. Massive transfusion is uncommon in civilian trauma, occurring in only 1% to 3% of trauma admissions. As a result of a higher proportion of penetrating injury in combat casualties, it has occurred in approximately 8% of Operation Iraqi Freedom admissions and in as many as 16% during the Vietnam conflict. Despite its potential to reduce early mortality, massive transfusion is not without risk. It requires extensive blood-banking resources and is associated with high mortality.. This review describes the clinical problems associated with massive transfusion and surveys the nonsurgical management of hemorrhage, including transfusion of blood products, use of hemostatic bandages/agents, and treatment with hemostatic medications.

Topics: Acidosis; Antifibrinolytic Agents; Bandages; Blood Coagulation Disorders; Blood Transfusion; Cause of Death; Critical Care; Deamino Arginine Vasopressin; Factor VIIa; Factor VIII; Fibrinogen; Hemorrhage; Hemostatics; Humans; Hyperkalemia; Hypocalcemia; Hypothermia; Military Medicine; Recombinant Proteins; Resuscitation; Risk Factors; Transfusion Reaction; United States; Wounds and Injuries; Zeolites

Patients with severe forms of von Willebrand's disease (VWD) may have frequent haemarthroses, especially when factor VIII (FVIII) levels are below 10 U/dL, so that some of them develop target joints like patients with severe haemophilia A. Some patients have recurrent gastrointestinal bleeding, often without lesions in the gastrointestinal tract, and need treatment every day or every other day. Finally, there are children who have epistaxis frequently and severely enough to cause anaemia. In these frequent and severe bleeders, the optimal therapy may be secondary long-term prophylaxis with von Willebrand factor (VWF)/FVIII concentrates rather than on-demand treatment on the occasion of bleeding episodes. The largest experience on such prophylaxis in VWD has been in Sweden in 35 patients with severe forms of VWD. Long-term prophylaxis was also implemented in a cohort of Italian patients with VWD: prophylaxis was used in seven patients with types 3 (n = 1 ), 2A (n = 4), 2M (n = 1) and type 1 (n = 1) VWD because of recurrent gastrointestinal bleeds and in four patients with type 3 VWD because of joint bleeds. Prophylaxis prevented bleeding completely in eight patients and largely reduced hospitalisation for blood transfusions in the remaining three. The cost-effectiveness of these prophylaxis regimens versus on-demand therapy will now be investigated in one large international study

Topics: Clinical Trials as Topic; Deamino Arginine Vasopressin; Drug Administration Schedule; Drug Combinations; Epistaxis; Factor VIII; Female; Fibrinogen; Gastrointestinal Hemorrhage; Hemarthrosis; Hemorrhage; Humans; Male; Multicenter Studies as Topic; Prospective Studies; Retrospective Studies; Secondary Prevention; von Willebrand Diseases; von Willebrand Factor

Inherited deficiencies of plasma proteins involved in blood coagulation generally lead to lifelong bleeding disorders. The severity of these disorders is generally inversely proportional to the degree of factor deficiency. Among all the autosomal recessive rare bleeding disorders, which include afibrinogenaemia, factor (F) II, FV, FV + VIII, FVII, FX, FXI, FXIII, the combined deficiency of coagulation FV and FVIII (F5F8D or FV + FVIII) is exceptional because it is due to mutations in genes encoding proteins involved in the FV and FVIII intracellular transport (LMAN1 and MCFD2) rather than DNA defects in the genes that encode the corresponding coagulation factors. F5F8D is estimated to be extremely rare (1:1.000.000) in the general population, but an increased frequency is observed in regions where consanguineous marriages is practiced. F5F8D is characterized by concomitantly low levels (usually between 5% and 20%) of both FV and FVIII, and is associated with a mild to moderate bleeding tendency. Treatment of bleeding episodes requires a source of both FV and FVIII; replacement of FV is achieved through the use of fresh frozen plasma, and that of FVIII by desmopressin or specific FVIII concentrates, plasma-derived or recombinant FVIII products. We focus here on the clinical, molecular, treatment-related and diagnostic features of F5F8D.

Topics: Blood Coagulation; Coagulants; Deamino Arginine Vasopressin; DNA Mutational Analysis; Factor V Deficiency; Factor VIII; Female; Hemophilia A; Hemorrhage; Hemostatics; Humans; Male; Mannose-Binding Lectins; Membrane Proteins; Mutation; Plasma; Pregnancy; Pregnancy Complications, Hematologic; Rare Diseases; Vesicular Transport Proteins

The aim of the treatment for von Willebrand disease (VWD) is to correct the dual defect of haemostasis, i.e. the abnormal platelet adhesion as a result of reduced and/or dysfunctional von Willebrand factor (VWF) and the abnormal coagulation expressed by low levels of factor VIII (FVIII). Correction of both deficiencies can be achieved by administering the synthetic peptide desmopressin (DDAVP) or, in cases unresponsive to this agent, the plasma concentrates containing VWF and FVIII (VWF/FVIII). DDAVP is the treatment of choice for type 1 VWD because it can induce release of normal VWF from cellular compartments, but the drug can be clinically useful also in other VWD types, including acquired von Willebrand syndrome (AVWS). A test dose of DDAVP at the time of diagnosis is recommended to establish the individual patterns of biological response and to predict clinical efficacy during bleeding and surgery. DDAVP is not effective in VWD type 3 and in severe forms of VWD 1 and 2. It can induce transient thrombocytopenia in patients with VWD type 2B. The results of several retrospective studies on the use of DDAVP in VWD management have been reported by many authors in different countries for the last 30 years. However, despite the widespread use of DDAVP in the treatment of VWD, there are only a few prospective clinical trials in a large number of cases on DDAVP efficacy and safety aimed at determining benefits and limits of this therapeutic approach. An investigator-driven observational prospective study on clinical efficacy of DDAVP in 200 patients with VWD types 1 and 2 has been recently organized: the effectiveness and safety of DDAVP will be evaluated prospectively for 24 months during bleeding episodes and minor or major surgeries in the VWD patients who were exposed to an infusion trial at enrollment.

Topics: Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; History, 20th Century; History, 21st Century; Humans; von Willebrand Diseases

Acquired von Willebrand's syndrome type I is the supposed main underlying cause of bleeding tendency in hypothyroid patients. The purpose of this systematic review was to summarize the published evidence on the association between hypothyroidism and acquired von Willebrand's syndrome. All published clinical epidemiological and interventional studies, case reports and in vitro studies that investigated the association between hypothyroidism and acquired von Willebrand's syndrome were identified by a computer-assisted search of the MEDLINE and EMBASE electronic databases. A quality assessment was performed for clinical epidemiological studies. A total of 41 papers were included. A total of 22 epidemiological in vivo studies, two in vitro studies and 47 case reports were finally analyzed. No high quality in vivo study was identified. Almost all bleeding episodes described in the case reports were mucocutaneous. von Willebrand factor (VWF) antigen value was available for 23 patients: median value 28 U/dL (range: 4-45); VWF activity was available for 24 patients: median value 28.5 U/dL (range: <3-55); factor VIII activity was available for 16 patients: median value 47 U/dL (range: 9-74). Acquired von Willebrand's syndrome may be the main factor responsible for bleeding diathesis in overt hypothyroid patients. Even if bleeding episodes are mainly mild and mucocutaneous, blood transfusion, drug administration or surgical procedure may be required.

Topics: Adolescent; Adult; Aged; Bleeding Time; Child; Deamino Arginine Vasopressin; Disease Susceptibility; Female; Hemorrhage; Hemostatics; Humans; Hypothyroidism; Male; Middle Aged; Thyroxine; von Willebrand Diseases; von Willebrand Factor

Topics: Antigens; Autoimmune Diseases; Cardiovascular Diseases; Deamino Arginine Vasopressin; Disease Management; Hemorrhage; Humans; Immunosuppressive Agents; Incidence; Lupus Erythematosus, Systemic; Lymphoproliferative Disorders; Myeloproliferative Disorders; Neoplasms; Prospective Studies; Registries; von Willebrand Diseases; von Willebrand Factor

Topics: Aminocaproic Acid; Aprotinin; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Meta-Analysis as Topic; Orthopedics; Perioperative Care; Postoperative Hemorrhage; Thoracic Surgery; Tranexamic Acid

The current standard set of von Willebrand factor (VWF) parameters used to differentiate type 1 from type 2 VWD include bleeding times (BTs), factor VIII coagulant activity (FVIII:C), VWF antigen (VWF:Ag), VWF ristocetine cofactor activity (VWF:RCo), VWF collagen binding activity (VWF:CB), ristocetine induced platelet aggregation (RIPA), and analysis of VWF multimers in low and high resolution agarose gels and the response to DDAVP. The BTs and RIPA are normal in asymptomatic carriers of a mutant VWF allele, in dominant type 1, and in recessive type 2N VWD, and this category has a normal response of VWF parameters to DDAVP. The response of FVIII:C is compromised in type 2N VWD. The BTs and RIPA are usually normal in type Vicenza and mild type 2A VWD, and these two VWD variants show a transiently good response of BT and VWF parameters followed by short in vivo half life times of VWF parameters. The BTS are strongly prolonged and RIPA typically absent in recessive severe type 1 and 3 VWD, in dominant type 2A and in recessive type 2C (very likely also 2D) VWD and consequently associated with low or absent platelet VWF, and no or poor response of VWF parameters to DDAVP. The BTs are prolonged and RIPA increased in dominant type 2B VWD, that is featured by normal platelet VWF and a poor response of BT and functional VWF to DDAVP. The BTs are prolonged and RIPA decreased in dominant type 2A and 2U, that all have low VWF platelet, very low VWF:RCo values as compared to VWF:Ag, and a poor response of functional VWF to DDAVP. VWD type 2M is featured by the presence of all VWF multimers in a low resolution agarose gel, normal or slightly prolonged BT, decreased RIPA, a poor response of VWF:RCo and a good response of FVIII and VWF:CB to DDAVP and therefore clearly in between dominant type 1 and 2U. The existing recommendations for prophylaxis and treatment of bleedings in type 2 VWD patients with FVIII/VWF concentrates are mainly derived from pharmocokinetic studies in type 3 VWD patients. FVIII/VWF concentrates should be characterised by labelling with FVIII:C, VWF:RCo, VWF:CB and VWF multimeric pattern to determine their safety and efficacy in prospective management studies. As the bleeding tendency is moderate in type 2 and severe in type 3 VWD and the FVIII:C levels are near normal in type 2 and very low in type 3 VWD patients. Proper recommendations of FVIII/VWF concentrates using VWF:RCo unit dosing for the prophylaxis and treatment of bleeding episodes are pr

Topics: Deamino Arginine Vasopressin; Drug Combinations; Factor VIII; Hemorrhage; Humans; Premedication; von Willebrand Diseases; von Willebrand Factor

Coagulopathy after trauma is a major cause for uncontrolled hemorrhage in trauma victims. Approximately 40% of trauma related deaths are attributed to or caused by exsanguination. Therefore the prevention of coagulopathy is regarded as the leading cause of avoidable death in these patients. Massive hemorrhage after trauma is usually caused by a combination of surgical and coagulopathic bleeding. Coagulopathic bleeding is multifactorial, including dilution and consumption of both platelets and coagulation factors, as well as dysfunction of the coagulation system. Because of the high mortality associated with hypothermia, acidosis and progressive coagulopathy, this vicious circle is often referred to as the lethal triad, potentially leading to exsanguination. To overcome this coagulopahty-related bleeding an empiric therapy is often instituted by replacing blood components. However, the use of transfusion of red blood cells has been shown to be associated with post-injury infection and multiple organ failure. In the management of mass bleeding it is therefore crucial to have a clear strategy to prevent coagulopathy and to minimize the need for blood transfusion.

Topics: Acidosis; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Substitutes; Blood Transfusion; Deamino Arginine Vasopressin; Factor VIIa; Fibrinogen; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Hypothermia; Multiple Trauma; Plasma; Platelet Transfusion; Preoperative Care; Prothrombin

Uremic bleeding syndrome is a recognized consequence of renal failure and can result in clinically significant sequelae. Although the pathophysiology of the condition has yet to be fully elucidated, it is believed to be multifactorial. This article is a review of both the normal hemostatic and homeostatic mechanisms that operate within the body to prevent unnecessary bleeding, as well as an in-depth discussion of the dysfunctional components that contribute to the complications associated with uremic bleeding syndrome. As a result of the multifactorial nature of this syndrome, prevention and treatment options can include one or a combination of the following: dialysis, erythropoietin, cryoprecipitate, desmopressin, and conjugated estrogens. Here, these treatment options are compared with regard to their mechanism of action, and onset and duration of efficacy. An extensive review of the clinical trials that have evaluated each treatment is also presented. Lastly, we have created an evidence-based treatment algorithm to help guide clinicians through most clinical scenarios, and answered common questions related to the management of uremic bleeding.

Topics: Deamino Arginine Vasopressin; Erythropoietin; Estrogens, Conjugated (USP); Evidence-Based Medicine; Factor VIII; Fibrinogen; Hemorrhage; Humans; Practice Guidelines as Topic; Renal Dialysis; Renal Insufficiency; Uremia; von Willebrand Factor

Desmopressin, a synthetic derivative of the antidiuretic hormone vasopressin, is the treatment of choice for most patients with von Willebrand disease and mild hemophilia A. Moreover, the compound has been shown to be useful in a variety of inherited and acquired hemorrhagic conditions, including some congenital platelet function defects, chronic liver disease, uremia, and hemostatic defects induced by the therapeutic use of antithrombotic drugs such as aspirin and ticlopidine. Finally, desmopressin has been used as a blood saving agent in patients undergoing operations characterized by large blood loss and transfusion requirements, but studies suggest that this is not as effective as other methods. This review briefly summarizes the current clinical indications on the use of desmopressin as a hemostatic agent.

Topics: Deamino Arginine Vasopressin; Drug-Related Side Effects and Adverse Reactions; Hemophilia A; Hemorrhage; Hemostatics; Humans; von Willebrand Diseases

Topics: Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Loss, Surgical; Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Factor VIIa; Hemorrhage; Humans; Recombinant Proteins

Von Willebrand disease (VWD) is the most frequent inherited bleeding disorder and is due to quantitative (types 1 and 3) or qualitative (type 2) defects of von Willebrand factor (VWF). VWD is inherited by autosomal dominant or recessive patterns, but women with mild forms are more symptomatic. VWD is classified in six VWD types (1, 2A, 2B, 2M, 2N, 3) with peculiar phenotype and genotype. The ristocetin cofactor activity (VWF:RCo) is the most useful test for VWD diagnosis, because it can mimic the interactions of VWF with its platelet receptor. Knowledge of the segments of VWF involved in the binding to its receptor and to factor VIII prompted the search for mutations in specific exons of the VWF gene, with mutations causing VWD types 2A, 2B, 2M, 2N localized in exons 18-28. In case of VWD types 1 and 3 the mutations are spread within the entire gene. Desmopressin (DDAVP) is the treatment of choice for type 1 VWD because it can induce release of normal VWF from cellular compartments. In type 3 and in severe forms of types 1 and 2 VWD, DDAVP is not effective and plasma virally inactivated VWF concentrates should be used in bleedings, surgery, and secondary long-term prophylaxis.

Topics: Blood Component Transfusion; Deamino Arginine Vasopressin; Diagnosis, Differential; Female; Hemorrhage; Hemostatics; Humans; Inheritance Patterns; Male; Mutation; von Willebrand Diseases; von Willebrand Factor

The aim of treatment of von Willebrand's disease (VWD) is to correct the dual defect of haemostasis, i.e. the abnormal platelet adhesion due to reduced and/or dysfunctional von Willebrand factor (VWF) and the abnormal coagulation expressed by low levels of factor VIII (FVIII). Desmopressin (DDAVP) is the treatment of choice for type 1 VWD because it can induce release of normal VWF from cellular compartments. Prospective studies on biological response versus clinical efficacy of DDAVP in VWD type 1 and 2 are in progress to further explore its benefits and limits as therapeutic option. In type 3 and in severe forms of type 1 and 2 VWD, DDAVP is not effective and for these patients plasma virally inactivated concentrates containing VWF and FVIII are the mainstay of treatment. Several intermediate- and high-purity VWF/FVIII concentrates are available and have been shown to be effective in clinical practice (bleeding and surgery). New VWF products almost devoid of FVIII are now under evaluation in clinical practice. Although thrombotic events are rare in VWD patients receiving repeated infusions of concentrates, there is some concern that sustained high FVIII levels may increase risk of postoperative venous thromboembolism. Dosage and timing of VWF/FVIII administrations should be planned to keep FVIII level between 50 and 150 U/dL. Appropriate dosage and timing in repeated infusions are also very important in patients exposed to secondary long term prophylaxis for recurrent bleedings.

Topics: Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Treatment Outcome; von Willebrand Diseases; von Willebrand Factor

Patients with essential thrombocythemia (ET) and polycythemia vera (PV), complicated by microvascular ischemic or thrombotic events, have shortened platelet survival, increased beta-thromboglobulin, platelet factor 4, and thrombomodulin levels, and increased urinary thromboxane B2 excretion. These are all reversible by inhibition of platelet cyclooxygenase 1 with aspirin, and are therefore indicative of platelet activation and platelet-mediated thrombotic processes. The thrombotic tendency persists as long as platelet counts are above the upper limit of normal (400 x 10 (9)/L). Despite strong evidence of in vivo platelet activation, the ex vivo platelet function tests are impaired. Platelet dysfunction in ET and PV typically is characterized by a missing second-wave adrenaline aggregation, an increased adenosine diphosphate aggregation threshold, and reduced secretion products, but a normal arachidonic acid or collagen-induced aggregation. The proposed concept is that platelets in thrombocythemia (ET and PV) are hypersensitive. Due to the existing high shear stress in the microvasculature (end-arterial circulation), platelets spontaneously activate, secrete their products, form aggregates mediated by von Willebrand factor (vWF) that transiently plug the microcirculation, deaggregate, and then recirculate as exhausted defective platelets with secondary storage pool disease on ex vivo analysis. At increasing platelet counts from below to above 1000 x 10 (9)/L, the thrombotic condition changes into an overt spontaneous bleeding tendency as a result of a functional vWF deficiency that is caused by proteolysis of large vWF multimers. This is consistent with acquired type 2 von Willebrand syndrome (AvWS). AvWS is reversible by reduction of the platelet count to normal. The acquired JAK2 V617F gain of function mutation is the cause of trilinear myeloproliferative disease with the sequential occurrence of ET and PV. Heterozygous JAK2 V617F mutation with slightly increased kinase activity is enough for the induction of spontaneous megakaryopoiesis and erythropoiesis, and an increase of hypersensitive platelets is the cause of aspirin-sensitive, platelet-mediated microvascular ischemic and thrombotic complications in ET and early PV mimicking ET. Homozygous JAK2 mutation with pronounced increase of kinase activity is associated with pronounced trilinear megakaryocyte, erythroid, and granulocytic myeloproliferation, with the most frequent clinical picture of classic

Topics: Aspirin; Bleeding Time; Blood Platelets; Deamino Arginine Vasopressin; Hemorrhage; Humans; Microcirculation; Mutation; Platelet Activation; Platelet Function Tests; Polycythemia Vera; Thrombocythemia, Essential; Thrombosis; von Willebrand Factor

Treatment of type 3 von Willebrand disease (vWD) relies on infusion with plasma-derived factor concentrates containing von Willebrand factor (vWF). Patients with types 1 and 2 vWD who do not respond satisfactorily after receiving desmopressin need treatment with concentrates. The rationale for long-term prophylaxis in vWD is obvious: prophylaxis has been successfully used in hemophilia, and joint hemorrhages with development of hemophilic arthropathy can occur, especially in type 3 vWD. In Sweden, prophylaxis for vWD began during the 1960s, and we now have experience from a cohort of 37 patients treated for a median of 11 years (range, 2 to 45 years). The majority of subjects (n = 28) have type 3 vWD. The mean dose used for treatment is 24 units factor VIII/kg body weight given one to three times weekly. Indications for prophylaxis have included joint bleeds, bleeds from nose and mouth, menorrhagia and gastrointestinal bleeds. The annual number of bleeds has decreased dramatically following onset of prophylaxis. We conclude that long-term prophylactic treatment of vWD is warranted in the majority of cases with type 3 and in some cases, depending on the clinical phenotype, for patients with other subtypes. Additional studies are ongoing in an international effort, the von Willebrand Disease Prophylaxis Network.

Topics: Adolescent; Adult; Blood Transfusion; Child; Child, Preschool; Deamino Arginine Vasopressin; Factor VIII; Female; Hemophilia A; Hemorrhage; Humans; Infant; Male; Middle Aged; von Willebrand Diseases

The current standard for the diagnosis and management of patients with congenital von Willebrand disease (vWD) includes bleeding times (BTs), PFA-100 closure time (PFA-CT), factor (F) VIII:coagulant activity (C), vWF:antigen (Ag), vWF:ristocetin cofactor activity (RCo), a sensitive vWF:collagen-binding activity (CB), ristocetin-induced platelet aggregation (RIPA), analysis of vWF multimers in low- and high-resolution agarose gels, and the response to desmopressin. Guidelines and recommendations for prophylaxis and treatment of bleedings in vWD patients with vWF/FVIII concentrates should be derived from analysis of the content of these concentrates and from pharmacokinetic studies in different types of vWD patients with severe type 1, 2, or 3 vWD. The vWF/FVIII concentrates should be characterized by labeling with FVIII:C, vWF:RCo, vWF:CB, and vWF multimeric pattern, which will determine their predicted efficacy and safety in prospective management studies. Because the bleeding tendency is moderate in type 2 and severe in type 3 vWD, and because the FVIII:C levels are subnormal in type 2 and very low in type 3 vWD patients, new guidelines using vWF:RCo unit dosing for the prophylaxis and treatment of bleeding episodes are proposed. Such guidelines should be stratified for the severity of bleeding, the type of surgery (either minor or major), and also for the severity and type of vWD (i.e., either type 2 or 3 vWD).

Topics: Coagulants; Deamino Arginine Vasopressin; Factor VIII; Guidelines as Topic; Hemorrhage; Humans; Infusions, Intravenous; von Willebrand Diseases; von Willebrand Factor

Inhibitor patients do not always respond satisfactorily to treatment with bypassing agents, and options to the standard practice are sometimes needed. Temporary inhibitor removal may be achieved using extracorporeal immunoadsorption. This technique uses a column system including either protein A or antihuman IgG. Immunoadsorption may be used as part of an immune tolerance protocol, or in the case of acute bleeds or prior to surgery, thus rendering the patient more responsive to ordinary replacement therapy with factor VIII or factor IX. Desmopressin is a valuable haemostatic agent in many situations and can be especially recommended in mild haemophilia complicated by an inhibitor. Antifibrinolytics are often administered as an adjunct therapy to the treatment protocol and have also been reported to have a direct anti-inhibitor effect.

Topics: Antifibrinolytic Agents; Coagulants; Deamino Arginine Vasopressin; Extracorporeal Circulation; Factor IX; Factor VIII; Hemophilia A; Hemorrhage; Humans; Immunosorbent Techniques; Staphylococcal Protein A

von Willebrand disease (VWD), the most common inherited bleeding disorder, is caused by a quantitative (type 1 and 3) or qualitative (type 2) defect of von Willebrand factor (VWF). In this review, the present knowledge regarding the diagnosis and the management of VWD is briefly analyzed.

Topics: Antigens; Biopolymers; Case Management; Deamino Arginine Vasopressin; Disease Management; Factor VIII; Genes, Dominant; Genes, Recessive; Hemorrhage; Hemostatic Techniques; Humans; Phenotype; Platelet Count; Protein Subunits; Retrospective Studies; von Willebrand Diseases; von Willebrand Factor

The bleeding tendency in von Willebrand disease (VWD) is heterogeneous and some patients with the mildest form of the disease have no significant bleeding symptoms throughout their lives. In some cases, the most difficult task for a clinician is to decide whether any treatment is actually required. However, cases with moderate to severe factor VIII (FVIII) and von Willebrand factor (VWF) deficiency usually require treatment to stop or prevent bleeding. Increasing autologous FVIII/VWF by desmopressin administration or providing normal allogeneic VWF through the infusion of plasma-derived concentrates can correct FVIII and VWF deficiencies and normalize or shorten bleeding time (BT). FVIII levels are the best predictors of soft tissue or surgical bleeding, while BT normalization, reflecting the correction of platelet-dependent functions of VWF, is considered a reliable indicator of an effective treatment of mucosal bleeding. Recombinant concentrates of FVIII are not indicated (apart from cases with alloantibodies against exogenous VWF), since they are devoid of VWF and lack its stabilizing effect on circulating FVIII. A very-high-purity concentrate of VWF has recently been made available, but its advantages over conventional concentrates containing both FVIII and VWF moieties are not obvious. The best way to select the appropriate treatment is to perform a test infusion with desmopressin in any patient with clinically significant VWD, provided that he/she has no contraindication to the compound or belongs to subtype with an anticipated lack of response (for example, type 3 VWD with FVIII/VWF lower than 5%).

Topics: Bleeding Time; Deamino Arginine Vasopressin; Factor VIII; Female; Hemorrhage; Hemostatics; Humans; Male; Postoperative Hemorrhage; von Willebrand Diseases; von Willebrand Factor

Topics: Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Pregnancy Complications, Hematologic; von Willebrand Diseases

Recessive type 3 von Willebrand disease (vWD) is a severe hemophilia-like bleeding disorder caused by homozygosity or double heterozygosity for two nonsense mutations (null alleles) and characterized by a strongly prolonged bleeding time (BT), absence of ristocetin-induced platelet aggregation (RIPA), absence of von Willebrand factor (vWF) protein, and prolonged activated partial thromboplastin time (APTT) due to factor VIII (FVIIIC): deficiency. Recessive severe type 1 vWD is caused by homozygosity or double heterozygosity for a missense mutation and differs from type 3 vWD by the detectable presence vWF:antigen (Ag) and FVIII:C levels between 0.09 and 0.40 U/mL. Carriers of one null allele or missense mutations are usually asymptomatic at vWF levels of 50% of normal. Mild recessive type 1 vWD may be due to a missense mutations, or one missense mutation plus blood group O. The so-called dominant type 1 vWD secretion defect and type 1 Vicenza are caused by a heterozygous missense mutation in the vWF gene that produces a mutant vWF protein having a dominant effect on the normal vWF protein produced by the normal vWF allele with regard to the defective processing, storage secretion, and/or proteolysis of vWF in endothelial cells and clearing from plasma consistent with a type 2 phenotype of vWD. Typical type 2 vWD patients, except 2N, show a defective vWF protein, decreased ratios for vWF:ristocetin cofactor [vWF:RCo]/vWF:Ag and vWF:collagen binding factor [vWF:CB]/vWF:Ag and prolonged BT. The BT is normal and FVIII:C levels clearly are lower than vWF:Ag in type 2N vWD. Multimeric analysis of vWF in plasma demonstrates that proteolysis of vWF is increased in type 2A and 2B vWD, with increased triplet structure of each band (not present in types 2M and 2U). Proteolysis of vWF is minimal in type 2C, 2D, and 2E variants that show aberrant multimeric structure of individual oligomers. vWD 2B differs from 2A by normal vWF in platelets, and increased RIPA. RIPA is normal in mild, decreased in moderate, and absent in severe type 2A vWD. RIPA is decreased or absent in 2M, 2U, 2C, and 2D; variable in 2E; and normal in 2N and dominant type 1. vWD 2M is usually mild and features decreased vWF:RCo and RIPA, and a normal or near-normal vWF multimeric pattern in a low-resolution agarose gel. vWD 2A-like or unclassifiable (2U) is distinct from 2A and 2B and typically features low vWF:RCo and RIPA with the relative lack of large vWF multimers. vWD type 2C is recessive; the

Topics: Blood Coagulation Factors; Blood Group Antigens; Deamino Arginine Vasopressin; Hemorrhage; Humans; Mutation; von Willebrand Diseases

A variety of treatment options are available at present for patients with von Willebrand disease (vWD), some of which are affordable for patients in developing countries. For most patients who have type 1 vWD, desmopressin acetate (DDAVP) is the treatment of first choice, at least for minor bleedings and for prophylaxis. It is advisable, however, to use a test dose first to note the patient's response. DDAVP is safe to use, affordable, and easy to administer. However, most patients with type 2 vWD and all patients with type 3 fail to respond to DDAVP. For these patients, other options are used. Almost all patients with vWD will benefit from fresh frozen plasma and from cryoprecipitate, and these are viable options for developing countries. Both have certain disadvantages, but they can, depending upon the circumstances and facilities, be produced in developing countries. In developed countries, factor VIII/von Willebrand factor concentrates are widely used, especially for major bleedings and for surgeries on these patients. These concentrates are safe and virus inactivated, but costly. Ancillary treatment modalities such as antifibrinolytic agents and certain hormones are usually given in conjunction with other modalities. The treatment of patients with antibodies to vWF is also described, and monitoring needs during therapy are reviewed.

Topics: Blood Coagulation Factors; Chemotherapy, Adjuvant; Deamino Arginine Vasopressin; Developing Countries; Disease Management; Hemorrhage; Humans; Practice Guidelines as Topic; Treatment Outcome; von Willebrand Diseases

Haemophilia A and B are the most common of the inherited bleeding disorders. Haemophilia in the newborn presents a number of challenges in terms of both diagnosis and management which reflect features unique to this age group. In the presence of a family history of haemophilia optimal management requires close co-operation between three individual specialist groups - obstetricians, haematologists and neonatologists, who each have an important role to play in ensuring a safe outcome for these infants. More problematic is where a family history is absent or has not been adequately elucidated in which case the diagnosis of haemophilia in the neonate will be unsuspected. Diagnostic difficulties may then arise due to failure to recognise the presence of abnormal bleeding, which is often different from that typically observed in older children with haemophilia. In addition, diagnostic investigations are complicated by physiological differences in the neonatal haemostatic system. Although major bleeding is relatively uncommon, the incidence of intracranial haemorrhage is higher during the first few days of life than at any other stage in childhood, which relates to the trauma of delivery. Controversy, however, remains on optimal strategies for both prevention and management of this potentially devastating complication.

Topics: Deamino Arginine Vasopressin; Factor IX; Factor VIII; Hemophilia A; Hemophilia B; Hemorrhage; Hemostatics; Humans; Infant, Newborn; Male; Pedigree; Vitamin K; Vitamin K Deficiency Bleeding

Pharmacological approaches to reduce blood transfusion include the protease inhibitor aprotinin, lysine-analogue antifibrinolytics synthetic arginine-vasopressin derivatives (DDAVP) and recombinant factor VII (rfVIIa). These agents are known to prevent the need for blood after major surgery (cardiac, hepatic, and orthopaedic). Among the nonhemostatic agents erythropoietin (EPO) may be effective to reduce blood requirements in medical and surgical patients. Aprotinin is consistently effective in reducing blood transfusion in cardiac and hepatic surgical procedures, but there is little data to support its use in elective orthopaedic surgery. Antifibrinolytics show no evidence of efficacy in cardiac and hepatic surgery and its use is not warranted in orthopaedic surgery. Limited data suggest that DDAVP may be effective when a defect in platelet function is demonstrated. rFVIIa emerges as a promising haemostatic agent with proven benefit to reduce bleeding in haemophiliacs with inhibitors but might also be effective in patients with thrombocytopenia and thrombopathy, as well as in life-threatening hemorrhage in postsurgical patients. Ongoing studies will established its role a possible "universal haemostatic agent". Hematopoietic cytokines, such as EPO, may have a place to avoid blood transfusion in a variety of clinical conditions, including cancer and critically ill patients.

Topics: Antifibrinolytic Agents; Aprotinin; Blood Loss, Surgical; Blood Transfusion; Deamino Arginine Vasopressin; Erythropoietin; Factor VIIa; Hematologic Diseases; Hemorrhage; Hemostatics; Humans

During the last couple of decades improved pathophysiological insight, use of improved diagnostic tools, and improved understanding of treatment requirements, have converged on an improved safety of treatment and quality of life for the patient suffering VWD. The scientific development in this area has elucidated a vast heterogeneity in VWD now appreciated as a vastly heterogeneous group of bleeding disorders. In some subtypes, dysfunctional VWF protein characteristics are clarified and logically linked with the distinct site of the VWF gene mutation abolishing specific functions of VWF, while in other subtypes such relationships have not yet been established. With the most frequently occurring variant, designated type 1, the quantitative loss in VWF seems to correlate with its reduced function. However, we are only at the beginning of the era of molecular genetics of this specific variant. Medical evidence based guidelines by ordinary standards for treatment of VWD do not exist. Therefore, treatment is based on a mechanistic approach and empirical knowledge. The review presented here focuses on the management of bleeding in VWD. Its basis is a mixture of data reported to literature and the authors' personal clinical observations. Our intention is the presentation and discussion of current issues related to VWD as well as the various pharmaceutical treatment options available for patients afflicted with von Willebrand's disease, together with some theoretical thoughts on possible future modalities.

Topics: Blood Platelets; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Mutation; Receptors, Collagen; von Willebrand Diseases; von Willebrand Factor

Topics: Antifibrinolytic Agents; Blood Transfusion; Deamino Arginine Vasopressin; Fibrin Tissue Adhesive; Hemorrhage; Hemostatics; Humans; Serine Proteinase Inhibitors; Transfusion Reaction; Vitamin K

Acquired von Willebrand disease (AvWD) is a relatively rare acquired bleeding disorder that usually occurs in elderly patients, in whom its recognition may be delayed. Patients usually present predominantly with mucocutaneous bleeding, with no previous history of bleeding abnormalities and no clinically meaningful family history. Various underlying diseases have been associated with AvWD, most commonly hematoproliferative disorders, including monoclonal gammopathies, lymphoproliferative disorders, and myeloproliferative disorders. The pathogenesis of AvWD remains incompletely understood but includes autoantibodies directed against the von Willebrand factor (vWF), leading to a more rapid clearance from the circulation or interference with its function, adsorption of vWF by tumor cells, and nonimmunologic mechanisms of destruction. Laboratory evaluation usually reveals a pattern of prolonged bleeding time and decreased levels of vWF antigen, ristocetin cofactor activity, and factor VIII coagulant activity consistent with a diagnosis of vWD. Acquired vWD is distinguished from the congenital form by age at presentation, absence of a personal and family history of bleeding disorders, and, often, presence of a hematoproliferative or autoimmune disorder. The severity of the bleeding varies considerably among patients. Therapeutic options include desmopressin and certain factor VIII concentrates that also contain vWF. Successful treatment of the associated illness can reverse the clinical and laboratory manifestations. Intravenous immunoglobulins have also shown some efficacy in the management of AvWD, especially cases associated with monoclonal gammopathies. Awareness of AvWD is essential for diagnosis and appropriate management.

Topics: Age Distribution; Age of Onset; Aged; Autoimmune Diseases; Comorbidity; Deamino Arginine Vasopressin; Diagnosis, Differential; Factor VIII; Hemorrhage; Hemostatics; Humans; Lymphoproliferative Disorders; Myeloproliferative Disorders; Paraproteinemias; Prevalence; Risk Factors; Severity of Illness Index; Treatment Outcome; von Willebrand Diseases

Over the last 4 decades, there have been very significant advances in the treatment of haemophilia. Plasma products first became available in the 1960s, beginning with cryoprecipitate and then intermediate-purity plasma concentrates, for the treatment of haemophilia A and B. The disasters of viral infections amongst people with haemophilia in the 1980s served to stimulate both the development of techniques of viral inactivation of concentrates and the manufacture of purer products. We therefore now have safe plasma products that are also pure in that they are concentrates of only the deficient protein responsible for the congenital coagulopathy. Preparations of specific coagulation proteins obtained using recombinant biotechnology techniques have been available since 1995. By contrast, pharmacological options for the treatment of the haemophilia remain very limited. The only therapeutic alternatives of real practical value which have been available in the last 30 years for the treatment of haemophilic patients are desmopressin, antifibrinolytic agents, aprotinin, concentrated oestrogens, and local haemostatic agents such as topical thrombin or fibrin glue. This article aims to assess the pharmacological basis and accumulated experience relating to these drugs when used for the prevention and treatment of bleeding in patients with haemorrhagic disorders.

Topics: Antifibrinolytic Agents; Contraindications; Deamino Arginine Vasopressin; Hemophilia A; Hemophilia B; Hemorrhage; Humans

von Willebrand disease (vWD) is a very common autosomal inherited bleeding disorder, caused by a quantitative deficiency or a qualitative structural defect of von Willebrand factor (vWF). Two main therapeutic options are available for the treatment of spontaneous bleeding episodes and for prevention of bleeding: desmopressin (DDAVP) and replacement therapy with plasma products. DDAVP is the treatment of choice for most patients with type 1 vWD. In patients with the type 3 disease and in most subjects with type 2 disease, DDAVP alone is ineffective or contraindicated, and it is usually necessary to switch to plasma concentrates containing both factor VIII (FVIII) and vWF. Concentrates subjected to virucidal treatment (e.g. solvent/detergent treatment) during manufacture should always be used in preference to cryoprecipitate. A recombinant vWF concentrate is now undergoing preclinical development and preliminary data suggest it possesses good haemostatic function and may correct the bleeding in vWD after its administration in several animal models. Although treatment of vWD is relatively simple (assuming access to even basic laboratory facilities), actual diagnosis is often far from straightforward, and the patients should be well characterized phenotypically to tailor the treatment to the different types and subtypes of the disease. It is probably wise to refer samples for the characterization to expert laboratories.

Topics: Chemotherapy, Adjuvant; Deamino Arginine Vasopressin; Factor VIII; Female; Hemorrhage; Humans; Male; Pregnancy; von Willebrand Diseases; von Willebrand Factor

Von Willebrand disease (vWD) is a frequent inherited disorder of hemostasis that affects both sexes. Two abnormalities are characteristic of the disease, which is caused by a deficiency or a defect in the multimeric glycoprotein called von Willebrand factor: low platelet adhesion to injured blood vessels and defective intrinsic coagulation owing to low plasma levels of factor VIII. There are 2 main options available for the treatment of spontaneous bleeding episodes and for bleeding prophylaxis: desmopressin and transfusional therapy with plasma products. Desmopressin is the treatment of choice for most patients with type 1 vWD, who account for approximately 70% to 80% of cases. This nontransfusional hemostatic agent raises endogenous factor VIII and von Willebrand factor 3 to 5 times and thereby corrects both the intrinsic coagulation and the primary hemostasis defects. In patients with the more severe type 3 and in most patients with type 2 disease, desmopressin is ineffective or is contraindicated and it is usually necessary to resort to plasma concentrates containing both factor VIII and von Willebrand factor. Concentrates treated with virucidal methods should be preferred to cryoprecipitate because they are equally effective and are perceived as safer. (Blood. 2001;97:1915-1919)

Topics: Blood Loss, Surgical; Combined Modality Therapy; Contraindications; Deamino Arginine Vasopressin; Endothelium, Vascular; Factor VIII; Female; Hemorrhage; Humans; Isoantibodies; Male; Myocardial Infarction; Postoperative Hemorrhage; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic; Receptors, Vasopressin; Safety; Stroke; Thrombocytopenia; Transfusion Reaction; Virus Diseases; von Willebrand Diseases; von Willebrand Factor

Topics: Antifibrinolytic Agents; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Factor VIII; Hemorrhage; Humans; Platelet Transfusion; United Kingdom; Vasopressins; von Willebrand Factor

Topics: Coagulation Protein Disorders; Deamino Arginine Vasopressin; Hemorrhage; Humans

Topics: Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Blood Coagulation Disorders; Blood Loss, Surgical; Cardiac Surgical Procedures; Contraindications; Deamino Arginine Vasopressin; Estrogens, Conjugated (USP); Hemorrhage; Hemostatics; Humans; Safety; Tranexamic Acid; Uremia

Topics: Aminocaproates; Antifibrinolytic Agents; Aprotinin; Blood Coagulation Disorders; Blood Loss, Surgical; Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Estrogens, Conjugated (USP); Hemorrhage; Hemostatics; Humans; Liver Transplantation; Tranexamic Acid

Desmopressin is a well tolerated and convenient haemostatic drug that can be used in a number of clinical conditions with bleeding diathesis. It has several effects on the haemostatic system, causing endogenous release of coagulation factor VIII, von Willebrand factor, tissue plasminogen activator and also increasing platelet adhesiveness and shortening bleeding time. The effect is virtually immediate and lasts for several hours. Side-effects are few and mostly mild. Desmopressin is suitable for home use in selected patients with bleeding diathesis. The optimal dosage is 0.3 microgram kg-1 intravenously, but the drug may also be administered subcutaneously or intranasally. In addition to the established indications, haemophilia A, von Willebrand's disease and platelet dysfunction, the drug may also be used safely in other patients with unexpected bleeding during or after surgery. The effectiveness of general prophylactic use of desmopressin, in order to diminish surgical blood loss and transfusion requirements, has not been proven, except in patients with known bleeding diathesis caused by congenital or acquired haemostatic disorders, e.g. in those taking aspirin.

Topics: Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans

This paper discusses clinical experience of the use of desmopressin in patients with either congenital or acquired bleeding disorders. The bleeding disorders reviewed herein are haemophilia A, von Willebrand's disease and platelet function disorders (congenital bleeding disorders); uraemia, liver cirrhosis and drug-induced bleeding (acquired bleeding disorders).

Topics: Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Thrombosis; von Willebrand Diseases

Topics: Animals; Blood Loss, Surgical; Deamino Arginine Vasopressin; Factor VIII; Female; Hemophilia A; Hemorrhage; Hemorrhagic Disorders; History, 18th Century; History, 20th Century; Humans; Italy; Kidney Diseases; Liver Diseases; Male; Platelet Adhesiveness; Rabbits; von Willebrand Diseases; von Willebrand Factor

Recent years have witnessed advances in the treatment of haemophilia such as the introduction of prophylaxis, continuous infusion and pharmacological treatment with desmopressin (DDAVP). Prophylactic treatment on a long-term basis appears to be effective in preventing the development of arthropathy in severe haemophilia. The largest body of experience is that from Sweden, where prophylaxis is started at the age of 1-2 years. The dosage used is 25-40 U factor VIII/IX per kilogram bodyweight given three times or twice weekly, respectively. In some cases an intravenous access device has to be used during the first years of treatment. The patients grow up like normal boys and can live virtually normal lives. The beneficial psychological impact of prophylaxis on the family cannot be overestimated. Side-effects are not more frequent with prophylaxis than with on-demand treatment. The feasibility of continuous infusion of factor VIII/IX concentrates during bleeding episodes, or as cover for surgery, has been documented. This mode of delivery increases convenience and the cost-benefit ratio of the treatment, with savings in postoperative replacement of factor concentrate of about 50-75%. Many modern concentrates are stable enough for the purpose, and several pump systems, including portable ones, are available. The haemostatic drug DDAVP can be effectively used in most cases of mild haemophilia A. Intravenous administration is to be preferred as cover for surgery or in the case of severe bleeds. There is an effective nasal spray which can also be used for home therapy in mild or moderate bleedings.

Topics: Adolescent; Catheterization, Central Venous; Catheterization, Peripheral; Child; Child, Preschool; Deamino Arginine Vasopressin; Factor IX; Factor VIII; Female; Hemarthrosis; Hemophilia A; Hemophilia B; Hemorrhage; Hemostatics; Humans; Infant; Infusions, Intravenous; Injections, Intravenous; Male; Practice Guidelines as Topic; Treatment Outcome; World Health Organization

Factor VIII auto-antibody inhibitors, though rare, may present significant and often life-threatening haemorrhage. These auto-antibodies, arising predominantly in older individuals, occur in association with autoimmune disorders, lymphoproliferative disorders, solid tumours, medications and the postpartum state. Almost half of the patients develop auto-antibodies spontaneously without an underlying medical condition. Factor VIII auto-antibody inhibitors are characterized as polyclonal IgG immunoglobulins directed against the FVIII procoagulant activity. Laboratory diagnosis is made by performing the aPTT clotting time in conjunction with a mixing study, and subsequently with specific factor assays. Auto-antibodies are quantified most commonly utilizing the Bethesda assay. Acquired inhibitors to other coagulation factors, including factors IX, XI, XIII, vWF protein, and the vitamin K-dependent proteins are extremely rare. The principles of therapy are similar to those which apply to the management of factor VIII auto-antibodies. Treatment of patients with acquired factor VIII auto-antibody inhibitors varies depending upon the underlying medical condition, the titre of the inhibitor, and the clinical presentation. Acutely bleeding patients with high-titre auto-antibodies generally respond well with infusions of porcine factor VIII concentrate, PCCs or rFVIIa. Extracorporeal plasmapheresis with exchange will acutely reduce circulating antibodies and can be used in conjunction with factor infusions and/or IgIV. Haemorrhage in a patient with a low titre auto-antibody will usually respond to high doses of human factor VIII concentrate. DDAVP may also increase factor VIII levels in patients with low-titre inhibitors. Long-term reduction of auto-antibodies can be achieved by immuno-suppressive regimens using steroids and/or cytotoxic agents, IgIV and interferon-alpha. The selection of the appropriate treatment depends upon the associated medical condition, likelihood of spontaneous remission, risk of toxicities of therapy and cost. Determining the efficacy and safety of new treatment modalities for factor VIII auto-antibodies and other coagulation factor inhibitors will require multicentre randomized clinical trials.

Topics: Adult; Aging; Animals; Antibodies, Anti-Idiotypic; Autoantibodies; Autoimmune Diseases; Blood Coagulation Disorders; Blood Coagulation Factors; Deamino Arginine Vasopressin; Factor VIIa; Factor VIII; Female; Hemophilia A; Hemorrhage; Humans; Immunization; Immunoglobulin G; Immunoglobulins, Intravenous; Immunosuppressive Agents; Incidence; Interferon-alpha; Isoantibodies; Male; Plasma Exchange; Plasmapheresis; Pregnancy; Prothrombin; Puerperal Disorders; Recombinant Proteins; Swine

Topics: Blood Platelets; Combined Modality Therapy; Cryotherapy; Deamino Arginine Vasopressin; Endothelium, Vascular; Estrogens; Hemorrhage; Humans; Kidney Transplantation; Peritoneal Dialysis; Renal Agents; Renal Dialysis; Uremia; von Willebrand Factor

Topics: Aged; Cerebrovascular Disorders; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Drug Evaluation; Hemorrhage; Humans; Middle Aged; Myocardial Infarction; Postoperative Complications; Prevalence; Risk; Thromboembolism

Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Blood Transfusion; Cardiopulmonary Bypass; Combined Modality Therapy; Deamino Arginine Vasopressin; Disseminated Intravascular Coagulation; Extracorporeal Circulation; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Thrombocytopenia; Thrombosis

Topics: Bleeding Time; Deamino Arginine Vasopressin; Hemorrhage; Humans

Postoperative bleeding is caused by alterations in the normal process of hemostasis or by a surgical problem. The role of platelets, coagulation proteins, and fibrinolysis in the control of postoperative bleeding is reviewed, as are preoperative and intraoperative factors that interfere with these normal processes. Current treatment of postoperative bleeding is discussed, including the use of positive end-expiratory pressure, control of hypertension, medication, and blood products.

Topics: Blood Coagulation; Blood Transfusion; Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Fibrinolysis; Hemorrhage; Hemostasis; Hemostatic Techniques; Humans; Intraoperative Care; Postoperative Complications; Preoperative Care

One patient with an acquired factor VIII inhibitor is reported in which an acute lower intestinal hemorrhage was successfully managed using Desmopressin (DDAVP). The patient initially had a factor VIII level of 10% with a inhibitor titer of 1.9 Bethesda units. Following administration of DDAVP the factor VIII level rose to 86% and there was a decrease in the number and volume of bloody stools. The inhibitor disappeared following treatment with corticosteroids, however the patient ultimately expired due to complications of ischemic colitis. This case and 21 previously reported cases of acquired hemophilia treated with DDAVP are reviewed. The data support a role for DDAVP in the treatment of non life threatening hemorrhage in patients with acquired hemophilia and low titer factor VIII inhibitors (< 5 Bethesda units or factor VIII > or = 5%).

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Child; Deamino Arginine Vasopressin; Factor VIII; Female; Hemophilia A; Hemorrhage; Humans; Intestinal Diseases; Male; Middle Aged

Over the past few years considerable progress has been made in elucidating the molecular genetics of hemophilia A, in carrier detection and prenatal diagnosis, and in the production of safer clotting factor concentrates. Recombinant FVIII, shown to be safe and effective in ongoing prelicensure clinical trials that began in the spring of 1987, should soon be licensed and commercially available. There is now considerable interest in beginning prophylactic therapy regimens at 1 or 2 years of age, in an attempt to prevent chronic joint disease and other complications of serious bleeding episodes. The possibility of gene insertion therapy for persons with hemophilia now seems to be a realistic one--perhaps achievable in the 1990s. Although many problems remain--major problems resulting from HIV, HCV, and HBV infections; how to deal with existing musculoskeletal problems; how to pay for the higher-priced new technologies; high titer inhibitors; just to name a few--the many recent scientific advances and their clinical applications make this an exciting time. This is truly, as indicated in the title of the proceedings of the XIX Congress of the World Federation of Hemophilia, a new decade of hopes and challenges.

Topics: Child, Preschool; Deamino Arginine Vasopressin; Dental Care; Factor VIII; Fetal Diseases; Hemarthrosis; Hemophilia A; Hemorrhage; Humans; Infant; Infant, Newborn; Prenatal Diagnosis; Prevalence; Recombinant Proteins; Virus Diseases

Recent unraveling of the molecular and cellular biology of vWF and clearer knowledge of the pathophysiology of vWD have dramatically advanced our understanding of this group of disorders. Nonetheless, safe, effective, therapeutic management remains a formidable challenge for the clinician caring for these patients.

Topics: Blood Component Transfusion; Deamino Arginine Vasopressin; Factor VIII; Female; Growth Hormone; Hemorrhage; Humans; Male; Surgical Procedures, Operative; von Willebrand Diseases; von Willebrand Factor

A broad, open, inquisitive, and semiskeptical mind must be used when approaching the bleeding patient. As in most endeavors in medicine, the history and physical examination provide an important baseline. Key laboratory tests must be quickly ordered and interpreted. Using this data base, one can quickly determine whether the hemorrhagic disorder is congenital or acquired, severe or mild, and progressive or stable. Hemostasis may fail owing to deficiencies of platelets, the plasma coagulation protein system, or endothelial disturbances. A precise diagnosis and appreciation of the tempo of the disorder will guide specific therapy.

Topics: Blood Coagulation Factors; Deamino Arginine Vasopressin; Diagnosis, Differential; Hemophilia A; Hemorrhage; Hemorrhagic Disorders; Humans

Desmopressin (1-deamino-8-D-arginine vasopressin) is a synthetic analogue of the antidiuretic hormone L-arginine vasopressin. Because it can raise circulating levels of factor VIII and von Willebrand factor, desmopressin is used for nontransfusional treatment of mild and moderate hemophilia and von Willebrand disease. Desmopressin also shortens the prolonged skin bleeding time in patients suffering from von Willebrand disease and is given to prevent or stop excessive bleeding in such conditions.

Topics: Animals; Bleeding Time; Deamino Arginine Vasopressin; Drug Evaluation; Endothelium, Vascular; Factor VIII; Hemodynamics; Hemophilia A; Hemorrhage; Humans; Liver; Stimulation, Chemical; von Willebrand Diseases

Activation and inhibition of the haemostatic system was reviewed including the interaction between the four biological systems involved in haemostasis: the vessel wall, the platelets, the coagulation system and the fibrinolytic system. The haemostatic mechanism is initiated at the site of injury through local activation of surfaces and release of tissue thromboplastin, resulting in formation and deposition of fibrin. The coagulation process is regulated by physiological anticoagulants. Activation of fibrinolysis is triggered by the presence of fibrin, and the role of tissue-type plasminogen activators (t-PA) at the site of fibrin formation in particular is emphasized. The process is regulated by physiological inhibitors, of which alpha 2-antiplasmin, histidine-rich glycoprotein and plasminogen activator inhibitor are reported to be of major physiological significance. The role of fibrinolysis in the regulation of the dynamic haemostatic balance is discussed, elucidated through examples of congenital deficiencies of the coagulation and the fibrinoytic system. Pharmacological inhibitors of fibrinolysis (i.e. epsilon-aminocaproic acid and tranexamic acid) and their possible effect on the haemostatic system are described. The systemic effects on the fibrinolytic system of surgery and oral surgery is reviewed, and it is concluded, that oral surgery has insignificant effects on blood fibrinolysis. In contrast, oral surgery induces changes of fibrinolysis in the oral environment; initially the fibrinolytic activity of saliva is reduced, due to the presence of inhibitors of fibrinolysis originating from the blood and the wound exudate. When bleeding and exudation cease, the fibrinolytic activity of the saliva will increase. Plasminogen and plasminogen activator, identified as t-PA are present in the oral environment under physiological conditions. Plasminogen is secreted in the saliva and the sources of t-PA include oral epithelial cells and gingival crevicular fluid. The presence of plasminogen and t-PA in the oral environment implies that when fibrin is present (i.e. after surgery), fibrinolysis is triggered. Haemorrhagic complications to oral surgery in patients without known defects of the coagulation system is reviewed. It is concluded that the investigations conducted to the present day do not permit final conclusions with respect to the pathophysiological role of defects in the coagulation and the fibrinolytic systems for the development of bleeding after

Topics: Anticoagulants; Blood Coagulation; Blood Platelets; Deamino Arginine Vasopressin; Fibrin; Fibrinolysis; Gingiva; Hemophilia A; Hemorrhage; Hemostasis; Hemostasis, Surgical; Humans; Mouth Mucosa; Saliva; Surgery, Oral; Tissue Plasminogen Activator; von Willebrand Diseases

Topics: Deamino Arginine Vasopressin; Factor IX; Factor VIII; Female; Genetic Carrier Screening; Hemophilia A; Hemorrhage; Hepatitis B; HIV Infections; Humans; Infant, Newborn; Pregnancy; Prenatal Diagnosis; Recombinant Proteins

Topics: Blood Loss, Surgical; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Hemorrhage; Humans

Following two early promising reports that treatment with intravenous DDAVP was helpful in reducing postoperative hemorrhage and the amount of transfusion with homologous blood products in patients who had undergone cardiac surgery with CPB, these results were not repeated in any of the follow-up studies. At the present time, the routine prophylactic use of DDAVP in cardiac surgery cannot be recommended for patients undergoing closure of atrial septal defect, valve repair or replacement, primary CABG, or in children requiring cardiac surgery. The use of DDAVP in complicated procedures or for control of severe postoperative bleeding remains controversial. In the authors' opinion, DDAVP should not be used in cardiac surgery except in patients with a presurgical DDAVP-responsive coagulopathy.

Topics: Blood Loss, Surgical; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Hemorrhage; Humans

Topics: Deamino Arginine Vasopressin; Hemorrhage; Hemostasis; Hemostasis, Surgical; Humans

The pathogenesis, clinical manifestations, and management of uremic bleeding are discussed, and the role of pharmacologic intervention in the treatment of this disorder is emphasized. Care of the patient with uremia is frequently complicated by spontaneous, life-threatening bleeding episodes. Although not completely elucidated, this bleeding tendency may be associated with ineffective binding of the von Willebrand Factor (a component of factor VIII) to platelet membranes, acquired storage-pool deficiency, and anemia. Uremic patients may develop a number of clinical manifestations, including epistaxis, purpura, and bleeding from the gastrointestinal tract. Dialysis, while frequently effective for the short term, does not completely correct platelet dysfunction. Red-blood-cell transfusions may partially reduce bleeding time; however, their use places the patient at risk for viral infection. Cryoprecipitate is often used in acute situations because of its short onset of action. Desmopressin is likewise effective when an immediate effect is desired. Conjugated-estrogen therapy appears beneficial for patients in whom a long-lasting effect is desired. Management of uremic bleeding may include dialysis, red-blood-cell transfusions, cryoprecipitate, desmopressin, and conjugated estrogens. Adverse effects, particularly the risk of viral infection, as well as duration of action, must be considered in therapy selection.

Topics: Blood Transfusion; Deamino Arginine Vasopressin; Estrogens, Conjugated (USP); Hemorrhage; Humans; Renal Dialysis; Uremia

Desmopressin (DDAVP) has been used both prophylactically and therapeutically in the management of excessive bleeding after cardiopulmonary bypass. A series of four consecutive cases is presented in which DDAVP was used to treat excessive bleeding, associated with aspirin antiplatelet therapy in three cases and after all other measures had failed in one. The therapeutic use of DDAVP in aspirin-related bleeding after bypass has not been reported previously. There was no measured haemodynamic effect of the regimen used. Bleeding ceased promptly after administration of DDAVP in all cases. No morbidity was observed in any of the patients. The indications for use of DDAVP and postulated mechanisms of action are discussed.

Topics: Adult; Aged; Angina, Unstable; Aspirin; Blood Coagulation Tests; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Drug Evaluation; Hemorrhage; Humans; Infusions, Intravenous; Middle Aged; Reoperation; Retrospective Studies

Topics: Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Hemorrhage; Humans; Postoperative Complications

Renal insufficiency is associated with a bleeding tendency. Hemorrhagic manifestations are usually mild (i.e., ecchymoses or purpura) but can be severe in occasional patients who may have gastrointestinal tract or intracranial bleeding. Modern techniques for the management of uremia have definitely reduced the incidence of severe bleeding episodes in patients with renal failure, but hemorrhages still represent a major clinical problem, particularly for patients undergoing surgery or invasive procedures. Although the pathogenesis of uremic bleeding has not been completely elucidated, in the past 10 years a number of studies have contributed substantially to our knowledge of the cause of uremic bleeding tendency and have indicated new therapeutic strategies. The present review will focus mainly on modern concepts of the cause of uremic bleeding and will critically analyze the various therapeutic approaches.

Topics: Aspirin; Blood Platelet Disorders; Deamino Arginine Vasopressin; Estrogens; Hemorrhage; Humans; Uremia

Topics: Anemia; Aspirin; Bleeding Time; Blood Platelets; Blood Transfusion; Cryoprotective Agents; Deamino Arginine Vasopressin; Erythrocyte Transfusion; Erythropoietin; Estrogens; Hemorrhage; Humans; Parathyroid Hormone; Platelet Adhesiveness; Platelet Aggregation; Thromboxane A2; Uremia; von Willebrand Factor

Hemophilia A and von Willebrand's disease are hereditary disorders associated with qualitative and quantitative abnormalities of clotting factor VIII. A major clinical feature is excessive or abnormal bleeding often necessitating the use of transfusions of pooled blood products to achieve hemostasis. Exposure to blood products places the recipient at risk for infection by the hepatitis B virus or the human immunodeficiency virus. A synthetic analog of arginine vasopressin, 1-desamino-8-D-arginine vasopressin, has been shown to increase the plasma levels of factor VIII coagulant activity and von Willebrand's factor, and clinically to improve abnormal bleeding, obviating the need to use blood products.

Topics: Deamino Arginine Vasopressin; Hemorrhage; Humans

Topics: Blood Platelet Disorders; Blood Transfusion; Deamino Arginine Vasopressin; Hemorrhage; Hepatitis, Viral, Human; Humans; Infant, Newborn; Plasma Exchange; Platelet Transfusion; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic; Thrombocytopenia; Transfusion Reaction; von Willebrand Diseases

Haemophilia is a congenital, life-long disorder that may cause major disabilities. The goal of comprehensive care is to prevent problems when possible, to treat early in order to minimize morbidity, and to restore function to disabled patients. The co-ordinated efforts of many experts are needed for success.

Topics: Aminocaproic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Blood Coagulation Factors; Blood Transfusion; Deamino Arginine Vasopressin; Dental Care; Estrogens; Factor IX; Factor IXa; Factor VIII; Hemophilia A; Hemophilia B; Hemorrhage; Humans; Oral Hygiene; Plasma; Progesterone; Self Administration; Surgical Procedures, Operative; Swine; Synovitis

Topics: Acquired Immunodeficiency Syndrome; Analgesics; Anti-Inflammatory Agents; Antifibrinolytic Agents; Blood Transfusion; Child; Child, Preschool; Danazol; Deamino Arginine Vasopressin; Factor IX; Factor VIII; Fibrinogen; Hemarthrosis; Hemophilia A; Hemorrhage; Humans; Infant; Infant, Newborn; Male; Plasma; von Willebrand Diseases

Treatment of hemophilia and von Willebrand's disease has become easier in recent years because of the development of more effective factor replacement products. The median age and the life expectancy of patients with hemophilia have risen markedly, as has the median age at death.

Topics: Acquired Immunodeficiency Syndrome; Antigens; Blood Coagulation Factors; Cerebral Hemorrhage; Danazol; Deamino Arginine Vasopressin; Factor VIII; Female; Gastrointestinal Hemorrhage; Hemophilia A; Hemorrhage; Hepatitis B; Hepatitis C; Humans; Pregnancy; Surgical Procedures, Operative; Thrombosis; Tooth Extraction; von Willebrand Diseases

Purpose The vasopressin analog desmopressin (dDAVP) is known to increase plasma levels of hemostatic factors, and preclinical studies in colorectal cancer models have demonstrated that it hampers tumor vascularization and metastatic progression. We evaluated safety and preliminary efficacy of dDAVP in rectal cancer patients with bleeding, before receiving specific oncologic treatment with surgery, chemotherapy and/or radiotherapy. Methods Patients with rectal cancer having moderate or severe rectal bleeding were enrolled in an open-label, dose-finding trial. Intravenous infusions of dDAVP were administered during two consecutive days in doses from 0.25 to 2.0 µg/kg, using single or twice daily regimen. Bleeding was graded using a score based on the Chutkan scale and tumor perfusion was evaluated by dynamic contrast-enhanced magnetic resonance imaging. Results The trial accrued a total of 32 patients. Dose-limiting toxicity occurred in patients receiving 1 µg/kg or higher. The most prominent treatment-related severe adverse event was hyponatremia. Most patients receiving the maximum tolerated dose of 0.5 µg/kg showed at least a partial hemostatic response and 58% developed a complete response with absence of bleeding at day 4 and/or at the last follow-up at day 14. Tumor perfusion was decreased in two-thirds of patients after dDAVP treatment. Conclusions dDAVP appeared as a promising hemostatic agent in rectal cancer patients with bleeding. Randomized clinical trials to confirm its effectiveness are warranted.Clinical trial registration www.clinicaltrials.gov NCT01623206.

Topics: Adult; Aged; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Infusions, Intravenous; Male; Middle Aged; Rectal Neoplasms; Treatment Outcome; Young Adult

Rhinoplasty is associated with intraoperative bleeding which affects the quality of the operation and may increase the time of surgery. The aim of this study was to assess the role of nasal spray of desmopressin on reduction in intraoperative bleeding during elective open rhinoplasty.. Conducting an interventional study in our hospital, all patient data including demographic information, medical history and laboratory tests before surgery were collected. Patients who were randomly divided into two study groups, received nasal desmopressin spray or placebo spray, 60 min before starting open septorhinoplasty. The measured variables included: bleeding volume, the operative field quality in regard to bleeding (Boezaart score), the surgeons' satisfaction in regard to bleeding during surgery (Likert scale), postoperative bruising, postoperative bleeding and menstruation.. Thirty cases were studied; 13 (46.3%) people received placebo and 17 (56.7%) received desmopressin. The Boezaart score, satisfaction scores, bleeding volume, upper eyelid ecchymosis in the group receiving desmopressin were significantly better than the control group. Postoperative bleeding was also less in the desmopressin group, but not significant as other variables. In women of each group, menstruation had no effect on the amount of bleeding, surgical field quality and surgeon satisfaction compared with non-menstruation women.. Nasal desmopressin use is an effective method for reducing intraoperative and postoperative bleeding and diminished postoperative ecchymosis which improves surgeons' satisfaction. So using the nasal form of desmopressin could be considered as method of controlling bleeding and ecchymosis in open rhinoplasty.. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Topics: Deamino Arginine Vasopressin; Double-Blind Method; Female; Hemorrhage; Hemostatics; Humans; Intraoperative Complications; Male; Nasal Sprays; Postoperative Hemorrhage; Prospective Studies; Rhinoplasty

Blood loss after cardiac surgery can be caused by impaired platelet (PLT) function after cardiopulmonary bypass. Desmopressin or 1-deamino-8-D-arginine vasopressin (DDAVP) is a synthetic analog of vasopressin. DDAVP can increase the level of von Willebrand factor and coagulation factor VIII, thus it may enhance PLT function and improve coagulation. In this study, we assessed the effects of DDAVP on PLT aggregation and blood loss in patients undergoing cardiac surgery.. A total of 102 patients undergoing valvular heart surgery (from October 2010 to June 2011) were divided into DDAVP group (n = 52) and control group (n = 50). A dose of DDAVP (0.3 μg/kg) was administered to the patients intravenously when they were being re-warmed. At the same time, an equal volume of saline was given to the patients in the control group. PLT aggregation rate was measured with the AggRAM four-way PLT aggregation measurement instrument. The blood loss and transfusion, hemoglobin levels, PLT counts, and urine outputs at different time were recorded and compared.. The postoperative blood loss in the first 6 h was significantly reduced in DDAVP group (202 ± 119 ml vs. 258 ± 143 ml, P = 0.023). The incidence of fresh frozen plasma (FFP) transfusion was decreased postoperatively in DDAVP group (3.8% vs. 12%, P = 0.015). There was no significant difference in the PLT aggregation, urine volumes, red blood cell transfusions and blood loss after 24 h between two groups.. A single dose of DDAVP can reduce the first 6 h blood loss and FFP transfusion postoperatively in patients undergoing valvular heart surgery, but has no effect on PLT aggregation.

Topics: Adult; Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation

Analyses of the bleeding tendency by means of the bleeding score (BS) have been proposed until now to confirm diagnosis but not to predict clinical outcomes in patients with inherited von Willebrand disease (VWD). We prospectively followed up, for 1 year, 796 Italian patients with different types of VWD to determine whether the previous BS of European VWD1 is useful to predict the occurrence of spontaneous bleeds severe enough to require replacement therapy with desmopressin (DDAVP) and/or von Willebrand factor (VWF)/factor VIII concentrates. Among the 796 patients included, 75 (9.4%) needed treatment of 232 spontaneous bleeding events. BS >10 and VWF:ristocetin cofactor activity <10 U/dL were associated with the risk of bleeding, but only a BS >10 remained highly associated in a multivariable Cox proportional hazard model (adjusted hazard ratio: 7.27 [95% confidence interval, 3.83-13.83]). Although the bleeding event-free survival was different in VWD types, only a BS >10 could predict for each type which patient had bleeding events severe enough to require treatment with DDAVP and/or concentrates. Therefore, BS can be considered a simple predictor of clinical outcomes of VWD and may identify patients needing intensive therapeutic regimens.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Deamino Arginine Vasopressin; Disease-Free Survival; Factor VIII; Female; Follow-Up Studies; Hemorrhage; Hemostatics; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Severity of Illness Index; Survival Rate; von Willebrand Diseases; von Willebrand Factor

Accelerated clearance of von Willebrand factor (VWF) has been recently identified as a major pathophysiologic mechanism inducing low VWF in some patients with von Willebrand disease (VWD). The frequency of bleeding and the best treatment of these patients have never been evaluated prospectively in large series of patients. It was the aim of the present study to prospectively evaluate clinical events of 60 heterozygous patients with VWD Vicenza (VWD-VI) carrying R1205H VWF mutation and 23 with C1130F mutation, both characterised by markedly increased VWF clearance. During 71 months of follow-up, 65% of patients with VWD-VI and 61% with C1130F required treatment. The rate of spontaneous bleeding requiring consultation/treatment was 7.5/100 patients-year in patients with C1130F mutation vs. 1.9/100 patients-year in those with R1205H (p=0.004). This difference persisted also by multivariate analysis adjusted for sex, age and blood group (hazard ratio [HR]=3.3 for C1130F, 95% confidence interval [CI] 1.16-9.27) and females were at greater risk of bleeding (HR=3, 95%CI 1.01-9.93) because of menorrhagia. Only 3/15 (20 %) women in fertile age with VWD-VI compared to 8/9 (89 %) with C1130F mutation required consultation/treatment for menorrhagia (iron supplementation, combined oral contraceptives, tranexamic acid). Almost all dental extractions, minor surgeries and deliveries occurring during follow-up were successfully managed with desmopressin. Major surgery required factor VIII/VWF concentrates, but a few cases benefited from desmopressin. In conclusion, similar to patients with type 1 VWD, also in patients with increased VWF clearance desmopressin maintains a major therapeutic role.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Hemorrhage; Hemostatics; Humans; Infant; Italy; Male; Menorrhagia; Middle Aged; Mutation; Prospective Studies; Risk; Sex Factors; von Willebrand Disease, Type 1; von Willebrand Diseases; von Willebrand Factor

Bleeding complications occur in one-third of percutaneous kidney biopsies and increase costs of the hospital stay. The aim of the study was to evaluate the effect of prebiopsy administration of desmopressin acetate versus placebo in the incidence of postbiopsy bleeding complications.. Double-blind randomized controlled clinical trial.. We enrolled all patients with serum creatinine level ≤1.5 mg/dL and/or estimated glomerular filtration rate ≥60 mL/min/1.73 m(2) and normal coagulation parameters undergoing ultrasound-guided biopsy of the native kidney in our unit from August 2008 to December 2009.. We examined prebiopsy subcutaneous administration of desmopressin acetate, 0.3 μg/kg, compared with placebo.. The primary outcome was incidence of bleeding complications. Secondary outcomes were hematoma size, postbiopsy hemoglobin level, coagulation parameters, glomerular filtration rate, blood pressure, and length of hospital stay.. 162 adult patients (88 men and 74 women) were enrolled; 80 were allocated to desmopressin treatment, and 82, to the placebo group. Desmopressin compared with placebo significantly decreased the risk of postbiopsy bleeding (11 of 80 [13.7%] vs 25 of 82 [30.5%]; relative risk, 0.45; 95% CI, 0.24-0.85; P = 0.01), hematoma size (median, 208 [25th-75th percentile, 120-300] vs 380 [25th-75th percentile, 270-570] mm(2); P = 0.006] in the 36 patients who experienced bleeding, and mean hospital stay (4.9 ± 1.1 vs 5.9 ± 1.7 days; P = 0.004); postbiopsy hemoglobin levels were not affected significantly in either group.. Single-center design of the study.. Prebiopsy desmopressin administration decreases the risk of bleeding and hematoma size in patients undergoing percutaneous kidney biopsy without a cost increase.

Topics: Adult; Biopsy; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Hemorrhage; Hemostatics; Humans; Incidence; Injections, Subcutaneous; Kidney; Kidney Diseases; Male; Retrospective Studies; Treatment Outcome; Ultrasonography

An open-label multicentre trial was conducted to evaluate high-dose DDAVP (desmopressin acetate) intranasal spray (Stimate; 1.5 mg mL(-1)), for the control of bleeding in 333 patients with mild haemophilia A, mild or moderate type 1 von Willebrand disease, or symptomatic carriers of haemophilia A. Overall, 278 patients received 2170 doses of high-dose DDAVP intranasal spray (1.5 mg mL(-1)). Using study-defined guidelines, patients evaluated the efficacy of high-dose DDAVP intranasal spray (1.5 mg mL(-1)) as 'excellent' or 'good' in 743 (95%) of 784 bleeding episodes. It demonstrated 'excellent' results in 384 (93%) of 413 administrations for prophylaxis and in eight of eight uses prior to acute surgical or dental procedures. When used for the treatment of menorrhagia, the efficacy of high-dose DDAVP intranasal spray (1.5 mg mL(-1)) was rated as 'excellent' after 655 (92%) of 721 daily uses. Of 2170 doses of high-dose DDAVP intranasal spray (1.5 mg mL(-1)), 172 (8%) were associated with adverse events. A total of 272 adverse events were reported among 80 patients. Of these, 239 (88%) were mild or moderate in intensity and only one patient was removed from the study due to an adverse event. These results demonstrate the safety and efficacy of high-dose DDAVP intranasal spray (1.5 mg mL(-1)) for control of bleeding episodes in patients with mildly decreased levels of factor VIII, von Willebrand factor, or both.

Topics: Administration, Intranasal; Adolescent; Adult; Blood Loss, Surgical; Child; Child, Preschool; Cohort Studies; Consumer Product Safety; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Hemophilia A; Hemorrhage; Heterozygote; Humans; Male; Menorrhagia; Middle Aged; Therapeutic Equivalency; von Willebrand Diseases

Bleeding after dental extractions is very frequent in patients with von Willebrand disease (vWD) and in the past often necessitated transfusions with factor VIII/von Willebrand factor concentrates (vWFc). To evaluate the benefits of a standard local therapy on bleeding complications during oral surgery, 63 consecutive patients with vWD were analysed retrospectively. All types of vWD were included: type 1 (n=31), type 2 (n=22) and type 3 (n=10). All the patients had dental extractions or periodontal surgery at the same hospital by the same oral surgeons. All cases had been given tranexamic acid (TA) before and for 7 days after surgery. As additional local therapy fibrin glue (FG) was used during surgery in several patients. Additional systemic therapies were: desmopressin (DDAVP, 0.3 microg kg-1) and fVIII/vWF concentrates (vWFc, 40 U kg-1) given as a single dose before surgery. The 29 subjects (46%) treated locally did not bleed. Among the remaining cases, 24 (38%) were given DDAVP as additional systemic therapy and 6 (9.5%) received vWFc. There was bleeding after surgery in only two cases who had been given local FG (type 2 B) or systemic vWFc (type 3), but bleeding was stopped with an additional local application of FG. Our data suggest that a standard local therapy with TA and FG with DDAVP can prevent bleeding complications during oral surgery in the majority of patients (84%) with vWD and reduce the need for concentrates, with all their possible complications and high costs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Deamino Arginine Vasopressin; Diagnosis, Differential; Disease Management; Factor VIII; Female; Fibrin Tissue Adhesive; Hemorrhage; Hemostasis; Hospitalization; Humans; Male; Middle Aged; Oral Hemorrhage; Oral Surgical Procedures; Periodontal Diseases; Postoperative Hemorrhage; Retrospective Studies; Tooth Extraction; Tranexamic Acid; von Willebrand Diseases; von Willebrand Factor

Patients with monoclonal gammopathies of uncertain significance (MGUS) may develop an acquired bleeding disorder similar to congenital von Willebrand disease, called acquired von Willebrand syndrome (AvWS). In these patients, measures to improve hemostasis are required to prevent or treat bleeding episodes. We diagnosed 10 patients with MGUS and AvWS: 8 had IgGkappa (3) or lambda (5) MGUS and 2 IgM-kappa MGUS. Three therapeutic approaches were compared in them: (1) desmopressin (DDAVP), (2) factor VIII/von Willebrand factor (FVIII/vWF) concentrate, and (3) high-dose (1 g/kg/d for 2 days) intravenous Ig (IVIg). In patients with IgG-MGUS, DDAVP and FVIII/vWF concentrate increased factor VIII and von Willebrand factor in plasma, but only transiently. IVIg determined a more sustained improvement of the laboratory abnormalities and prevented bleeding during surgery (short-term therapy). In addition to the standard 2-day infusion protocol, a long-term IVIg therapy was performed in 2 patients with IgG-MGUS: repeated (every 21 days) single infusions of IVIg did improve laboratory abnormalities and stopped chronic gastrointestinal bleeding. On the other hand, IVIg failed to correct laboratories abnormalities in patients with IgM-MGUS. These comparative data obtained in a relative large and homogeneous group of patients with AvWS and MGUS confirm that DDAVP and FVIII/vWF concentrates improve the bleeding time (BT) and FVIII/vWF measurements only transiently, whereas IVIg provides a sustained treatment of AvWS associated with IgG-MGUS, but not with IgM-MGUS.

Topics: Adult; Aged; Autoimmune Diseases; Bleeding Time; Cross-Over Studies; Deamino Arginine Vasopressin; Factor VIII; Female; Hemorrhage; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Paraproteinemias; Paraproteins; Treatment Outcome; von Willebrand Diseases; von Willebrand Factor

Desmopressin is the treatment of choice in most patients with von Willebrand disease (vWD) and mild hemophilia A (HA). Several studies have demonstrated that the intravenous and subcutaneous route of administration are equivalent in terms of pharmacokinetics and clinical efficacy. Home therapy of vWD and mild HA is desirable but so far there have been only a few case reports and no prospective studies. We report the results of a prospective study of home therapy in patients with vWD and mild-moderate HA using concentrated desmopressin self-administered subcutaneously. Clinical efficacy and safety were assessed by the patient using a questionnaire and direct interview. The patients were instructed on self-administration and dosage, reasons for treatment, recognition of side effects and recording clinical efficacy. The study lasted 12 months (range 6-17). During this time, 43/100 (43%) of the enrolled vWD patients (median basal VIII:C 24%, range 9-49) and 36/69 (52%) of HA patients (median basal VIII:C 10%, range 5-34) self-administered the drug. A total of 127 bleeding episodes requiring treatment occurred in patients with vWD and 92 in HA patients. There were 10 treatment failures of which 7 required in-hospital treatment. Overall, in 94% of treatments (excluding menorrhagia) the response was scored as excellent or good. In 86% of treated episodes of menorrhagia the response was scored as excellent or good. According to the patients, 81% of clinical situations would have required in-hospital treatment. Mild flushing, with or without headache, was the only consistent side-effect, reported in about 30% of treatments. In conclusion, home therapy with subcutaneous desmopressin for von Willebrand disease and hemophilia A was well accepted by the patients and proved feasible, efficacious and safe for the prevention or prompt treatment of bleeding.

Topics: Adolescent; Adult; Aged; Child; Deamino Arginine Vasopressin; Hemophilia A; Hemorrhage; Humans; Infusions, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Prospective Studies; Self Administration; Treatment Outcome; von Willebrand Diseases

Patients on cardiopulmonary bypass (CPB) have an increased susceptibility to postoperative bleeding. Previous reports using desmopressin acetate (DDAVP) for the prevention of postoperative bleeding have given contradictory results, whereas the protease inhibitor aprotinin has been shown to reduce blood loss after this type of surgery. This randomized study was performed to assess the efficacy of DDAVP versus aprotinin in the prevention of bleeding after CPB.. One hundred nine of 122 eligible patients were randomized to four different groups: Group A (n = 28) received aprotinin starting with a bolus of 2 x 10(6) KIU followed by a continuous infusion of 0.5 x 10(6) KIU/h until the end of surgery; group B (n = 25) received of DDAVP 0.3 micrograms/kg i.v. on completion of CPB; group C (n = 28) received two doses of DDAVP, the first as in group B and an additional dose 6 hours after surgery; group D (n = 28) received no treatment. There was a marked reduction of postoperative blood loss either at 12 hours (P < .01) or 72 hours (P < .02) in the aprotinin group compared with all other groups, whereas no significant effect was observed in either of the two DDAVP regimens. A significant reduction in the amount of blood used was observed only in the aprotinin group (P < .01). Of the plasma fibrinolytic components assayed, there was a significant reduction of the fibrin degradation product generation in the aprotinin group (P < .001), whereas a significant systemic hyperfibrinolysis was observed in both DDAVP-treated groups and the control group. No side effects related to the study drugs were observed in any patient.. Aprotinin inhibited fibrinolysis; this correlated with a significant reduction of postoperative blood loss and need for blood replacement after CPB. Neither one nor two doses of DDAVP had a beneficial effect. Aprotinin offers a better alternative than DDAVP in the prevention of bleeding after CPB.

Topics: Aprotinin; Blood Loss, Surgical; Blood Transfusion; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Female; Fibrinolysis; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies

Although laboratory coagulation tests permit a rational approach to both diagnosis and management of coagulation disorders after cardiopulmonary bypass, their clinical utility is limited by delays in obtaining results. This study was designed to evaluate prospectively the impact of on-site coagulation testing on blood product use, operative time, and intraoperative management of microvascular bleeding. Patients who underwent cardiac procedures involving cardiopulmonary bypass and subsequently developed microvascular bleeding were randomly assigned to receive either standard therapy (n = 36) or therapy defined by a treatment algorithm based on results from an on-site coagulation monitoring laboratory (n = 30). No differences were found between treatment groups in hematologic assay data, operative procedures, or duration of cardiopulmonary bypass. Patients treated in accordance with on-site laboratory results (algorithm therapy) received significantly less intraoperative fresh frozen plasma (0.4 +/- 1.1 U versus 2.4 +/- 2.8 U; p = 0.0006) during the treatment interval, had shorter operative times, and had less mediastinal chest tube drainage during the initial perioperative interval (158 +/- 169 ml versus 326 +/- 258 ml; p = 0.003) than did patients in the standard therapy group. Patients who underwent algorithm therapy also received fewer platelet (1.6 +/- 5.9 versus 6.4 +/- 8.2 U; p = 0.02) and red blood cell (1.9 +/- 1.7 U versus 4.1 +/- 4.1 U; p = 0.01) transfusions after the operation. Nine of 36 (25%) standard group patients received initial therapy which differed from that which would have been guided by the on-site algorithm protocol. Our findings indicate that rapid and accurate coagulation test results can guide specific therapy and optimize treatment of microvascular bleeding in patients who undergo cardiac operations.

Topics: Blood Coagulation Tests; Blood Transfusion; Cardiac Surgical Procedures; Clinical Protocols; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostasis, Surgical; Humans; Intraoperative Complications; Male; Microcirculation; Monitoring, Intraoperative; Plasma; Platelet Transfusion; Prospective Studies; Protamines

Aspirin induces a haemorrhagic diathesis that persists for at least 1 week after discontinuation of the drug. The effect of the vasopressin analogue desmopressin was studied in 12 patients treated with aspirin who were undergoing cholecystectomy. Desmopressin was given to six of these patients. There were five postoperative bleeding complications; all occurred in patients who had not received desmopressin (P < 0.05). The bleeding time was prolonged in aspirin-treated patients and normalized by desmopressin (P < 0.05). Desmopressin can be used safely to prevent bleeding induced by aspirin.

Topics: Adult; Aged; Aspirin; Bleeding Time; Cholecystectomy; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications

Cardiopulmonary bypass during open-heart surgery is sometimes associated with excessive perioperative bleeding. Following a non-randomized study suggesting that desmopressin acetate (desmopressin) reduced blood product requirements in these patients, we conducted a double-blind, placebo-controlled randomized trial of desmopressin (0.3 micrograms/kg, i. v.) in 92 patients with overt bleeding and a prolonged bleeding time. Mean blood loss during the first 24 h post-treatment was similar in the desmopressin and placebo groups (582 vs 465 ml, respectively; p = 0.15). Red-cell (p = 0.76), fresh frozen plasma (r = 0.66) and platelet unit (p = 0.74) requirements were also similar. The haemostatic effect of desmopressin has been attributed to the release of von Willebrand factor (vWF) and a reduced bleeding time. In our study, vWF and factor VIII:C levels increased while the bleeding time decreased significantly at 90 min and 24 h in both groups and, although vWF and factor VIII:C levels were slightly higher in desmopressin-treated patients at 90 min, the difference was not significant. Thrombin-antithrombin III complex, fibrinogen degradation product and tissue plasminogen activator levels, reflecting activation of the coagulation and fibrinolytic systems, respectively, decreased uniformly in both groups. We conclude that desmopressin is not useful in reducing blood loss or blood product requirements in patients with excessive immediate postoperative bleeding.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Transfusion; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Double-Blind Method; Female; Hemorrhage; Hemostasis; Humans; Male; Middle Aged; Postoperative Complications

It has been suggested that desmopressin acetate has been effective in reducing hemorrhage after coronary artery bypass grafting in patients receiving aspirin before operation. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine the effectiveness and safety of desmopressin in these patients. Sixty-five patients pretreated with aspirin within 7 days before their scheduled elective coronary artery bypass grafting were randomized to receive desmopressin (0.3 micrograms/kg) or placebo after cessation of bypass and reversal of heparin with protamine. The demographic characteristics and last dose of aspirin were similar in both groups. There was a significant reduction in postoperative blood loss noted between groups for both chest tube blood loss (833 +/- 311 ml for the 1-desamino-8-D-arginine vasopressin [desmopressin] group versus 1176 +/- 674 ml for the placebo group; p = 0.016) and total blood loss (1215 +/- 381 ml for the desmopressin group versus 1637 +/- 761 ml for the placebo group; p = 0.0097). Despite the differences in blood loss between the two groups, the red cell transfusions were not significantly different, but the use of platelets was less in the desmopressin group and almost achieved statistical significance (p = 0.053). Neither was there a difference in the occurrence of thrombotic complications between groups. It appears that desmopressin in this specific subgroup of patients receiving preoperative aspirin is effective as a prophylactic agent for reduction of postsurgical hemorrhage.

Topics: Aged; Aspirin; Blood Coagulation Factors; Cardiopulmonary Bypass; Coronary Artery Bypass; Deamino Arginine Vasopressin; Double-Blind Method; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Function Tests; Postoperative Complications; Prospective Studies; Treatment Outcome

We report a study undertaken to test the biological effect of intranasal 1-deamino-8-D-arginine vasopressin (DDAVP) and its efficacy in the treatment of bleedings in patients with mild factor VIII deficiency. The biological study was carried out in 20 patients: an increase of factor VIII:C and von Willebrand factor antigen levels was observed after inhalation of DDAVP at average post/pre inhalation ratios of 2.80 and 1.72, respectively. No relevant alterations of fibrinolysis were noted. In fact, we only observed a simultaneous increase of tissue plasminogen activator and plasminogen activator inhibitor, without modification of D-dimer. In 10 cases intranasal DDAVP has been used in the prevention or in the treatment of bleeding complications: no bleedings were observed.

Topics: Administration, Intranasal; Adolescent; Adult; Child; Deamino Arginine Vasopressin; Drug Evaluation; Factor VIII; Fibrinolysis; Hemophilia A; Hemorrhage; Humans; Immunologic Factors; Middle Aged

Topics: Adolescent; Deamino Arginine Vasopressin; Double-Blind Method; Female; Hemorrhage; Hemostasis, Surgical; Humans; Infusions, Intravenous; Intraoperative Complications; Male; Randomized Controlled Trials as Topic; Scoliosis; Spinal Fusion

Bleeding in coronary artery bypass procedures increases morbidity and exposes patients to the risks associated with blood transfusion. Desmopressin acetate (DDAVP), a synthetic vasopressin analogue, may limit bleeding during cardiac surgery. In a prospective randomized trial, the authors evaluated the ability of DDAVP to reduce perioperative bleeding during uncomplicated coronary bypass operations. Sixty-two patients who underwent coronary artery bypass grafting were randomized to receive intraoperatively either a placebo or DDAVP. Both groups were similar with respect to operative characteristics and preoperative hematologic profiles, von Willebrand factor levels increased postoperatively in both placebo (2.77 +/- 1.06 versus 2.17 +/- 1.51 U) and DDAVP groups (2.75 +/- 0.94 versus 1.80 +/- 0.88 U). Only the increase in the DDAVP groups was significant (p less than 0.001). There was no difference in total blood loss between the placebo (1826 +/- 849 ml) and DDAVP groups (1716 +/- 688 ml). Total red cell transfusions were similar in placebo (3.4 +/- 1.3 units of blood) and DDAVP groups (3.6 +/- 0.8 units). These results do not support the intraoperative use of DDAVP to reduce perioperative bleeding in routine coronary artery bypass surgery.

Topics: Blood Transfusion; Coronary Artery Bypass; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Count; Postoperative Complications; Prospective Studies; Randomized Controlled Trials as Topic; von Willebrand Factor

We investigated the effect of an intraoperative desmopressin acetate infusion on blood loss after cardiac operation in 60 children, by using a prospective, randomized, double-blind trial. Thirty patients received a desmopressin dose of 0.3 microgram/kg intravenously over 15 minutes at the conclusion of cardiac bypass, and 30 received a saline placebo. The two groups were comparable with respect to age, sex, cardiac lesion, presence of cyanosis, and prevalence of Down's syndrome. Results showed no significant difference in postoperative blood loss between the two groups (30.5 +/- 37.9 ml/kg in the placebo group versus 40.0 +/- 33.1 ml/kg in the desmopressin group). Postoperative bleeding time, total urine output, postinfusion hemodynamics, and postoperative coagulation studies did not differ significantly between the two groups. We conclude that postbypass desmopressin infusion does not reduce blood loss in children undergoing cardiac operations.

Topics: Cardiac Surgical Procedures; Child, Preschool; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Female; Hemorrhage; Hemostasis, Surgical; Humans; Infusions, Intravenous; Intraoperative Period; Male; Postoperative Complications; Prospective Studies; Random Allocation; Urine

Previous studies have suggested that desmopressin may reduce the bleeding diathesis that often complicates open-heart surgery. To pursue this question further, we performed a double-blind, randomized, placebo-controlled trial to determine whether the previously reported beneficial effect of desmopressin on hemostasis during complex cardiac surgery was applicable to all elective cardiac surgical procedures involving cardiopulmonary bypass. In 150 consecutive patients, most of whom underwent primary coronary-artery bypass grafting, we compared the effects of intravenous desmopressin (0.3 microgram per kilogram of body weight) with those of saline placebo on postoperative blood loss and the need to replace blood products. The median amount of blood lost within the first 24 hours after operation was similar in the desmopressin and placebo groups (865 vs. 738 ml; P = 0.26). The postoperative use of blood replacement products did not differ significantly between the groups (1025 ml [95 percent confidence interval, 300 to 4140 ml] in the desmopressin group and 860 ml [247 to 5346 ml] in the placebo group). Desmopressin is believed to exert its hemostatic effect by releasing von Willebrand factor. The level of ristocetin cofactor, a functional index of the level of von Willebrand factor, was increased approximately twofold from base line in both treatment groups 90 minutes and 24 hours after the administration of medication. Similarly, the levels of von Willebrand factor multimers increased uniformly in both groups. These findings may be consistent with a normal stress response of von Willebrand factor to major surgery and could explain our failure to detect a therapeutic effect of desmopressin. We conclude that the majority of patients who undergo elective cardiac surgery receive no hemostatic benefit from the use of desmopressin.

Topics: Adult; Aged; Blood Transfusion; Blood Volume; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Hemorrhage; Hemostatics; Humans; Middle Aged; Postoperative Complications; Random Allocation; Time Factors; von Willebrand Factor

It has been suggested that desmopressin acetate (DDAVP) administration reduces blood loss after cardiac surgery. We have investigated the effect of DDAVP administration in a double-blind, randomized, prospective trial including 100 patients placed on cardiopulmonary bypass during surgery. Fifty patients received 0.3 micrograms/kg DDAVP and 50 patients received a placebo administered in a 50 ml saline solution over 15 min when cardiopulmonary bypass had been concluded. Results showed no significant differences either in total blood loss per square meter (458 +/- 206 ml in the DDAVP group vs 536 +/- 304 ml in the placebo group) or in necessity for red cell transfusions (1642 +/- 705 ml in the DDAVP group vs 1574 +/- 645 ml in the placebo group) in the first 72 hr after surgery. Only intraoperative blood loss per square meter was significantly lower (p less than .02) in the DDAVP group (131 +/- 106 ml) as compared with the placebo group (193 +/- 137 ml). The prolongation of bleeding time and the decrease of factor VIII:C and factor VIII:von Willebrand factor 90 min after treatment were significantly lower (p less than .001) in the DDAVP group as compared with the placebo group. We conclude that the administration of DDAVP in patients placed on cardiopulmonary bypass during surgery does not reduce total blood loss and is only effective in reducing intraoperative bleeding.

Topics: Blood Transfusion; Cardiopulmonary Bypass; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Erythrocyte Transfusion; Hemorrhage; Humans; Intraoperative Complications; Postoperative Complications; Prospective Studies; Random Allocation; Time Factors

Impairment of platelet function commonly occurs after cardiopulmonary bypass, and may result in substantial bleeding. Because desmopressin acetate (a synthetic analogue of vasopressin) shortens bleeding time in a variety of platelet disorders, a controlled clinical trial of intravenous desmopressin was performed in 39 patients with excessive mediastinal bleeding (greater than 100 ml/h) and a prolonged template bleeding time (greater than 10 minutes) more than 2 hours after termination of cardiopulmonary bypass. Twenty-three desmopressin recipients and 16 control patients (no desmopressin) were similar in surgical procedure, pump time, platelet count, template bleeding time and amount of bleeding before therapy (p = NS). Compared with the control group, the patients receiving desmopressin (20 micrograms; mean 0.3 micrograms/kg) utilized fewer blood products (29 +/- 19 versus 15 +/- 13 units/patient; p less than 0.05), especially platelets (12 +/- 9 versus 4 +/- 7 units/patient; p = 0.004), while achieving a similarly effective reduction in mediastinal bleeding (4.8- and 4.3-fold, p = 0.001 for both). Severe platelet dysfunction was partially corrected within 1 hour after desmopressin infusion, during which interval no blood products were administered: the template bleeding time shortened (from 17 to 12.5 minutes, p less than 0.05), whereas the platelet count remained unchanged (at 96 +/- 35 and 105 +/- 31 X 10(3)/mm3, p = NS). The plasma levels of two factor VIII components increased: procoagulant activity (VIII:C) from 0.97 +/- 0.43 to 1.52 +/- 0.74 units/ml (p less than 0.05) and von Willebrand factor (VIII:vWF) from 1.28 to 1.78 units/ml (p less than 0.05); these increases correlated with the shortening of the bleeding time (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Platelet Disorders; Blood Transfusion; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Hematologic Tests; Hemorrhage; Humans; Myocardial Infarction; Postoperative Period; Reoperation

Bleeding after cardiopulmonary bypass remains a cause for concern, requiring reexploration of the chest in approximately 3 percent of patients who have had operations on the heart. We examined the possibility that this problem might be alleviated by desmopressin acetate (DDAVP), which increases the plasma level of von Willebrand factor and improves hemostasis in mild hemophilia and other conditions associated with defective platelet function. In a double-blind, prospective, randomized trial, we studied the effect of intraoperative desmopressin acetate in 70 patients undergoing various cardiac operations requiring cardiopulmonary bypass. Patients undergoing uncomplicated primary coronary-artery bypass grafting were not included. The drug significantly reduced mean operative and early postoperative blood loss (1317 +/- 486 ml in the treated group vs. 2210 +/- 1415 ml in the placebo group); of the 14 patients whose 24-hour blood loss exceeded 2000 ml, 11 had received the placebo. Plasma levels of von Willebrand factor were higher after desmopressin acetate than after placebo. Patients with the most bleeding had relatively low levels of von Willebrand factor before operation, suggesting a role for this factor in the hemorrhagic tendency induced by extracorporeal circulation. There were no untoward side effects of desmopressin acetate. We conclude that the administration of desmopressin acetate can be recommended to reduce blood loss in patients undergoing complex cardiac operations. The beneficial effect of the drug on hemostasis after cardiopulmonary bypass may be related to its effect on von Willebrand factor.

Topics: Adult; Aged; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Female; Hemorrhage; Hemostasis; Humans; Intraoperative Care; Male; Middle Aged; Postoperative Complications; Prospective Studies; Random Allocation; von Willebrand Factor

In a randomized double-blind cross-over trial we gave either 1-deamino-8-D-arginine vasopressin or placebo to 12 patients with uremia, hemorrhagic tendencies, and prolonged bleeding times. After vasopressin infusion, all patients had shortened bleeding times, with the effect lasting for at least four hours in most cases. Platelet count, platelet cyclic AMP levels, platelet retention on glass beads, plasma fibronectin, serum thromboxane B2 and residual prothrombin, hematocrit, and plasma osmolarity were unchanged after vasopressin. A consistent post-infusion increase in factor VIII coagulant activity and, to a lesser extent, in factor VIII-related antigen and ristocetin cofactor accompanied the shortening of bleeding time. In addition, vasopressin induced the appearance in plasma of larger von Willebrand-factor multimers than those present in the resting state. The compound was given to nine additional patients with acute or chronic renal failure and prolonged bleeding times, before major surgery or renal biopsy. In these patients, shortening of the bleeding time was associated with normal hemostasis. Our findings indicate that 1-deamino-8-D-arginine vasopressin can be used for temporary correction of bleeding time and may prevent surgical bleeding in patients with uremia.

Topics: Adult; Antigens; Arginine Vasopressin; Bleeding Time; Clinical Trials as Topic; Deamino Arginine Vasopressin; Double-Blind Method; Factor VIII; Female; Fibrinogen; Hemorrhage; Humans; Male; Middle Aged; Platelet Function Tests; Postoperative Complications; Random Allocation; Uremia; von Willebrand Factor

Peri-procedural management of von Willebrand disease (VWD) utilizes von Willebrand factor (VWF) concentrates or desmopressin (DDAVP) to increase VWF levels. DDAVP is safe, easily administered, and inexpensive. Currently, a consensus definition for adequate DDAVP response is lacking, and outcomes of peri-procedural DDAVP use in VWD patients are seldom reported.. This single-centre retrospective review aims to characterize DDAVP-responsiveness and assess clinical outcomes of peri-procedural DDAVP use in VWD.. We reviewed records for all our adult VWD patients (age ≥18 years) who underwent DDAVP challenge testing between January 2007 and January 2022. DDAVP-responsiveness was assessed using six definitions. Bleeding outcomes following procedures covered by DDAVP were classified as excessive or expected bleeding.. Eighty-four of 94 (89.4%) patients were DDAVP-responsive by our definition (1-h VWF Activity/Factor VIII ≥0.50 IU/mL). However, the proportion of DDAVP-responders varied from 53.2% to 91.5%, depending on the literature definition used. Ninety-nine procedures pre-treated with DDAVP were performed during the study period. Eighty-six (86.7%) procedures (31 major; 55 minor) were covered with only DDAVP ± tranexamic acid (TXA). Excessive bleeding occurred following 4/31 major procedures and 2/55 minor procedures (both performed in a single patient with a bleeding score of 16). When covered with DDAVP+Factor ± TXA, one each of 10 major and 3 minor procedures (performed in 2 patients with bleeding scores 15-16) resulted in post-procedural bleeding.. Peri-procedural DDAVP prophylaxis appears to be effective among individuals with VWD. Beyond DDAVP-responsiveness, patient bleeding history and procedure invasiveness should be considered in determining suitability for DDAVP prophylaxis.

Topics: Adolescent; Adult; Deamino Arginine Vasopressin; Factor VIII; Hemorrhage; Humans; Retrospective Studies; Tranexamic Acid; von Willebrand Diseases; von Willebrand Factor

Trauma teams are often faced with patients on antithrombotic (AT) drugs, which is challenging when bleeding occurs. We sought to compare the effects of different AT medications on head injury severity and hypothesized that AT reversal would not improve mortality in severe traumatic brain injury (TBI) patients.. An Eastern Association for the Surgery of Trauma-sponsored prospective, multicentered, observational study of 15 trauma centers was performed. Patient demographics, injury burden, comorbidities, AT agents, and reversal attempts were collected. Outcomes of interest were head injury severity and in-hospital mortality.. Analysis was performed on 2,793 patients. The majority of patients were on aspirin (acetylsalicylic acid [ASA], 46.1%). Patients on a platelet chemoreceptor blocker (P2Y12) had the highest mean Injury Severity Score (9.1 ± 8.1). Patients taking P2Y12 inhibitors ± ASA, and ASA-warfarin had the highest head Abbreviated Injury Scale (AIS) mean (1.2 ± 1.6). On risk-adjusted analysis, warfarin-ASA was associated with a higher head AIS (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.34-4.42) after controlling for Injury Severity Score, Charlson Comorbidity Index, initial Glasgow Coma Scale score, and initial systolic blood pressure. Among patients with severe TBI (head AIS score, ≥3) on antiplatelet therapy, reversal with desmopressin (DDAVP) and/or platelet transfusion did not improve survival (82.9% reversal vs. 90.4% none, p = 0.30). In severe TBI patients taking Xa inhibitors who received prothrombin complex concentrate, survival was not improved (84.6% reversal vs. 84.6% none, p = 0.68). With risk adjustment as described previously, mortality was not improved with reversal attempts (antiplatelet agents: OR 0.83; 85% CI, 0.12-5.9 [p = 0.85]; Xa inhibitors: OR, 0.76; 95% CI, 0.12-4.64; p = 0.77).. Reversal attempts appear to confer no mortality benefit in severe TBI patients on antiplatelet agents or Xa inhibitors. Combination therapy was associated with severity of head injury among patients taking preinjury AT therapy, with ASA-warfarin possessing the greatest risk.. Prognostic, level II.

Topics: Aged; Anticoagulant Reversal Agents; Aspirin; Brain Injuries, Traumatic; Cardiovascular Diseases; Comorbidity; Deamino Arginine Vasopressin; Factor Xa Inhibitors; Female; Fibrinolytic Agents; Hemorrhage; Hospital Mortality; Humans; Male; Platelet Transfusion; Risk Assessment; Trauma Severity Indices; Treatment Outcome; United States; Warfarin

Patients undergoing coronary artery bypass graft (CABG) surgery or carotid endarterectomy (CEA) continue antiplatelet therapy perioperatively, which may increase bleeding risk. We aimed to investigate whether Rotational thromboelastometry (ROTEM

Topics: Aspirin; Clopidogrel; Deamino Arginine Vasopressin; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Ticlopidine; Vascular Surgical Procedures

Data are limited on prostate cancer (PC) management in patients with haemophilia (PWH).. To describe PC screening and diagnosis, treatment modalities and bleeding complications in a group of unselected PWH followed at French Haemophilia Treatment Centres (HTCs) PATIENTS AND METHODS: PC screening, management and bleeding complications were retrospectively investigated at 14 French HTCs between 2003 and 2018.. Among> 1549 > 50-year-old PWHs, 73 (4.7%) underwent PC screening (median age 71.1 years; 67/6 HA/HB, 17/56 severe-moderate/mild). At diagnosis, haematuria was infrequent. Prophylaxis was administered during 76/86 (88%) prostate biopsies (PB) (n = 67 clotting factor concentrates, CFC; n = 9 desmopressin; n = 17 associated with tranexamic acid, TA). Bleeding (11/86, 12.8%) occurred mainly post-prophylaxis (median delay: 7 days): haematuria (9/11, 81.8%), and rectal bleeding (2/11, 18.2%) including one major (1.2%). PC was confirmed in 50/86 PB and in two prostatectomy specimens (total n = 50 patients, n = 6 with only active surveillance). Surgery (n = 28/44 patients) was managed with CFC. Fifteen patients had radiotherapy/brachytherapy, 10 had hormone therapy; CFC-based prophylaxis was only prescribed for brachytherapy (n = 2). Major bleedings occurred in 3/28 (10.7%) and 2/15 (13.3%) patients who underwent surgery and radio/brachytherapy, respectively. No bleeding risk factor was found.. Our data indicate that PB requires prophylaxis for atleast 7 days, using CFC, desmopressin or TA in function of haemophilia severity. PC surgery should be considered at high bleeding risk. Long-term post-procedural CFC or oral TA could be discussed. Radiotherapy/brachytherapy also should be managed with prophylaxis (CFC or TA).

Topics: Aged; Biopsy; Deamino Arginine Vasopressin; Hematuria; Hemophilia A; Hemorrhage; Humans; Male; Middle Aged; Prostate; Prostatic Neoplasms; Retrospective Studies

Although COVID-19 is associated with high von Willebrand factor (vWF) parameters promoting thrombosis, venovenous extracorporeal membrane oxygenation (vvECMO) is associated with the development of acquired von Willebrand syndrome (AVWS) promoting bleeding. This study was designed to assess both the incidence and severity of AVWS in COVID-19 patients undergoing vvECMO, and the benefit of comprehensive vWF analyses.. Prospective observational study.. ICU at a tertiary-care center.. Twenty-seven consecutive COVID-19 patients with acute respiratory distress syndrome (ARDS) requiring vvECMO.. Comprehensive vWF analyses (including sodium dodecyl-sulfate polyacrylamide gel electrophoresis) were performed before, during, and after vvECMO. In a subgroup of 12 patients with AVWS, effectiveness of treatment with desmopressin was assessed. The patients' mean age was 53 years (range, 23-73), 70% were male, and all had various comorbidities. Following markedly elevated vwf antigen (vWF: Ag; mean, 546% ( sd , 282]), vWF collagen binding capacity (mean, 469% [ sd , 271]), vWF activity (vWF:A; mean, 383% [ sd , 132]), and factor VIII activity (mean, 302% [ sd , 106]), and only borderline decreases in high-molecular-weight (HMW) vWF multimers before vvECMO, all of these variables decreased and HMW vWF multimers became undetectable within hours following initiation of vvECMO. All variables fully recovered within 3-38 hours after discontinuation of vvECMO. During vvECMO, decreases in the vWF:A/vWF:Ag ratio correlated with absent HMW vWF multimers. Desmopressin did not affect vWF parameters.. In patients with COVID-19-associated ARDS, AVWS developed soon after initiation of vvECMO. The vWF:A/vWF:Ag ratio was a suitable screening test for AVWS. As desmopressin was ineffective, bleeding during vvECMO-associated AVWS should preferably be treated with concentrates containing vWF.

Topics: Adult; Aged; COVID-19; Deamino Arginine Vasopressin; Extracorporeal Membrane Oxygenation; Female; Hemorrhage; Humans; Male; Middle Aged; Respiratory Distress Syndrome; von Willebrand Diseases; von Willebrand Factor; Young Adult

Deficiency or dysfunction of von Willebrand factor (VWF) is associated with a bleeding disorder known as von Willebrand disease (VWD). The clinical manifestations of VWD are heterogeneous, and are in part dictated by the structural or functional defects of VWF. The tools to control bleeding in VWD are dominated by VWF concentrates, desmopressin and antifibrinolytic therapy. In view of these treatments being considered as effective, it is surprising that quality-of-life studies consistently demonstrate a significant mental and physical burden in VWD patients, particularly in women. Apparently, the current weaponry to support the management of VWD is insufficient to fully address the needs of the patients. It is important therefore to continue to search for innovative treatment options which could better serve the VWD patients. In this short review, two of such options are discussed in more detail: emicizumab to correct for the deficiency of factor VIII (FVIII), and the pegylated aptamer BT200 to increase endogenous levels of the VWF/FVIII complex.

Topics: Antifibrinolytic Agents; Deamino Arginine Vasopressin; Factor VIII; Female; Hemorrhage; Hemostatics; Humans; von Willebrand Diseases; von Willebrand Factor

BACKGROUND von Willebrand disease (VWD) is characterized by a bleeding tendency due to abnormalities in von Willebrand factor (VWF). Severe traumatic brain injury (TBI) can induce secondary coagulopathy and hemostatic disorders. We herein present a rare case of multiple trauma, including severe TBI, in a patient with VWD who was successfully treated with repeated factor VIII/VWF transfusion in addition to standard critical care. CASE REPORT A 22-year-old man with type 2A VWD sustained head and lower limb injuries in a traffic accident and was comatose. Computed tomography indicated multiple trauma, including severe TBI (left-sided traumatic epidural hematoma, left-sided traumatic subdural hematoma, traumatic subarachnoid hemorrhage, skull fracture, and skull base fracture). The patient underwent emergency craniotomy for hematoma removal, external decompression, and intracranial pressure monitoring along with massive transfusion and repeated perioperative transfusion of factor VIII/VWF concentrates according to the level of bleeding. He recovered consciousness and eventually survived without neurological deficits. CONCLUSIONS Multiple trauma including TBI in patients with VWD is a critical condition. The active transfusion of factor VIII/VWF is essential for controlling hemorrhage early and in the perioperative period.

Topics: Adult; Brain Injuries, Traumatic; Deamino Arginine Vasopressin; Factor VIII; Hematoma; Hemorrhage; Humans; Male; Multiple Trauma; von Willebrand Diseases; von Willebrand Factor; Young Adult

Percutaneous renal biopsy (PRB) is invasive, and bleeding-related complications are a concern. Desmopressin (DDAVP) is a selective type 2 vasopressin receptor-agonist also used for haemostasis.. To evaluate the side effects of intravenous (IV) weight-adjusted desmopressin preceding PRB.. This was a retrospective study of renal biopsies performed by nephrologists from 2013 to 2017 in patients who received single-dose DDAVP pre-PRB.. Of 482 PRBs, 65 (13.5%) received DDAVP (0.3 µg/kg); 55.4% of the PRBs were native kidneys. Desmopressin indications were altered platelet function analyser (PFA)-100 results (75.3% of the patients), urea >24.9 mmol/L (15.5%), antiplatelet drugs (6.1%) and thrombocytopaenia (3%). Of the 65 patients, 30.7% had minor asymptomatic complications, and 3 patients had major complications. Pre-PRB haemoglobin (Hb) <100 g/L was a risk factor for Hb decrease >10 g/L, and altered collagen-epinephrine (Col-Epi) time was a significant risk factor for overall complications. Mean sodium decrease was 0.6 ± 3 mmol/L. Hyponatraemia without neurological symptoms was diagnosed in two patients; no cardiovascular events occurred.. Hyponatraemia after single-dose DDAVP is rare. A single IV dose of desmopressin adjusted to the patient's weight is safe as pre-PRB bleeding prophylaxis.

Topics: Biopsy; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Retrospective Studies

Topics: Biopsy; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Hyponatremia

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles. Clinical manifestations include a bleeding diathesis due to a platelet delta storage pool deficiency, oculocutaneous albinism, inflammatory bowel disease, neutropenia, and pulmonary fibrosis. Ten genes associated with HPS are identified to date, and each gene encodes a protein subunit of either Biogenesis of Lysosome-related Organelles Complex (BLOC)-1, BLOC-2, BLOC-3, or the Adaptor Protein-3 complex. Several genetic variants and phenotypic heterogeneities are reported in individuals with HPS, who generally exhibit easy bruisability and increased bleeding. Desmopressin, pro-coagulants, or platelet transfusion may be used as prophylaxis or treatment for excessive bleeding in patients with HPS. However, response to desmopressin can be variable. Platelets are effective in preventing or treating bleeding in individuals with HPS, but platelets should be transfused judiciously to limit alloimmunization in patients with HPS who are at risk of developing pulmonary fibrosis and may be potential candidates for lung transplantation. The discovery of new genes associated with HPS in people with excessive bleeding and hypopigmentation of unknown etiology may be facilitated by the use of next-generation sequencing or panel-based genetic testing.

Topics: Aminocaproic Acid; Antifibrinolytic Agents; Blood Platelets; Carrier Proteins; Contusions; Deamino Arginine Vasopressin; Hemorrhage; Hermanski-Pudlak Syndrome; Humans; Hypopigmentation; Lysosomes; Nerve Tissue Proteins; Proteins; Tranexamic Acid

von Willebrand disease (VWD) is a quantitative or qualitative defect in von Willebrand factor (VWF) resulting in mucocutaneous bleeding symptoms and hemorrhage following hemostatic challenges, such as trauma or surgery. VWD-specific therapy, DDAVP (1-desamino-8-D-arginine vasopressin) and VWF concentrates, is necessary periprocedurally to ensure adequate hemostasis. The aging VWD patient may complicate this matter. The plasma concentration of many coagulation proteins, including VWF, increases with age. While it has been established that VWF levels increase with age in a healthy population, emerging research demonstrates this occurs in certain subtypes of VWD, too. Thus, the management of periprocedural VWD-specific therapy in the aging VWD patient is problematic when VWF levels increase over time to normal, and hematologists are left with uncertainty regarding whether or not periprocedural VWD-specific therapy is still necessary. In this article, we will review the current state of the literature regarding the effect of age on VWF levels in the healthy population and VWD while exploring possible etiologies for this phenomenon. Further, we will detail how this affects bleeding symptoms and highlight what research remains to be done to optimize care in this patient population.

Topics: Aged; Aging; Blood Coagulation Factors; Deamino Arginine Vasopressin; Diverticulitis; Female; Hemorrhage; Humans; Preoperative Care; von Willebrand Diseases; von Willebrand Factor

Topics: Clinical Decision Rules; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Hemorrhage; Hemostatics; Humans; Male; Middle Aged; Prevalence; Research Design; Retrospective Studies; Risk Assessment; von Willebrand Diseases; von Willebrand Factor

The bleeding phenotype of patients with type 1 von Willebrand disease (VWD) is very heterogeneous. We hypothesized that this heterogeneity may partly be explained by variability in response of von Willebrand factor (VWF) and factor VIII (FVIII) levels to stress during hemostatic challenges. We therefore investigated whether VWF and FVIII levels after administration of desmopressin, which mimic in vivo hemostatic response during hemostatic challenges, explain the heterogeneity in bleeding phenotype of patients with type 1 VWD. We performed a retrospective cohort study in 122 patients with type 1 VWD. All patients received a test dose of desmopressin shortly after diagnosis. Patients' mean age was 47 ± 14 years, and the mean Tosetto bleeding score was 10 ± 7. Higher FVIII activity during the complete time course after desmopressin administration (1, 3, and 5-6 hours), and higher VWF and FVIII levels combined at 3 hours after desmopressin administration, were associated with a lower bleeding score: β = -0.9 (-1.7; -0.1) and β = -1.2 (-1.9; -0.5), respectively, adjusted for age, sex, body mass index (BMI), and comorbidities. Patients with FVIII activity in the highest quartile 3 hours after desmopressin administration had a much lower bleeding score compared with patients in the other 3 quartiles (β = -5.1 [-8.2; -2.0]) and also had a lower chance of an abnormal bleeding score (odds ratio = 0.2 [0.1-0.5]), both adjusted for age, sex, BMI, and comorbidities. In conclusion, VWF and FVIII levels after desmopressin administration, which mimic hemostatic response to hemostatic challenges, are associated with the bleeding phenotype of patients with type 1 VWD. This may partly explain the variability in bleeding phenotype of these patients.

Topics: Adult; Biomarkers; Blood Coagulation; Deamino Arginine Vasopressin; Factor VIII; Female; Hemorrhage; Hemostatics; Humans; Male; Middle Aged; Phenotype; Retrospective Studies; Time Factors; Treatment Outcome; von Willebrand Disease, Type 1; von Willebrand Factor

Topics: Accidents, Traffic; Arm Injuries; Deamino Arginine Vasopressin; Electroencephalography; Hematoma; Hemorrhage; Hemostatics; Humans; Hyponatremia; Male; Middle Aged; Multiple Trauma; Nasal Bone; Saline Solution, Hypertonic; Seizures; Skull Fractures; von Willebrand Diseases

Topics: Biopsy; Deamino Arginine Vasopressin; Hemorrhage; Humans; Hyponatremia; Kidney; Uremia

Topics: Aged; Biopsy; Deamino Arginine Vasopressin; Hemorrhage; Humans; Pilot Projects; Renal Insufficiency

Acute heparin-induced thrombocytopenia (HIT) patients present a myriad of anticoagulation management challenges, in clinical settings where unfractionated heparin (UFH) is the traditional drug of choice. UFH use in cardiac surgery is a known entity that has been subject to rigorous research. Research has, thus, led to its unparalleled use and the development of well-established protocols for cardiac surgery. In comparison to UFH, bivalirudin use for acute HIT patients requiring urgent cardiac surgery with cardiopulmonary bypass (CPB) is still in its infancy. We describe the tailored post-CPB management of refractory bleeding in a 65-year-old infective endocarditis, acute HIT patient with renal failure who underwent urgent aortic valve replacement and mitral valve repair with bivalirudin anticoagulation. A management approach that entailed a combination of continuous venovenous haemofiltration (CVVH), 4-Factor prothrombin complex concentrate (PCC) (Beriplex), recombinant factor VIIa (rFactor VIIa) and desmopressin (DDAVP) were consecutively used post-operatively in theatre. Based on this case study experience, two modifications to institutional protocols are recommended. The first is the use of CVVH in theatre to eliminate bivalirudin in renal failure patients or in patients where bivalirudin elimination is prolonged. Secondly, a 'rescue therapy/intervention' algorithm for the swift identification of refractory bleeding post-CPB is also recommended. Rescue therapy agents, such as a 4-Factor PCCs and rFactor VIIa, should be incorporated into the protocol after a robust evidence-based search and agreement with the haematologist. The aim of these recommendations is to reduce the risk of bleeding associated with bivalirudin use for inexperienced institutions and experienced institutions alike, until larger randomized, controlled studies provide more in-depth knowledge to expand our clinical practice.

Topics: Acute Disease; Aged; Anticoagulants; Aortic Valve; Blood Coagulation Factors; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Factor VIIa; Hemorrhage; Hemostatics; Heparin; Hirudins; Humans; Male; Mitral Valve; Peptide Fragments; Recombinant Proteins; Renal Insufficiency; Thrombocytopenia

Psychiatric medications, particularly the selective serotonin reuptake inhibitors, have been associated with increased surgical bleeding. This study aims to compare intraoperative surgical bleeding between cosmetic surgery patients who are and are not taking psychiatric medications.. The charts of 392 consecutive patients who underwent cosmetic facial surgery at the senior author's practice were reviewed. Independent variables included self-reported psychiatric history, psychiatric diagnoses, and psychiatric medications as documented in the preoperative history and physical examination. The primary endpoint was administration of desmopressin (DDAVP), our proxy for increased surgical bleeding. Significant predictors of these endpoints were determined via Chi-squared testing.. One hundred and seventeen patients had a psychiatric diagnosis (30%), and 129 patients were taking some class of psychiatric medication (33%). Seventy-two patients received DDAVP (18%). A psychiatric diagnosis did not predict DDAVP administration (14.3% for patients with a psychiatric diagnosis vs. 20.88% for those without, p = 0.14). The use of a psychiatric medication was not associated with DDAVP administration (14.7 vs. 21%, p = 0.14). Male gender significantly predicted DDAVP administration (27.8 vs. 16.9% for females, p = 0.04).. The use of psychiatric medications does not predict increased intraoperative surgical bleeding. This is useful given the prevalence of psychiatric medication use among this patient population and obviates the need for discontinuation of these medications, which otherwise could be consequential.. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Topics: Adult; Antidepressive Agents; Blood Loss, Surgical; Cohort Studies; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Hemorrhage; Hemostatics; Humans; Incidence; Intraoperative Care; Male; Middle Aged; Mood Disorders; Retrospective Studies; Rhytidoplasty; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

The pharmacokinetics and pharmacodynamics of desmopressin are appropriate for adjusted body weight-based dosing, particularly in obese patients.. The objective of this study was to describe desmopressin dosing strategies, with emphasis on hemostatic outcomes among patients without preexisting bleeding disorders.. This was a single-center, retrospective cohort study of patients who received intravenous weight-based desmopressin for a hemostatic indication. Demographics, comorbidities, treatment setting, indication, site of bleeding, and outcomes were collected from the medical record. Primary outcomes included need for procedural intervention to achieve hemostasis, transfusion requirement, and death. Association between desmopressin dose and outcome was evaluated using χ. A total of 109 patients were included (n = 26, dose adjustment; n = 83, no dose adjustment). Baseline characteristics were well-matched between groups: mean (SD) age of 57.0 (13.5) years; mean (SD) Charlson Comorbidity Score of 6.5 (2.8); 37% were obese; 76% were critically ill; 81% were actively bleeding without differences in site of bleeding; and crude mortality was 39%. No differences in death, mean units of packed red blood cells transfused, or need for procedural hemostasis were observed between adjusted weight- and actual weight-based desmopressin dosing.. When used adjunctively to blood product transfusion in actively bleeding patients, use of adjusted body weight-based desmopressin did not negatively affect clinical outcomes. More data are needed to confirm this dosing strategy.

Topics: Adult; Aged; Blood Coagulation Disorders; Blood Transfusion; Body Weight; Critical Illness; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostatics; Humans; Male; Middle Aged; Obesity; Retrospective Studies

Prasugrel is a thienopyridine that inhibits platelet aggregation more rapidly and effectively than clopidogrel, with an increased bleeding risk.. The current study aimed to evaluate the efficacy of three nonspecific haemostatic drugs - recombinant activated factor VII (rFVIIa), tranexamic acid and desmopressin (DDAVP) - to limit blood loss after administration of prasugrel in a rabbit model of bleeding while also evaluating any prothrombotic effects.. Randomised, placebo-controlled study.. Faculty of Medicine, University of Geneva, Switzerland, in 2013.. Anaesthetised and artificially ventilated rabbits (n=56).. Animals were randomly allocated to one of five groups: control (placebo-placebo), prasugrel-placebo, rFVIIa (prasugrel-rFVIIa 150 μg kg), tranexamic acid (prasugrel-tranexamic acid 20 mg kg) or DDAVP (prasugrel-DDAVP 1 μg kg). Two hours after an oral prasugrel loading dose (4 mg kg), a stenosis and an injury were inflicted on the carotid artery to induce cyclic flow reductions (CFRs) due to thrombosis. Haemostatic drugs were administered during the ensuing observation period.. Standardised hepatosplenic sections were performed to evaluate the primary endpoint of blood loss, monitored for 15 min. Ear-immersion bleeding time and incidence of CFRs were secondary endpoints.. Prasugrel decreased ADP-induced platelet aggregation (light transmission method) from 66 ± 4% (mean ± SD) to 41 ± 7% (P < 0.001) and doubled blood loss: 10.7 g (10.1 to12.7) [median (interquartile range)] vs. 20.0 g (17.0 to 24.4), P = 0.003 in the control and prasugrel-placebo groups, respectively. rFVIIa, tranexamic acid and DDAVP reduced neither hepatosplenic blood loss [19.7 g (14.0 to 27.6), 25.2 g (22.6 to 28.7) and 22.9 g (16.8 to 28.8), respectively] nor bleeding time compared with placebo. Regarding safety, rVIIa induced three or more CFRs in 5/12 rabbits, vs. 0/12 in the prasugrel-placebo group (P = 0.037), whereas tranexamic acid and DDAVP did not increase them.. The three studied haemostatic drugs rFVIIa, tranexamic acid and DDAVP failed to reduce prasugrel-related bleeding in this model. rFVIIa-treated rabbits were more prone to arterial thrombotic events.. NA.

Topics: Administration, Intravenous; Animals; Antifibrinolytic Agents; Deamino Arginine Vasopressin; Drug Evaluation, Preclinical; Factor VIIa; Hemorrhage; Hemostatics; Male; Models, Animal; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Rabbits; Random Allocation; Recombinant Proteins; Tranexamic Acid

To evaluate whether the administration of desmopressin alters the risk for renal biopsy complications.. A multicenter registry containing 576 native kidney biopsies (NKb) with a serum creatinine above 150 μmol/L in 527 patients (372 men and 155 women, median age 61 years) was used. Most of the data were prospective. At one of the hospitals all biopsies with creatinine above 150 μmol/L received desmopressin before biopsies (NKb 204). These were compared to outcome of biopsy complications against other centres where desmopressin was not given (NKb 372). Fisher's exact test, χ. In NKb with creatinine >150 μmol/L, those with desmopressin had less overall (3.4% vs 8.4%, OR 0.39, CI 0.17-0.90) whereas major or minor complications were not different. While desmopressin did not exhibit difference in complications in men, women received less major (0% vs 8.6%, P = 0.03) and overall complications (0% vs 12.1%, P = 0.006). A multiple logistic regression revealed that, after adjusting for BMI, age and sex, prophylaxis with desmopressin showed less major (OR 0.38, CI 0.15-0.96) and overall complications (OR 0.36, CI 0.15-0.85).. Desmopressin given before a native kidney biopsy in patients with impaired renal function can reduce the risk for complications.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Chi-Square Distribution; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostatics; Humans; Kidney; Kidney Diseases; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Pilot Projects; Predictive Value of Tests; Prospective Studies; Protective Factors; Registries; Retrospective Studies; Risk Factors; Sweden; Young Adult

Despite the increased worldwide awareness, over the last decade, of the platelet-type von Willebrand Disease (PT-VWD), many uncertainties remain around this rare platelet bleeding disorder. This report aims to correctly identify and study the phenotype of new patients and highlights the diagnostic and therapeutic challenges this disease remains to pose. We describe four PT-VWD cases confirmed by genetic analysis in which either the diagnosis and/or the treatment posed challenge. We provide the details of the clinical presentation, laboratory analysis, and the treatment and the responses in each case. We show that in addition to type 2B VWD, PT-VWD can be misdiagnosed as idiopathic thrombocytopenic purpura, neonatal alloimmune thrombocytopenia, and unexplained gestational thrombocytopenia. The disease can be diagnosed as early as 1 year of age and with phenotypically normal parents. Bleeding in some patients can be managed successfully using Humate P and DDAVP combined with tranexamic acid with no significant thrombocytopenia. We provide for the first time an evidence of an efficient response to rFVIIa in PT-VWD. Anaphylactic reaction to VWF preparations may be related to PT-VWD and the development of HLA antibodies is not uncommon. Progressive thrombocytopenia with normal VWF levels can be seen with PT-VWD and the platelet count was normalized at 2.5 weeks postpartum in one case. We conclude that these studies represent a record of clinical observations/interventions that help improve diagnoses/management of PT-VWD, highlight the variations in age and clinical presentations, laboratory diagnostic approaches, the importance of genetic testing for accurate diagnosis and consideration of therapeutic alternatives.

Topics: Adolescent; Child, Preschool; Deamino Arginine Vasopressin; Drug Therapy, Combination; Factor VIIa; Factor VIII; Female; Hemorrhage; Humans; Infant, Newborn; Male; Recombinant Proteins; Tranexamic Acid; von Willebrand Diseases

Essentials Factor VIII levels vary in mild and moderate hemophilia A (MHA) patients with the same mutation. We aimed to estimate the variation and determinants of factor VIII levels among MHA patients. Age and genotype explain 59% of the observed inter-individual variation in factor VIII levels. Intra-individual variation accounted for 45% of the variation in the three largest mutation groups.. Background The bleeding phenotype in patients with mild/moderate hemophilia A (MHA) is inversely associated with the residual plasma concentration of factor VIII (FVIII:C). Within a group of patients with the same F8 missense mutation, baseline FVIII:C may vary, because, in healthy individuals, von Willebrand factor (VWF) levels, ABO blood group and age are also known to influence baseline FVIII:C. Our understanding of the pathophysiologic process of the causative genetic event leading to reduced baseline FVIII:C in MHA patients is still limited. Objectives To estimate the variation and determinants of baseline FVIII:C among MHA patients with the same F8 missense mutation. Methods Three hundred and forty-six patients carrying mutations that were present in at least 10 patients in the cohort were selected from the INSIGHT and the RISE studies, which are cohort studies including data of 3534 MHA patients from Europe, Canada, and Australia. Baseline FVIII:C was measured with a one-stage clotting assay. We used Levene's test, univariate and multivariate linear regression, and mixed-model analyses. Results For 59% of patients, the observed variation in baseline FVIII:C was explained by age and genotype. Compared to FVIII:C in patients with Arg612Cys, FVIII:C was significantly different in patients with eight other F8 missense mutations. Intra-individual variation explained 45% of the observed variance in baseline FVIII:C among patients with the same mutation. Conclusion Our results indicate that baseline FVIII:C levels are not exclusively determined by F8 genotype in MHA patients. Insights into other factors may provide potential novel targets for the treatment of MHA.

Topics: ABO Blood-Group System; Adult; Blood Coagulation; Deamino Arginine Vasopressin; Factor VIII; Genetic Variation; Genotype; Hemophilia A; Hemorrhage; Humans; Male; Middle Aged; Multivariate Analysis; Mutation; Mutation, Missense; Observer Variation; Phenotype; Protein Conformation; Retrospective Studies; von Willebrand Factor; Young Adult

Type 2 von Willebrand disease (VWD) includes a wide range of qualitative abnormalities of von Willebrand factor structure and function resulting in a variable bleeding tendency. According to the current classification, 4 different subtypes can be identified, each with distinctive phenotypic and therapeutic characteristics. Current available laboratory methods allow a straightforward approach to VWD subtyping, and although the precise molecular characterization remains complex, it is not required for appropriate treatment of the vast majority of cases. Desmopressin can be useful only in a few type 2 cases compared with patients with actual quantitative deficiency (type 1), most often in variants with a nearly normal multimeric pattern (type 2M). However, since no laboratory test accurately predicts response to desmopressin, a trial test should always be performed in all type 2 VWD patients, with the exception of type 2B ones. Replacement therapy with plasma-derived von Willebrand factor-factor VIII concentrates represents the safe mainstay of treatment of all patients, particularly those not responding to desmopressin or requiring a sustained hemostatic correction because of major surgery or bleeding. A significant patient bleeding history correlates with increased bleeding risk and should be considered in tailoring the optimal antihemorrhagic prophylaxis in the individual patient.

Topics: Adult; Aged; Child, Preschool; Deamino Arginine Vasopressin; Drug Combinations; Factor VIII; Female; Hemorrhage; Hemostasis; Hemostatics; Humans; Male; Mutation; Pregnancy; Pregnancy Complications, Hematologic; von Willebrand Disease, Type 2; von Willebrand Factor

Liver disease results in complex alterations of all 3 phases of hemostasis. It is now recognized that hemostasis is rebalanced in chronic liver disease. The fall in clotting factor levels is accompanied by a parallel fall in anticoagulant proteins. High von Willebrand factor levels counteract defects in primary hemostasis. Conventional coagulation tests do not fully reflect the derangement in hemostasis and do not accurately predict the risk of bleeding. Global coagulation assays (thrombin generation, thromboelastography) reflect the interaction between procoagulant factors, anticoagulant factors, platelets, and the fibrinolytic system and show promise for assessing bleeding risk and guiding therapy. These assays are not yet commercially approved or validated. Prevention of bleeding should not be aimed at correcting conventional coagulation tests. Thrombopoietin receptor agonists were shown to increase the platelet count in cirrhotic patients undergoing invasive procedures but may increase the risk of thrombosis. Rebalanced hemostasis in liver disease is precarious and may be tipped toward hemorrhage or thrombosis depending on coexisting circumstantial risk factors. Bacterial infection may impair hemostasis in cirrhosis by triggering the release of endogenous heparinoids. There are no evidence-based guidelines for hemostatic therapy of acute hemorrhage in liver disease. There is currently inadequate evidence to support the use of recombinant FVIIa, prothrombin complex concentrates, or tranexamic acid in acute variceal or other hemorrhage.

Topics: ADAM Proteins; ADAMTS13 Protein; Antifibrinolytic Agents; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Deamino Arginine Vasopressin; Factor VIIa; Fibrinolysis; Hemorrhage; Hemostasis; Humans; International Normalized Ratio; Liver Diseases; Plasma; Prothrombin Time; Receptors, Thrombopoietin; Recombinant Proteins; Risk Factors; Thrombelastography; Thrombin; Vitamin K

In this issue of Blood, Federici et al present compelling evidence that bleeding score (BS) predicts the risk of future bleeding in von Willebrand disease (VWD) patients.

Topics: Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostatics; Humans; Male; Severity of Illness Index; von Willebrand Diseases; von Willebrand Factor

Topics: Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; von Willebrand Diseases; von Willebrand Factor

Hemophilia A and von Willebrand disease (VWD) are distinct bleeding disorders with a spectrum of clinical phenotypes. They are characterized by mutations in either factor VIII (F8) or von Willebrand factor (VWF) genes, respectively. The pattern of inheritance and appropriate laboratory evaluation differentiates these diseases, and treatment strategies for both are different. Here, we report a male patient with hemophilia A and VWD Type 2 Normandy (N) mutations who presented with life-threatening bleeding. We document his medical history, clinical course, management, and diagnostic work up.

Topics: Biopsy, Needle; Deamino Arginine Vasopressin; Factor VIII; Hemophilia A; Hemorrhage; Heterozygote; Humans; Male; Middle Aged; Postoperative Hemorrhage; Shock, Hemorrhagic; Treatment Outcome; von Willebrand Disease, Type 2

Inherited disorders of platelet function are a heterogeneous group. For optimal prevention and management of bleeding, classification and diagnosis of the underlying defect are highly recommended. An interdisciplinary guideline for a diagnostic approach has been published (AWMF # 086-003 S2K; Hämostaseologie 2014; 34: 201-212). Underlying platelet disorder, platelet count, age and clinical situation modify treatment. Exclusive transfusion of platelet concentrates may be inappropriate as potentially adverse effects can outweigh its benefit. A stepwise and individually adjusted approach for restitution and maintenance of haemostasis is recommended. Administration of antifibrinolytics is generally endorsed, but is of particular use in Quebec disease. Restricted to older children, desmopressin is favourable in storage pool disease and unclassified platelet disorders. Although licensed only for patients with Glanzmann thrombasthenia and alloantibodies, in clinical practice rFVIIa is widely used in inherited platelet disorders with severe bleeding tendency. This guideline aims at presenting the best available advice for the management of patients with inherited platelet function disorders.

Topics: Anti-Arrhythmia Agents; Blood Platelet Disorders; Child; Child, Preschool; Deamino Arginine Vasopressin; Factor VIIa; Female; Germany; Hematology; Hemorrhage; Hemostatics; Humans; Infant; Infant, Newborn; Male; Pediatrics; Platelet Transfusion; Practice Guidelines as Topic

Recent studies have suggested a unifying pathophysiological concept to explain the underlying defects of von Willebrand factor (VWF) causing von Willebrand disease (VWD) and have highlighted the relevance of simple VWF related activities in producing a useful diagnosis. A standardized bleeding history condensed into a final bleeding score and few widely available laboratory tests, such as VWF ristocetin cofactor activity, VWF antigen and factor VIII (FVIII), in the index case and in his/her relatives are of critical importance. Ristocetin-induced platelet aggregation (RIPA) should also be tested. Trial with desmopressin should be carried out in patients, except those with virtual absence of VWF or with increased RIPA. Desmopressin should be used in all responsive patients as first choice. Substitutive treatment with VWF/FVIII containing products should be used in unresponsive patients, in those with heightened response to desmopressin or in those undergoing interventions requiring good hemostasis for more than 3-5 days. Special consideration should be deserved to the treatment of menorrhagia and parturition.

Topics: Deamino Arginine Vasopressin; Factor VIII; Female; Hemorrhage; Hemostasis; Hemostatics; Humans; Male; Menorrhagia; Menstruation; Pregnancy; Pregnancy Complications, Hematologic; von Willebrand Diseases; von Willebrand Factor

This is a case report involving a middle-aged Jehovah's Witness patient who underwent a redo aortic valve replacement, coronary artery bypass graft, and Maze procedure facilitated by cardiopulmonary bypass. The consent process included a discussion of the management of bleeding and hemostasis in the perioperative period in the context of the patients' religious choice and the possible consequences of avoiding transfusion in massive bleeding. The medical team agreed to abide by the patient's wishes with respect to the blood and blood products deemed unacceptable by the patient irrespective of the consequences. The consent included a discussion of manufactured hemostatic agents that are designated by the Hospital Liaison Committee Network for Jehovah's Witnesses as subject to personal decision. There was also a discussion of recombinant agents available, all of which are acceptable to Jehovah's Witness patients. The patient accepted the use of cryoprecipitate, prothrombin complex concentrate, and recombinant factor VIIa.. After separation from cardiopulmonary bypass and protamine administration, blood loss was 350 mL over a ten-minute period. The international normalized ratio (INR) was 3.5 at that time. Cryoprecipitate 15 U, 1-deamino-8-D-arginine vasopressin 16 U, and a prothrombin complex concentrate, Octaplex®, 60 mL were administered. Blood loss improved significantly. The INR in the cardiac surgical intensive care unit was 1.3. The sample was taken approximately one hour following the administration of the hemostatic agents. The patient's chest was closed, and chest tube drainage was 310 mL over the next 12 hr.. This is a novel case involving the use of prothrombin complex concentrate in the setting of a Jehovah's Witness patient undergoing a complex operative procedure.

Topics: Aortic Valve; Blood Coagulation Factors; Deamino Arginine Vasopressin; Heart Valve Prosthesis Implantation; Hemorrhage; Humans; International Normalized Ratio; Jehovah's Witnesses; Male; Middle Aged; Whole Blood Coagulation Time

Topics: Adult; Deamino Arginine Vasopressin; Female; Fibrin; Fibrinogen; Hemorrhage; Hemostatics; Humans; Male; Thrombelastography; Treatment Outcome

Recombinant activated factor VII (rFVIIa) is approved for prevention and treatment of bleeding in hemophilia patients with inhibitors to FVIII (hemophilia A) or IX (hemophilia B), patients with congenital and acquired hemophilia and in patients with FVII deficiency or Glantzmann thrombasthenia (last indication is approved only in Europe). Off-labeled, the drug has been prescribed for prevention, or treatment of bleeding in severe hepatic disease, neonatal coagulopathies, high-risk surgical procedures, trauma, thrombocytopenia and platelet function disorders, as well as for urgent reversal of oral anticoagulation. Here we report a case of a 53-year-old female patient with delayed graft function after kidney transplantation, who had kidney biopsy complicated with prolonged bleeding. After unsuccessful treatment with desmopressin, the patient was treated with rFVIIa and the bleeding stopped immediately. Only few anecdotal reports of use of rFVIIa for treatment of bleeding in uremic patients have been published thus far. To our knowledge, this is the first case that describes use of rFVIIa for management of bleeding as a complication of renal biopsy in a uremic patient in the early kidney posttransplantation period.

Topics: Biopsy; Deamino Arginine Vasopressin; Drug Administration Schedule; Factor VIIa; Female; Hemorrhage; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Middle Aged; Recombinant Proteins; Uremia

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Coagulation Factors; Deamino Arginine Vasopressin; Europe; Factor VIIa; Factor VIII; Female; Hemophilia A; Hemorrhage; Hemostatics; Humans; Incidence; Male; Middle Aged; Recombinant Proteins; Registries; Treatment Outcome; Young Adult

Massive hemorrhage is the leading cause of death in the first few hours following multiple trauma, therefore, early and aggressive treatment of clotting disorders and surgical intervention to stop the bleeding are of utmost importance. However, commonly performed clotting tests have a considerable latency of at least 30-45 min, whereas hemoglobin (Hb) levels can be tested very quickly. If a multiple trauma patient has already received fluid resuscitation, a certain relationship may be observed between the hemoglobin value and the development of clotting disturbances. Hence, hemoglobin may be a useful and rapidly available parameter for guiding the initial treatment of clotting disturbances in multiple trauma patients.. A Hb-guided algorithm has been developed to initiate initial clotting therapy. The algorithm contains three stages of different aggressive clotting therapy with fibrinogen, prothrombin complex concentrate (PCC), factor VIIa, tranexamic acid and desmopressin, depending on the first Hb value measured. For admission Hb levels > 5.5 mmol/l (≈8.8 g/dl) coagulation therapy is managed on the basis of the laboratory tests and if in doubt 2 g fibrinogen is administered. For admission Hb levels between 5.5 mmol/l (≈8.8 g/dl) and 4 mmol/l (≈6.5 g/dl) 2-4 g fibrinogen and 2,500-3,000 IU PCC are administered and tranexamic acid and desmopressin administration should be considered. For admission Hb levels < 4 mmol/l (≈6.5 g/dl) 4-6 g fibrinogen, 3,000-5,000 IU PCC and 1 mg factor VIIa should be administered and tranexamic acid and desmopression should be considered. All drugs mentioned should be stored in a special "coagulation box" in the hospital pharmacy and this box is brought immediately to the patient on demand. In addition to the use of clotting factors, infusions should be performed with balanced crystalloids and transfusions with an RBC/FFP ratio of 2:1-1:1. To assess the efficiency of the algorithm the routinely measured clotting parameters at trauma bay admission were compared with intensive care unit (ICU) admission and the standardized mortality ratio (SMR) was calculated.. During a 6-month investigation period 71 severe multiple trauma patients were admitted to the trauma center and 19 patients were treated using the coagulation box of which 13 required massive transfusions. The routinely used clotting parameters markedly improved between admission to the trauma bay and ICU admission: Quick 61% versus 97% (p < 0.001), partial prothromboplastin time (PTT) 50 s versus 42 s (not significant), fibrinogen 1.7 g/l versus 2.15 g/l (not significant). Of the 19 patients 11 (58%) survived. The revised injury severity classification (RISC) predicted a survival rate of 40%, which corresponds to an SMR of 0.69, thus implying a higher survival rate than predicted.. The Hb-driven algorithm, in combination with the coagulation box and the early use of clotting factors, may be a simple and effective tool for improving coagulopathy in multiple trauma patients.

Topics: Aged; Algorithms; Anticoagulants; Blood Coagulation Tests; Critical Care; Crystalloid Solutions; Deamino Arginine Vasopressin; Factor VIIa; Female; Fibrinogen; Fluid Therapy; Hemodynamics; Hemoglobins; Hemorrhage; Humans; Injury Severity Score; Isotonic Solutions; Male; Middle Aged; Multiple Trauma; Plasma Substitutes; Resuscitation; Survival Rate; Tranexamic Acid

Experimental studies of uncontrolled hemorrhage demonstrated that permissive hypotension (PH) reduces blood loss, but its effect on clot formation remains unexplored. Desmopressin (DDAVP) enhances platelet adhesion promoting stronger clots. We hypothesized PH and DDAVP have additive effects and reduce bleeding in uncontrolled hemorrhage.. Rabbits (n = 42) randomized as follows: sham; normal blood pressure (NBP) resuscitation; PH resuscitation-60% baseline mean arterial pressure; NBP plus DDAVP 1 hour before (DDAVP NBP) or 15 minutes after beginning of shock (DDAVP T1 NBP); and PH plus DDAVP 1 hour before (DDAVP PH) or 15 minutes after beginning of shock (DDAVP T1 PH). Fluid resuscitation started 15 minutes after aortic injury and ended at 85 minutes. Intraabdominal blood loss was calculated, aortic clot sent for electron microscopy. Activated partial thromboplastin time, platelet count, thromboelastometry, arterial blood gases, and complete blood count were performed at baseline and 85 minutes. Analysis of variance was used for comparison.. NBP received more fluid volume and had greater intraabdominal blood loss. DDAVP, when administered preshock, significantly reduced blood loss in NBP and fluid requirement when given postshock. Platelets, arterial blood gas, complete blood count, and activated partial thromboplastin time were similar at 85 minutes. NBP delayed clot formation and worsened thrombodynamic potential on thromboelastometry, whereas PH and DDAVP improved. Electron microscopy showed lack of fibrin on NBP clots, whereas DDAVP and PH clots displayed exuberant fibrin/platelet aggregates. DDAVP NBP presented intermediate clots.. PH reduced bleeding and improved hemostasis compared with normotensive resuscitation. DDAVP given preshock exerted similar effects with normotensive resuscitation.

Topics: Animals; Blood Coagulation; Blood Pressure; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Hypotension; Male; Rabbits; Resuscitation; Shock, Hemorrhagic; Thrombelastography

Bleeding and clotting disturbances are not uncommon in trauma patients and require an early and consequent therapy. Under the prevalent pathophysiological circumstances of hypothermia, acidosis and clotting disturbances, desmopressin seems to be a possible option to control diffuse bleeding. We report about 2 trauma patients with diffuse bleeding and in whom desmopressin was used successfully to control bleeding from the point of view of the authors. We discuss the advantages and disadvantages of desmopressin in the 2 patients.

Topics: Adult; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Male; Multiple Trauma; Treatment Outcome; Young Adult

1) Compare rates of post-tonsillectomy bleeding in pediatric patients with and without von Willebrand disease (vWD). 2) Identify factors that may increase the risk for post-tonsillectomy bleeding in children with and without vWD.. Historical cohort study.. Tertiary care, university-based pediatric hospital.. Medical records were examined for 99 patients with vWD and 99 patients without vWD younger than 18 years who underwent tonsillectomy with or without adenoidectomy from August 1997 to October 2005. Subjects were matched for age, year of surgery, type of surgery, and indication for surgery.. Post-tonsillectomy hemorrhage occurred in eight of 99 (8%) vWD patients and in six of 99 (6%) non-vWD patients (P = 0.58, odds ratio 1.36, 95% CI 0.45-4.08). A two-sample test of proportions demonstrated lower and upper limits of -0.051 and 0.092. Four of eight children with vWD and two of six non-vWD patients required surgical intervention for control of bleeding. Ninety-three of 99 vWD patients received desmopressin acetate (DDAVP) preoperatively. In patients with vWD who responded to DDAVP challenge, there was no increased likelihood of post-tonsillectomy bleeding compared with non-vWD patients. No significant difference in the number of bleeding events was noted on the basis of demographics, preoperative laboratories, or use of aminocaproic acid.. Children with vWD undergoing tonsillectomy have a postoperative bleeding rate similar to that of a matched group. However, the sample size was not sufficient to eliminate the possibility of a clinically important difference between the two groups.

Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Male; Postoperative Complications; Tonsillectomy; von Willebrand Diseases

The diagnosis and management of von Willebrand disease (VWD) in paediatrics is challenging. Our aim was to review patient's characteristics related to biological and clinical response to DDAVP in children with low von Willebrand factor (VWF) levels and bleeding history from a single institution. We included a retrospective cohort of 221 children (median age 11 years; 137 females): 27 type 1 (VWF levels within 15-30 IU dL-1) and 194 possible type 1 (VWF levels within 31-49 IU dL-1). The DDAVP infusion-test was performed in 214/221 children, 93.4% of whom showed good response. Patients with type 1 were at higher risk of DDAVP-test failure: 9/26 (34.6%) vs. 18/188 (9.6%) with possible type 1 (RR 3.44, 1.75-6.79; p= 0.002, Fisher's exact test). In 68 children, the clinical response to DDAVP was evaluated 87 times: i) to stop bleeding: menorrhagia (13), mucocutaneous (12), haemarthrosis (1); and ii) to prevent surgical bleeding: adenotonsillectomy (17), major (15) and minor surgery (10); and dental procedures (19). No major adverse events or bleeding were observed. The treatment was effective with one single dose of DDAVP in almost all patients, without antifibrinolytic or local therapy, except in a girl with severe haemorrhage during menarche who required replacement therapy. In conclusion, patients with VWD type 1 were at higher risk of no response to DDAVP infusion-test. In this series, one dose of DDAVP proved effective and safe for children with VWD. Since this is a safe, effective and affordable therapy, we consider that a wider use should be promoted, especially in developing countries.

Topics: Adolescent; Argentina; Biomarkers; Child; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostatics; Humans; Infusions, Intravenous; Male; Treatment Outcome; von Willebrand Diseases; von Willebrand Factor

Ehlers-Danlos Syndrome (EDS) is caused by heritable collagen defects and may be associated with bleeding symptoms. Desmopressin has been described in case reports to decrease bleeding times in these patients. This study sought to assess bleeding time responsiveness to desmopressin therapy in a cohort of children with EDS-associated bleeding manifestations. A retrospective chart review of children with EDS referred for bleeding symptoms was utilized. Twenty-six children were included; 19 (73%) had a desmopressin challenge. The mean bleeding time was 11.26 (+/-4.39) min, decreasing to 5.95 (+/-2.41) min with treatment (P < 0.01). Desmopressin normalizes bleeding times in children with EDS.

Topics: Adolescent; Bleeding Time; Case-Control Studies; Child; Child, Preschool; Deamino Arginine Vasopressin; Ehlers-Danlos Syndrome; Female; Hemorrhage; Hemostatics; Humans; Infant; Male; Retrospective Studies

Fearing the devastating neurological complications in a parturient with the von Willebrand disease secondary to paucity of studies defining the guidelines to assess the risk of bleeding complications, anesthesiologists are often reluctant to administer neuroaxial anesthesia. We present a case report of a parturient with type I von Willebrand disease who presented for induction of labor at 39 weeks of gestation. After consultation with the hematologist well ahead of the conception, appropriate laboratory workup including clotting factor levels including FVIII, vWF:RcoF, vWF:Ag on different occasions peripartum, and provision of adequate prophylactic medical treatment, she underwent Cesarean section under epidural anesthesia without neurological or bleeding complications. von Willebrand disease is the most common inherited bleeding disorder that may result in various bleeding complications in a parturient as a result of hemostatic challenges during pregnancy. Yet the recommendations are based on anecdotal observations of the authors of small case series and surveys. Our case report emphasizes the importance of advanced planning, careful patient assessment, and multi-disciplinary team approach for the successful regional anesthesia as suggested by the guidelines based on clinical experiences.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Obstetrical; Cesarean Section; Deamino Arginine Vasopressin; Factor VIII; Female; Hemorrhage; Hemostatics; Humans; Pregnancy; Pregnancy Complications, Hematologic; von Willebrand Diseases

Topics: Adult; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Hypothermia, Induced; Male

Topics: Aged, 80 and over; Aspirin; Blood Gas Analysis; Combined Modality Therapy; Deamino Arginine Vasopressin; Erythrocyte Transfusion; Hematoma; Hemorrhage; Hemorrhagic Disorders; Humans; Kidney Failure, Chronic; Male; Platelet Aggregation Inhibitors; Platelet Transfusion; Punctures; Radial Artery; Respiratory Insufficiency

Desmopressin (1-deamino-8-D-arginine vasopressin (DDAVP)) has been shown to be an effective treatment option when administered both intravenously [1,2] and subcutaneously [3] to children with inherited bleeding disorders. We demonstrate here, both the efficacy and acceptability of a new intranasal DDAVP preparation, providing a cost effective treatment with good outcomes for children with bleed disorders.

Topics: Administration, Intranasal; Adolescent; Child; Cohort Studies; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Female; Hemophilia A; Hemorrhage; Hemostatics; Humans; Male; Treatment Outcome

Recently, three multicentre prospective international studies have been carried out to evaluate the clinical efficacy and safety of Fanhdi [high-purity, double-inactivated plasma-derived factor VIII/von Willebrand factor (VWF) concentrate] in patients with von Willebrand's disease (VWD). Pharmacokinetic parameters, clinical efficacy and safety of Fanhdi in acute bleedings episodes or invasive procedures were determined in this population.. Pharmacokinetic parameters observed were similar to previous reported for other highly purified plasma-derived FVIII/VWF concentrate. The mean in vivo recovery (IU dL(-1) per IU kg(-1)) was 1.9 +/- 0.6 for VWF:RCof; 2.1 +/- 0.6 for VWF:Ag and 2.6 +/- 0.6 for FVIII:C. The mean half-life (h) was 14.4 +/- 10.5 for VWF:RCof; 27.5 +/- 11.0 for VWF:Ag and 33.4 +/- 16.4 for FVIII:C. Therapeutic benefit of Fanhdi in VWD patients treated during bleeding episodes was clearly demonstrated. The achievement of haemostasis was excellent or good in 100% of the cases (major or minor bleeding episodes). Also, the clinical efficacy of Fanhdi in preventing excessive bleeding during surgery showed a very good profile. Efficacy was rated as excellent in six cases (three major/three minor surgical procedures) and good in three cases (two major/one minor surgical procedures). In addition, the product was well tolerated and no adverse events potentially related to the study drug were reported.. Fanhdi is an effective and safe plasma-derived FVIII/VWF concentrate that can be used as an alternative to the current replacement therapy in patients with VWD to provide an adequate haemostasis during surgical procedures and treatment of bleeding episodes.

Topics: Acute Disease; Coagulants; Deamino Arginine Vasopressin; Factor VIII; Half-Life; Hemorrhage; Hemostasis, Surgical; Humans; Prospective Studies; von Willebrand Diseases; von Willebrand Factor

Chick embryos are capable of functional spinal cord regeneration following crush injury until embryonic day 13. Developmental changes occurring thereafter result in failure to regenerate. Secondary injury mechanisms can result in apoptotic cell death and make a major contribution to cell loss after trauma. We report here that around embryonic day 13 there is a dramatic increase in blood vessel numbers in the spinal cord, and that the extent of hemorrhage in response to injury increases with developmental age. This is paralleled by increased apoptosis and subsequent cavitation in spinal cords injured at embryonic day 15 as compared with embryonic day 11. Following spinal cord injury at embryonic day 15, apoptotic cell death is extensive and spreads to the same extent as the hemorrhage. When hemorrhage is reduced by treatment with the hemostatic drug desmopressin the extent of apoptosis and cavity formation in spinal cords injured at embryonic day 15 decreases. Furthermore, manipulations of embryonic day 11 spinal cords that increase hemorrhage also increase apoptosis and result in cavitation in contrast to the effective repair typical of this stage. Altogether these results suggest that cavity formation occurring at developmental stages non-permissive for regeneration is largely due to changes in the extent of apoptosis that are related to vascularization and hemorrhage.

Topics: Animals; Apoptosis; Chick Embryo; Deamino Arginine Vasopressin; Embryonic Development; Hemorrhage; Immunohistochemistry; In Situ Nick-End Labeling; Neovascularization, Pathologic; Nerve Regeneration; Reverse Transcriptase Polymerase Chain Reaction; Spinal Cord; Spinal Cord Injuries

In this case report, we describe the successful use of desmopressin as prophylaxis against hemorrhage in a patient with a bleeding tendency associated with Marfan syndrome and a platelet function defect undergoing cardiovascular surgery.

Topics: Deamino Arginine Vasopressin; Follow-Up Studies; Hemorrhage; Hemostatics; Humans; Injections, Subcutaneous; Male; Marfan Syndrome; Middle Aged; Treatment Outcome

Topics: Adult; Aminocaproic Acid; Antiphospholipid Syndrome; Aprotinin; Blood Coagulation Tests; Blood Loss, Surgical; Combined Modality Therapy; Contraindications; Crystalloid Solutions; Deamino Arginine Vasopressin; Disseminated Intravascular Coagulation; Erythrocyte Transfusion; Factor VII; Factor VIIa; Female; Fluid Therapy; Hemorrhage; Hemostatics; Humans; Isotonic Solutions; Lupus Coagulation Inhibitor; Plasma; Platelet Transfusion; Pressure; Recombinant Proteins; Retroperitoneal Neoplasms; Shock; Thrombophlebitis; Tranexamic Acid

Several FDA-approved intravenous drugs are used to reduce surgical bleeding. This series of studies tested whether these drugs (aprotinin, desmopressin, tranexamic acid, epsilon-aminocaproic acid) could reduce bleeding due to traumatic injuries in two models of uncontrolled hemorrhage in rats. In the first phase of each study, a nonlethal tail bleeding model was used that incorporated limited fluid resuscitation (lactate Ringer's solution). Four doses of vehicle or the test substance were given successively with bleeding time and blood loss measured after each dose. In the second phase of each study, a lethal liver injury was produced by excising a section of the median lobe (approximately 0.8% of body weight) and an infusion of either vehicle or the test substance was immediately begun. This model included aggressive fluid resuscitation and a severe dilutional coagulopathy. Blood loss, survival time and mortality rate were recorded. Three studies were performed, testing each of the drugs singly and in combination. None of the drugs significantly reduced either bleeding time or blood loss in the tail bleeding model, nor were blood loss, survival time or mortality rate altered in the liver injury model. Taken together, these results suggest that these FDA-approved drugs, when used either singly or in combination, are not efficacious in these models of traumatic uncontrolled hemorrhage.

Topics: Aminocaproic Acid; Animals; Antifibrinolytic Agents; Aprotinin; Deamino Arginine Vasopressin; Disease Models, Animal; Drug Approval; Drug Therapy, Combination; Hemorrhage; Hemostatics; Infusions, Intravenous; Liver; Male; Rats; Rats, Sprague-Dawley; Survival Analysis; Tail; Tranexamic Acid; Wounds and Injuries

We undertook an international, multicenter study to describe the clinical picture and to estimate the bleeding risk in a group of obligatory carriers of type 3 von Willebrand disease (VWD).. Obligatory carriers (OC) of type 3 VWD were identified by the presence of offspring with type 3 VWD or by being an offspring of a type 3 patient. Normal controls were age- and sex-matched with the obligatory carriers. A physician-administered standardized questionnaire was used to evaluate hemorrhagic symptoms at presentation. A score system ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion) was used to quantitate bleeding manifestations. Odds ratios were computed for each symptom.. Ten centers participated to the study, enrolling a total of 35 type 3 VWD families, with 70 OC. A total of 215 normal controls and 42 OC for type 1 VWD were also included. About 40% of type 3 OC had at least one bleeding symptom compared to 23% of normal controls and 81.8% of type 1 OC (P < 0.0001 by chi-squared test), showing that type 3 OC clearly represent a distinct population from type 1 OC. The clinical situations associated with an increase of bleeding risk in type 3 OC were epistaxis [odds ratio 3.6; 90% confidence intervals (CI) 1.84-21.5], cutaneous bleeding (odds ratio 5.5; 90% CI 2.5-14.1) and postsurgical bleeding (odds ratio 16.3; 90% CI 4.5-59). The severity of bleeding score correlated with the degree of factor (F) VIII reduction in plasma.. OC for type 3 VWD represent a distinctive population from type 1 OC. These patients, however, present with more frequent bleeding symptoms in comparison to normal controls, especially in case of significantly low FVIII. Desmopressin and/or tranexamic acid might be useful to prevent or treat bleeding in these cases.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Child; Child, Preschool; Deamino Arginine Vasopressin; Factor VIII; Female; Hemorrhage; Heterozygote; Humans; Infant; Male; Middle Aged; Odds Ratio; Risk; Surveys and Questionnaires; Tranexamic Acid; von Willebrand Diseases; von Willebrand Factor

The Consensus Document on Alternatives to Allogenic Blood Transfusion (AABT) has been drawn up by a panel of experts from 5 scientific societies. The Spanish Societies of Anesthesiology (SEDAR), Critical Care Medicine and Coronary Units (SEMICYUC), Hematology and Hemotherapy (AEHH), Blood Transfusion (SETS) and Thrombosis and Hemostasis (SETH) have sponsored and participated in this Consensus Document. Alternatives to blood transfusion have been divided into pharmacological and non-pharmacological, with 4 modules and 12 topics. The main objective variable was the reduction of allogenic blood transfusions and/or the number of transfused patients. The extent to which this objective was achieved by each AABT was evaluated using the Delphi method, which classifies the grade of recommendation from A (supported by controlled studies) to E (non-controlled studies and expert opinion). The experts concluded that most of the indications for AABT were based on middle or low grades of recommendation, "C", "D", or "E", thus indicating the need for further controlled studies.

Topics: Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Blood Loss, Surgical; Blood Substitutes; Blood Transfusion, Autologous; Colloids; Crystalloid Solutions; Deamino Arginine Vasopressin; Evidence-Based Medicine; Factor VIIa; Hematinics; Hemodilution; Hemorrhage; Hemostatics; Humans; Iron; Isotonic Solutions; Operative Blood Salvage; Postoperative Hemorrhage; Premedication; Randomized Controlled Trials as Topic; Recombinant Proteins; Tranexamic Acid

We report the case of a 2-year-old female child with a pelvic vascular malformation complicated by chronic low-grade bleeding. Treatment with intranasal desmopressin significantly reduced vaginal bleeding. Therefore, we suggest that intermittent use of intranasal desmopressin may be useful in the treatment of chronically bleeding low-flow vascular malformations.

Topics: Administration, Intranasal; Child, Preschool; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostatics; Humans; Pelvis; Vaginal Diseases; Vascular Diseases

Thrombocytopenia is a common condition in the critical care setting. Repetitive platelet transfusion might lead to formation of alloantibodies. HLA class I and human platelet antigen antibodies can lead to transfusion-refractory thrombocytopenia. Transfusion of cross-matched platelets often is effective in these patients. We report on the successful use of recombinant activated factor VII in an acute bleeding situation in a multi-transfused patient presenting with positive HLA class I alloantibody status and thrombocytopenia associated with platelet dysfunction refractory to even transfusion of cross-matched platelets. The 41-year-old female patient developed HLA class I antibodies during former episodes of massive transfusion. Her former medical history was empty concerning hemorrhagic events. During this specific bleeding episode the patient suffered from intractable profuse bleeding from the nasopharynx and oral cavity. Global coagulation tests were within the normal range. Platelet dysfunction was confirmed by PFA100. Initially the patient responded well to Desmopressin infusion, but after 36 h she became thrombocytopenic and refractory to even transfusion of cross-matched platelets. Recombinant activated factor VII was chosen as the last resort. Two identical boli of 160 microg/kg NovoSeven each were injected via a central line within an interval of 3 h. After the first injection bleeding was significantly reduced and vasopressor support discontinued. After the second bolus bleeding completely ceased and did not reoccur. We did not observe any side effects. The pluripotent hemostatic agent recombinant activated factor VII might be a new option in the treatment of hemorrhagic episodes in patients presenting with this rare disorder, especially when the patient is refractory to cross-matched platelets or matched platelets are not available.

Topics: Adult; Blood Platelet Disorders; Deamino Arginine Vasopressin; Disease Management; Factor VII; Factor VIIa; Female; Hemorrhage; Histocompatibility Antigens Class I; Humans; Isoantibodies; Oral Hemorrhage; Platelet Function Tests; Platelet Transfusion; Recombinant Proteins; Salvage Therapy; Thrombocytopenia

Desmopressin (DDAVP) is used to improve hemostasis in patients with bleeding disorders. The side effects of DDAVP in adults and children are benign. However, there has been concern regarding the development of hyponatremia and seizures after the use of DDAVP in young children. The authors describe three children under 3 years of age who developed hyponatremia (two also developed seizures) following intravenous administration of DDAVP at a standard dose of 0.3 mug/kg. Fluid restriction, avoidance of hypo-osmolar fluid, and close monitoring of fluid and electrolytes for 12 to 24 hours after the administration of DDAVP in children younger than 3 years of age is recommended.

Topics: Child, Preschool; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostatics; Humans; Hyponatremia; Infant; Male; Seizures; Treatment Outcome

Topics: Adult; Antifibrinolytic Agents; Bernard-Soulier Syndrome; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostatics; Humans; Pregnancy; Pregnancy Complications, Hematologic; Risk Factors; Tranexamic Acid

Topics: Antifibrinolytic Agents; Antithrombins; Blood Loss, Surgical; Deamino Arginine Vasopressin; Fibrinogen; Hematologic Diseases; Hemorrhage; Hemostatics; Humans; Monitoring, Intraoperative; Surgical Procedures, Operative

Maternal administration of DDAVP induces maternal and fetal plasma hyponatremia, accentuates fetal urine flow, and increases amniotic fluid volume. Fetal hemorrhage represents an acute stress that results in fetal AVP secretion and reduced urine flow rate. In view of the potential therapeutic use of DDAVP for pregnancies with reduced amniotic fluid volume, we sought to examine the impact of maternal hypotonicity during acute fetal hemorrhage. Chronically catheterized pregnant ewes (130 +/- 2 days) were allocated to control or to DDAVP-induced hyponatremia groups. In the latter group, tap water (2,000 ml) was administered intragastrically to the ewe followed by DDAVP (20 microg bolus, 4 microg/h) and a maintenance intravenous infusion of 5% dextrose water for 4 h to achieve maternal hyponatremia of 10-12 meq/l. Thereafter, ovine fetuses from both groups were continuously hemorrhaged to 30% of estimated blood volume over a 60-min period. DDAVP caused similar degree of reductions in plasma sodium and osmolality in pregnant ewes and their fetuses. In response to hemorrhage, DDAVP fetuses showed greater reduction in hematocrit than control fetuses (14 vs. 10%). Both groups of fetuses demonstrated similar increases in plasma AVP concentration. However, the AVP-hemorrhage threshold was greater in DDAVP fetuses (22.5%) than in control (17.5%). Hemorrhage had no significant impact on plasma osmolality, electrolyte levels, or cardiovascular responses in either group of fetuses. Despite similar increases in plasma AVP, DDAVP fetuses preserved fetal urine flow rates, with values threefold those of control fetuses. These results suggest that under conditions of acute fetal stress of hemorrhage, maternal DDAVP may preserve fetal urine flow and amniotic fluid volume.

Topics: Acute Disease; Animals; Deamino Arginine Vasopressin; Diuresis; Female; Fetal Diseases; Hematocrit; Hemorrhage; Hyponatremia; Kidney; Maternal-Fetal Exchange; Pregnancy; Sheep, Domestic; Water

Topics: Aged; Aged, 80 and over; Aminocaproic Acid; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Autoantibodies; Autoimmune Diseases; B-Lymphocyte Subsets; Blue Toe Syndrome; Bradycardia; Combined Modality Therapy; Compartment Syndromes; Deamino Arginine Vasopressin; Factor VII; Factor VIIa; Factor VIII; Female; Hematoma; Hemorrhage; Humans; Immunoglobulins, Intravenous; Pacemaker, Artificial; Plasmapheresis; Platelet Transfusion; Postoperative Hemorrhage; Recombinant Proteins; Rituximab

The primary objective of this study was to investigate the correlation between fibrinolytic activity in menstrual fluid and total menstrual blood loss during menstruation. We also wanted to evaluate the influence of desmopressin nasal inhalation on the local fibrinolytic activity in menstrual fluid. Six women with objectively verified menorrhagia and six women with normal menstrual blood loss were examined. With a slender catheter introduced through the cervical canal, menstrual fluid was collected on the day in the cycle when the most intense bleeding occurred. The fibrinolytic activity in menstrual fluid was measured both as plasmin content using an amidolytic method with chromogenic substrate and with a fibrin plate method. A significant correlation between the amount of menstrual blood loss and fibrinolytic activity was found in menstrual fluid of both groups and with both methods. We could not find an increased fibrinolytic activity in menstrual fluid when the women with menorrhagia were treated with desmopressin nasal inhalation. Knowledge of the local factors influencing monthly blood loss can be valuable when searching for more effective medical treatment of menorrhagia. Apprehension that desmopressin should increase local fibrinolytic activity in menstrual fluid could not be confirmed.

Topics: Administration, Inhalation; Blood Coagulation Tests; Case-Control Studies; Deamino Arginine Vasopressin; Female; Fibrinolysin; Fibrinolysis; Hemorrhage; Humans; Menorrhagia; Menstruation

Two patients, a man aged 69 and a woman aged 64, were diagnosed with Von-Willebrand syndrome caused by monoclonal gammopathy. The man, who was admitted for hip surgery, had a history of long episodes of epistaxis. The patient was treated with immunoglobulin and the hip operation was carried out with no complications. The woman suffered from haemorrhagic diathesis. She was advised that should she undergo an invasive procedure then treatment with a prophylactic with intravenous immunoglobulin or Von-Willebrand factor (VWF)/factor-VIII-concentrates must be administered. Acquired Von-Willebrand syndrome is a rare condition with an estimated prevalence of 0.04-0.13%. It is linked to a large number of underlying diseases such as paraproteinaemia, multiple myeloma (Kahler's disease), myeloproliferative disease, lymphoproliferative disease, auto-immune disease, solid tumours and hypothyroidism. Recognition depends on a careful case-history and identification of the underlying disease. For its diagnosis VWF antigen. VWF propeptide, activated partial thromboplastin time and factor VIII are of importance. Technically, it is difficult to show the presence of VWF antibodies as it concerns a heterogeneous group of antibodies. There are two pillars of treatment: symptomatic treatment of the bleeding tendencies using desmopressin, VWF-concentrate or intravenous gammaglobulin, and treatment of the underlying disease. The latter form of treatment can lead to acquired Von-Willebrand-syndrome disappearing altogether.

Topics: Aged; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostatics; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Paraproteinemias; von Willebrand Diseases; von Willebrand Factor

Topics: Adenocarcinoma; Aged; Carcinoma, Transitional Cell; Deamino Arginine Vasopressin; Hemorrhage; Humans; Intraoperative Complications; Male; Osteogenesis Imperfecta; Prostatic Neoplasms; Urinary Bladder Neoplasms

We report a quite rare case of acquired type 3-like von Willebrand syndrome (vWS) that preceded full-blown systemic lupus erythematosus (SLE). A 16-year-old woman with no previous disease history and no family history of hemorrhagic diathesis was referred to our hospital because of recurrent epistaxis and gingival bleeding. She was diagnosed as having atypical type 3 von Willebrand disease because of prolonged bleeding time with normal platelet count and prolonged activated partial thromboplastin time (aPTT), and an almost complete absence of von Willebrand factor (vWF) antigen, ristocetin cofactor activity (vWF:RCo) and ristocetin-induced platelet agglutination (RIPA). Furthermore, electrophoretic analysis of plasma vWF revealed a trace amount of vWF and an absence of the multimeric form of vWF. Infusions of either vasopressin or factor VIII/vWF concentrates improved bleeding symptoms and corrected the aPTT and RIPA. However, she complained of low-grade fever, general fatigue and polyarthralgia 5 months later, and leukocytepenia and hypo-complementemia developed. Anti-double-stranded DNA antibodies and lupus erythematosus cells became positive. These findings were compatible with SLE. Mixing the patient's platelet-poor plasma (PPP) with normal platelet-rich plasma (PRP) (PPP/PRP = 2/1) resulted in a complete inhibition of RIPA, suggesting the presence of vWF inhibitor in her plasma. Treatment with prednisolone (40 mg/day) started and the bleeding tendency gradually improved. One month later, all of the laboratory data including aPTT, bleeding time, RIPA and vWF:RCo became normal. These findings indicate that she has an acquired type 3-like vWS associated with SLE.

Topics: Adolescent; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Lupus Erythematosus, Systemic; Prednisolone; von Willebrand Diseases

Twelve years prior to hospitalization because of a severe bleeding, a 70 year old patient was diagnosed with a May-Hegglin anomaly, which is a rare autosomal dominant inherited form of thrombocytopenia.. The blood smear contained signs of the May-Hegglin anomaly: Döhle's inclusion bodies and giant platelets. Platelet counts were around 30 G/l. Coronary angiography revealed a highly severe left main stenosis.. Even using maximum drug therapy, angina pectoris could not be stabilized. Therefore emergency coronary artery bypass grafting had to be performed. Before skin incision 3 micrograms/kg DDAVP (Desmopressin) were administered and after extracorporeal circulation 8 units of platelets were transfused. In addition, perioperative coagulation management was performed according to usual standards. There were no bleeding complications. The patient could leave the clinic after 11 days in stable condition.. Patients showing May-Hegglin anomaly, even with serious thrombocytopenia, can be operated using extracorporal circulation without a high risk of bleeding.

Topics: Adult; Angina Pectoris; Blood Coagulation; Blood Platelets; Coronary Artery Bypass; Deamino Arginine Vasopressin; Hemorrhage; Humans; Inclusion Bodies; Male; Thrombocytopenia

Acquired von Willebrand syndrome (AvWS) has been reported in eight children with Wilms tumor (nephroblastoma in four boys and four girls) at a mean age of 3.3 years (range, 0.33-9 years). Only three of eight patients with AvWS in Wilms tumor presented with mild mucocutaneous bleeding symptoms. The AvWS in seven children with Wilms tumor featured either undetectable or very low von Willebrand factor antigen (vWF.Ag) levels (mean, 3%) and decreased values for vWF ristocetin cofactor (RCF) activity (mean, 20%) and factor VIII coagulant (VIIIc) activity (mean, 16%). The response to 1-desamino-8-arginine vasopressin (DDAVP) was good in two and poor in one patient. Multimeric analysis of the vWF showed a normal pattern of type I von Willebrand disease (vWD) in three patients and an absence of multimers consistent with type III vWD in two patients. The higher functional levels, as compared with antigen levels, with increased ratios for factor VIIIc/vWFAg (mean, 5.3) and vWF.RCF/vWF.Ag (mean, 6.6) in seven patients with Wilms tumor are unexplained physiologically and are not consistent with type I vWF deficiency. The absence of vWD in the patient's family, and the return of factor VIII-vWF parameters to normal after chemotherapy or surgical removal of the Wilms tumor, support the diagnosis of AvWS causally related to the Wilms tumor. The causative agent is thought to be hyaluronic acid secreted by nephroblastoma cells of the Wilms tumor. Prospective studies to determine the nature of AvWS in children with Wilms tumor are warranted.

Topics: Child; Child, Preschool; Deamino Arginine Vasopressin; Factor VIII; Female; Genetic Variation; Hemorrhage; Humans; Hyaluronic Acid; Infant; Male; Neuroblastoma; Treatment Outcome; von Willebrand Diseases; von Willebrand Factor; Wilms Tumor

Acquired von Willebrand syndrome (AvWS) in systemic lupus erythematodes (SLE) is caused by autoantibodies directed against the circulating von Willebrand factor (vWF)/factor VIII (FVIII) complex. The autoantibody-vWF/FVIII antigen complex is cleared rapidly from the circulation, leading to a moderate to severe quantitative and qualitative deficiency of both vWF and FVIIIc. Consequently, AvWS in SLE is featured by a prolonged bleeding time and normal platelet count, a prolonged activated partial thromboplastin time (APTT) and normal prothrombin time (PT), decreased or absent ristocetin-induced platelet aggregation (RIPA), and type II vWF deficiency on multimeric analysis of the vWF protein. Acquired von Willebrand syndrome type II in SLE responds poorly to 1-desamino-8-D-arginine vasopressin (DDAVP) and FVIII concentrate, but responds transiently well to high-dose gammaglobulin given intravenously. All reported cases of AvWS in SLE were cured by appropriate treatment of the underlying autoimmune disease with prednisone or immunosuppression.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Deamino Arginine Vasopressin; Factor VIII; Female; Hemorrhage; Hemostatics; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Prednisone; Severity of Illness Index; Treatment Outcome; von Willebrand Diseases

The optimal treatment of patients with von Willebrand's disease (vWD) remains to be defined. Moreover, it has not been firmly established which, if any, commonly measured parameters of von Willebrand factor (vWF) protein in the plasma are useful in guiding treatment. To better understand what guidelines physicians follow in the management of vWD, we surveyed 194 North American physicians who are members of the Hemophilia Research Society. Ninety-nine per cent of responding physicians depend on factor VIII (FVIII):C, vWF:RCo activity and vWF:AG to diagnose vWD, while only 49% use the bleeding time. The minimal goals of treatment for patients undergoing major surgery/trauma or central nervous system haemorrhage were FVIII:C and vWF:RCo activity greater than 80% while levels of more than 50% for minor surgery and dental extractions were considered adequate. Treatment of vWD was based on the type of vWD with type 1 patients being treated most often with desmopressin acetate (DDAVP) alone, types 2A and 2B patients with a combination of DDAVP and a vWF-containing FVIII product, type 3 patients with vWF-containing concentrate. Viral infections, including human immunodeficiency virus, hepatitis A, B and C viruses, and parvovirus have been seen in vWD and the efficacy of viral attenuation processes is a major criterion for the selection of treatment by physicians. Based on this survey, prospective studies need to be designed to address the clinical efficacy, safety and predictive value of laboratory monitoring of patients with vWD.

Topics: Ambulatory Care Facilities; Data Collection; Deamino Arginine Vasopressin; Disease Management; Factor VIII; Hemorrhage; Humans; Infections; North America; Partial Thromboplastin Time; Societies, Scientific; von Willebrand Diseases; von Willebrand Factor

Topics: Antifibrinolytic Agents; Contusions; Deamino Arginine Vasopressin; Diagnosis, Differential; Female; Hemorrhage; Hemostatics; Humans; Male; Societies, Medical; von Willebrand Diseases

Topics: Adolescent; Adult; Aged; Blood Transfusion; Child; Deamino Arginine Vasopressin; Factor VIII; Factor XI; Factor XI Deficiency; Female; Hemorrhage; Heterozygote; Humans; Male; Middle Aged; Partial Thromboplastin Time; von Willebrand Factor

Topics: Deamino Arginine Vasopressin; Factor VIII; Female; Hemorrhage; Heterozygote; Humans; Mutation, Missense; Phenotype; Point Mutation; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic; von Willebrand Diseases; von Willebrand Factor

The management of unexpected bleeding must be directed at the specific abnormality identified, as there is no universally effective and safe procoagulant product. Where practical, a purely pharmaceutical approach obviates the residual risks of exposure to plasma-derived products. Desmopressin is often effective in bleeding due to mild haemophilia A, Type I von Willebrand's disease and some platelet function disorders. Where replacement therapy is necessary, it should be as specific as possible, preferably using purified components singly or in combination. Recombinant proteins provide the greatest margin of safety, but it must be borne in mind that these are biologicals, and that they may contain human and animal plasma-derived proteins. Where specific replacement is unavailable or impractical, plasma or crudely fractionated plasma derivatives may be used. In the case of inhibitor antibodies to factor VIII, high dose human factor VIII or porcine factor VIII may be used. Where replacement therapy is impossible due to a high inhibitory titre, it may be necessary to bypass the specific haemostatic defect using activated prothrombin complex concentrates or recombinant activated factor VIIa. The latter product is being studied in patients with various disorders of platelet function, and in the more global haemostatic failure that accompanies end-stage liver disease. Ancillary methods are often of great value in securing haemostasis. These may be derived from pharmacological or biological sources, and their sites of action may be systemic or topical. Examples include antifibrinolytic lysine analogues, corticosteroids where inflammation accompanies bleeding, and the topical application of fibrin sealants or thrombin. Simple physical measures such as pressure, ice, or splinting are also valuable adjunctive measures. Finally, it must be emphasized that the ultimate control of bleeding often depends upon effective management of the inciting cause, such as eliminating the trigger for DIC, or suppressing the causative antibody of ITP. These principles will be presented using a practical algorithmic approach. The initial question when considering treatment should be whether or not the patient is acutely unstable. Instability may be due to one of two causes: the volume of blood loss leading to a compromised cardio-vascular status, or the site of the bleed. The relevance of the site of the bleed is independent of the volume of blood loss, so for example, a closed bleed

Topics: Algorithms; Blood Transfusion; Coagulation Protein Disorders; Contraindications; Deamino Arginine Vasopressin; Factor VIII; Hemorrhage; Hemostatics; Humans; Plasma; Platelet Transfusion

Topics: Blood Transfusion; Contraindications; Deamino Arginine Vasopressin; Emergencies; Factor IX; Factor VIII; Hemophilia A; Hemophilia B; Hemorrhage; Hemostatics; Humans; Male; Risk Factors; Wounds and Injuries

Desmopressin (DDAVP) may shorten bleeding time in patients with disorders of platelet function, but its mechanism of action in these conditions is still a matter of debate. In particular, contrasting results have been obtained concerning the ability of DDAVP to interact with platelets and to activate them directly. To gain further information on the DDAVP-platelet interaction, we studied the in vitro and ex vivo effects of DDAVP on platelet function.. Platelet responses to DDAVP both as a single agent and in conjunction with agonists of platelet activation were investigated. For in vitro experiments platelets were obtained from healthy adult volunteers, while the ex vivo effects of DDAVP were studied in 12 patients with a bleeding disorder receiving a test dose of this drug.. DDAVP in vitro did not induce either platelet aggregation or surface expression of the activation-dependent antigens; it did, however, greatly inhibit platelet aggregation response to vasopressin (AVP) and increased the maximal extent of platelet aggregation induced by collagen and ADP. DDAVP infusion did not promote the expression of activation antigens, but significantly enhanced ex vivo platelet aggregation stimulated by ADP and collagen. This priming effect was observed in patients with von Willebrand's disease, hemophilia A, May-Hegglin anomaly, gray platelet syndrome and Ehlers-Danlos syndrome. In all these patients bleeding time was shortened by DDAVP infusion. In contrast, neither platelet aggregation nor bleeding time was modified in two subjects with Glanzmann's thrombasthenia.. Our in vitro experiments indicate that DDAVP interacts directly with platelets and facilitates their activation via other agonists. In vivo results suggest that this effect occurs and is clinically relevant in patients with platelet dysfunction responding to DDAVP with a shortening of bleeding time.

Topics: Adenosine Diphosphate; Antigens, CD; Bleeding Time; Blood Platelets; Collagen; Deamino Arginine Vasopressin; Hemorrhage; Humans; Platelet Activation; Platelet Aggregation

Topics: Aged; Autoantibodies; Deamino Arginine Vasopressin; Drug Therapy, Combination; Factor VIII; Female; Hematoma; Hemophilia A; Hemorrhage; Humans; Immunoglobulins; Prednisone

Twenty six patients with mild or moderate haemophilia A and inhibitors are described. The inhibitor was detected at a median age of 33 years, after a median of 5.5 bleeding episodes. This usually following intensive replacement therapy. The median presenting inhibitor titre was antihuman 11.6 BU/ml, antiporcine 1.45 BU/ml. Plasma basal factor VIII level declined from a median of 0.08 IU/ml to 0.01 IU/ml following the inhibitor development. This caused spontaneous bleeding in 22 and a bleeding pattern similar to acquired haemophilia in 17. Bleeding was often severe and caused two deaths. The inhibitor disappeared spontaneously, or following immune tolerance induction, in 16 cases after a median of 9 months (range 0.5-46), with a return to the original baseline VIIIC level and bleeding pattern accompanied inhibitor loss. The inhibitor persisted in the remainder of the cases over a median period of 99 months (range 17-433 months) of follow-up. Inhibitors are an uncommon complication of mild haemophilia which frequently persist and may be associated with severe, life-threatening, haemorrhage. Forty-one percent of treated haemophilic family members had a history of factor VIII inhibitors, suggesting a familial predisposition to develop inhibitors in these kindreds. Sixteen patients from 11 families were genotyped. Seven different missense mutations affecting the light chain were detected and two in the A2 domain. Five patients from three families had a mutation causing a substitution of Trp2229 by Cys in the C2 domain which appears to predispose to inhibitor formation since 7 of the 18 affected individuals have a history of inhibitor development.

Topics: Adolescent; Adult; Aged; Antibody Specificity; Autoantibodies; Blood Transfusion; Child; Deamino Arginine Vasopressin; DNA Mutational Analysis; Epitopes; Factor VIII; Genotype; Hemophilia A; Hemorrhage; Humans; Male; Middle Aged; Pedigree; Point Mutation; Prevalence; Prospective Studies; Protein Conformation; Retrospective Studies

Of 260 patients enrolled, 25 patients (9.6%) were associated with acquired von Willebrand syndrome (AvWS). We studied 25 patients with AvWS, retrospectively. AvWS was diagnosed by reduced levels of von Willebrand factor (vWF) (decrease of von Willebrand factor antigen [vWF:Ag] and von Willebrand ristocetin cofactor [vWF:RCoF]), a decrease of ristocetin-induced platelet agglutination (RIPA), sometimes decreased high-molecular-weight multimers, and prolonged bleeding time with neither prior nor family histories of bleeding problems and the evidence of normal vWF:RCoF in their families. The inhibitor of vWF was determined by mixing patient plasma with pooled normal plasma. Eight patients in this study had the inhibitors to vWF that were of the IgG class; the subclasses were IgG1 (7 cases) and IgG2 (1 case). Multimeric analysis of vWF showed selective loss of large multimers in most patients with AvWS similar to that of congenital type-2 von Willebrand disease (vWD). All inhibitors blocked ristocetin-mediated vWF binding to platelets. Five out of 6 IgGs evaluated here recognized the 39/34-kD fragment (residues 480/481-718) and Fragment III (residues 1-1365) that implied binding domain of glycoprotein Ib (GPIb), whereas 1 recognized Fragment I (residues 911-1365). A close relationship was found between the presence of the inhibitor and bleeding tendency. Of the 7 patients with inhibitors, 6 patients (86%) had a bleeding tendency, as well as 1 of the 15 patients without inhibitors (6%). The efficacy of treatment of underlying diseases and/or therapy with deamino D-arginine vasopressin (DDAVP) for the treatment of AvWS also depends on the presence of an inhibitor. Four of 8 patients with inhibitors (50%) had poor response to treatment of the underlying disease and/or therapy with DDAVP, as well as 1 of the 16 patients without inhibitors (6%). These results indicate that patients with AvWS developing inhibitors to vWF are likely to have bleeding problems and might be resistant to treatment of underlying diseases and/or therapy with DDAVP for bleeding to AvWS. We also showed evidence that intravenous immunoglobulin therapy (0.3 g/kg, 3 days) was effective to correct a hemostatic defect and manage severe bleeding in a patient with AvWS developing inhibitors. We might consider an additional treatment including expensive high-dose immunoglobulin therapy when uncontrollable bleeding is continued after the treatment of the underlying diseases and/or therapy with DDAVP.

Topics: Adult; Aged; Aged, 80 and over; Autoimmune Diseases; Deamino Arginine Vasopressin; Epitopes; Female; Hematologic Diseases; Hemorrhage; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Male; Middle Aged; Molecular Weight; Peptide Fragments; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIb-IX Complex; Retrospective Studies; von Willebrand Diseases; von Willebrand Factor

Topics: Administration, Intranasal; Adolescent; Adult; Bleeding Time; Blood Coagulation; Child; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Hemorrhage; Humans; Renal Agents; Treatment Outcome; Uremia

Topics: Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans

Vasovagal reflexes, such as hypotension and bradycardia, are induced by rapid hemorrhage and mimic neurocardiogenic reflexes in mammals. We examined the role of vasopressin in the neurocardiogenic responses to mild, rapid hemorrhage (1 mL/100 g for 30 seconds) and severe hemorrhage (1 mL/100 g body wt for 30 seconds repeated three times at 11-minute intervals) in homozygous Brattleboro and Long-Evans rats. Mild, rapid hemorrhage induced severe bradycardia and hypotension only in Long-Evans rats. Exogenous vasopressin (1.85 pmol/kg per minute for 1 hour) restored both the bradycardic and hypotensive responses in Brattleboro rats. DDAVP, a vasopressin V2-receptor agonist (0.19 pmol/kg per minute for 24 hours), did not affect the cardiovascular responses to hemorrhage in Brattleboro rats, although it maintained urine production within normal limits. However, OPC-31260 (21.6 mumol/kg IV), a vasopressin V2-receptor antagonist, attenuated both the hypotensive and bradycardic responses to hemorrhage in Long-Evans rats. A vasopressin V1-receptor antagonist attenuated bradycardia and delayed the recovery of arterial pressure after hemorrhage but did not affect the hypotension that occurred immediately after hemorrhage in Long-Evans rats. Methylatropine also attenuated both the bradycardic and hypotensive responses induced by hemorrhage, but propranolol had no effect on the cardiovascular responses to hemorrhage in Long-Evans rats. The recovery of arterial pressure after repeated hemorrhage was less adequate in Brattleboro rats than in Long-Evans rats. Our results suggest that the neurocardiogenic responses to hemorrhage, especially hypotension, may be related to vasodilation induced by a V2-receptor-mediated mechanism and by the vagal reflex, both of which are substantiated by the existence of vasopressin. The coexistence of V1- and V2-receptor mechanisms may be necessary for the hypotensive response to hemorrhage. We found that a V2-receptor antagonist attenuated the hypotension mediated by the so-called neurocardiogenic reflex.

Topics: Acute Disease; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Autonomic Nerve Block; Benzazepines; Cardiovascular System; Deamino Arginine Vasopressin; Diabetes Insipidus; Heart; Hemorrhage; Male; Nervous System; Rats; Rats, Brattleboro; Rats, Inbred Strains; Receptors, Vasopressin; Recurrence; Vasopressins

Hirudin is a potent thrombin inhibitor derived from the leech Hirudo medicinalis salivary gland which has considerable potential for therapeutic use in thrombotic disease. The major risk attendant its use is hemorrhage. This study investigates the hypothesis that the prohemostatic effects of DDAVP infusion can curtail the hemorrhagic effect induced by ongoing hirudin administration. In a randomized and blinded manner, rabbits were exposed to a 15-min intravenous infusion of DDAVP or saline midway through a continuous two-h intravenous infusion of hirudin. Bleeding time was monitored by full thickness ear punctures performed before, during and after hirudin exposure. Hirudin induced a significant hemorrhagic state, manifest as a 7-10-fold prolongation of the primary bleeding time. DDAVP reduced the mean duration of primary bleeding from 10.8 min to 5.9 min (p = 0.001) as well as the number of sites which bled for longer than 6 or 20 min (46% vs 27%, p = 0.002; and 18% vs 5%, p = 0.002, respectively). Although there was no difference in the incidence of spontaneous rebleeding from these sites (44 vs 36%, p = 0.21), rebleeding did not persist as long in animals that received DDAVP (8 vs 16 min, p = 0.005), and fewer sites rebled for longer than 20 min (8 vs 27%, p = 0.027). Results were essentially the same for two different commercial recombinant hirudin preparations. DDAVP appears to attenuate the bleeding caused by continuous hirudin infusion in rabbits and establishes a foundation for clinical assessment in patients.

Topics: Animals; Antithrombins; Deamino Arginine Vasopressin; Double-Blind Method; Drug Therapy, Combination; Hemorrhage; Hemostatics; Hirudins; Infusions, Intravenous; Male; Rabbits; Random Allocation

This study is designed to evaluate the clinical outcome of uremic bleeding treated with DDAVP. DDAVP was given intravenously in nine ESRD patients who had undergone A/V fistula surgery and showed oozing of the operation site for more than one hour.. Hemostasis was observed by removing the blood from the wound site with a piece of filter paper for 3 hours after DDAVP administration. vWF, t-PA antigen, t-PA activity, total fibrinolytic activity in euglobulin fraction, fibrinopeptide A and FDP were measured before and after DDAVP administration.. Cessation of the oozing did not occur within 3 hours after DDAVP administration in all of the cases. vWF levels and t-PA antigen were significantly increased after DDAVP administration peaked at 30 min for vWF and 60 min for t-PA antigen. t-PA activity increased in 6 cases and euglobulin fibrinolytic activity increased in 7 cases, respectively. These values fell towards pre-administration levels 120 min after the administration. There was no difference in fibrinopeptide A levels before and after DDAVP administration. FDP became positive in 4 cases after DDAVP administration.. DDAVP increased both vWF and t-PA levels and cessation of the oozing from post-operative AV-fistula wounds did not occur within 3 hours after DDAVP administration in all of the cases. These results suggest that the effect of DDAVP should be reassessed in the treatment of uremic bleeding.

Topics: Adult; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostasis; Humans; Male; Middle Aged; Tissue Plasminogen Activator; Uremia; von Willebrand Factor

An international registry was established by the Subcommittee on von Willebrand Factor of the SSC/ISTH on the treatment of patients with types of von Willebrand disease (vWD) unresponsive to DDAVP infusion. Data was collected on 76 surgical events in 64 patients from 19 treatment centers. Thirty-three non-mucosal, 12 mucosal, 10 orthopedic and 21 dental procedures were reported. In the 76 surgical events, 14 cases prophylactically received cryoprecipitate while 62 received factor VIII (FVIII) concentrate. Surgical hemostasis was reported as satisfactory, good, or excellent in 75 of the 76 cases. Post-infusion bleeding times were measured in only three of 14 surgical events treated with cryoprecipitate. All three cases had a reduction but not correction of the bleeding time. The post-infusion bleeding time was measured in 27 of 62 cases in which FVIII concentrates were used. The bleeding time time was normalized in 15, reduced but not normalized in eight, and not changed from baseline in four. Data was also collected from 16 treatment centers on 50 serious bleeding events in 35 patients. These included 19 gastrointestinal, 15 other mucosal, four central nervous system, seven orthopedic, and five other mucosal, four central nervous system, seven orthopedic, and five other bleeds. Eleven cases received cryoprecipitate and 39 received FVIII concentrate as primary therapy. The efficacy of treatment was considered good or excellent in 49 of 50 cases. Post-infusion bleeding times were measured in only 15 of the 50 reported bleeding events. The post-infusion bleeding time was normalized in six, decreased but not normalized in eight, and not changed from baseline in one. In this retrospective survey, FVIII concentrates were subjectively as efficacious as cryoprecipitate in both the surgical setting and for the treatment of severe bleeds in patients with types of vWd unresponsive to DDAVP. Since the bleeding time was monitored during therapy in only a minority of these cases, a definitive relationship between the efficacy of therapy and normalization or reduction of the bleeding time in these two clinical settings cannot be established from this study. A prospective study on the use of FVIII and/or vWf concentrates in these clinical settings is necessary to address this issue.

Topics: Cryoglobulins; Deamino Arginine Vasopressin; Drug Resistance; Factor VIII; Health Surveys; Hemorrhage; Humans; Registries; von Willebrand Diseases

With few exceptions, 1-desamino-8-D-arginine vassopressin (DDAVP) has been shown to be useful in securing haemostasis in patients with von Willebrand's disease (vWd). In type IIB vWd, DDAVP has been reported to have no beneficial effects and to be contraindicated because it causes or worsens thrombocytopenia, due to in vivo platelet aggregation. Nevertheless, it was previously demonstrated that DDAVP may have clinical utility in some patients with type IIB vWd. Additional findings obtained in seven type IIB vWd patients of different kindreds undergoing minor surgical procedures are now reported. It was observed that DDAVP corrected the bleeding time in every case, with effects lasting for 2 h. Mean platelet counts decreased 30 min after DDAVP to variable degrees, depending on the anticoagulant used for blood collection, but were normal 2 h later. Furthermore DDAVP normalized FVIII, von Willebrand factor (vWf) antigen (vWf:Ag), and to a lesser extent, vWf ristocetin cofactor activity (vWf:RCoF). Intermediate and large vWf multimers appeared after 30 min. There were no bleeding complications during or after surgery, nor evidence of thrombosis. It was thus confirmed that DDAVP has clinical utility in the prevention of bleeding symptoms in different type IIB vWd patients. Therefore, despite the transitory thrombocytopenia and the incomplete restoration of larger vWf multimers, the use of this drug should be reconsidered for patients with type IIB vWd.

Topics: Deamino Arginine Vasopressin; Factor VIII; Hemorrhage; Humans; Intraoperative Complications; Kinetics; Platelet Count; Thrombocytopenia; von Willebrand Diseases; von Willebrand Factor

An 82-year-old patient with acquired von Willebrand's disease in association with a non-Hodgkin's lymphoma and a benign IgG-lambda monoclonal paraproteinemia is described with severe recurring nasopharyngeal bleedings, who responded poorly to desmopressin (DDAVP) and factor VIII/von Willebrand factor concentrates but was successfully treated with high-dose e intravenous gamma-globulin therapy.

Topics: Aged; Aged, 80 and over; Autoantibodies; Autoimmune Diseases; Deamino Arginine Vasopressin; Factor VIII; Hemorrhage; Humans; Immunoglobulin lambda-Chains; Immunoglobulin M; Immunoglobulins, Intravenous; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Male; Monoclonal Gammopathy of Undetermined Significance; von Willebrand Diseases; von Willebrand Factor

DDAVP, an analog of vasopressin, has been shown to have hemostatic activity. Although it has been used clinically to control bleeding, there have been very few attempts to characterize this agent in experimental animals. We describe a new animal model which is fast, reliable and inexpensive, and which may be used to screen novel analogs of the peptide. Under sodium pentobarbital anesthesia, rats were bilaterally nephrectomized and implanted with indwelling intravenous cannulae. The next day they were re-anesthetized, a standardized cut was made in the tail and the tail was allowed to bleed into warm isotonic saline (25 ml). After 10 min., the tail was removed from the saline and the blood loss was measured either by laser nephelometry or by colorimetric analysis. DDAVP was then injected intravenously and the rat was allowed to rest quietly for 30 min., after which time a second incision was made in the tail and blood loss again measured for 10 min. Unlike bleeding time which was highly variable, blood loss proved to be a reliable index of the hemostatic activity. Thus we were able to demonstrate that DDAVP reduced blood loss in the uremic rats, whereas it was without effect in intact rats.

Topics: Animals; Bleeding Time; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Rats; Reproducibility of Results; Uremia

An acquired factor VIII inhibitor was found in an 82-year-old woman who presented with numerous spontaneously appearing ecchymoses. Coagulation studies revealed the presence of a prolonged activated partial thromboplastin time that was not corrected by 1:1 mixture with normal fresh plasma after a 2-h incubation. Factor VIII:C was 4%, and the titer for factor VIII inhibitor was 9 Bethesda units. Three months later, after a retroperitoneal hemorrhage, a lymphocytosis was found in her peripheral blood with morphological and surface immunophenotype characteristics of B-cell chronic lymphocytic leukemia, later confirmed by bone marrow morphological and immunocytochemical examinations. To our knowledge, this is the first report of an autoimmune factor VIII inhibitor associated with chronic lymphocytic leukemia.

Topics: Aged; Aged, 80 and over; Deamino Arginine Vasopressin; Ecchymosis; Factor VIII; Female; Follow-Up Studies; Hemorrhage; Humans; Immunoglobulins, Intravenous; Immunophenotyping; Leukemia, Lymphocytic, Chronic, B-Cell; Partial Thromboplastin Time; Prednisone; Time Factors

The effect of desmopressin (DDAVP) on protein C (PC) and PC inhibitors was investigated in 7 uremic predialysis patients, 7 hemodialysis patients and 7 controls. Significant decrease in PC activity was observed in all groups after DDAVP administration. Desmopressin did not influence PC antigen and two well-known PC inhibitors, plasminogen activator inhibitor-3 and alpha 1-antitrypsin. Thus, it is suggested that DDAVP-induced decrease in PC activity is not related to the changes in PC inhibitors; further studies are needed to clarify the precise mechanisms of the effect of DDAVP on PC in uremia.

Topics: Adult; alpha 1-Antitrypsin; Antigens; Blood Coagulation; Deamino Arginine Vasopressin; Hemorrhage; Humans; Middle Aged; Plasminogen Inactivators; Protein C; Renal Dialysis; Uremia

The infusion of a high dose of recombinant desulphatohirudin HVI (CGP 39393) for 40 min at 30 micrograms/kg/min, resulted in a prolongation of bleeding time in the rat when evaluated using transection of the tail. The prolonged bleeding was evident both immediately, and 30 min after cessation of the infusion of hirudin (CGP 39393). Bleeding time returned to normal after 60 min. The effect of several agents, reported to be successful in reducing bleeding tendencies in man, were evaluated in this rat model. The agents were administered immediately following cessation of the CGP 39393 infusion and their ability to normalize the prolonged bleeding-time, observed at 30 min after cessation of the CGP 39393 infusion, determined. Desmopressin (DDAVP), recombinant factor VIII and Vueffe reduced the bleeding time to the control range but did not exert any significant effects on the bleeding time in rats which did not receive CGP 39393. Epsilon-aminocaproic acid (EACA) and recombinant factor VII were ineffective, at the doses used. In conclusion, DDAVP, factor VIII and Vueffe are effective in reversing the effect of direct thrombin inhibition on bleeding in the rat.

Topics: Aminocaproic Acid; Animals; Bleeding Time; Blood Coagulation; Deamino Arginine Vasopressin; Factor VIIa; Factor VIII; Fibrinolytic Agents; Hemorrhage; Hirudins; Male; Peptides; Rats; Rats, Wistar; Recombinant Proteins

Topics: Adult; Bernard-Soulier Syndrome; Deamino Arginine Vasopressin; Female; Hemorrhage; Hemostasis; Humans; von Willebrand Factor

Easy bruisability raises the issue of bleeding during otolaryngological surgery. Ten female patients with easy bruisability were evaluated by aspirin challenge; clinical history and screening coagulation studies in these patients had revealed no evidence of a bleeding disorder. The baseline Ivy bleeding time (BT) test (4.5 to 9.5 minutes) was found to be normal in 6 patients and prolonged in 4 patients. Following treatment with aspirin, the bleeding time prolonged significantly in the three groups evaluated: normal controls (6.0 +/- 1.5 minutes vs. 8.4 +/- 2.0 minutes), patients with easy bruisability and a normal baseline (7.8 +/- 1.3 minutes vs. 12.0 +/- 1.6 minutes), and patients with easy bruisability and an abnormal baseline (11.0 +/- 0.7 minutes vs. 14.5 +/- 0.9 minutes). Administration of DDAVP (desmopressin acetate) 0.3 microgram/kg normalized the prolonged bleeding times in all groups after 7 days of daily aspirin therapy. Performing bleeding times before aspirin challenge, after aspirin challenge, and after DDAVP therapy following aspirin challenge is both a useful way of confirming aspirin sensitivity in patients with easy bruisability as well as a useful way of documenting improved hemostasis after DDAVP administration.

Topics: Adult; Aspirin; Bleeding Time; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Middle Aged

Desmopressin (1-desamino-8-D-arginine vasopressin), an established hemostatic agent for the treatment of bleeding in mild hemophilia A, von Willebrand's disease, or platelet disorders, has mostly been given parenterally as intravenous or subcutaneous injections. Intranasal administration by spray has been shown to yield significant and highly reproducible increases in the plasma concentrations of factor VIII and von Willebrand factor and platelet adhesiveness, and to be suitable for self-administration at home, as it is easy to handle and does not involve the use of needles. This paper presents data from a questionnaire answered by 78 patients with mild hemophilia A, von Willebrand's disease, or platelet disorders, who had used the spray at home to treat bleeding symptoms. The patients experienced decreased blood loss and shortened duration of epistaxis, menorrhagia, tissue bleeding, and bleeding in connection with minor surgery or tooth extraction. The use of factor VIII concentrates was diminished, as were the number of visits to outpatient care and absence from school or work.

Topics: Adult; Blood Coagulation Disorders; Blood Platelet Disorders; Child; Deamino Arginine Vasopressin; Female; Hemophilia A; Hemorrhage; Humans; Male; Self Administration; Socioeconomic Factors; Surveys and Questionnaires; von Willebrand Diseases

Desmopressin (DDAVP) 0.3 micrograms/kg was administered intravenously to three normal volunteers and 12 patients with von Willebrand's disease (vWD), congenital or acquired platelet function defect, or uremic bleeding to assess its effects and side effects. DDAVP significantly shortened the bleeding time as compared with basal values. The mean peak post-DDAVP level of factor VIII coagulant activity increased 5.9 +/- 0.5 (mean +/- SEM) fold, von Willebrand factor antigen increased 3.7 +/- 0.3 fold, von Willebrand factor ristocetin cofactor activity increased 4.6 +/- 0.6 fold and the tissue-type plasminogen activator antigen increased 3.4 +/- 0.6 fold. Analysis of the multimeric structure of the von Willebrand factor revealed that type I vWD had complete correction after DDAVP infusion transiently. Except for a mild drop in both systolic and diastolic blood pressures, few side effects were noted. By concomitant intravenous infusion of DDAVP and oral administration of tranexamic acid, we successfully treated two cases of type I vWD undergoing tooth extraction, and one case of acquired bleeding disorder undergoing a biopsy of a mandibular mass, and a uremic patient complicated by intractable traumatic hematuria. Our experiences confirmed that most patients with vWD and some patients with congenital or acquired bleeding disorders can be treated effectively by DDAVP infusion without the need for plasma product replacement. In this study we found that a patient with a variant form of type I vWD had prolongation of the bleeding time, thrombocytopenia and platelet aggregation after DDAVP infusion.

Topics: Adolescent; Adult; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Infusions, Intravenous; Male; Regression Analysis

Whether or not 1-desamino-8-D-arginine-vasopressin (DDAVP) reduces blood pressure or affects the release of arginine vasopressin (AVP) and renin is controversial, although evidence suggests AVP and renin are important in maintaining blood pressure during hemorrhage. We therefore investigated the effect of DDAVP on endogenous release of AVP and renin and on blood pressure during hemorrhage in dogs. In the control group the hemorrhage was performed at a rate of 0.4 ml.kg-1.min-1 for 40 min from the femoral artery. The plasma AVP concentration and renin activity (PRA) increased progressively in response to the hemorrhage, from 7.5 +/- 0.5 to 40.3 +/- 7.3 pg.ml-1, and from 11.8 +/- 1.5 to 20.5 +/- 4.2 ng.ml-1.h-1, respectively, while blood pressure decreased slightly. In the DDAVP group, intravenous infusion of DDAVP (2.5 ng.kg-1.min-1 for 40 min) and hemorrhage were simultaneously performed. The plasma DDAVP concentration increased progressively to 218 +/- 21.0 pg.ml-1. There was no significant difference, however, between the control and DDAVP groups in the response of AVP, PRA and blood pressure. The results suggested that DDAVP may not affect the release of AVP and renin or blood pressure during hemorrhage.

Topics: Aldosterone; Analysis of Variance; Animals; Arginine Vasopressin; Blood Pressure; Deamino Arginine Vasopressin; Dogs; Heart Rate; Hemorrhage; Infusions, Intravenous; Kidney; Male; Pituitary Gland, Posterior; Renin; Time Factors

Topics: Benzamidines; Blood Transfusion; Deamino Arginine Vasopressin; Gabexate; Guanidines; Hemorrhage; Heparin; Humans; Kidney Failure, Chronic; Molecular Weight; Protease Inhibitors; Renal Dialysis; Uremia

Of 150 consecutive patients who underwent dacryocystorhinostomy, postoperative hemorrhage requiring treatment occurred in 2 patients, both of whom had endogenous platelet dysfunction without thrombocytopenia. The first patient had macroglobulinemia, and the second patient had congenital platelet hypofunction. Prophylactic 1-deamino-8-D-arginine vasopressin (desmopressin; DDAVP) was used successfully to decrease intraoperative bleeding in the second patient. Of the 15 patients with exogenous platelet dysfunction secondary to the use of aspirin or nonsteroidal anti-inflammatory agents within 1 week of operation, none had hemorrhaging. Dacryocystorhinostomy should be undertaken cautiously and with hematologic consultation in patients with blood dyscrasias.

Topics: Adult; Aged; Aged, 80 and over; Blood Loss, Surgical; Blood Platelet Disorders; Dacryocystitis; Dacryocystorhinostomy; Deamino Arginine Vasopressin; Epistaxis; Female; Hemorrhage; Humans; Lacrimal Apparatus Diseases; Male; Nasolacrimal Duct; Postoperative Complications; Waldenstrom Macroglobulinemia

Three hundred four patients with diffuse renal disease underwent 307 consecutive percutaneous biopsies with use of nonenhanced computed tomographic (CT) guidance and the 14-gauge Vim Silverman needle. Satisfactory tissue for histopathologic diagnosis was obtained in 100% of cases. Precise data collection before and after the last 241 biopsies enabled diagnosis of 18 hemorrhagic complications (7.5%). The conditions of five patients stabilized without intervention. Thirteen patients received blood transfusions, and one required therapeutic embolization. One death occurred in a patient with advanced systemic lupus erythematosus. Two nonhemorrhagic complications were fevers after biopsy, both of which resolved without sequelae. Review of medical records revealed increased hemorrhagic complication rates in dialysis patients, female patients, patients who underwent left-sided biopsies, and patients pretreated with 1-deamino-8-D-arginine vasopressin to reverse uremic platelet dysfunction. No complications were associated with biopsies in 14 pediatric patients (younger than 16 years) and 10 renal transplant recipients. Risk of hemorrhagic complications had no correlation with patient age (when older than age 16 years) and 10 renal transplant recipients. Risk of hemorrhagic complications had no correlation with patient age (when older than age 16 years), creatinine level, hematocrit, pathologic features of resultant biopsy specimen, or whether the patient was admitted solely for the biopsy.

Topics: Adult; Biopsy, Needle; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Kidney; Kidney Diseases; Male; Needles; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed

The treatment with desmopressin prior to surgery of patients with mild haemophilia A (HA) and Von Willebrand's disease (VWD) was retrospectively evaluated in a general hospital, from 1978 until 1987. From a group of 87 treated patients, 40 patients are reported (21 VWD, 19 HA) of which plasma factor VIII (FVIII) and Von Willebrand factor (VWF) concentrations were determined before, and twice after desmopressin treatment. Desmopressin was administered intravenously at a dose of 0.4 micrograms/kg body weight. Tranexamic acid was used only when surgery in the mouth cavity was performed, at a dose of 1 gram three times a day. Side effects were seen only in 5 patients (3 VWD, 2 HA). No significant difference between both groups was seen in bleeding tendency, transfusion necessity and side effects (chi 2 test). In both groups, FVIII and VWF concentrations increased significantly after 20 and 60 minutes following DDAVP administration (paired t-test). After 360 minutes, the FVIII concentration increased significantly in both groups, however, only in the VWD patients did VWF increase significantly. In neither group did initial FVIII concentrations correlate with the increase in FVIII (linear regression analysis). One female patient reacted differently to DDAVP, with a decrease in FVIII and VWF values. Desmopressin is a safe and effective agent in the management and prophylaxis of bleeding tendency in patients with mild HA and mild VWD.

Topics: Deamino Arginine Vasopressin; Factor VIII; Hemophilia A; Hemorrhage; Humans; Premedication; Retrospective Studies; Surgical Procedures, Operative; von Willebrand Diseases; von Willebrand Factor

Topics: Deamino Arginine Vasopressin; Factor VIII; Fibrinogen; Hemorrhage; Humans; Uremia

Topics: Adult; Anemia, Sickle Cell; Deamino Arginine Vasopressin; Hemophilia A; Hemorrhage; Humans; Male

Topics: Adult; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Estrogens, Conjugated (USP); Hemorrhage; Humans; Male; Postoperative Complications

Topics: Deamino Arginine Vasopressin; Hemorrhage; Humans; Hypotension; Postoperative Complications

The mechanism by which treatment with thrombolytic agents causes bleeding is not known. Recently, frequency of bleeding events has been shown to correlate with bleeding time, particularly in individuals treated with aspirin. We examined the effects of streptokinase (20,000-60,000 IU/kg) on bleeding time in 40 rabbits pretreated with aspirin, a model for fibrinolytic therapy. We then tested the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) (0.3 microgram/kg), an agent known to reduce bleeding time in a variety of bleeding disorders, in 20 rabbits and compared the results with those of a control group of rabbits receiving normal saline placebo. Aspirin increased the bleeding time from a baseline mean +/- SEM value of 119 +/- 15 to 191 +/- 34 seconds in the control group and from 114 +/- 6 to 188 +/- 18 seconds in the experimental group. The addition of streptokinase increased the bleeding time to 592 +/- 119 seconds in the control group and 810 +/- 114 seconds in the experimental group (p = NS). Subsequent infusion of DDAVP decreased the bleeding time in the experimental group to 302 +/- 29 seconds (p less than 0.01 versus streptokinase) compared with 572 +/- 79 seconds (p = NS versus streptokinase) in the control animals given saline placebo. In a subset of rabbits receiving aspirin and streptokinase (40,000-60,000 IU/kg), samples were obtained for platelet aggregation (n = 16), von Willebrand factor antigen concentration (n = 17), and von Willebrand factor multimer distribution (n = 14). Maximal rates of ADP-induced platelet aggregation were not affected by DDAVP infusion, nor was the plasma concentration of von Willebrand factor antigen, quantified by an immunoradiometric assay, significantly affected by DDAVP infusion. Furthermore, the von Willebrand factor multimer ratio decreased with DDAVP administration. These findings indicate that aspirin and streptokinase combined result in a marked increase in bleeding time that can be reduced by DDAVP. This effect of DDAVP is not accompanied by an increase in platelet aggregation response, plasma von Willebrand factor antigen concentration, or von Willebrand factor multimer ratio.

Topics: Animals; Antigens; Aspirin; Bleeding Time; Deamino Arginine Vasopressin; Female; Hemorrhage; Platelet Aggregation; Rabbits; Retroperitoneal Space; Streptokinase; von Willebrand Factor

Topics: Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Hemorrhage; Humans; Platelet Aggregation; Postoperative Complications; von Willebrand Factor

Topics: Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Hemorrhage; Humans; Intraoperative Period

A Case of delivery in a 23-year-old woman after a prophylactic infusion of DDAVP is described. She had a life-long history of easy bruising and frequent epistaxis, with the diagnosis of vWD being made when she was 14 years old. A hemostatic examination showed a prolonged bleeding time, a moderate reduction in the factor VIII level (VIII: C) and von Willebrand Factor Antigen (vWF: Ag), decreased platelet aggregation by ristocetin, and depletion of platelet retention. In April, 1988, in the 34th week of pregnancy, she was admitted to our clinic in order to avoid abnormal bleeding during labor. On admission, the level of factor VIII, ristocetin aggregation, and platelet retention were normal, but the bleeding time remained prolonged. The diagnosis of vWD type I was made on the normal multimeric structure. The DDAVP infusion test revealed a shortening of the bleeding time and an increase in the vWF: Ag. In the 41st week of pregnancy, labor was induced, accompanied by infusion of DDAVP, she gave birth to an infant without any abnormal bleeding. Since conventional treatments with human plasma derivatives may cause complicating viral infections, we propose the infusion of DDAVP is one of the treatments to prevent the abnormal bleeding of the patient with vWD during labor.

Topics: Adult; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Labor, Obstetric; Obstetric Labor Complications; Pregnancy; Pregnancy Complications, Hematologic; von Willebrand Diseases

Topics: Administration, Intranasal; Administration, Topical; Antifibrinolytic Agents; Deamino Arginine Vasopressin; Hemophilia A; Hemorrhage; Hemorrhagic Disorders; Hemostatics; Humans; Injections, Subcutaneous; Liver Cirrhosis; Surgical Procedures, Operative; Uremia; von Willebrand Diseases

Desmopressin (DDAVP), a synthetic vasopressin, temporarily corrects bleeding abnormalities associated with mild hemophilia A, von Willebrand disease, and disorders of platelet function. The side effects of DDAVP are considered benign although most of its use has been in adults and older children. We report four children under the age of 2 years who became hyponatremic after intravenous DDAVP administration (0.3 microgram/kg). Three of them developed grand mal seizures. A review of the literature and these cases indicate that associated risk factors for hyponatremia after DDAVP administration include stress, surgery, anesthesia and narcotics (endogenous release of antidiuretic hormone), vomiting (loss of Na+), liver disease (hindered metabolism of DDAVP), renal tubular acidosis (chronically low serum Na+), multiple doses of DDAVP, and overhydration with hyponatremic fluids. DDAVP is not a benign drug in this age group and shows a serious potential for hyponatremia and seizures. Fluid restriction, avoidance of hyponatremic solutions, and close monitoring of serum electrolytes and urine output for at least 15-20 hr after the administration of DDAVP, when used in children under the age of 2 years, is warranted.

Topics: Deamino Arginine Vasopressin; Epilepsy, Tonic-Clonic; Hematologic Diseases; Hemorrhage; Humans; Hyponatremia; Infant; Male

Topics: Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Hemorrhage; Humans; Postoperative Complications

Topics: Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Hemorrhage; Humans; Postoperative Complications

In our study, we wanted to evaluate the clinical effect of s.c. DDAVP on haemostasis in different kinds of bleeding disorders. A total of 109 patients was treated with DDAVP s.c. at a dose of 0.4 microgram/Kg body weight. An effect of DDAVP on F VIII modalities was found after s.c. injection in all patients, but in comparison to i.v. DDAVP, the effect seems to be somewhat less. From our data, the patients blood groups do not influence the amount of F VIII modalities. Furthermore, the s.c. injection of DDAVP was found to be effective in patients with disorders of primary haemostasis. A number of operations was performed under the use of s.c. DDAVP in 24 patients with different kinds of bleeding disorders, in none of them, bleeding complications occurred.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Bleeding Time; Child; Child, Preschool; Deamino Arginine Vasopressin; Hemophilia A; Hemorrhage; Humans; Infusions, Intravenous; Injections, Subcutaneous; Middle Aged; von Willebrand Diseases

Topics: Adult; Deamino Arginine Vasopressin; Erythropoietin; Female; Hemorrhage; Humans; Uremia

A 63-year-old male had major postoperative bleeding complications following the excision of a basal cell carcinoma. The patient denied a prior history of bleeding complications and had normal coagulation screening studies. After coagulation evaluation, he was found to have mild hemophilia A with 23% of normal Factor VIII C. We discuss an approach to the evaluation of coagulation in patients with perioperative and postoperative bleeding. Also, we outline treatment alternatives for patients with hemophilia A who need cutaneous surgery.

Topics: Blood Coagulation; Carcinoma, Basal Cell; Deamino Arginine Vasopressin; Dermatologic Surgical Procedures; Factor VIII; Hemophilia A; Hemorrhage; Hemostasis, Surgical; Humans; Male; Middle Aged; Platelet Count; Postoperative Complications; Skin Neoplasms

Desmopressin (DDAVP) has gained wide acceptance as the drug of first choice in the treatment or prevention of haemorrhages in the majority of patients with von Willebrand's disease (vWd). However, data concerning the clinical effectiveness of DDAVP refer generally to mild vWd, with factor VIII and vW factor levels usually above 20% of normal. In 14 patients with type I vWd characterized by very low plasma levels of factor VIII coagulant activity (VIII:C) and vWf, measured as ristocetin cofactor activity (lower than 20% and 3% of normal respectively), but with a normal intraplatelet content of vWf, a test infusion of DDAVP (0.4 microgram/kg) elicited a very marked increase of VIII:C and vWf and normalized the bleeding time. All these patients subsequently underwent tooth extraction after DDAVP infusion. The incidence of bleeding was remarkably low, with only two minor late bleeding episodes easily stopped by repeating DDAVP infusion. Compared to the cases of type I vWd with unknown intraplatelet vWf content reported in the literature, this subgroup of patients had a more marked, albeit short-lived, increment of VIII:C and vWf.

Topics: Adolescent; Adult; Antigens; Blood Platelets; Deamino Arginine Vasopressin; Factor VIII; Female; Hemorrhage; Humans; Male; Middle Aged; Tooth Extraction; von Willebrand Diseases; von Willebrand Factor

Topics: Animals; Deamino Arginine Vasopressin; Dog Diseases; Dogs; Female; Hemorrhage; Intraoperative Complications; Spinal Cord Compression; von Willebrand Diseases

1-deamino-8D-arginine vasopressin was given subcutaneously at the dosage of 0.3 micrograms/Kg. b.w. to 24 mild factor VIII deficient patients (16 mild, 2 moderate hemophiliacs and 6 patients with von Willebrand's Disease), to treat bleedings (10 episodes) or to prevent bleeding during and after dental extractions (6 extractions) and surgery (11 interventions). None of the patients who underwent surgery bled. The vasopressin analogue was effective in the early treatment of muscle hematomas and promptly stopped all mucosal hemorrhages. Most of the patients treated for "spontaneous" bleedings performed self-injections at home. The drug was administered in two pharmaceutical forms (4 and 40 micrograms/ml): no differences in the clinical outcome were found. No significant side effects were recorded. The subcutaneous route of DDAVP administration thus seems to be particularly useful (mainly in the concentrated pharmaceutical form) in treating mild factor VIII deficiencies even on self- and home-treatment basis.

Topics: Deamino Arginine Vasopressin; Hemophilia A; Hemorrhage; Humans; Injections, Subcutaneous; Surgical Procedures, Operative; Tooth Extraction; von Willebrand Diseases

An elderly patient with evidence of atherosclerosis and uremic bleeding diathesis developed two foci of cerebral thrombosis immediately after an infusion of desmopressin (DDAVP). Because large molecular weight multimers of von Willebrand factor (vWF) have been demonstrated to cause platelet aggregation under conditions of elevated fluid shear stress as occurs in atherosclerotic vessels, we investigated his plasma vWF at the time of the event and compared it to baseline values obtained 2 weeks later. Unusually large vWF multimers induced by the DDAVP infusion were present and likely contributed to the thrombotic process. Consequently, we believe DDAVP should be given with greater caution to patients with atherosclerosis.

Topics: Aged; Deamino Arginine Vasopressin; Hemorrhage; Humans; Intracranial Embolism and Thrombosis; Male; Uremia; von Willebrand Factor

Desmopressin has been used as a hemostatic agent in numerous hematological and nonhematological diseases. We report a case of surgical hemorrhage secondary to prolonged bleeding time of unexplained origin controlled with desmopressin.

Topics: Aged; Aged, 80 and over; Bleeding Time; Deamino Arginine Vasopressin; Hemorrhage; Hemostasis, Surgical; Humans; Male; Nephrectomy; Platelet Function Tests; Postoperative Complications

The multimeric and subunit patterns of plasma von Willebrand factor (vWF) were analyzed in eight patients with myeloproliferative syndrome (MS) in order to investigate the possible existence of heterogeneity in the "in vivo" proteolytic cleavage of the protein, previously observed in this entity. Six patients lacked large vWF multimers, five of them having normal bleeding times (BT) and clinically documented episodes of thrombotic origin, whereas one patient had long BT and bleeding symptoms. Seven patients showed a relative increase in the 176 kDa subunit fragment while the 189 kDa polypeptide was increased in only one. In addition, another patient (and prior to any therapy) showed the presence of a new fragment of approximately 95 kDa which disappeared after Busulfan therapy. The collection of blood from these patients with proteinase inhibitors did not correct the abnormalities. The infusion of DDAVP to two patients with abnormal vWF was accompanied by: the appearance of larger vWF multimers which disappeared rapidly from plasma; an increase in the relative proportion of the satellite bands of each multimer and a further increase of the 176 kDa fragment. These data point to some heterogeneity in the vWF abnormality present in MS which may be related in part to a variable degree of proteolysis of vWF occurring "in vivo" rather than "in vitro", and which may be associated to either a thrombotic or a bleeding diathesis. They also suggest that despite the presence of abnormal, already proteolyzed vWF, DDAVP-enhanced proteolysis occurs in MS to a similar extent to what is described in normal individuals.

Topics: Deamino Arginine Vasopressin; Hemorrhage; Humans; Myeloproliferative Disorders; Protein Conformation; Syndrome; Thrombosis; von Willebrand Factor

Topics: Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Hemorrhage; Humans; Postoperative Complications

Desmopressin was administered intravenously to 68 patients with hemophilia and von Willebrand's disease of mild or moderate severity to assess the safety, reproducibility, and range of response to this new therapeutic alternative. A rise in factor VIII-von Willebrand factor levels was seen in 64 patients, and the magnitude was sufficient to provide normal hemostasis in 55 to 68 spontaneous or traumatic bleeding episodes, dental procedures, or operations. Thus, our experience shows that most patients with mild or moderate hemophilia and von Willebrand's disease can be treated effectively without plasma derivatives. Patients who had two or more infusions of desmopressin at different times had similar responses each time, and members of the same family also had similar responses after desmopressin infusions. Because this drug can be administered without significant side effects, it should have an important role in the management of patients with mild or moderate hemophilia and von Willebrand's disease.

Topics: Adolescent; Adult; Aged; Arginine Vasopressin; Autoantibodies; Child; Child, Preschool; Deamino Arginine Vasopressin; Dental Care; Factor VIII; Female; Hemophilia A; Hemorrhage; Heterozygote; Humans; Male; Middle Aged; Premedication; Preoperative Care; von Willebrand Diseases

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Biopsy; Bleeding Time; Blood Transfusion; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Kidney; Male; Middle Aged; Platelet Function Tests

Of 120 patients presenting with mild bleeding disorders, 63 were found to have a definite coagulopathy. The commonest disorders were haemophilia, Christmas disease and von Willebrand's disease (vWd), the latter being predominant. Diagnosis led to prophylactic treatment prior to surgery in 18 patients with prevention of excessive haemorrhage. Three patients who had received blood products developed hepatitis. DDAVP (desamino-cys-1-8-D-arginine vasopressin) is the treatment of choice in suitable mildly affected patients with haemophilia A and vWd. Examination of blood group distribution suggests an excess of group O among patients with bleeding disorders, especially those with vWd.

Topics: Adult; Arginine Vasopressin; Deamino Arginine Vasopressin; Female; Hemophilia A; Hemophilia B; Hemorrhage; Humans; Male; Middle Aged; Postoperative Complications; Tooth Extraction; von Willebrand Diseases

1-deamino-8-D-arginine-vasopressin (DDAVP), was used in a wide spectrum of clinical situations employing two different dosages (0.3 and 0.4 microgram/kg b.w.) for the management of 43 patients with factor VIII deficiencies--mild and moderate haemophilia A and von Willebrand's disease (vWD). In most instances, the drug was given in association with antifibrinolytics. Twenty-five dental extractions were carried out with two different protocols: one based upon a single infusion and the other based upon three infusions. Bleeding occurred in three patients regardless of the protocol used. The vasopressin analogue promptly stopped bleeding in 12 'spontaneous' open bleeds (haematuria, epistaxis, menometrorrhagia, gum bleeding) and it appears to be also effective in closed bleeds. DDAVP was used to minimize blood loss during surgical interventions and to avoid haemorrhage in the postoperative period. Nine surgical procedures were carried out in six vWD patients and three haemophiliacs. Bleeding occurred late in the postoperative period on one occasion only. No difference was demonstrated between the two doses of the drug either in terms of clinical benefit or rise of factor VIII coagulant activity. The efficacy of DDAVP and the absence of side-effects make this vasopressin analogue worthy of consideration as a reliable alternative to factor VIII concentrates in a wide variety of clinical situations.

Topics: Antigens; Arginine Vasopressin; Deamino Arginine Vasopressin; Factor VIII; Hemophilia A; Hemorrhage; Humans; Intraoperative Care; Postoperative Care; Tooth Extraction; von Willebrand Diseases; von Willebrand Factor

Topics: Adolescent; Adult; Arginine Vasopressin; Deamino Arginine Vasopressin; Hemophilia A; Hemorrhage; Humans; von Willebrand Diseases

Topics: Deamino Arginine Vasopressin; Factor VIII; Hemorrhage; Humans; Platelet Adhesiveness; Uremia; von Willebrand Factor

Intravenous administration of 0.4 micrograms DDAVP/kg body weight in 16 normal controls, 34 patients with haemophilia A and 30 patients with von Willebrand's disease (vWd) was followed by an increase in FVIII: C from 230 to 410%, in FVIIIR:Ag from 160 to 260% and FVIIIR:RC of from 160 to 320%. Additionally, in the patients with vWd, a shortening of the bleeding time and improvement in platelet retention was observed. In 7 haemophiliacs with pretreatment levels of FVIII: C ranging from between 11 and 43% dental extractions were performed successfully after DDAVP whereas in 2 patients with FVIII: C levels of 5 and 6%, respectively, severe bleeding necessitated administration of factor VIII concentrates. In 8 haemophiliacs (FVIII: C between 6.5 and 50%) and 2 patients with vWd (FVIII: C 18 and 36%, respectively) DDAVP enabled minor surgery and successful therapy of spontaneous or traumatic bleeding complications. However, severe postoperative bleeding after stomach surgery in 2 haemophiliacs (FVIII: C 23 and 40%, respectively) and severe menstrual bleeding in one patient with vWd (FVIII: C 15%) required administration of factor VIII concentrates. At present DDAVP therapy should be restricted to minor surgery and non-life-threatening, spontaneous or traumatic bleeding complications in patients with pretreatment FVIII: C levels higher than 10%.

Topics: Arginine Vasopressin; Deamino Arginine Vasopressin; Factor VIII; Fatigue; Flushing; Hemophilia A; Hemorrhage; Humans; Hypertension; Surgical Procedures, Operative; Tooth Extraction; von Willebrand Diseases

Topics: Adult; Arginine Vasopressin; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Ovarian Diseases; Ovarian Neoplasms; Postoperative Complications; von Willebrand Diseases

Topics: Arginine Vasopressin; Blood Coagulation; Deamino Arginine Vasopressin; Female; Hemorrhage; Humans; Preoperative Care; Time Factors; Tooth Extraction; von Willebrand Diseases

1-Deamino-8-d-arginine vasopressin (D.D.A.V.P.) infusion causes a marked increase in factor-VIII (antihaemophilic-factor)-related properties in patients with moderate and mild haemophilia and von Willebrand's disease (vWd). The possibility was therefore evaluated that such an autologous factor-VII response might be haemostatically effective, allowing patients to undergo surgery without plasma concentrates. 0.3 microng/kg of D.D.A.V.P. given before dental surgery and repeated in the early postoperative period was followed by a two to three fold rise in factor-VIII coagulant activity (VII C.A.) in four patients with moderate and mild haemophilia. In two, there was no abnormal bleeding after dental extraction, whereas plasma concentrates were necessary to control oozing from the sockets in the remaining two patients. A higher D.D.A.V.P. dosage (0.4-0.5 microng/kg) in patients with higherstarting VII C.A. (9% or more) was followed by a more marked response (four to six fold). VII C.A. levels up to 100% of average normal were achieved and dental extraction and major surgery (such as cholecystectomy, thoracotomy, and two tonsillectomies) were carried out successfullly in six patients with mild haemophilis and in two with vWd. The mean half-life of autologous VII C.A. was 9.4 h (range 7.5-11.6). Plasma and urine osmolality showed no consistent variation after drug administration. Thus D.D.A.V.P. appears a promision pharmacological alternative to plasma concentrates in the management of some patients with haemophilis and vWd.

Topics: Adolescent; Adult; Biopsy; Blood Coagulation Tests; Cholecystectomy; Deamino Arginine Vasopressin; Drug Evaluation; Factor VIII; Female; Hemophilia A; Hemorrhage; Hemostasis, Surgical; Humans; Infusions, Parenteral; Male; Middle Aged; Postoperative Care; Postoperative Complications; Preoperative Care; Thoracic Surgery; Thorax; Tonsillectomy; Tooth Extraction; Vasopressins; von Willebrand Diseases

Topics: Blood Coagulation; Deamino Arginine Vasopressin; Hemophilia A; Hemorrhage; Humans; Vasopressins; von Willebrand Diseases