deamino-arginine-vasopressin and Blood-Platelet-Disorders

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

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

Increased intra-operative and postoperative blood loss might be caused by acquired platelet function disorders. In particular because conventional coagulation analyses and platelet count fail to detect impaired platelet function, implementation of bedside-tests for platelet function in the peri-operative period is desirable according to the results of retrospective studies. Following adequate adjustment of basic conditions of haemostasis (e.g. temperature, pH, Ca2+-concentration, haematocrit) a pharmacological approach with desmopressin (1-desamino-8-d-arginine vasopressin; DDAVP) or tranexamic acid potentially represents a low cost alternative to platelet transfusions with minor side effects.

Topics: Antifibrinolytic Agents; Blood Loss, Surgical; Blood Platelet Disorders; Deamino Arginine Vasopressin; Factor VIIa; Fibrinogen; Hemostasis; Humans; Monitoring, Intraoperative; Perioperative Care; Platelet Function Tests; Platelet Transfusion; Recombinant Proteins; Tranexamic Acid

Desmopressin (l-deamino-8-D-arginine vasopressin, DDAVP) is a synthetic analogue of the antidiuretic hormone vasopressin. Like the natural antidiuretic hormone, desmopressin increases the plasma levels of factor VIII and von Willebrand factor (vWF), with the advantage, compared to vasopressin, that it produces little or no vasoconstriction, no increase in blood pressure, and no contraction of the uterus or gastrointestinal tract, so that it is well tolerated when administered to humans. In 1977, desmopressin was used for the first time in patients with mild hemophilia A and von Willebrand disease (vWD) for the prevention and treatment of bleeding, first during dental extractions and then during major surgical procedures. The clinical indications for desmopressin rapidly expanded beyond hemophilia and vWD. The compound was shown to be efficacious even in bleeding disorders not involving a deficiency or dysfunction of factor VIII or vWF, including congenital and acquired defects of platelet function and such frequent abnormalities of hemostasis as those associated with chronic kidney and liver diseases. Desmopressin has also been used prophylactically in patients undergoing surgical operations characterized by large blood loss and transfusion requirements.

Topics: Blood Loss, Surgical; Blood Platelet Disorders; Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Hemostatics; Humans; Perioperative Care

Following the first clinical use in haemophilia and von Willebrand disease in 1977, the synthetic analogue of vasopressin 1-deamino-8-D-arginine vasopressin (DDAVP, desmopressin) was successfully employed for the management of a series of bleeding disorders, including congenital and acquired defects of platelet function. In this setting, few haemostatic approaches are available and, in particular for severe bleeding and major invasive procedures, the transfusion of platelet concentrates is the first-choice treatment. Therefore, DDAVP was (and remains) an attractive therapeutic alternative, being well tolerated, cost-saving, administrable at home (by the intranasal or subcutaneous concentrated formulations) and, in particular, enabling the avoidance of blood product exposition and the related risks (allergic reactions, transfusion transmitted infections). Despite three decades of clinical use, cellular mechanisms of haemostatic effects of DDAVP in platelet defects remain poorly known and the excellent results reported in some case series have not been strengthened by rigorous clinical trials, hampered by the rarity and the heterogeneity of these disorders. However, clinical experience more than evidence-based medicine reserved an established place to DDAVP in the management of inherited platelet disorders. This review will focus the available clinical data and the open issues of DDAVP in this setting.

Topics: Bleeding Time; Blood Platelet Disorders; Deamino Arginine Vasopressin; Hemostatics; Humans

Topics: Bernard-Soulier Syndrome; Blood Platelet Disorders; Deamino Arginine Vasopressin; Female; Fetal Diseases; Hemostatics; Humans; Platelet Aggregation; Platelet Storage Pool Deficiency; Pregnancy; Pregnancy Complications, Hematologic; Prenatal Diagnosis; von Willebrand Diseases

Topics: Blood Platelet Disorders; Deamino Arginine Vasopressin; Hemostasis, Surgical; Hemostatics; Humans

Platelets provide for primary hemostasis by forming a hemostatic plug at sites of vascular damage. They also provide a surface for the assembly of the coagulation protein complexes that generate thrombin, serve as a nidus for fibrin clots, and secrete factors involved in wound repair. Normal platelet function can be divided into four phases: adhesion, aggregation, secretion, and expression of procoagulant activity. Platelet adhesion initiates plug formation as platelets adhere to the connective tissue at the edges of a wound within seconds after vascular damage. When damage occurs in regions of slow blood flow, platelets adhere to subendothelial collagen, fibronectin, and laminin. However, when damage occurs in regions of rapid flow, platelet adhesion requires the presence of subendothelial von Willebrand factor (vWf) and a specific platelet receptor, the glycoprotein Ib/IX (GPIb/IX) complex. Following initial adhesion, platelets aggregate to complete the formation of a hemostatic plug. Platelet aggregation requires active platelet metabolism, platelet stimulation by agonists such as ADP, thrombin, collagen, or epinephrine; the presence of calcium or magnesium ions and specific plasma proteins such as fibrinogen or vWf; and a platelet receptor, the glycoprotein IIb/IIIa (GPIIb/IIIa) complex. Thus, platelet stimulation results in the generation of intracellular second messengers that transmit the stimulus back to the platelet surface, exposing protein binding sites on GPIIb/IIIa. Fibrinogen (or vWf) then binds to GPIIb/IIIa and crosslinks adjacent platelets to produce platelet aggregates. Platelet stimulation also results in platelet secretion and the elaboration of platelet procoagulant activity. During secretion, substances are released to propagate the aggregation response and to promote wound healing; the expression of procoagulant activity localizes thrombin generation to the site of vascular damage. Disorders of platelet function can be divided into those of congenital and those of acquired origin. Although congenital disorders are uncommon, acquired disorders are encountered frequently in clinical practice. Congenital absence of GPIb/IX and GPIIb/IIIa results in the Bernard-Soulier syndrome (BSS) and Glanzmann thrombasthenia (GT), respectively. Each is an autosomal recessive bleeding disorder in which absence of a protein complex renders the affected platelets incapable of undergoing either vWf-mediated adhesion (BSS) or fibrinogen-mediated aggregat

Topics: Adrenal Cortex Hormones; Antifibrinolytic Agents; Blood Coagulation; Blood Component Transfusion; Blood Platelet Disorders; Blood Platelets; Clot Retraction; Deamino Arginine Vasopressin; Drug-Related Side Effects and Adverse Reactions; Estrogens, Conjugated (USP); Humans; Platelet Activation; Platelet Adhesiveness; Platelet Aggregation; Signal Transduction

Topics: Blood Platelet Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Platelet Aggregation

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

Since the pressor and antidiuretic properties of the native hormone were characterized, chemists have been working to synthesize vasopressin analogues selective for particular biologic activities. Desmopressin has had the longest clinical track record. Subsequently, three more analogues have been formulated and have found specific clinical application. Their actions and uses are reviewed.

Topics: Blood Platelet Disorders; Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Diabetes Insipidus; Hemophilia A; Humans; Liver Cirrhosis; Uremia; von Willebrand Diseases

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

Patients with severe aortic valve stenosis have a markedly reduced platelet function as measured by a prolonged collagen adenosine diphosphate closure time (CADP-CT) determined by the platelet function analyzer PFA-100. We hypothesized that such patients may benefit from desmopressin when they present with prolonged CADP-CT due to the specific action of desmopressin on von Willebrand factor (VWF) and CADP-CT.. In this double-blind, randomized placebo controlled trial, 43 patients undergoing aortic valve replacement (due to severe aortic valve stenosis with CADP-CT>170 seconds) were given desmopressin 0.3 μg/kg or saline intravenously after induction of anesthesia. Measurement of CADP-CT, factor VIII activity, von Willebrand factor antigen, GpIb binding activity, ristocetin cofactor activity, collagen-binding activity, and multimers were performed after induction of anesthesia, one hour after desmopressin infusion, and 24 hours postoperatively.. In the majority of patients, baseline values of von Willebrand factor related indices were normal, but increased one hour after infusion of desmopressin by 73% to 90% as compared with placebo. Selective loss of high molecular weight multimers was seen only in a minority of patients. The CADP-CT was greater than 170 seconds in 92% of screened patients, and desmopressin shortened CADP-CT by 48% versus baseline and reduced postoperative blood loss by 42% (p<0.001).. Prolonged CADP-CT indicates platelet dysfunction in severe aortic valve stenosis, and can guide the use of desmopressin as an effective prohemostatic agent in patients with severe aortic valve stenosis.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Blood Platelet Disorders; Deamino Arginine Vasopressin; Double-Blind Method; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Hemostatics; Hospital Mortality; Humans; Infusions, Intravenous; Male; Middle Aged; Postoperative Hemorrhage; Preoperative Care; Reference Values; Risk Assessment; Severity of Illness Index; Survival Analysis; Time Factors; Treatment Outcome

Desmopressin decreases bleeding time in uremic patients. Although bleeding time is the most frequently used measure of global platelet function, this test has important disadvantages. In vitro closure time (CT) is a relatively new and efficient test of primary hemostasis. We designed a prospective randomized study to evaluate the effect of desmopressin on platelet function, as measured by in vitro CT, in uremic patients.. Forty-eight uremic patients, about to commence hemodialysis and with prolonged CT, were randomized to infusion with desmopressin (n = 24) or saline alone (n = 24). Complete blood count, prothrombin time, activated partial thrombin time, levels of plasma fibrinogen, von Willebrand factor (VWF), factor VIII (FVIII) and CT were measured before and 1 h after desmopressin or saline infusion.. Following desmopressin infusion, collagen/epinephrine and collagen/adenosine diphosphate CT were significantly shortened from 212 +/- 58 to 152 +/- 45 s (p = 0.01) and from 189 +/- 78 to 147 +/- 58 s (p = 0.012), respectively; levels of FVIII and VWF were significantly increased from 188 +/- 66 to 252 +/- 93% (p = 0.017) and from 113 +/- 9 to 121 +/- 9% (p = 0.043), respectively. There were no significant changes in the control group.. Desmopressin improved platelet dysfunction and increased the plasma concentrations of VWF and FVIII, suggesting that desmopressin may play a role in improving the bleeding tendency in uremic patients.

Topics: Adult; Aged; Aged, 80 and over; Blood Platelet Disorders; Blood Platelets; Deamino Arginine Vasopressin; Female; Hemostasis; Humans; Male; Middle Aged; Platelet Count; Prospective Studies; Time Factors; Uremia

In a prospective study, 254 of 5649 unselected patients scheduled for surgery at our hospital were identified preoperatively as having either acquired (n=182) or inherited (n=72) impaired primary hemostasis (platelet dysfunction including von Willebrand disease). All patients were initially pretreated with desmopressin (DDAVP). Response to DDAVP or subsequent treatment(s) was defined as correction of any one of the abnormal PFA-100 platelet function tests. The non-responders were additionally treated with tranexamic acid or aprotinin; those with von Willebrand disease (vWD) received factor VIII concentrates with von Willebrand factor (vWF). Those still unresponsive to therapy received conjugated estrogens and, as a last attempt, a platelet transfusion. The administration of DDAVP led to a correction of platelet dysfunction in 229 of the 254 patients treated (90.2%). Tranexamic acid was effective in 12 of 16, aprotinin in 3 of 5, and factor VIII concentrates with vWF in all 4 patients with unresponsive to DDAVP. The remaining 6 patients were pretreated with conjugated estrogens, and 2 of these patients were additionally treated with platelet transfusion. The frequency of blood transfusion was lower, but not statistically significant (9.4% vs. 12.2%: p = 0.202) in preoperatively treated patients with impaired hemostasis than in patients without impaired hemostasis. In a retrospective group, the frequency of blood transfusion was statistically significant higher (89.3% vs. 11.3%: p < 0.001) in patients without preoperative correction of impaired hemostasis than in patients without impaired hemostasis. Preoperative correction of impaired primary hemostasis is possible in nearly all patients affected, and results in a reduction of homologous blood transfusions.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bleeding Time; Blood Platelet Disorders; Blood Platelets; Blood Transfusion; Deamino Arginine Vasopressin; Female; Hemostasis; Humans; Male; Middle Aged; Preoperative Care; von Willebrand Diseases

To evaluate the hemostatic effects of desmopressin (DDAVP) in dogs with aspirin-induced platelet dysfunction and hemostatic impairment in chronic liver diseases, 3 microg/kg DDAVP was administrated subcutaneously. In aspirin-induced platelet dysfunction dogs (n=5), prolonged BMBT (buccal mucosal bleeding time) was shortened significantly after DDAVP injection (2.2 +/- 1.2 min, P<0.05). In dogs with chronic liver diseases (n=4), activated partial thromboplastin time (APTT) tended to shorten by 0.9 to 3.0 sec, and prolonged BMBT was shortened in two cases for 4.2 and 1.7 min after DDAVP injection. Therefore, the present results indicated that DDAVP shortened the prolonged BMBT in dogs with aspirin-induced platelet dysfunction and chronic liver disease. DDAVP might be helpful in hemostasis under invasive procedures such as biopsy or surgery for dogs with hemostatic impairment.

Topics: Animals; Aspirin; Blood Coagulation; Blood Platelet Disorders; Blood Platelets; Deamino Arginine Vasopressin; Dog Diseases; Dogs; Factor VIII; Hemostasis; Injections, Subcutaneous; Liver Diseases

DDAVP has been shown to provide hemostasis in patients with bleeding disorder. Thirty-one episodes of intravenous DDAVP administration (0.3-0.4 microgram/kg) in 22 patients with bleeding disorder were studied. There were 13 patients with hemophilia A, 1 with type I vWD and 8 with inherited and acquired platelet dysfunction. The age ranged from 2.3-26 yrs (mean +/- SD = 10 +/- 4.8). None of the 3 severe hemophilia A patients responded to the treatment. Two out of five episodes in 4 moderate hemophilia A patients responded clinically and had minute increments of F VIII:C. Ten out of eleven episodes (91%) in 6 mild hemophilia A patients had good responses. The dental procedures for these patients were successfully performed without blood component transfusion. The increments of F VIII:C ranged from 1.5-6.8 folds over the baseline levels (mean +/- SD = 2.5 +/- 1.4). In addition, two episodes of epistaxis in a vWD patient responded excellently and one dental procedure was successfully performed by giving DDAVP. The increments of F VIII:C and vWF:Ag ranged from 2.8-12.5 and 2.9-8 fold over the baseline levels respectively. The prolonged bleeding times were shorten to 6.5-7 minutes. Only three out of eight episodes in 8 inherited and acquired platelet dysfunction patients showed temporary responses. The bleeding time responses did not correlate with in vitro platelet aggregation.

Topics: Adolescent; Adult; Blood Coagulation Tests; Blood Platelet Disorders; Child; Child, Preschool; Deamino Arginine Vasopressin; Drug Costs; Hemophilia A; Humans; Infusions, Intravenous; Treatment Outcome; von Willebrand Diseases

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

Topics: Blood Platelet Disorders; Deamino Arginine Vasopressin; Hemostatics; Humans; von Willebrand Diseases; von Willebrand Factor

Pre-injury anti-platelet use has been associated with increased risk of progression of traumatic intracranial hemorrhage (TICH) and worse outcomes. VerifyNow® assays assess platelet inhibition due to aspirin/clopidogrel. This study assesses the outcomes of patients with TICH and platelet dysfunction treated with desmopressin and/or platelets.. We performed a retrospective chart review of patients with mild TICH at a level 1 trauma center 1/1/2013-6/1/2016. Patients with documented platelet dysfunction who received desmopressin and/or platelets were compared to those who were untreated. Primary outcomes were progression of TICH and neurologic outcomes at discharge.. Of 565 patients with a mild TICH, 200 patients had evidence of platelet dysfunction (a positive VerifyNow® assay). Patients had similar baseline demographics, injury characteristics, and rate of TICH progression; but patients who received desmopressin and/or platelets had worse Glasgow Outcomes Score at discharge.. Treatment of patients with mild TICH and platelet dysfunction with desmopressin and/or platelets did not affect TICH progression but correlated with worse neurologic status at discharge.

Topics: Aged; Blood Platelet Disorders; Deamino Arginine Vasopressin; Disease Progression; Female; Hemostatics; Humans; Intracranial Hemorrhage, Traumatic; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Transfusion; Retrospective Studies; Trauma Centers; Treatment Outcome

Platelet dysfunction (PD) is an independent predictor of mortality in patients with severe traumatic brain injury (sTBI). Platelet transfusions (PLTs) have been shown to be an effective treatment strategy to reverse platelet inhibition. Their use is contingent on availability and may be associated with increased cost and transfusion-related complications, making desmopressin (DDAVP) attractive. We hypothesized that DDAVP would correct PD similarly to PLTs in patients with sTBI.. This retrospective study evaluated all blunt trauma patients admitted to an urban, level 1 trauma center from July 2015 to October 2016 with sTBI (defined as head abbreviated injury scale [AIS] ≥3) and PD (defined as adenosine diphosphate [ADP] inhibition ≥60% on thromboelastography) and subsequently received treatment. Per our institutional practice, patients with sTBI and PD are transfused one unit of apheresis platelets to reverse inhibition. During a platelet shortage, we interchanged DDAVP for the initial treatment. Patients were classified as receiving DDAVP or PLT based on the initial treatment.. A total of 57 patients were included (DDAVP, n = 23; PLT, n = 34). Patients who received DDAVP were more severely injured (injury severity score, 29 vs. 23; p = 0.045), but there was no difference in head AIS (4 vs. 4, p = 0.16). There was no difference between the two groups in admission platelet count (244 ± 68 × 10/μL vs. 265 ± 66 × 10/μL, p = 0.24) or other coagulation parameters such as prothrombin time, partial thromboplastin time, or international normalized ratio. Before treatment, both groups had similar ADP inhibition as measured by thromboelastography (ADP, 86% vs. 89%, p = 0.34). After treatment, both the DDAVP and PLT groups had similar correction of platelet ADP inhibition (p = 0.28).. In patients with severe traumatic brain injury and PD, DDAVP may be an alternative to PLTs to correct PD.. Therapeutic, level IV.

Topics: Abbreviated Injury Scale; Adult; Blood Platelet Disorders; Blood Platelets; Brain Injuries, Traumatic; Deamino Arginine Vasopressin; Female; Head Injuries, Closed; Hemostatics; Humans; International Normalized Ratio; Male; Middle Aged; Platelet Transfusion; Retrospective Studies; Thrombelastography; Treatment Outcome; Young Adult

Bleeding contributes to the high mortality of venovenous extracorporeal membrane oxygenation (vvECMO). The development of acquired von Willebrand syndrome (AVWS) has been identified as relevant pathology during ECMO. This study was performed to determine the onset of AVWS after implantation and the recovery of von Willebrand factor (VWF) parameters after explantation of ECMO in a large cohort of patients.. VWF parameters of 59 patients treated with vvECMO at a university ECMO center were obtained before ECMO implantation, during therapy, and after explantation. In a subgroup of patients, light transmission aggregometry of platelets and flow-cytometric quantification of platelet granule secretion were performed.. All patients developed severe AVWS hours after implantation of vvECMO. After explantation, AVWS recovered within 3 hours in 60%, within 6 hours in 86%, and in all patients within 1 day. Aggregometry showed hypoaggregability of platelets after stimulation with ADP, ristocetin, collagen, and epinephrine. Flow-cytometric platelet analyses revealed severely reduced expression of CD62 and CD63.. All patients during vvECMO support rapidly develop AVWS and platelet dysfunction, resulting in severe impairment of coagulation. After explantation, AVWS overwhelmingly recovers within hours, resulting in a hypercoagulative state. These findings augment the need for novel extracorporeal technologies with reduced shear stress, and shift the emphasis for intense anti-coagulation during ECMO instead to a time-point after explantation.

Topics: Adult; Aged; Anticoagulants; Blood Platelet Disorders; Deamino Arginine Vasopressin; Drug Combinations; Erythrocyte Transfusion; Extracorporeal Membrane Oxygenation; Factor VIII; Female; Follow-Up Studies; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Transfusion; Remission, Spontaneous; Thrombocytopenia; von Willebrand Diseases; von Willebrand Factor

1-deamino-8-d-arginine vasopressin (desmopressin [DDAVP]) is clinically efficacious in patients with mild platelet function disorders but it is not known which mechanisms mediate this effect. Our aim was to evaluate the impact of in vivo DDAVP administration in these patients. We assessed von Willebrand factor (VWF), factor VIII, platelet activation and aggregation, platelet-dependent thrombin generation, and platelet intracellular Na(+)/Ca(2+) fluxes, before and 2 and 4 hours after DDAVP (0.3 µg/kg). We found (1) no significant changes for P-selectin expression, PAC-1 binding, δ-granule content and secretion, and platelet-aggregation; (2) significant decreases of secretion of α-granules and GPIIb-IIIa activation induced by adenosine 5'-diphosphate, convulxin, and thrombin; (3) significant increases of procoagulant platelets induced by convulxin/thrombin and platelet-dependent thrombin generation; and (4) significant increases of intracellular Na(+)/Ca(2+) concentrations. We show that in vivo DDAVP selectively and markedly enhances the ability to form procoagulant platelets and increases platelet-dependent thrombin generation by enhancing Na(+)/Ca(2+) mobilization. This report indicates that the beneficial hemostatic effect of DDAVP is not limited to an increase in large VWF multimers. An enhancement of platelet procoagulant activity appears to be an additional and (at least in platelet disorders) -possibly clinically relevant mechanism of DDAVP's action.

Topics: Adolescent; Adult; Aged; Blood Platelet Disorders; Blood Platelets; Calcium; Cytoplasmic Granules; Deamino Arginine Vasopressin; Factor VIII; Female; Humans; Male; Middle Aged; Platelet Adhesiveness; Platelet Aggregation; Platelet Membrane Glycoproteins; Sodium; Thrombin; von Willebrand Factor; Young Adult

Topics: Blood Platelet Disorders; Blood Platelets; Deamino Arginine Vasopressin; Female; Humans; Male

Desmopressin (DDAVP) 1-deamino-8-D-arginine vasopressin is used in patients with bleeding disorders, including mild factor VIII deficiency, types 1 and 2 von Willebrand disease, and platelet function defects, undergoing surgeries to help control bleeding. We conducted a retrospective chart review of bleeding disorder patients undergoing inpatient surgery at Toledo Children's Hospital, OH, from 2005 to 2009. Our study population included 107 patients aged 2 to 19 years with platelet function defects and von Willebrand disease. Our study aimed to evaluate the extent of hyponatremia caused by DDAVP and to propose a safe and effective treatment regimen for these patients. The mean change in sodium level before and after DDAVP was statistically significant within each age group. Thirteen patients had second dose of DDAVP withheld, and 11 patients had postoperative sodium levels ≤ 130 mEq/L. There were 2 patients with significant complications: a 6-year-old with postoperative bleeding and a 2-year-old with post-DDAVP tonic-clonic seizures. We conclude that DDAVP causes significant hyponatremia, despite appropriate fluid restrictions. On the basis of our analysis, we recommend monitoring sodium levels before each dose of DDAVP and fluid restriction. These patients should be observed in the hospital setting after DDAVP administration for complications such as seizures and postoperative bleeding.

Topics: Adolescent; Blood Coagulation Disorders; Blood Loss, Surgical; Blood Platelet Disorders; Child; Child, Preschool; Deamino Arginine Vasopressin; Hemophilia A; Hemostatics; Humans; Hyponatremia; Intraoperative Period; Postoperative Complications; Postoperative Period; Retrospective Studies; Sodium; von Willebrand Diseases; Water-Electrolyte Imbalance; Young Adult

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

Topics: Aspirin; Blood Platelet Disorders; Deamino Arginine Vasopressin; Hemostatics; Humans; Platelet Aggregation Inhibitors

Despite about 3 decades of clinical experience with the therapy of inherited thrombocytopathies (HTP) with desmopressin (DDAVP) the mechanisms of haemostatic effects of DDAVP in these diseases remain unclear. Therefore platelet function diagnostics was carried out in whole blood (WB) from children with aspirin-like defect as one of the clinically mild forms of HTP after DDAVP administration.. 11 children (age range: 3-16 years) were treated with DDAVP i.v. (0.3 μg/kg as short infusion). Before, after 120, and 240 min of DDAVP administration the following parameters were measured: platelet aggregation (PA) and ATP release induced by ADP, collagen, ristocetin and thrombin; PFA-100 closure times (CT), factor VIII activity (FVIII:C), Von Willebrand factor antigen (VWF:Ag), collagen binding activity (VWF:CB) and blood count.. PA, ATP release and blood count were not influenced by DDAVP administration. PFA-100 CTs were markedly reduced at 120 and 240 min after DDAVP, respectively. FVIII:C, VWF:Ag and VWF:CB were increased after 120 min.. The DDAVP-induced improvement of primary haemostasis in patients with aspirin-like defect is mainly due to the marked increase of the VWF. For the evaluation of the clinical effect of DDAVP administration in patients with aspirin-like defect the investigation of a larger group of patients is needed.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Adolescent; Aspirin; Blood Platelet Disorders; Blood Platelets; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Hemostasis; Hemostatics; Humans; Infusions, Intravenous; Male; Platelet Aggregation; Platelet Function Tests; Thrombin; von Willebrand Factor

Desmopressin (DDAVP, Minirin® parenteral), which induces the release of von-Willebrand factor from endogenous stores, is indicated in von Willebrand disease type 1 (VWD 1). In the present study effectiveness of DDAVP was tested and side effects were recorded in patients with VWD 1, von Willebrand disease type 2 (VWD 2) or thrombocytopathy (TCP).. Subjects were analysed prior to and after Minirin parenteral infusion (0.4 μg/kg body weight (b.w.) over 60 minutes) for partial thromboplastin time (PTT, seconds), ADP/epinephrine triggered platelet-function analyzer (PFA-100) occlusion time (seconds), factor VIII activity (FVIII, %), VWF as ristocetin cofactor activity (VWF:RCo, %) and VWF antigen (VWF:Ag, %). Side effects of DDAVP during operative interventions were recorded per questionnaires by the patients.. The mean ± standard deviation dose (n = 165 patients) of Minirin parenteral administered was 0.37 ± 0.02 μg/kg b.w., most often upcoming dental operations (57%) necessitated testing. Coagulation parameters of patients with VWD 1 or TCP normalised in almost all patients, but only in approximately 50% of patients with VWD 2 respectively. Appraisal of effectiveness of Minirin parenteral as good was 96% in case of VWD 1 and 95 % in case of TCP. During minor surgeries (n = 23) in 91% of the patients no complications and in 2 patients (9%) postoperative haemorrhages without need for further interventions occurred, but 83% of the patients reported adverse reactions in the questionnaires, although Minirin parenteral was well tolerated by all patients during DDAVP efficacy tests.. Desmopressin is well tolerated and affective in patients with VWD 1 and thrombocytopathy.

Topics: Administration, Rectal; Adult; Aged; Blood Platelet Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Male; Middle Aged; Treatment Outcome; von Willebrand Disease, Type 1; von Willebrand Disease, Type 2

Inherited disorders of platelets constitute a group of rare diseases that give rise to bleeding syndromes of variety severity, with more severe cases being first diagnosed during infancy and childhood. To appropriate diagnose a platelet function disorder during early childhood the knowledge of the physiological characteristics of platelets in the paediatric population is mandatory. Apart from thrombocytopenia which is quite common in neonates and children the present overview is aimed to focus on inherited platelet function disorders. Furthermore, knowledge on platelet maturation and reference values according to age are given, and a diagnostic strategy specifically adapted to a pediatric population is presented on the bases of plasmatic and molecular laboratory methodologies. Finally, therapeutic approaches are briefly summarized (antifibrinolytic agents, Desmopressin, HLA-matched platelets, recombinant factor VIIa).

Topics: Antifibrinolytic Agents; Blood Platelet Disorders; Child; Deamino Arginine Vasopressin; Diagnosis, Differential; DNA Mutational Analysis; Factor VIIa; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Molecular Motor Proteins; Myosin Heavy Chains; Partial Thromboplastin Time; Platelet Count; Platelet Function Tests; Platelet Transfusion; Recombinant Proteins; Syndrome; Thrombocytopenia; von Willebrand Diseases; von Willebrand Factor

Intranasal desmopressin (IN-DDAVP) is used for home treatment of menorrhagia in women with inherited bleeding disorders. The effect of IN-DDAVP on laboratory haemostatic parameters in women with menorrhagia related to platelet dysfunction is unknown. We evaluated the effects of IN-DDAVP on haemostatic parameters in women with menorrhagia and platelet dysfunction and correlated them with menstrual flow. Eleven women (aged 18-45) with menorrhagia and haemostatic abnormalities had determination of von Willebrand factor antigen (VWF:Ag), von Willebrand factor ristocetin cofactor (VWF:RCo) activity, factor VIII coagulant activity (FVIII:C), platelet aggregation and platelet adenosine tri-phosphate (ATP) release pre-IN-DDAVP and 60-min post-IN-DDAVP. Eight of eleven women underwent platelet function analyzer (PFA-100) closure time determination with collagen/adrenaline and collagen/adenosine diphosphate cartridges pretreatment and post-treatment. IN-DDAVP was administered during two consecutive menstrual cycles. Menstrual flow was assessed during each cycle using a pictorial blood assessment chart. Treatment with IN-DDAVP resulted in elevated VWF levels and shortened PFA-100 closure time with significant inverse correlation between shortening of PFA-100 closure times and increases in VWF levels. There were also significant inverse correlations between changes in menstrual flow and changes in VWF:Ag (P = 0.02), VWF:RCo (P = 0.04) and FVIII:C (P = 0.006), following treatment. In vitro platelet aggregation and platelet ATP release response did not correct and did not correlate with changes in menstrual flow. Our results demonstrate a correlation between haemostatic parameters and menstrual flow following IN-DDAVP in women with menorrhagia and platelet dysfunction.

Topics: Adenosine Triphosphate; Administration, Intranasal; Adolescent; Adult; Bleeding Time; Blood Platelet Disorders; Deamino Arginine Vasopressin; Factor VIII; Female; Hemostatics; Humans; Menorrhagia; Middle Aged; Platelet Aggregation; Severity of Illness Index; von Willebrand Factor

Topics: Blood Loss, Surgical; Blood Platelet Disorders; Blood Transfusion; Deamino Arginine Vasopressin; Hemostatics; Humans; Platelet Function Tests; Preoperative Care; Sensitivity and Specificity; Time Factors

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

Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by oculocutaneous albinism, a bleeding diathesis, and in a subset of patients, pulmonary fibrosis. Lung transplantation, the only curative therapy for pulmonary fibrosis, has not been previously reported as a successful treatment strategy for patients with HPS because the bleeding diathesis was thought to contraindicate major thoracic surgery. We successfully performed bilateral sequential lung transplantation in a patient with pulmonary fibrosis and HPS after transfusion of 6 units of platelets. Lung transplantation is a viable therapeutic option in patients with pulmonary fibrosis and only a mild bleeding diathesis associated with HPS.

Topics: Adult; Blood Platelet Disorders; Deamino Arginine Vasopressin; Hemorrhagic Disorders; Hemostatics; Hermanski-Pudlak Syndrome; Humans; Lung Transplantation; Male; Membrane Proteins; Platelet Transfusion; Pulmonary Fibrosis; Treatment Outcome

An Arg60-to-Leu mutation was found in the first cytoplasmic loop of the PLT TxA2 receptor as a new congenital PLT disorder characterized by impaired responsiveness to TxA2. However, it has not been clarified whether DDAVP is effective in correcting the bleeding time (BT) in this PLT disorder.. DDAVP (0.4 microg/kg) was intravenously administered over 20 minutes in five patients with this PLT disorder, and template BT, PLT retention to glass beads, PLT aggregation, and a coagulation study were performed before and after the infusion of DDAVP. PLT TxA2 synthesis defects (cyclo-oxygenase deficiency, volunteers taking aspirin), thrombasthenia, and Bernard-Soulier syndrome were also included in this study.. The normalization of BT was found in all patients with this PLT disorder, and one of the patients successfully underwent oral surgical procedures with DDAVP as the only hemostatic agent. DDAVP was also efficacious in the TxA2 synthesis defect but not in other disorders. FVIII coagulation activity, vWF antigen, and ristocetin cofactor significantly increased in all patients after DDAVP, but no changes were seen in the PLT retention rate and PLT aggregation study after DDAVP infusion.. DDAVP was effective in correcting BT in patients with impaired responsiveness to TxA2 as well as impaired production of TxA2.

Topics: Bleeding Time; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Middle Aged; Periodontal Cyst; Preoperative Care; Receptors, Thromboxane; Thromboxane A2; Tooth Extraction

Topics: Blood Platelet Disorders; Deamino Arginine Vasopressin; Hemostatics; Humans; von Willebrand Factor

This study evaluated the effectiveness of a protocol to prevent bleeding after dental extraction in patients with hemophilia, von Willebrand's disease (VWD), or platelet disorders.. Replacement therapy was used in cases involving general anesthesia, and nerve trunk infiltration was used in patients with severe bleeding disorders (severe-to-moderate hemophilia or type 2-3 VWD). Desmopressin was used in good responders with mild hemophilia A, type 1 VWD, and platelet disorders. Local hemostatic measures and antifibrinolytic treatment were used systematically.. Ninety-three patients underwent 103 dental extractions; 2 of these patients had secondary bleeding requiring surgical hemostasis.. The indication for replacement therapy depended on the type of anesthesia that was used. Coagulation factor concentrates or desmopressin were necessary to avoid upper airway hematoma with general anesthesia or nerve trunk infiltration. With local anesthesia, substitutive treatment was indicated in patients with severe-to-moderate hemophilia and type 2-3 VWD. Inexpensive desmopressin was effective in those who responded well. Local hemostatic measures and antifibrinolytic treatment were performed systematically.

Topics: Adolescent; Adult; Aged; Antifibrinolytic Agents; Blood Platelet Disorders; Blood Transfusion; Child; Clinical Protocols; Deamino Arginine Vasopressin; Dental Care for Chronically Ill; Female; Hemophilia A; Hemorrhagic Disorders; Hemostatics; Humans; Male; Middle Aged; Oral Hemorrhage; Retrospective Studies; Tooth Extraction; von Willebrand Diseases

Techniques measuring platelet aggregation in vitro under the high shear rate conditions that can be found in the microcirculation could reflect the status of primary hemostasis better than the turbidimetric technique. We studied platelet aggregation at high shear in patients with prolonged bleeding time caused by congenital platelet secretion defects such as delta-storage pool deficiency and primary secretion defect. Two different techniques were used: shear-induced platelet aggregation in a cone-and-plate viscometer and the filter aggregation test. With both techniques, platelet aggregation at high shear rate was defective in 14 patients with delta-storage pool deficiency and in 8 with primary secretion defect. There was a statistically significant correlation between platelet aggregation at high shear rate and the bleeding time. In patients with delta-storage pool deficiency, platelet aggregation at high shear rate and the bleeding time were significantly correlated with the platelet serotonin content. The intravenous infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) (0.3 micrograms/kg) increased the plasma concentration of von Willebrand factor (vWf), shortened the bleeding time, and potentiated platelet aggregation at high shear rate in all patients. Because platelet aggregation at high shear rate requires vWf, the effect of DDAVP is probably due to the induced increase in plasma vWf. Therefore, platelet aggregation at high shear rate is defective in patients with congenital defects of platelet secretion and is potentiated by DDAVP. Potentiation of platelet aggregation at high shear rate may be one mechanism by which DDAVP shortens the prolonged bleeding time of patients with congenital defects of platelet secretion.

Topics: Bleeding Time; Blood Platelet Disorders; Blood Platelets; Deamino Arginine Vasopressin; Humans; Platelet Aggregation; Platelet Storage Pool Deficiency; von Willebrand Factor

The in vitro measurement of platelet aggregation (PA) at the high shear levels that can be found in the microcirculation may provide useful informations on primary haemostasis, which is usually explored in vivo with the skin bleeding time (BT). PA at high shear requires von Willebrand factor (vWf) and the platelet glycoprotein (GP) complexes Ib/IX/V and IIb/IIIa; controversial results have been reported on its requirement of released adenosine diphosphate (ADP). Due to its dependence on vWf, PA at high shear may be affected by the vasopressin analogue DDAVP, which increases the plasma vWf levels and shortens the prolonged BT of patients with congenital or acquired defects of platelet function. We studied PA at high shear, BT and plasma vWf levels in a patient with congenital impairment of platelet responses to ADP before and after the i.v. infusion of 0.3 micrograms/kg DDAVP. Two methods to study PA at high shear were used: shear-induced PA (SIPA) and the filter aggregation test. With both methods, PA at high shear of the patient was impaired. The infusion of DDAVP increased plasma vWf levels, shortened the prolonged BT and potentiated PA at high shear of the patient. In conclusion, PA at high shear is impaired in a patient with congenital defect of platelet responses to ADP and prolonged BT and is potentiated by DDAVP. Our results suggest that released ADP plays an important role in PA at high shear and that potentiation of PA at high shear by DDAVP may be one mechanism by which the drug shortens the prolonged BT of patients with congenital or acquired defects of platelet function.

Topics: Adenosine Diphosphate; Bleeding Time; Blood Platelet Disorders; Blood Platelets; Cells, Cultured; Deamino Arginine Vasopressin; Humans; Platelet Aggregation; Stress, Mechanical; von Willebrand Factor

1-deamino-8-D-Arginine vasopressin (DDAVP) shortens the bleeding time in some patients with platelet dysfunction and decreases blood loss in some cardiopulmonary bypass patients. We studied platelet membrane glycoproteins in patients with von Willebrand disease (vWD), disorders of platelet function, and in cardiopulmonary bypass patients after infusion of 0.3 microgram/kg of DDAVP. Platelets from 8 cardiopulmonary bypass patients, receiving DDAVP immediately after surgery, were compared to those of 14 patients not receiving DDAVP. We also studied 12 patients with vWD, and 8 patients with platelet dysfunction receiving DDAVP. Fixed platelets, stained with monoclonal fluorescein (FITC)-labeled antibodies directed against GPIb (CD42b antigen), GPIb/IX, GPIIb/IIIa (CD41a antigen), CD63 antigen (a platelet activation protein), and P-selectin (CD62 antigen) were studied by flow cytometry. Binding of CD42b monoclonal antibody (MoAb) and anti-GPIb/IX to platelets from both groups of bypass patients increased during the 18-20 hr after surgery, but the group receiving DDAVP showed the greater increase (P = 0.032). Platelets from patients receiving DDAVP for vWD or for platelet dysfunction, had increases in CD42b MoAb and anti-GPIb/IX binding (P < 0.01) that coincided with shortening of their bleeding time. No changes were seen in binding of other antibodies. When platelets from normal donors were incubated with DDAVP for 20 hr, there were increases in platelet surface CD42b MoAb binding, while immunogold-stained transmission electron micrographs of permeabilized platelets demonstrated decreases in cytoplasmic CD42b MoAb binding. DDAVP increases platelet membrane GPIb expression in a variety of patients and may account for improvement in hemostasis seen in some studies. Redistribution of GPIb from the cytoplasm to the membrane may account for this increased expression.

Topics: Adult; Aged; Aged, 80 and over; Blood Platelet Disorders; Blood Platelets; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Female; Humans; Male; Middle Aged; Platelet Membrane Glycoproteins; von Willebrand Diseases

Topics: Adult; Bleeding Time; Blood Platelet Disorders; Deamino Arginine Vasopressin; Female; Humans; Infusions, Parenteral; Male; Middle Aged; Platelet Storage Pool Deficiency

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

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

Desmopressin and ethamsylate were evaluated for possible synergistic effects on the bleeding time. The drugs were administered individually and together to 12 patients with markedly prolonged bleeding times known to be relatively or absolutely unresponsive to desmopressin alone. The bleeding disorders studied included Glanzmann's thrombasthenia (one), other disorders of platelet function (four), pseudo-von Willebrand disease (one), and von Willebrand disease type I (three), type II (two), and type III (one). Desmopressin alone shortened the bleeding time from 23.9 +/- 1.5 to 19.5 +/- 2.3 min (p = 0.03). Ethamsylate alone was without effect. Desmopressin and ethamsylate together shortened the bleeding time to 11.2 +/- 1.4 min (p less than 0.01 compared to baseline, p = 0.02 compared to desmopressin alone). The combination was ineffective in three patients, with Glanzmann's thrombasthenia (one), and von Willebrand disease type I (one) and type III (one). Toxic effects of the drugs were not observed. Five patients received desmopressin and ethamsylate prior to dental work with mandibular block (one), heart surgery requiring cardiopulmonary bypass (two), and adenotonsillectomy surgery (two). Normal hemostasis was achieved in each case. A synergistic shortening of the bleeding time was observed with the combination of desmopressin and ethamsylate in a wide range of bleeding disorders.

Topics: Adolescent; Adult; Aged; Bleeding Time; Blood Platelet Disorders; Child; Child, Preschool; Deamino Arginine Vasopressin; Drug Synergism; Drug Therapy, Combination; Ethamsylate; Female; Humans; Infant; Male; Middle Aged

The qualitative platelet disorder of uraemia results in decreased primary haemostatic capacity which can result in significant blood loss during invasive procedures. Treatments of the disorder tend to be empirical and include measures such as aggressive dialysis, conjugated oestrogens, and use of DDAVP. Improvement in platelet function is typically monitored by repeated bleeding times. The variability of the bleeding time is an all too recognized limitation of its usefulness. We report here the case of a 35-year old male with end stage renal disease who presented with intractable bleeding secondary to peptic ulcer disease and haemorrhagic gastritis. Platelet function tests including bleeding time, platelet aggregation studies, and clot retraction measurements were monitored before and after intravenous administration of DDAVP (0.3 microgram/kg). The bleeding time which had been 8 min before DDAVP did not change. Platelet aggregation studies revealed improved aggregation by both collagen and adenosine diphosphate. Clot retraction forces were dramatically enhanced after DDAVP. Pre-DDAVP clots containing 72 x 10(9) platelets per 1 and 1 g fibrinogen per 1 produced 90 dynes/cm2 of force at 800 s post-thrombin addition. Identical clots formed with blood drawn 2 h post-DDAVP produced 750 dynes/cm2. The DDAVP dose was repeated after 8 h with obvious slowing of blood loss. The marked effect of DDAVP on clot retraction may allow monitoring of DDAVP therapy utilizing this technique.

Topics: Adenosine Diphosphate; Adult; Bleeding Time; Blood Platelet Disorders; Clot Retraction; Collagen; Deamino Arginine Vasopressin; Humans; Male; Platelet Aggregation; Uremia

Topics: Blood Component Transfusion; Blood Platelet Disorders; Deamino Arginine Vasopressin; Hematologic Diseases; Humans; Kidney Failure, Chronic; Platelet Adhesiveness; Platelet Aggregation

A term parturient with documented platelet dysfunction presented to the case room for induction of labour. Since this bleeding abnormality contraindicated the use of lumbar epidural analgesia (LEA), we elected to use an iv fentanyl patient-controlled analgesia (PCA) technique for pain relief during labour. The patient received a 50 micrograms fentanyl loading dose after which 20 micrograms boluses of fentanyl were self-administered every three minutes as required. The patient received a total of 400 micrograms of fentanyl over the 3 1/2 hr of active labour. Mother and neonate tolerated the fentanyl without sequelae. If facilities to monitor the neonate and mother are present, this method of analgesia is useful in those patients where LEA is contraindicated.

Topics: Adult; Analgesia, Obstetrical; Analgesia, Patient-Controlled; Blood Platelet Disorders; Deamino Arginine Vasopressin; Female; Fentanyl; Humans; Injections, Intravenous; Labor, Induced; Pregnancy; Pregnancy Complications, Hematologic

Twenty-one patients with prolonged bleeding times secondary to inherited disorders of platelet function and eight patients with prolonged bleeding times secondary to acquired platelet dysfunction were given 0.3 micrograms per kilogram of DDAVP, 1-deamino-8-D-arginine vasopressin, intravenously. Sixteen of twenty-two DDAVP trials in patients with inherited platelet dysfunction (73%) and seven of the nine DDAVP trials in patients with acquired platelet dysfunction (78%) resulted in normalization or shortening of the prolonged bleeding times by at least 4 min. The bleeding time response did not correlate with changes in the levels of von Willebrand factor (vWf) antigen or ristocetin cofactor activity, nor was it associated with changes in vWf multimeric analysis or in vitro platelet aggregations following the administration of DDAVP. Shortening of the bleeding time with DDAVP was seen in patients with a failure to release/storage pool type defect, thromboxane synthesis type defect, Bernard-Soulier syndrome, Glanzmann's thrombasthenia, the May-Hegglin anomaly, liver disease, nonuremic renal disease, myelofibrosis, and Tangier's disease.

Topics: Adolescent; Adult; Bleeding Time; Blood Platelet Disorders; Child; Child, Preschool; Deamino Arginine Vasopressin; Hemostasis; Humans; Platelet Aggregation; von Willebrand Factor

We reported a 33-year-old woman with thrombasthenia (type II) in whom 1-deamino-8-D-arginine vasopressin (DDAVP) was available for the hemostasis control during breast tumor resection. She has had recurrent nasal bleeding and purpura since 2 years old. On the first admission to our hospital because of hematuria at 18 years old, she was diagnosed as thrombasthenia (type II) from hemostatic studies. At 20 years old, she had a healthy baby by the cesarean section with transfusion of fresh blood and platelet concentrates. On the 5th admission for the breast tumor resection, defect of glycoprotein II b-III a of her platelets was confirmed by using SDS gel electrophoresis. Recently, there are some reports on availability of DDAVP for hemostatic control in platelet dysfunction of various etiologies as well as mild hemophilia and von Willebrand disease. So, DDAVP (0.4 microgram/kg) was used for hemostasis control. After 1 hour, the bleeding time was shortened from over 10 to 4 min, platelet adhesiveness to glass beads increased from 1.8 to 37%. Furthermore, the levels of Ristocetin cofactor and von Willebrand factor antigen (especially large multimer) also increased. But platelet aggregation with various inducers remained unchanged before and after infusion. Breast tumor (fibroadenoma) resection.

Topics: Adult; Bleeding Time; Blood Platelet Disorders; Breast Neoplasms; Deamino Arginine Vasopressin; Female; Hemostasis; Humans; Thrombasthenia

The effect of the synthetic vasopressin derivative 1-desamino-8D-arginine vasopressin (DDAVP = desmopressin) on bleeding time was studied in three patients with Hermansky Pudlak syndrome. A good response was observed in this type of storage pool disease. DDAVP might be useful in managing the bleeding disorder found in patients with the Hermansky-Pudlak syndrome.

Topics: Adolescent; Adult; Albinism; Bleeding Time; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Humans; Male; Platelet Function Tests; Platelet Storage Pool Deficiency; Serotonin; Syndrome

Topics: Bleeding Time; Blood Platelet Disorders; Blood Transfusion; Deamino Arginine Vasopressin; Humans

Topics: Adult; Bernard-Soulier Syndrome; Blood Coagulation; Blood Platelet Disorders; Deamino Arginine Vasopressin; Female; Humans

Topics: Adolescent; Adult; Aged; Bleeding Time; Blood Coagulation; Blood Platelet Disorders; Child; Deamino Arginine Vasopressin; Double-Blind Method; Female; Humans; Male; Middle Aged; Platelet Storage Pool Deficiency; Preoperative Care

Topics: Adult; Bernard-Soulier Syndrome; Bleeding Time; Blood Platelet Disorders; Deamino Arginine Vasopressin; Humans; Male

The Gray platelet syndrome is a rare disorder characterised by the absence of platelet alpha-granules and their contents. We describe a new patient and the effects of infusions of 1-deamino-8-arginine vasopressin (DDAVP). The patient had a prolonged skin bleeding time and his platelets had reduced numbers of alpha-granules, increased vacuolation and reduced retention on glass beads. Platelet von Willebrand factor antigen (vWf:Ag) was undetectable and levels of platelet fibrinogen, beta-thromboglobulin, platelet factor 4 and thrombospondin were reduced. All tests of plasma coagulation factors were normal, including Factor VIII (F.VIII:C), vWf:Ag, ristocetin cofactor (R:CoF) and botrocetin cofactor. Platelet ATP, ADP, platelet albumin, surface membrane glycoproteins and 14C-serotonin uptake were also normal. Infusions of DDAVP increased plasma F.VIII:C, vWf:Ag and R:CoF and shortened the bleeding time on two occasions. This suggests that DDAVP shortens the bleeding time by releasing vWf:Ag and/or other proteins from cellular storage sites other than the platelet.

Topics: Adult; Bleeding Time; Blood Platelet Disorders; Blood Platelets; Deamino Arginine Vasopressin; Humans; Male; Syndrome; von Willebrand Factor

In 37 patients with prolonged bleeding time, where thrombocytopenia, von Willebrand's disease or deficiency of other coagulation factors could be excluded, we have evaluated the effect of a DDAVP-infusion (0.2 ug/kg) together with tranexamic acid (10 mg/kg). Patients with acquired impairment of primary hemostasis were not included, except two cases where this could have been a contributing factor. The bleeding time was completely normalized in 27 cases and partially corrected in three more patients. The predominant feature among those, who did not respond, was a pattern compatible with thrombasthenia or cyclooxygenase deficiency, as assessed by platelet aggregation studies. Among the patients, in whom DDAVP was effective, this drug was thereafter successfully used as an alternative to blood products in 8 cases during and after surgery or delivery.

Topics: Adolescent; Adult; Aged; Blood Coagulation; Blood Platelet Disorders; Child; Deamino Arginine Vasopressin; Female; Humans; Male; Middle Aged; Pregnancy; Pregnancy Complications, Hematologic; Tranexamic Acid

Platelet function was evaluated in 20 patients with chronic myelocytic leukemia (CML), all Ph positive. Seven showed abnormal epinephrine-induced aggregation, while four had impaired both ADP- and collagen-induced aggregation. The platelets of all patients aggregated with arachidonic acid, thus ruling out cyclooxygenase or lipoxygenase deficiency. The intracellular concentrations of ATP and ADP were significantly below normal, and the ratio of ATP/ADP was greater than normal in all 12 patients. ATP released from platelets by Lumi-aggregometer was reduced. In four patients with abnormal ristocetin-induced aggregation, vWF:Ag, RCoF, and FVIII:C were all reduced. No significant inactivation of factor VIII was induced in normal plasma by incubation with patient's plasma. The crossed immunoelectrophoretic analysis revealed that vWF:Ag in these patients was mainly composed of more anodic component as compared with that of normal plasma. The ratio of vWF:Ag/RCoF was significantly greater than normal. A marked increase of factor VIII and a rapid return of vWF:Ag and RCoF to the baseline after the 1-deamino-8-arginine vasopressin (DDAVP) infusion were observed. Transient increase in vWF:Ag after the infusion of DDAVP appeared with less anodic forms and in the same relative proportion as that in normal plasma. The present study shows that in some patients with CML storage pool disease occurs with acquired von Willebrand disease.

Topics: Adenosine Triphosphate; Adult; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Deamino Arginine Vasopressin; Humans; Leukemia, Myeloid; Middle Aged; Platelet Aggregation; Platelet Storage Pool Deficiency; von Willebrand Diseases

To evaluate the effect of 1-deamino-8-D-arginine vasopressin (DDAVP) in various bleeding disorders, 10 micrograms/m2 DDAVP was administered to subjects with von Willebrand disease (13), platelet function defects (12), von Willebrand disease and platelet defects together (8), or isolated prolongation of the bleeding time (5). DDAVP shortened the bleeding time similarly in all patient groups. Shortening of the bleeding time was also observed in 2 patients with aspirin-induced platelet defects and in 2 normal subjects. DDAVP administration was associated with falls in the platelet count, mean platelet volume, and partial thromboplastin time, and rises in platelet adhesion, factor VIII coagulant activity, factor VIII related antigen, and von Willebrand factor activity. The basal bleeding time was the only predictor of the magnitude of the bleeding-time correction. Normal haemostatis was achieved with DDAVP plus epsilon-aminocaproic acid and no blood product support during operations in 18 patients with bleeding disorders.

Topics: Adolescent; Adult; Aminocaproic Acid; Arginine Vasopressin; Aspirin; Bleeding Time; Blood Platelet Disorders; Blood Platelets; Child; Child, Preschool; Deamino Arginine Vasopressin; Drug Evaluation; Hemostasis; Hemostasis, Surgical; Humans; Partial Thromboplastin Time; Platelet Adhesiveness; Platelet Count; Platelet Function Tests; von Willebrand Diseases

Topics: Adolescent; Adult; Arginine Vasopressin; Blood Platelet Disorders; Deamino Arginine Vasopressin; Dentistry, Operative; Drug Evaluation; Female; Hemostatic Techniques; Humans; Male; Premedication