deamino-arginine-vasopressin and Blood-Coagulation-Disorders

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate (DDAVP) is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of DDAVP in these groups of pregnant women should be evaluated.This is an update of a Cochrane Review first published in 2013 and updated in 2015.. To evaluate the efficacy and safety of DDAVP in preventing and treating acute bleeding in pregnant women with bleeding disorders.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched several clinical trial registries and grey literature (27 August 2017).Date of most recent search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register: 01 October 2018.. Randomised and quasi-randomised controlled trials investigating the efficacy of DDAVP versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible.. No trials matching the selection criteria were eligible for inclusion.. No randomised controlled trials were identified investigating the relative effectiveness of DDAVP for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high-quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with DDAVP.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high-quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using DDAVP in this population are needed.Given that there are unlikely to be any trials published in this area, this review will no longer be regularly updated.

Topics: Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Pregnancy; Pregnancy Complications, Hematologic

Heavy menstrual bleeding without an organic lesion is mainly due to an imbalance of the various hormones which have a regulatory effect on the menstrual cycle. Another cause of heavy menstrual bleeding with no pelvic pathology, is the presence of an acquired or inherited bleeding disorder. The haemostatic system has a central role in controlling the amount and the duration of menstrual bleeding, thus abnormally prolonged or profuse bleeding does occur in most women affected by bleeding disorders. Whereas irregular, pre-menarchal or post-menopausal uterine bleeding is unusual in inherited or acquired haemorrhagic disorders, severe acute bleeding and heavy menstrual bleeding at menarche and chronic heavy menstrual bleeding during the entire reproductive life are common. This is an update of a previously published Cochrane Review.. To determine the efficacy and safety of non-surgical interventions versus each other, placebo or no treatment for reducing menstrual blood loss in women with bleeding disorders.. We searched the Cochrane Cystic Fibrosis Haemoglobinopathies Trials Register (25 August 2016), Embase (May 2013), LILACS (February 2013) and the WHO International Clinical Trial registry (February 2013).. Randomised controlled studies of non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women of reproductive age suffering from a congenital or acquired bleeding disorder.. Two authors independently assessed studies for inclusion, extracted data and assessed the risk of bias.. Three cross-over studies, with 175 women were included in the review. All three studies had an unclear risk of bias with regards to trial design and overall, the quality of evidence generated was judged to be poor.Two of the studies (n = 59) compared desmopressin (1-deamino-8-D-arginine vasopressin) with placebo. Menstrual blood loss was the primary outcome for both of these studies. Neither study found clear evidence of a difference between groups. The first of these reported a mean difference in menstrual blood loss in the desmopressin versus placebo group of 21.20 mL (95% confidence interval -19.00 to 61.50)The second study reported that even though there was an improvement of pictorial bleeding assessment chart scores with desmopressin and placebo when compared to pretreatment assessment, there was no clear evidence of difference in these scores when the two were compared to each other (results presented graphically, P = 0.51). The data from these studies could not be combined.The third study (n = 116) compared desmopressin with tranexamic acid (n = 116). This study found a decrease in pictorial bleeding assessment chart scores after both treatments as compared to baseline. The decrease in these scores was greater for tranexamic acid than for desmopressin, with a mean difference of 41.6 mL (95% confidence interval 19.6 to 63) (P < 0.0002).In relation to adverse events, across two studies, there was no clear evidence of a difference when placebo was compared to desmopressin, risk ratio 1.17 (95% confidence interval 0.41 to 3.34) . The same was also true when desmopressin was compared to tranexamic acid, risk ratio 1.17 (95% confidence interval 0.41 to 3.34).Only the study that compared desmopressin to tranexamic acid assessed quality of life. However, we are unable to present any data from this study, since no differences in this outcome between the two intervention groups were reported.. Evidence from randomised controlled studies on the effect of desmopressin when compared to placebo in reducing menstrual blood loss is very limited and inconclusive. Two studies, each with a very limited number of participants, have shown uncertain effects in menstrual blood loss and adverse effects. A non-randomised comparison in one of the studies points to the value of combining desmopressin and tranexamic acid, which needs to be tested in a formal randomised controlled study comparison.When tranexamic acid was compared to desmopressin, a single study showed a reduction in menstrual blood loss with tranexamic acid use compared to desmopressin.There is a need to evaluate non-surgical methods for treating of menorrhagia in women with bleeding disorders through randomised controlled studies. Such methods would be more acceptable than surgery for women wishing to retain their fertility. Given that women may need to use these treatments throughout their entire reproductive life, long-term side-effects should be evaluated.

Topics: Adult; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Menorrhagia; Randomized Controlled Trials as Topic; Tranexamic Acid

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated.This is an update of a Cochrane review first published in 2013.. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 18 June 2015.. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible.. No trials matching the selection criteria were eligible for inclusion.. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

Topics: Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Pregnancy; Pregnancy Complications, Hematologic

The purpose of this review is to highlight the use of tranexamic acid, point-of-care testing, algorithm-based treatment of trauma-associated coagulopathy with factor concentrates to reduce blood loss and transfusion requirements in order to improve outcome. In addition, the management of patients on new oral anticoagulants, drugs with renewed interest and the tolerance of relatively low hemoglobin levels in the context of trauma will be discussed.. Early administration of tranexamic acid reduces mortality without increasing the risk of thromboembolic events. Point-of-care testing is increasingly recommended. Goal-directed individualized coagulation algorithms with the use of factor concentrates allow reducing the amount of allogeneic blood products to be administered. Treatment of trauma patients with one of the new oral anticoagulants is challenging. Furthermore, new mechanisms have been discovered such as deep neuromuscular blockade to better tolerate acute anemia.. Applying Patient Blood Management concept to the trauma patient is possible and efficacious. Antihyperfibrinolytics such as tranexamic acid, point-of-care testing and coagulation algorithms with the use of factor concentrates allow a reduction of the number of transfusions, the costs and will likely ameliorate outcome of major trauma patients.

Topics: Anemia; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Deamino Arginine Vasopressin; Humans; Point-of-Care Systems; Tranexamic Acid; Trauma Centers

Heavy menstrual bleeding without an organic lesion is mainly due to an imbalance of the various hormones which have a regulatory effect on the menstrual cycle. Another cause of heavy menstrual bleeding with no pelvic pathology, is the presence of an acquired or inherited bleeding disorder. The haemostatic system has a central role in controlling the amount and the duration of menstrual bleeding, thus abnormally prolonged or profuse bleeding does occur in most women affected by bleeding disorders. Whereas irregular, pre-menarchal or post-menopausal uterine bleeding is unusual in inherited or acquired haemorrhagic disorders, severe acute bleeding and heavy menstrual bleeding at menarche and chronic heavy menstrual bleeding during the entire reproductive life are common.. To determine the efficacy and safety of non-surgical interventions versus each other, placebo or no treatment for reducing menstrual blood loss in women with bleeding disorders.. We searched the Cochrane Cystic Fibrosis Haemoglobinopathies Trials Register (13 March 2014), Embase (May 2013), LILACS (February 2013) and the WHO International Clinical Trial registry (February 2013).. Randomised controlled studies of non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women of reproductive age suffering from a congenital or acquired bleeding disorder.. Two authors independently assessed studies for inclusion, extracted data and assessed the risk of bias.. Three cross-over studies, with 175 participants were included in the review. All three studies had an unclear risk of bias with regards to trial design and overall, the quality of evidence generated was judged to be poor.Two of the studies (n = 59) compared desmopressin (1-deamino-8-D-arginine vasopressin) with placebo. Menstrual blood loss was the primary outcome for both of these studies. Neither study found clear evidence of a difference between groups. The first of these reported a mean difference in menstrual blood loss in the desmopressin versus placebo group of 21.20 mL (95% confidence interval -19.00 to 61.50)The second study reported that even though there was an improvement of pictorial bleeding assessment chart scores with desmopressin and placebo when compared to pretreatment assessment, there was no clear evidence of difference in these scores when the two were compared to each other (results presented graphically, P = 0.51). The data from these studies could not be combined.The third study (n = 116) compared desmopressin with tranexamic acid (n = 116). This study found a decrease in pictorial bleeding assessment chart scores after both treatments as compared to baseline. The decrease in these scores was greater for tranexamic acid than for desmopressin, with a mean difference of 41.6 mL (95% confidence interval 19.6 to 63) (P < 0.0002).In relation to adverse events, across two studies, there was no clear evidence of a difference when placebo was compared to desmopressin, risk ratio 1.17 (95% confidence interval 0.41 to 3.34) . The same was also true when desmopressin was compared to tranexamic acid, risk ratio 1.17 (95% confidence interval 0.41 to 3.34).Only the study that compared desmopressin to tranexamic acid assessed quality of life. However, we are unable to present any data from this study, since no differences in this outcome between the two intervention groups were reported.. Evidence from randomised controlled studies on the effect of desmopressin when compared to placebo in reducing menstrual blood loss is very limited and inconclusive. Two studies, each with a very limited number of participants, have shown uncertain effects in menstrual blood loss and adverse effects. A non-randomised comparison in one of the studies points to the value of combining desmopressin and tranexamic acid, which needs to be tested in a formal randomised controlled study comparison.When tranexamic acid was compared to desmopressin, a single study showed a reduction in menstrual blood loss with tranexamic acid use compared to desmopressin.There is a need to evaluate non-surgical methods for treating of menorrhagia in women with bleeding disorders through randomised controlled studies. Such methods would be more acceptable than surgery for women wishing to retain their fertility. Given that women may need to use these treatments throughout their entire reproductive life, long-term side-effects should be evaluated.

Topics: Adult; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Menorrhagia; Randomized Controlled Trials as Topic; Tranexamic Acid

Congenital bleeding disorders can cause obstetric haemorrhage during pregnancy, labour and following delivery. Desmopressin acetate is found to be an effective drug which can reduce the risk of haemorrhage and can also stop bleeding in certain congenital bleeding disorders. Its use in pregnancy has been controversial. Hence beneficial and adverse effects of desmopressin acetate in these groups of pregnant women should be evaluated.. To determine the efficacy of desmopressin acetate in preventing and treating acute bleeds during pregnancy in women with congenital bleeding disorders.. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coaguopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant and abstract books of conferences proceedings. We also searched for any randomised controlled trials in a registry of ongoing trials and the reference lists of relevant articles and reviews.Date of most recent search: 28 February 2013.. Randomised and quasi-randomised controlled trials investigating the efficacy of desmopressin acetate versus tranexamic acid or factor VIII or rFactor VII or fresh frozen plasma in preventing and treating congenital bleeding disorders during pregnancy were eligible.. No trials matching the selection criteria were eligible for inclusion.. The review did not identify any randomised controlled trials investigating the relative effectiveness of desmopressin acetate for bleeding during pregnancy in women with congenital bleeding disorders. In the absence of high quality evidence, clinicians need to use their clinical judgement and lower level evidence (e.g. from observational trials) to decide whether or not to treat women with congenital bleeding disorders with desmopressin acetate.Given the ethical considerations, future randomised controlled trials are unlikely. However, other high quality controlled studies (such as risk allocation designs, sequential design, parallel cohort design) to investigate the risks and benefits of using desmopressin acetate in this population are needed.

Topics: Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Pregnancy; Pregnancy Complications, Hematologic

Desmopressin (DDAVP) is commonly used for treatment and prevention of bleeding complications in patients with bleeding disorders including haemophilia A, von Willebrand's disease (VWD) and other less common disorders. This article reviews the current evidence for the use of DDAVP in pregnancy to clarify its efficacy and safety with regard to maternal and foetal outcome. A search of the literature found 30 studies that reported DDAVP use in pregnancy for prophylaxis or treatment of bleeding complications with 216 pregnancies reported in total. The most common indication was prophylaxis for prevention of bleeding during pregnancy and postpartum haemorrhage. DDAVP was used successfully in the first and early second trimester for bleeding prophylaxis in 50 pregnancies. No postpartum bleeding complications were reported in 167 out of 172 pregnancies when DDAVP was used for peripartum haemostatic cover. Twenty-nine studies reported no significant adverse events as a result of treatment with DDAVP. One case of water intoxication seizure and one case of premature labour following the use of DDAVP was reported in a single study. Other maternal side effects included facial flushing and headache and were reported by one study. These side effects were generally well tolerated by patients. There were no other significant adverse events reported in any of the studies as a result of DDAVP use. Foetal outcome was recorded in ten studies with no adverse foetal outcomes. In conclusion, this review shows that DDAVP in selected cases is effective in reducing bleeding complications associated with pregnancy and childbirth with a good safety record. Further research is needed to confirm these findings as they are based on the currently available evidence from small studies and case series only.

Topics: Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic

Topics: Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Factor VIIa; Humans; Protease Inhibitors

Evaluating the patient's individual bleeding history with a standardized questionnaire, using "point-of-care" - methods for coagulation analyses and providing autologous transfusion techniques are preconditions of a modern coagulation management. Therapy of coagulopathic patients should be based on structured hemotherapy algorithms. Surgical haemostasis and the maintenance of the basic conditions for haemostasis are elementary requirements for an effective therapy. In cases of diffuse bleeding, early antifibrinolytic therapy should be considered. Coagulation factor deficiencies should be corrected "goal-directed" using coagulation factor concentrates. Transfusion of fresh frozen plasma is only indicated in the clinical setting of massive transfusions. DDAVP and transfusion of platelet concentrates are options to optimize primary haemostasis. In cases of on-going bleeding, recombinant activated coagulation factor VII represents an option for "ultima-ratio" therapy.

Topics: Algorithms; Antifibrinolytic Agents; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Loss, Surgical; Blood Transfusion; Coagulation Protein Disorders; Deamino Arginine Vasopressin; Hemostasis; Humans; Hypotension, Controlled; Intraoperative Care; Plasma; Platelet Transfusion; Point-of-Care Systems; Transfusion Reaction

Bleeding after cardiac surgery remains a significant problem, increasing both length of stay and mortality, and is caused by multiple factors including dilutional changes, ongoing fibrinolysis, and platelet dysfunction. The evaluation of coagulopathy is problematic because of the long turnaround time of standard coagulation tests. Algorithms involving point of care testing, including thromboelastography and thromboelastometry, have been published; all have the potential to reduce transfusion requirements. Massive transfusion coagulopathy that occurs in trauma can also be seen in complex aortic surgery and other massive bleeding patients and should prompt consideration of a transfusion protocol involving fixed ratios of fresh frozen plasma, platelets, and red blood cells. Pharmacologic agents such as antifibrinolytics are commonly administered, but a multimodal approach to management is important. Recombinant and purified coagulation products are being studied and provide clinicians specific agents to treat targeted deficiencies. A general multi-modal approach is required and recommendations are made for the management of bleeding and coagulopathy in cardiac surgical patients.

Topics: Algorithms; Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Blood Coagulation Disorders; Blood Component Transfusion; Blood Transfusion; Blood Volume; Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Fibrinogen; Hemostatics; Recombinant Proteins; Thrombelastography; Tranexamic Acid

In the Netherlands, specialized care for patients with a bleeding disorder, including hemophilia, von Willebrand disease (VWD), and allied disorders, is concentrated in 13 Hemophilia Treatment Centers. The Dutch Hemophilia Treaters Society, the Dutch Hemophilia Nurses' Society, and the Netherlands Hemophilia Patients Society collaborate to optimize management of patients with a bleeding disorder. A recently updated consensus guideline of hemophilia and allied bleeding disorders provide guidance on the current optimal diagnostic strategy and treatment of VWD. Genetic testing is not routinely performed in the Netherlands. Desmopressin (DDAVP) is the choice of treatment in VWD patients responsive to DDAVP, as determined by a test infusion. Coagulation factor concentrates are used in nonresponsive individuals, in case of a contraindication for DDAVP, or in type 2B and type 3 VWD. These concentrates are available for all patients in the Netherlands; however, these may only be administered in a Hemophilia Treatment Center or under the care of a Hemophilia Treatment Center. Recently a study on moderate and severe VWD (the Willebrand in Netherlands study) was initiated to obtain more insight on VWD diagnosis, treatment, and the burden of the disease.

Topics: Blood Coagulation Disorders; Coagulants; Deamino Arginine Vasopressin; Genetic Testing; Geography; Hemostatics; Humans; Netherlands; von Willebrand Diseases; von Willebrand Factor

Disorders of coagulation are common adverse drug events encountered in critically ill patients and present a serious concern for intensive care unit (ICU) clinicians. Dosing strategies for medications used in the ICU are typically developed for use in noncritically ill patients and, therefore, do not account for the altered pharmacokinetic and pharmacodynamic properties encountered in the critically ill as well as the increased potential for drug-drug interactions, given the far greater number of medications ordered. This substantially increases the risk for coagulation-related adverse reactions, such as a bleeding or prothrombotic events. Although many medications used in the ICU have the potential to cause coagulation disorders, the exact incidence will vary based on the specific medication, dose, concomitant drug therapy, ICU setting, and patient-specific comorbidities. Clinicians must strongly consider these factors when evaluating the risk/benefit ratio for a particular therapy. This review surveys recent literature documenting the risk for adverse drug reactions specific to bleeding and/or clotting with commonly used medications in the ICU.

Topics: Anti-Infective Agents; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Colloids; Critical Care; Deamino Arginine Vasopressin; Drug-Related Side Effects and Adverse Reactions; Erythropoietin; Estrogens, Conjugated (USP); Factor VIIa; Fibrinolytic Agents; Fondaparinux; Hemostatics; Humans; Polysaccharides; Protein C; Recombinant Proteins; Thrombin; Thromboembolism; Vitamin K

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

After cardiac surgery with extracorporeal circulation, approximately 20% of patients show significant bleeding tendencies and 5% require re-intervention. In 50% of patients undergoing re-operation, no surgical cause can be determined, suggesting coagulopathy after cardiopulmonary bypass (CPB). For perioperative management of transfusion of blood products and coagulation factor concentrates, a clinical algorithm for the perioperative hemostatic therapy in patients undergoing cardiac surgery with CPB has been developed. The currently available evidence and the point of care methods routinely accessible in our institution (blood gas analysis, ACT, point of care Quick value, aPTT and platelet count) were used. The intervention with plasma products, coagulation factor concentrates and hemostatic drugs after extracorporeal circulation are described. Extensive bleeding history as well as the efficacy and side effects of antifibrinolytic treatment are discussed.

Topics: Algorithms; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Gas Analysis; Blood Transfusion; Deamino Arginine Vasopressin; Extracorporeal Circulation; Fibrinogen; Heparin; Heparin Antagonists; Humans; Partial Thromboplastin Time; Plasma; Platelet Count; Point-of-Care Systems; Postoperative Complications

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

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

Several major orthopedic surgical procedures including hip arthroplasty, femoral osteotomy, and spinal fusion may result in significant blood loss and the need for allogeneic blood transfusions. Due to the heightened awareness of the potential deleterious effects of allogeneic blood product administration, several techniques have been evaluated to determine their efficacy in limiting perioperative blood loss. The following article will discuss the options to limit the need for allogeneic blood product administration during orthopedic surgical procedures. These techniques include: general considerations, autologous transfusion therapy, intraoperative and postoperative blood salvage, pharmacologic manipulation of the coagulation cascade, and controlled hypotension. Undoubtedly, many of these techniques are effective alone; however, the goal of performing major orthopedic surgical procedures without the use of allogeneic blood products can only be accomplished by combining several of these techniques.

Topics: Aminocaproic Acid; Antifibrinolytic Agents; Aprotinin; Blood Coagulation Disorders; Blood Loss, Surgical; Blood Transfusion, Autologous; Deamino Arginine Vasopressin; Factor VII; Factor VIIa; Hemodilution; Hemostatic Techniques; Hemostatics; Humans; Hypotension, Controlled; Orthopedic Procedures; Postoperative Care; Preoperative Care; Recombinant Proteins; Tranexamic Acid

Excess perioperative bleeding remains a major complication following surgery, resulting in increased morbidity and mortality. The principal causes of non-surgical haemostatic perioperative bleeding are a pre-existing undetected bleeding disorder, related to the nature of the operation itself or from coagulation abnormalities arising from massive blood loss. Very often, it is a combination and coexistence of various pathologies. Identifying patients at risk remains a major component of preventing excessive blood loss. Understanding the haemostatic changes occurring in the perioperative period, especially in complex procedures like cardiopulmonary bypass and orthotopic liver transplantation is crucial in developing new strategies for the management of perioperative bleeding. Pharmacological interventions, especially aprotinin, tranexamic acid, desmopressin and increasingly, recombinant VIIa are being used both in prophylaxis and therapeutically to stop bleeding. The use of near patient testing like thromboelastography and platelet function analyser has allowed for more detailed assessment of the various steps of haemostasis. One of the main goals is to reduce the usage of allogeneic blood transfusion and its attendant risks.

Topics: Aprotinin; Blood Coagulation Disorders; Blood Loss, Surgical; Deamino Arginine Vasopressin; Factor VII; Fibrinolysis; Humans; Risk Factors; Tranexamic Acid

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: Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Loss, Surgical; Deamino Arginine Vasopressin; Hemostatics; Humans; Risk Factors

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

As in adults, desmopressin (DDAVP) can be used in children for prophylaxis of bleeding and to stop bleeding in many hereditary and acquired bleeding disorders. DDAVP is the treatment of choice in children with mild hemophilia and type 1 von Willebrand's disease (vWD). It is effective in some variants of vWD and in many patients with platelet function defects. It reduces the bleeding diathesis of children with uremia and drug-induced bleeding complications. In any case, a test dose of DDAVP has to be given to the patient to predict the hemostatic effect before relying on this drug for treatment. The response can be measured by shortening of the bleeding time (BT) and of partial thromboplastin time (PTT), indicating a rise of Factor (F) VIII or von Willebrand factor (vWF). Side effects such as facial flushing, transient headache, increased pulse rate, and drop in systolic blood pressure are mild and transient. They can be minimized when the dose is not exceeding 0.3 microg/kg body weight, and the infusion lasts at least 20 to 30 minutes. The strong antidiuretic action of DDAVP has some potential problems that are negligible in adults and older children when water intake is restricted. In infants and small children under the age of 18 months, however, DDAVP should be used with caution and with close surveillance in order to prevent water intoxication and electrolyte imbalance. The danger is increased when the patients receive parenteral fluid substitution. The advantages of DDAVP include the reduction in the use of plasma factor concentrates, thereby minimizing the danger of immunological or infectious complications, as well as the considerable reduction of costs realized by treatment with this form of medication. Fortunately, it can be applied successfully in the most frequent hereditary bleeding disorder, namely vWD type 1.

Topics: Blood Coagulation Disorders; Child; Deamino Arginine Vasopressin; Hemostatics; History, 18th Century; History, 20th Century; Humans; Renal Agents

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: Animals; Blood Coagulation Disorders; Cat Diseases; Cats; Deamino Arginine Vasopressin; Diabetes Insipidus; Dog Diseases; Dogs; Humans; Polyuria; von Willebrand Diseases

Topics: Aged; Blood Coagulation Disorders; Blood Coagulation Factors; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Hemorrhagic Disorders; Hemostasis; Humans; Male; Platelet Adhesiveness; Postoperative Complications; Signal Transduction; Thrombosis

Topics: Administration, Intranasal; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Hemophilia A; Humans; Injections, Intravenous; Injections, Subcutaneous; von Willebrand Diseases

Topics: Animals; Arginine Vasopressin; Blood Coagulation Disorders; Blood Coagulation Factors; Cyclic AMP; Deamino Arginine Vasopressin; Dinoprostone; Diuresis; Dogs; Humans; Kidney; Liver; Muscle, Smooth, Vascular; Organ Specificity; Rats; Receptors, Angiotensin; Receptors, Vasopressin; Second Messenger Systems; Vasodilation; Vasopressins

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Loss, Surgical; Blood Platelets; Deamino Arginine Vasopressin; Fibrinolysis; Hemophilia A; Hemostasis; Humans; von Willebrand Diseases

Desmopressin (1-deamino-8-D-arginine vasopressin, abbreviated DDAVP) is a synthetic analogue of the antidiuretic hormone L-arginine vasopressin. Because it can raise circulating levels of factor VIII coagulant activity (FVIII) and von Willebrand factor and shorten the prolonged bleeding time, DDAVP is established as a nontransfusional form of treatment for mild and moderate hemophilia and von Willebrand disease. Recently, DDAVP has also been purported to be useful for shortening the prolonged skin bleeding times that occur with uremia, cirrhosis, and platelet dysfunctions of various etiologies. Finally, there is evidence from controlled clinical trials that DDAVP can reduce blood loss and transfusion requirements for hemostatically normal individuals undergoing spinal fusion surgery and for patients undergoing cardiopulmonary bypass surgery. The purpose of this report is to review the therapeutic applications of DDAVP in congenital and acquired bleeding disorders and to discuss areas in which further basic and clinical research is needed.

Topics: Blood Coagulation Disorders; Deamino Arginine Vasopressin; Hemophilia A; Humans; Tachyphylaxis; Uremia; von Willebrand Diseases

At a time when the acquired immunodeficiency syndrome as well as hepatitis and other blood-borne diseases are a threat to patients with bleeding disorders who need treatment with blood products, it is rewarding to realize that a number of these patients can be safely and effectively treated with their own desmopressin-stimulated F.VIII:C and vWF. Desmopressin is clinically useful for treatment of patients with moderate and mild hemophilia. The limits of the clinical indications are established by the nature of the bleeding episode, the resting factor level, the level that must be achieved, and the length of time the level must be maintained to manage any given bleeding episode. In von Willebrand disease, desmopressin can be used more extensively to raise F.VIII:C levels than in classic hemophilia, because fewer of the patients have the severe form of the disease that is unresponsive to desmopressin. Increases in the level of F.VIII:C of about four times the resting value can be expected both in hemophilia and von Willebrand disease, but it must be borne in mind that the range of individual responses is large. Even though it is not easy to correct the prolonged bleeding time, particularly in patients with dysfunctional vWF, this drawback is of clinical relevance only in a minority of cases. A role for the use of desmopressin in acquired diseases of primary hemostasis has been proposed more recently, and experience is more limited than in congenital bleeding disorders. Uremia is probably the most firmly established indication because it has been shown that the bleeding time is often dramatically shortened by desmopressin, and hemorrhages can be stopped or prevented before surgical procedures. The indications for use of the compound in liver cirrhosis and congenital and acquired platelet dysfunctions are promising but much less established from a clinical standpoint. The bulk of available clinical experience is based on intravenous administration. Intranasal and subcutaneous administration have been successfully attempted and might be more convenient in selected circumstances, such as home treatment and the stimulation of blood donors to provide more abundant supplies of F.VIII:C and vWF. However, the responses after intranasal administration are less predictable and consistent than after intravenous administration. Desmopressin has few troublesome side-effects. Mild facial flushing, a small increase in heart rate, and, more rarely, mild headache can occur t

Topics: Administration, Cutaneous; Administration, Intranasal; Amino Acid Sequence; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Endothelium; Factor VIII; Fibrinolysis; Hemophilia A; Hemostasis; Humans; Injections, Intravenous; Tachyphylaxis; Uremia; von Willebrand Diseases; von Willebrand Factor

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Deamino Arginine Vasopressin; Dentistry, Operative; Drug Combinations; Factor IX; Factor VIII; Factor XIII; Fibrin Tissue Adhesive; Fibrinogen; Hemostatic Techniques; Hemostatics; Humans; Laser Therapy; Oral Hemorrhage; Thrombin

Desmopressin is frequently used in patients with bleeding disorders because of its prohaemostatic effects. In recent years desmopressin use increased due to reported high incidence of inhibitors in mild haemophilia after clotting factor infusion and the rising costs of clotting factor concentrates. The safety and frequency of side effects have hardly been assessed in well-designed studies.. We therefore prospectively evaluated side effects of desmopressin in a large unselected cohort of bleeding disorder patients, who received a desmopressin test dose.. Blood was drawn prior to, one, three, six and 24 h after desmopressin. Primary outcome was change in serum sodium, haematocrit, serum- and urine osmolality, body weight and vital signs. Self-reported side effects were evaluated as secondary outcome.. In total, 108 patients were included, median age 30 years, the majority of whom had von Willebrand disease type 1 (76%). A significant change in water balance parameters was observed. Four patients (4%) had hyponatraemia (≤135 mmol L(-1) ) after 24 h but no severe hyponatraemia occurred (≤125 mmol L(-1) ). After infusion, 41 (38%) patients were hypotensive (≤90 mmHg SBP and/or ≤60 mmHg DBP) and 10 (9%) presented with tachycardia (>100 min(-1) ). However, none of these effects sustained at 24 h. Infusion was discontinued in one patient because of tachycardia, nausea and malaise. Self-reported side effects included: headache, fatigue, flush and dizziness.. Observed side effects correspond with the known antidiuretic and vasomotor effects of desmopressin. Changes in parameters were temporary and not clinically relevant. In conclusion, our study supports desmopressin use as a safe treatment option in patients with various bleeding disorders.

Topics: Adolescent; Adult; Aged; Blood Coagulation Disorders; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Humans; Male; Middle Aged; Self Report; Young Adult

Cirrhotic patients waiting for liver transplantation who need dental extractions are given fresh frozen plasma and/or platelets to correct coagulopathy. This is costly and may be associated with transfusion reactions and fluid overload. We evaluated the efficacy of intranasal desmopressin as an alternative to transfusion to correct the coagulopathy of cirrhotic patients undergoing dental extraction.. Cirrhotic patients with platelet counts of 30,000 to 50,000/microL and/or international normalized ratio (INR) 2.0 to 3.0 were enrolled in a prospective, controlled, randomized clinical trial. Blood transfusion (fresh frozen plasma 10 mL/kg and/or 1 unit of single donor platelets, respectively) or intranasal desmopressin (300 microg) were given before dental extraction. A standard oral and maxillofacial surgical treatment protocol was performed by the same surgeon. Patients were followed for postextraction bleeding and side-effects over the next 24 to 48 hours.. No significant differences were noted between the 2 groups in gender, age, INR, platelet count, creatinine, total bilirubin, ALT, albumin, MELD score, or number of teeth removed (median 3 vs 4). The number of teeth removed ranged between 1 and 31 in the desmopressin group and 1 and 22 in the transfusion group. No patients in desmopressin group required rescue blood transfusion after extraction. One patient in the transfusion group had bleeding after the procedure and required an additional transfusion. Another patient experienced an allergic reaction at the end of transfusion, which was effectively treated with diphenhydramine. Treatment associated average costs were lower for desmopressin ($700/patient) compared with transfusion ($1,173/patient).. Intranasal desmopressin was as effective as blood transfusion in achieving hemostasis in cirrhotic patients with moderate coagulopathy undergoing dental extraction. Intranasal desmopressin was much more convenient, less expensive, and well tolerated.

Topics: Administration, Intranasal; Adult; Blood Coagulation Disorders; Blood Loss, Surgical; Blood Transfusion; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; International Normalized Ratio; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Plasma; Platelet Count; Platelet Transfusion; Premedication; Tooth Extraction

Platelet dysfunction is a major cause of excessive microvascular bleeding after cardiac surgery. A new point-of-care test (hemoSTATUS) can identify patients at risk of excessive bleeding. We aimed to find out whether patients who can benefit from desmopressin during cardiac surgery can be identified by this test.. We enrolled 203 patients scheduled for elective cardiac surgery in a prospective, double-blind, placebo-controlled trial. Patients with abnormal hemoSTATUS clot-ratio results (<60% of maximum in channel 5) after discontinuation of cardiopulmonary bypass were randomly assigned desmopressin (n=50) or placebo (n=51). Patients with normal clot ratios were included in an untreated control group (n=72).. Intraoperative platelet counts and clot ratios were significantly higher in the untreated control group than in the study-drug groups. In intensive care, clot ratios in patients who received desmopressin were similar to those in the untreated control group, despite significantly lower platelet counts, but were lower in the placebo group than in the other two groups (p=0.0001). Compared with the placebo group, patients who received desmopressin had less blood loss in 24 h (mean 624 [SD 209] vs 1028 mL [682] p=0.0004) and required less transfusion of red blood cells (1.1 [022] vs 2.2 U [0.32] p=0.009), platelets (0.1 [0.04] vs 1.9 U [4.5] p=0.0001), and fresh-frozen plasma (0.1 [0.07] vs 0.75 U [0.21] p=0.0008), and had less total blood-donor exposures (1.56 [0.31] vs 5.2 [0.8] p=0.0001). Placebo patients also had substantially higher blood loss and transfusion requirements than untreated control patients.. Patients identified with hemoSTATUS as being at increased risk of excessive bleeding after cardiac surgery can benefit from administration of desmopressin. Further studies are, however, needed to confirm these findings as well as to identify the mechanism of action and safety of desmopressin in the clinical setting.

Topics: Aged; Blood Coagulation Disorders; Blood Component Transfusion; Coronary Artery Bypass; Deamino Arginine Vasopressin; Double-Blind Method; Female; Hemostatics; Humans; Male; Middle Aged; Platelet Count; Point-of-Care Systems; Postoperative Complications; Postoperative Hemorrhage; Prospective Studies; Whole Blood Coagulation Time

To examine the impact of the underlying defective platelet mechanism on the response to 1-desamino-8-D-arginine vasopressin (DDAVP, Desmopressin), we studied the effect of intravenous infusion of 0.3 microgram/kg of DDAVP in a randomized double blind placebo-controlled trial with cross-over in 18 carefully characterized patients with congenital platelet defects (CPD) and BT > or = 9 min. Eleven patients had normal dense granule stores and normal thromboxane A2 (TxA2) production (Group I), 3 patients had normal granule stores but impaired TxA2 production (Group II), and 4 had delta-storage pool deficiency (Group III). DDAVP shortened BT at 50 min (DDAVP 14.6 +/- 2.2 vs placebo 19.6 +/- 2.3 min; n = 18; mean +/- SE; p = 0.003) and 4 h (17.0 +/- 2.2 vs 19.6 +/- 2.1 min, p = 0.055), and raised plasma FVIIIC and von Willebrand factor (vWF). At 50 min DDAVP shortened BT by > or = 5 min in 8 of 11 Group I patients (mean 9.7 +/- 1.3 vs 16.3 +/- 2.8 min; p < 0.008), 1 of 3 Group II patients (11.9 +/- 3.9 vs 17.7 +/- 6.6; p = NS) and none of Group III patients (mean 30 min both arms). Ten patients (Group I or II) were managed successfully during surgical procedures with DDAVP alone. We conclude that DDAVP shortens BT in majority of CPD patients with normal dense granule stores and suggest that BT response may be dependent on the underlying platelet defect. DDAVP is a useful modality in management of selected patients, particularly those with normal dense granule stores.

Topics: Bleeding Time; Blood Coagulation Disorders; Blood Platelets; Deamino Arginine Vasopressin; Double-Blind Method; Factor VIII; Hemostatics; Humans; Platelet Aggregation; Tissue Plasminogen Activator; von Willebrand Factor

Topics: Bleeding Time; Blood Coagulation Disorders; Blood Platelets; Deamino Arginine Vasopressin; Hemorrhagic Disorders; Humans

Recent data demonstrated that amongst patients undergoing elective surgery the prevalence of cirrhosis is 0.8% equating to approximately 25 million cirrhotic patients undergoing surgery each year worldwide. Overall, the presence of cirrhosis is independently associated with 47% increased risk of postoperative complications and over two and a half-increased risk of in-hospital mortality in patients undergoing elective surgery. In particular, perioperative patients with chronic liver disease have long been assumed to have a major bleeding risk on the basis of abnormal results for standard tests of hemostasis. However, recent evidence outlined significant changes to traditional knowledge and beliefs and, nowadays, with more sophisticated laboratory tests, it has been shown that patients with chronic liver disease may be in hemostatic balance as a result of concomitant changes in both pro- and antihemostatic pathways. The aim of this paper endorsed by the Liver Intensive Care Group of Europe was to provide an up-to-date overview of coagulation management in perioperative patients with chronic liver disease focusing on patient blood management, monitoring of hemostasis, and current role of hemostatic agents.

Topics: Anemia; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Loss, Surgical; Deamino Arginine Vasopressin; Elective Surgical Procedures; Europe; Factor VIIa; Fibrinogen; Fibrinolysis; Fibrinolytic Agents; Hemostasis; Hemostatic Techniques; Hemostatics; Humans; Liver Cirrhosis; Perioperative Care; Plasma; Platelet Function Tests; Platelet Transfusion; Postoperative Hemorrhage; Recombinant Proteins

Due to lack of patient/health care provider awareness causing delayed diagnosis, the bleeding phenotype and provider interventions in adolescents with heavy menstrual bleeding (HMB) and bleeding disorders (BD) may be different when compared to adults.. The aim of this study was to compare/characterize bleeding phenotype and provider interventions in postmenarchal adolescents < 18 years and premenopausal adults ≥ 18 years with HMB and BD.. Patient demographics, BD, and provider interventions/therapy details for HMB were compared between both age groups enrolled in the Centers for Disease Control and Prevention (CDC) Female Universal Data Collection (UDC) surveillance project in United States hemophilia treatment centres. Cross-sectional descriptive analyses including frequency distributions, summary statistics, bivariate and logistic regression analyses were performed.. Of 269 females (79 adolescents; median age 16 years, interquartile range (IQR) = 2; 190 adults; median age 27 years, IQR = 13) evaluated, BD distribution was similar in both groups. Compared to adolescents, adults more often had family history of bleeding (Adjusted odds ratios [AOR] = 2.6, 1.3-5.6), delay in diagnosis (AOR = 2.5, 1.2-4.9), bleeding with dental procedures (AOR = 2.0, 1.0-4.0), gastrointestinal bleeding (AOR = 4.6, 1.0-21.9), anaemia (AOR = 2.7, 1.4-5.2), utilized desmopressin less often (AOR = 0.4, 0.2-0.8) and underwent gynaecologic procedure/surgery more frequently (AOR = 5.9, 1.3-27.3).. Bleeding phenotypes of adolescents and adults with HMB and BD were different with more frequent bleeding complications, anaemia, gynaecologic procedures/surgeries, less desmopressin use and more delay in diagnosing BD in adults. Longitudinal studies are needed to determine whether improved patient/provider awareness and education will translate to early diagnosis and timely management of BD/HMB in adolescents that may prevent/reduce future haematologic/gynaecologic complications.

Topics: Adolescent; Adult; Anemia; Antifibrinolytic Agents; Blood Coagulation Disorders; Cross-Sectional Studies; Deamino Arginine Vasopressin; Delayed Diagnosis; Female; Gastrointestinal Hemorrhage; Hemostatics; Humans; Logistic Models; Menopause; Menorrhagia; Odds Ratio; Phenotype; Young Adult

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

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

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

Topics: Adolescent; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Delayed Graft Function; Female; Hemostatics; Humans; Kidney Failure, Chronic; Kidney Transplantation; Renal Dialysis; Time Factors; Treatment Outcome

We report an unusual case of severe abdominal arterial thrombosis in a young woman using oral desmopressin. Only a few cases with cerebrovascular accidents and coronary syndromes have been described so far, which could be attributed to intravenous administration of desmopressin. Because extensive diagnostic and laboratory investigations for (un)common coagulation disorders could not identify an alternative explanation associated with arterial thrombosis, we hypothesise that desmopressin in an oral dose of at least 200 ug once daily must have been sufficient to cause this dramatic vascular complication. Supportive of our hypothesis, we found remarkably high levels of factor VIII activity, Von Willebrand factor (vWF) antigen and vWF ristocetin cofactor activity (268%, 740%, 590% respectively). To the best of the authors' knowledge, this is the first report suggesting a relationship between oral desmopressin use and life-threatening abdominal arterial thrombosis.

Topics: Abdominal Pain; Adult; Blood Coagulation Disorders; Cerebrovascular Disorders; Deamino Arginine Vasopressin; Echocardiography; Factor VIII; Female; Hemostatics; Humans; Ristocetin; Thrombosis; Tomography, X-Ray Computed; von Willebrand Factor

Parenchymal hemorrhage is one of the most feared risks of stereotactic brain biopsies potentially resulting in neurological deficits or even a fatal outcome. Patients with disorders of the coagulation system are at particular risk, so identifying these is one of the main tasks prior to surgery. Some patients may have a bleeding tendency despite normal laboratory values of the hemostatic system.. We report the case of a patient with coagulopathy of unclear etiology undergoing a stereotactic brainstem biopsy.. A medication scheme with tranexamic acid and desmopressin effectively decreased the patient's bleeding time in vivo and the procedure was carried out without complications.

Topics: Adult; Antifibrinolytic Agents; Astrocytoma; Biopsy; Bleeding Time; Blood Coagulation Disorders; Brain Neoplasms; Brain Stem; Deamino Arginine Vasopressin; Female; Humans; Neurosurgical Procedures; Stereotaxic Techniques; Tranexamic Acid; Treatment Outcome

Topics: Anti-Inflammatory Agents, Non-Steroidal; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Menstrual Cycle; Menstruation Disturbances

Reproductive tract bleeding in women is a naturally occurring event during menstruation and childbirth. In women with menorrhagia, however, congenital bleeding disorders historically have been underdiagnosed. This consensus is intended to allow physicians to better recognize bleeding disorders as a cause of menorrhagia and consequently offer effective disease-specific therapies.

Topics: Adult; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Decision Trees; Factor VIII; Female; Hemostatics; Humans; Menorrhagia; Postpartum Hemorrhage; Pregnancy; Pregnancy Complications, Hematologic; Quality of Life; von Willebrand Diseases; von Willebrand Factor

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

Topics: Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Hemostatics; Humans; Hyponatremia; Middle Aged; Seizures

Topics: Adolescent; Adult; Blood Coagulation Disorders; Cohort Studies; Deamino Arginine Vasopressin; Drug Evaluation; Factor VIII; Female; Hemostatics; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy Trimester, Third; Retrospective Studies; von Willebrand Factor

Demographic changes and aggressive platelet inhibition have resulted in a marked increase in blood- and coagulation product expenditure and costs in cardiac surgery. We analyzed "bedside" coagulation test (ROTEM) in order to verify clot forming quality for the purpose of finding a cost-effective treatment path.. Annual treatment costs of all cardiosurgical patients were analyzed before (729 patients) and after (693 patients) implementation of "bedside" ROTEM. Cumulative numbers and costs of platelet concentrates (PltC), fresh frozen plasma (FFP), red blood cell units (RBC), and coagulation factors: pooled coagulation concentrates (PCC), recombinant factor VIIa (rFVIIa), factor XIII (FXIII), and fibrinogen were assessed. Average monthly numbers and costs were compared. Number of resternotomies and early mortality was assessed and compared in both periods.. After ROTEM implementation cumulative RBC expenditure showed 25% decrease while PltC exhibited 50% decrease. FFP expenditure remained unchanged. PCC, FXIII were markedly reduced (-80%) while rFVIIa were entirely omitted. Fibrinogen, however, increased two-fold. Cumulative average monthly costs of all blood products decreased from 66,000 euro to 45,000 euro (-32%). Coagulation factor average monthly costs decreased from 60,000 euro to 30,000 euro (-50%) yielding combined savings of 44%. In contrast, average monthly costs for ROTEM were 1.580 euro. Total number of resternotomies decreased from 6.6% to 5.5% while early mortality (5.9%; 6.0%) remained stable.. Cumulative costs for treatment of perioperative coagulation disorders can be reduced by "bedside" ROTEM analysis to achieve a selective substitution management. Saved costs for blood- and coagulation products clearly outweighed the expenses of ROTEM. Adequate differential coagulation management can therefore be cost-effective.

Topics: Aged; Antithrombin III; Aprotinin; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Cardiac Surgical Procedures; Cost-Benefit Analysis; Deamino Arginine Vasopressin; Erythrocytes; Female; Health Care Costs; Humans; Male; Plasma; Thrombelastography

We performed a retrospective study of tooth removal for patients with coagulation disorders.. The study included 67 patients divided into 3 groups according to their coagulation disorder. The first group included 31 patients with a congenital disorder, the second 19 patients receiving anticoagulant therapy, and the third 16 patients with an acquired disorder. The same surgical procedure was used for all patients: alveoli regulation, socket preparation with resorbable oxycellulose dressing, and sutures with separate stitches. Biological glue and celluloid splints were not used. Depending on the severity of the coagulation disorder, factor VIII or concentrated von Willebrand factor or Desmopressine was administered for patients in the first group. If possible, low-molecular-weight heparin replaced oral anticoagulation for patients in the second group. Platelet concentrates were administered for 2 of the patients in the third group.. Postoperative bleeding was noted in 4 patients in the first group, 2 in the second and 2 in the third.. We have abandoned the use of biological glue and celluloid splints. The rate of bleeding in the first and second group was similar to that reported in the literature. We were unable to find any comparable report for the third group.

Topics: Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Dental Care for Chronically Ill; Factor VIII; Hemostatics; Humans; Platelet Transfusion; Postoperative Hemorrhage; Retrospective Studies; Tooth Extraction; Tranexamic Acid; von Willebrand Factor

A patient with the genetic condition neurofibromatosis type I and no known coagulopathy undergoing cesarean delivery, had diffuse uterine and surgical site bleeding that was not correctable by oxytocin, methylergonovine and PGF2 alpha. Despite good uterine tone, hemorrhage continued from the uterus and the surrounding tissues, persisting even after surgical ligation of the uterine arteries. With no change in her condition, which was behaving clinically as a coagulopathy, an infusion of desmopressin acetate (DDAVP) was begun. The patient's bleeding promptly resolved shortly after infusion of this agent. A review of relevant literature suggests that platelet reactivity of patients with neurofibromatosis type 1 is attenuated in some in vitro conditions. Thus, there may be some theoretical basis for using DDAVP in patients with neurofibromatosis type 1 who have bleeding problems with no other known source, such as in the case presented here.

Topics: Adult; Anticoagulants; Blood Coagulation Disorders; Cesarean Section; Deamino Arginine Vasopressin; Female; Hematocrit; Humans; Infant, Newborn; Infusions, Intravenous; Intraoperative Complications; Neurofibromatosis 1; Obstetric Labor Complications; Pregnancy; Uterine Hemorrhage

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

We assessed a modified multichannel thromboelastogram for differentiation of the causes of coagulopathy after cardiopulmonary bypass and its suitability as a therapy guide. Thirty adult patients undergoing surgery with cardiopulmonary bypass, who revealed a coagulopathy as observed by a prolonged activated clotting time of >150 sec after the application of protamine, were enrolled. Therapy was based on the results obtained by the computerized four-channel thromboelastogram with baseline, heparinase (2 IU/mL), heparinase/abciximab (5 microg/mL), and heparinase/fresh frozen plasma (25%) channels. The mean activated clotting time before therapy was 162.2+/-7.8 sec. Based on differential diagnosis with the modified multichannel thromboelastogram, two patients received protamine (30 mg), five desmopressin (0.4 microg/kg), 19 patients three units of fresh frozen plasma, two patients platelet transfusions, and two patients both protamine (30 mg) and three units of fresh frozen plasma. After therapy, there was a significant (p < .01) decrease of the activated clotting time to a mean value of 127+/-8.3 sec. Therapy based on the synoptic modified multichannel thromboelastogram analysis provides a guide for effective therapy of coagulopathy. However, elaboration is desirable, and larger clinical trials are necessary for a final evaluation of the protocol.

Topics: Adult; Blood Coagulation Disorders; Blood Transfusion; Cardiopulmonary Bypass; Deamino Arginine Vasopressin; Diagnosis, Differential; Germany; Hemostatics; Heparin Antagonists; Heparin Lyase; Humans; Pilot Projects; Protamines; Thrombelastography

Cardiac surgery in Jehovah's Witness patients remains a challenge in the presence of concomitant congenital or acquired coagulation disorders and anaemia. We report a case of a 66-year-old female Jehovah's Witness suffering from severe calcified aortic valve stenosis requiring aortic valve replacement. The anaemic patient suffered from concomitant platelet dysfunction and deficiency of factors V and VII due to gammopathy of immunoglobulin G. The patient was preoperatively treated with recombinant erythropoietin in combination with folic acid and iron, which resulted in an increase of the haematocrit from 0.335 to 0.416 after 22 days of treatment. Haemostasis was improved by high dose aprotinin and additional desmopressin, which could be demonstrated to be effective by a preoperative test. The patients intra- and postoperative course was uneventful, her total chest tube loss was 130 ml, and she was able to be discharged without the need of any blood transfusions. The beneficial properties of erythropoietin and desmopressin in Jehovah's Witness patients are discussed.

Topics: Aged; Anemia; Aortic Valve Stenosis; Blood Coagulation Disorders; Blood Loss, Surgical; Blood Transfusion; Deamino Arginine Vasopressin; Erythropoietin; Female; Heart Valve Prosthesis Implantation; Hemostatics; Humans; Jehovah's Witnesses; Preoperative Care; Recombinant Proteins; Religion and Medicine

Desmopressin (DDAVP), a synthetic analogue of vasopressin has been successfully used in the treatment of type I von Willebrand's disease (VWD), mild factor VIII (FVIII) deficiency and intrinsic platelet function defects (PFDs) for almost three decades. However, there is limited published data documenting its efficacy and the reliability of circulating plasma FVIII:C as a surrogate marker of response to therapy in VWD. We report the haemostatic response to DDAVP in 133 consecutive patients (91 type I VWD, 20 mild FVIII deficiency and 22 PFDs). Minimal therapeutic response to DDAVP (0.3 microg/kg) was defined by normalization 30 min post- infusion of bleeding time for PFDs, factor VIII:C (FVIII:C) for mild haemophilia A, and von Willebrand factor antigen (VWF:Ag), von Willebrand factor functional activity (VWF:Ac) and FVIII:C for VWD. Nine out of 91 (10%) VWD patients failed to achieve minimal therapeutic response to DDAVP; plasma FVIII:C levels were an unreliable surrogate marker of DDAVP response as 6 out of 9 (67%) of these patients had normal post-infusion FVIII:C levels. Five out of the 20 (25%) patients with mild FVIII deficiency and 5 out of 22 (23%) patients with PFDs failed to achieve a minimal therapeutic response to DDAVP. DDAVP is an effective therapy in the majority of patients with type I VWD, PFDs and mild FVIII deficiency. The significant failure rate associated with this therapy supports the recent recommendations that response should be assessed in all patients at the time of diagnosis. FVIII:C is an unreliable guide of response to DDAVP in patients with VWD and therefore VWF:Ag and VWF:Ac should also be assessed. Failure to demonstrate the response of VWF:Ag, VWF:Ac and FVIII:C to DDAVP in patients with VWD is likely to increase the risk of haemorrhagic complications in patients with bleeding episodes or who are undergoing surgery.

Topics: ABO Blood-Group System; Adolescent; Adult; Blood Coagulation Disorders; Child; Child, Preschool; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Female; Hemophilia A; Hemostatics; Humans; Male; von Willebrand Diseases

Topics: Blood Coagulation Disorders; Blood Component Transfusion; Cardiopulmonary Bypass; Cryoprotective Agents; Deamino Arginine Vasopressin; Hemostatics; Humans; Plasma; Point-of-Care Systems; Postoperative Complications

Topics: Blood Coagulation Disorders; Cost-Benefit Analysis; Counseling; Deamino Arginine Vasopressin; Factor XI Deficiency; Female; Hemostatics; Humans; London; Menstruation; Obstetrics; Postpartum Period; Prenatal Diagnosis

We report on a case of Ehlers-Danlos syndrome, probable type VIII (EDS VIII) in a 6-year-old girl with severe periodontitis, extensive bruising of the shins, abnormal bleeding time, and thin body habitus. The structure and biosynthesis of types I and III colagen were normal. Desmopressin (DDAVP) was found to correct the bleeding time, and the patient underwent an uneventful dental procedure after DDAVP therapy. The finding of childhood or juvenile periodontitis should prompt consideration of a diagnosis of EDS, particularly type VIII, and alert the clinician to the possibility of a treatable bleeding abnormality.

Topics: Blood Coagulation Disorders; Child; Deamino Arginine Vasopressin; Ehlers-Danlos Syndrome; Female; Humans; Periodontitis; Time Factors

Topics: Administration, Intranasal; Blood Coagulation Disorders; Cost of Illness; Cost Savings; Deamino Arginine Vasopressin; Epistaxis; Humans; Quality of Life; Self Administration; Surveys and Questionnaires; Sweden

We describe the management of tonsil or tonsil and adenoid surgery in our hospital in 10 patients with inherited bleeding disorders, over a 10-year-period. The approach to the management of the haemostatic defect is outlined in detail. All underwent successful surgery, two patients had limited secondary haemorrhage. This report demonstrates that patients with inherited bleeding disorders can safely undergo adenotonsillectomy, providing there is close liaison between surgeons and haematologists throughout the peri-operative period.

Topics: Adenoidectomy; Blood Coagulation Disorders; Child; Child, Preschool; Deamino Arginine Vasopressin; Factor VII Deficiency; Female; Hemophilia A; Hemostasis, Surgical; Humans; Male; Tonsillectomy; Tranexamic Acid; von Willebrand Diseases

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

DDAVP infusion shortens the bleeding time in patients with some types of platelet dysfunction and may be useful for hemostatic control. In order to clarify the mechanism of DDAVP to correct or bypass the release defect, we examined the effect in 17 patients with prolonged bleeding time, i.e., 11 with various kinds of platelet dysfunction, 4 with idiopathic thrombocytopenic purpura (ITP), 1 with chronic myelocytic leukemia (CML), and in an aspirin-ingested volunteer. DDAVP shortened the bleeding time in 9 patients with platelet dysfunctions, one with ITP, and the one aspirin ingested volunteer. No improvement was found in the aggregability and the retention rates, and no signs of activation occurred in the platelet shape. The RCof was elevated in all of the patients after the infusion. Our data suggests that DDAVP improves the hemostasis through primary aggregation and release of dense bodies, and not directly through an increase of RCof.

Topics: Bleeding Time; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Hemostasis; Humans; Platelet Activation

Desmopressin acetate (DDAVP) is known to stimulate the release of tissue-type plasminogen activator (t-PA) from endothelial cells, but it is unclear whether the increased t-PA actually elicits the plasmin generation and fibrin(ogen)olysis in the circulating blood. We measured plasma levels of plasmin-alpha 2-plasmin inhibitor complex, fibrinogen degradation products (FgDP) and fibrin degradation products (FbDP) following desmopressin infusion in 19 patients with bleeding disorders or thrombophilia. Administration of desmopressin (0.3-0.4 microgram/kg) produced a 4.0-fold increase in plasmin-alpha 2-plasmin inhibitor complex at 30 min, whereas neither FgDP nor FbDP was elevated significantly. These findings indicate that desmopressin infusion provokes the generation of plasmin in vivo, but most of the plasmin generated is complexed to alpha 2-plasmin inhibitor and does not degradate fibrin or fibrinogen.

Topics: alpha-2-Antiplasmin; Antifibrinolytic Agents; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Infusions, Intravenous; Tissue Plasminogen Activator

1-Deamino-8-D-arginine vasopressin (DDAVP) was administered to 3 patients with spontaneous factor VIII inhibitors. In 2 patients with baseline factor VIII levels above 1%, a marked increase of factor VIII activity after DDAVP infusion could be observed. No rise of factor VIII activity after DDAVP was seen in the 3rd patient with a baseline factor VIII level of less than 1%. Daily infusion of DDAVP resulted in a reduction of the efficacy, but the full effect could be retained when DDAVP was given at 48-hour intervals. The effect of DDAVP infusion on factor VIII levels in the 2 responding patients was superior to the treatment with 30 U/kg factor VIII concentrate and approximately equivalent to infusion of 45 U/kg factor VIII concentrate. DDAVP may be a useful and less expensive treatment for patients with acquired factor VIII inhibitors and a baseline factor VIII level of more than 1%.

Topics: Aged; Blood Coagulation Disorders; Child; Deamino Arginine Vasopressin; Factor VIII; Humans; Male

A more concentrated desmopressin (DDAVP) preparation (40 micrograms/ml), which required small injection volumes (less than 1 ml), was studied in a double-blind trial in 10 healthy volunteers, 12 patients with haemophilia A, and 8 patients with uraemic bleeding. DDAVP was administered by subcutaneous injection at a dose of 0.4 micrograms/kg body weight. In healthy subjects, peak levels of DDAVP ranging from 480 to 638 pg/ml were reached 1 h after the subcutaneous injection and DDAVP was eliminated with a mean half-life of 3.1 h. DDAVP produced a 2.5-fold (3.0-fold) increase of factor VIII:C (factor VIII:Ag) and a 1.9-fold (2.2-fold) increase of von Willebrand factor:Ag (ristocetin cofactor) over baseline levels. Additionally, a 2.1-fold increase of tissue-type plasminogen activator antigen was observed. Factor VIII and von Willebrand factor were rapidly eliminated with a half-life ranging from 1.3 to 5.7 h and from 1.1 to 11.4 h, respectively. In haemophilia A patients, DDAVP produced a 2.3-fold increase of factor VIII:C 1 h after the injection. DDAVP was given on 8 occasions for management of bleeding, and only in 1 patient did a wound haematoma (after herniotomia) occur. In 7 of the 8 patients with uraemia the bleeding time shortened, and in all patients an increase of platelet retention and a decrease of platelet count was observed (p less than 0.05). No serious local or systemic untoward side effects were observed.

Topics: Adult; Antigens; Bleeding Time; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Drug Evaluation; Factor VIII; Female; Hemophilia A; Heterozygote; Humans; Injections, Subcutaneous; Male; Middle Aged; Uremia; von Willebrand Factor

Seven patients with a suspected mild bleeding disorder had consistently abnormal glass bead platelet retention. This was the only coagulation abnormality detected in six of these patients; the seventh individual showed evidence of mild von Willebrand disease. Nevertheless, platelets from the six that were studied behaved in a similar fashion in the two-stage platelet retention assay of McPherson and Zucker. This indicated that their platelets were defective in maintaining repetitive platelet-platelet interaction in the second phase of this assay but functioned normally in the first phase. Their one-stage platelet retention defects consistently normalized following the infusion of 1-deamino-8-D-arginine-vasopressin (d-DAVP). The duration of response was variable and easily defined by monitoring this parameter. These findings suggest platelet retention analysis may be useful in identifying mild bleeding disorder patients, who may benefit from d-DAVP.

Topics: Adult; Bleeding Time; Blood Coagulation Disorders; Blood Platelets; Cell Adhesion; Deamino Arginine Vasopressin; Drug Administration Schedule; Female; Glass; Humans; Infusions, Intravenous; Male; Microspheres; Middle Aged; Platelet Function Tests; Time Factors

Topics: Adult; Aged; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Factor XII; Female; Humans; Male; Middle Aged; Thrombosis

Topics: Adult; Aged; Bleeding Time; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; von Willebrand Factor

We report a case of inhibitor to factor VIII in a non-haemophilic patient. Immunosuppressive therapy with azathioprine was started, but without any advantage. Evaluation of the kinetics of exogenous factor VIII in vitro showed a rapid but incomplete neutralization of factor VIII. Following s.c. 1-deamino-8-D-arginine vasopressin (DDAVP) administration, a large and prolonged increase in factor VIII:C and von Willebrand factor antigen occurred together with complete inhibitor saturation. Therefore DDAVP may represent an important tool in the management of the bleeding episodes in these patients and evaluation of its suitability in the management of these patients should be carried out.

Topics: Blood Coagulation Disorders; Deamino Arginine Vasopressin; Factor VIII; Humans; In Vitro Techniques; Male; Middle Aged

The histories of two patients without hemophilia but with spontaneous acquired factor VIII inhibitors are reported. A protocol is suggested for the combined hematologic and dental management of such patients.

Topics: Aminocaproic Acid; Blood Coagulation Disorders; Cyclophosphamide; Deamino Arginine Vasopressin; Dental Care for Disabled; Factor VIII; Humans; Male; Middle Aged; Time Factors

The prolonged partial thromboplastin time observed in the plasma of a 36 year old asymptomatic man was related to the reduced prekallikrein activities (coagulant; antigenic; and amidolytic) and the absence of coagulant and immunologic activities of high molecular weight kininogen (HMWKg). The patient's plasma also exhibited impaired surface-mediated fibrinolysis and impaired generation of kallikrein. The coagulation defect was identified as the "Fitzgerald trait". The levels of CH50, C2, C4 and C-1 inactivator were normal. Venous occlusion in the patient gave rise to a normal release of extrinsic plasminogen activator from the vascular endothelium. The administration of DDAVP led to a FVIII/VWF response which was similar to that obtained in healthy subjects. No alteration could be observed in the contact phase proteins after DDAVP administration.

Topics: Adult; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Humans; Kallikreins; Kininogens; Kinins; Male; Prekallikrein; Protein Precursors; Syndrome; Tourniquets

Clinical and laboratory studies of two siblings, both suffering from gray platelet syndrome (GPS) are described. The patients had a mild bleeding disorder, their platelets were blue-gray in panoptic stains, and alpha-granules were markedly reduced, as shown by electron microscopy. The platelet content of platelet factor 4 and that of beta-thromboglobulin were significantly reduced (3%-7% of normal). Platelet count was decreased (33-150 X 10(9)/1) and small platelets were increased in platelet volume distribution. Bleeding time was prolonged on most occasions. Bone marrow aspiration was performed in one patient and revealed increased reticulin fibers, however, megakaryocyte count was normal. The mean platelet survival was 4.8 days using 111indium-labelled platelets. In this patient, platelet-associated IgG was within the normal range. Prednisone therapy failed to increase platelet count. Dental surgery was performed under cover of desmopressin and no bleeding complication occurred; however, no improvement of bleeding time was observed. The patient delivered a healthy male infant without hemorrhaging while under concurrent platelet transfusion therapy.

Topics: Adult; beta-Thromboglobulin; Blood Coagulation Disorders; Blood Platelets; Bone Marrow Examination; Cytoplasmic Granules; Deamino Arginine Vasopressin; Female; Humans; Male; Oral Hemorrhage; Platelet Count; Platelet Factor 4; Thrombocytopenia

Topics: Arginine Vasopressin; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Factor VIII; Female; Humans; Pregnancy; Puerperal Disorders

Twenty-one patients suffering from mild von Willebrand's disease (vWd) and patients suffering from mild or moderate hemophilia A received 1-desamino-8-D-arginine vasopressin (DDAVP) (Minirin, Ferring AG) s.c. at a dose of 0.4 microgram/kg body weight. Additionally, two hemophiliacs and 22 patients with vWd received DDAVP i.v. Within the observation period of 3 h Factor (F) VIII:C levels increased 2.4 X baseline levels in hemophiliacs, and the maximal effect was observed 3 h post DDAVP s.c. In patients with vWd post DDAVP s.c. (i.v.) a 2.7 (3.4), 2.1 (1.9) and 2.2 (2.8) fold increase for F VIII: C, F VIIIR:Ag and F VIII:Rcof was observed. In eight patients suffering from vWd with additional F XII deficiency a small and transitory but significant increase of F XII levels was detected post DDAVP s.c. No local or systemic side effects were observed. In five patients with vWd tooth extractions were performed without bleeding complications under DDAVP s.c. treatment. Two patients practiced self-treatment by injecting the drug s.c. at home. We thus conclude that s.c. DDAVP is an effective, reliable, and cost-reducing form of treatment that does not bring with it the risk of transmitting infectious diseases in patients with vWd and hemophilia and that can be administered at home.

Topics: Arginine Vasopressin; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Hemophilia A; Humans; Injections, Intravenous; Injections, Subcutaneous

Topics: Adult; Aged; Arginine Vasopressin; Blood Coagulation; Blood Coagulation Disorders; Chronic Disease; Deamino Arginine Vasopressin; Female; Humans; Liver Cirrhosis; Male; Middle Aged

Intravenous infusion of desmopressin (DDAVP, 0.4 micrograms/kg b.w. in 12') causes an increase in the level of extrinsic plasminogen activator, measured in plasma euglobulin fractions with added C1-inactivator on fibrin plates. A poor response or no response at all was elicited in two out of 21 patients with spontaneous thrombosis, 18/38 with hyperlipoproteinaemia and 10/14 with terminal renal insufficiency requiring haemodialysis. Haemodilution during the first 30' after starting the DDAVP-infusion occurred both in responders and in non-responders; so did haemodynamic reactions: increase in heart rate, drop in diastolic blood pressure, facial flushing. The rise of fibrinolytic activity was shown not to be associated with decreased hepatic blood flow. Normal factor VIII-rises in "non-responders" indicate the responsiveness of the receptive organs, including the hypothalamus, to DDAVP. Despite a normal baseline level of fibrinolytic activity in the blood, as occurs for instance in terminal renal insufficiency, the vascular endothelium may be refractory to stimulation. In some patients especially in type IV hyperlipoproteinaemia, a selective defect of the release of plasminogen activator is postulated. In subjects with low fibrinolytic activity at rest, as observed in spontaneous thromboembolism and in hypertriglyceridaemia, the failure to release plasminogen activator upon stimulation with DDAVP might be a consequence of an impairment of synthesis as well.

Topics: alpha-2-Antiplasmin; Antigens; Antithrombin III; Arginine Vasopressin; Blood Coagulation; Blood Coagulation Disorders; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Factor VIII; Fibrinolysis; Hematocrit; Hemodynamics; Humans; Hyperlipoproteinemias; Liver Circulation; Plasminogen; Thromboembolism; von Willebrand Factor