deamino-arginine-vasopressin and Thromboembolism

von Willebrand disease (VWD) is the most common inherited bleeding disorder characterised by a quantitative or qualitative deficiency in von Willebrand factor (VWF). During invasive surgical procedures, patients with VWD require additional treatment to maintain haemostasis; however, due to the complexity of VWD, there is a lack of consensus on the optimal management. In the perioperative period, patients are usually treated with VWF and factor FVIII (FVIII)-containing concentrates to provide an immediate haemostatic response to prevent excessive bleeding during both elective and emergency surgery. With the introduction of recombinant VWF (rVWF), there is a need for guidance on the use of the various VWF products in the perioperative period for all types of patients and surgeries. This review provides an overview of the current evidence for the surgical management of patients with VWD and, summarises the optimal treatment approach during the perioperative period, and highlights key unanswered questions and the research needed to address the evidence gaps.

Topics: Biomarkers; Blood Coagulation; Clinical Decision-Making; Deamino Arginine Vasopressin; Disease Management; Disease Susceptibility; Humans; Perioperative Care; Severity of Illness Index; Thromboembolism; von Willebrand Diseases; von Willebrand Factor

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

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

The population of elderly patients with von Willebrand Disease (VWD) is growing because of the improvement of medical care. The increase in comorbidities and their treatment as well as standard preventive measures like antiplatelet or anticoagulation therapy constitutes a challenge in the overall treatment of patients with coagulation disorders. Because of the lack of literature on older patients with VWD, we discuss different aspects related to ageing in those patients. Plasma levels of von Willebrand factor and factor VIII, bleeding symptoms, treatment requirements and comorbidities are possibly changing with age. Development of an evidence-based approach to the management of ageing VWD patients is therefore necessary.

Topics: Aged; Aging; Deamino Arginine Vasopressin; Factor VIII; Hemostasis; Humans; Thromboembolism; von Willebrand Diseases; von Willebrand Factor; Waterhouse-Friderichsen Syndrome

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

Von Willebrand disease (VWD) is the most common genetic bleeding disorder with a prevalence of approximately 1-2 percent confirmed in different population studies. The severity of the bleeding tendency is usually proportional to the degree of the VWF defect, although the large majority of cases diagnosed appear to have a mild disease. Patients with VWD may require short- or long-term prophylaxis treatment. Short-term prophylaxis is usually performed to prevent excessive bleeding following surgery or invasive procedures, while long-term prophylaxis may be needed to control recurrent mucosal and joint bleeding complicating the more severe forms of VWD. This review is focused on the current knowledge on replacement treatment for patients with VWD disease undergoing surgical or invasive procedures. On the whole, the published studies document the safety and efficacy of VWF/FVIII concentrates as surgical prophylaxis in VWD patients, in particular of Haemate P, the most widely used VWF/FVIII concentrate due to its high VWF:FVIII ratio. The recent literature data also show that the best management of VWD patients undergoing surgery is that to perform a pharmacokinetic study in order to strictly tailor for each VWD patient loading and maintenance doses of VWF/FVIII concentrates. Furthermore, the same studies underscore that, along with VWF levels, FVIII levels should be monitored in the peri-operative period in order to prevent exposures to high FVII levels, associated with an increased risk of venous thrombosis.

Topics: Blood Loss, Surgical; Clinical Trials as Topic; Cross-Over Studies; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Drug Combinations; Factor VIII; Half-Life; Humans; Infusions, Intravenous; Multicenter Studies as Topic; Postoperative Complications; Postoperative Hemorrhage; Retrospective Studies; Thromboembolism; Virus Inactivation; von Willebrand Diseases; von Willebrand Factor

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

Topics: Adrenocorticotropic Hormone; Anabolic Agents; Androgens; Clofibrate; Coronary Disease; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Fibrinolysis; Fibrinolytic Agents; Glucocorticoids; Humans; Inflammation; Male; Metformin; Phenformin; Plasminogen Activators; Postoperative Complications; Sulfonylurea Compounds; Thromboembolism; Thrombophlebitis; Vascular Diseases

Tissue hypoxia and reperfusion induce abnormal hemostatic function. Therefore, bleeding after total knee replacement (TKR) may be a result of a tourniquet-induced imbalance of the procoagulant and fibrinolytic systems. Because laboratory confirmation of tourniquet-induced abnormal hemostasis is difficult to obtain, indirect evidence must be sought.. A prospective, single-blind study of 40 patients undergoing TKR was performed. In the tranexamic acid (TA) group, in the 30 minutes before the limb tourniquet was deflated, an IV bolus dose of TA (15 mg/kg) was administered. Thereafter, a constant IV infusion of 10 mg per kg per hour was administered until 12 hours after tourniquet deflation. In the desmopressin group, desmopressin (0.3 mg/kg) and saline were administered by a similar protocol. No blood was administered intraoperatively. A postoperative Hct <27 percent constituted the postoperative transfusion trigger. Patients were examined daily for signs of lower-limb deep vein thrombosis, and they underwent lower-limb Doppler ultrasound on postoperative Day 5. Three months after surgery, the incidence of delayed thromboembolic events was assessed.. During the first 12 postoperative hours, blood accumulation in the surgical drain was significantly (p<0.05) lower in the TA group (162 mL +/- 129) than in the desmopressin group (342 mL +/- 169). From the sixth postoperative hour until 3 days postoperatively, Hct levels were significantly lower in the desmopressin group than in the TA group. Significantly more allogeneic blood was transfused in the desmopressin group (11 patients received 16 units) than in the TA group (3 patients each received 1 unit) (p<0.02). There were no clinical signs of deep vein thrombosis or abnormal Doppler ultrasound studies. Three months postoperatively, there were no thromboembolic events among the 37 patients interviewed.. TA induces better blood sparing than desmopressin. Therefore, a tourniquet-induced increase in fibrinolysis is the likely cause of delayed bleeding after TKR surgery. However, before routine administration, the effect of TA on the incidence of thromboembolic events requires further investigation.

Topics: Aged; Antifibrinolytic Agents; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Blood Transfusion; Deamino Arginine Vasopressin; Female; Hematocrit; Hemostatics; Humans; Male; Postoperative Care; Prospective Studies; Single-Blind Method; Thromboembolism; Tourniquets; Tranexamic Acid

The blood loss-reducing effect of desmopressin during dextran therapy was studied in a double-blind fashion in 79 elderly but otherwise healthy patients with preoperative normal bleeding time undergoing total hip replacement for primary coxarthrosis. An infusion of desmopressin (0.3 microgram/kg body weight) or placebo was randomly administered immediately after administration of spinal anaesthesia and six hours later. Haemostasis was evaluated on the basis of vWF: ristocetin cofactor activity, FVIII: C activity, human tissue plasminogen activator (tPA) plasminogen activator inhibitor type (PAI), beta-thromboglobuline (beta TG) and a clot impedance test (Sonoclot). There were no statistically significant differences (P > 0.05) in mean blood loss or transfusion requirements between the placebo and the desmopressin group. There was a significantly increase (P < 0.01) both in vWF: ristocetin cofactor and in FVIII: C activity after both infusions of desmopressin compared with placebo. There was no significant difference in beta TG, tPA, PAI or Sonoclot analysis between the groups. In conclusion, desmopressin did not reduce blood loss in patients undergoing total hip replacement.

Topics: Aged; Blood Loss, Surgical; Deamino Arginine Vasopressin; Dextrans; Double-Blind Method; Female; Hemostatics; Hip Prosthesis; Humans; Male; Middle Aged; Prospective Studies; Thromboembolism

The purpose of this study was to determine the effect of desmopressin acetate (DDAVP) on blood loss, transfusion requirements, and thromboembolic complications in patients undergoing elective aortic operations.. A randomized, double-blind trial was carried out during a 3-year period with patients receiving 20 micrograms DDAVP or identical-appearing placebo at the time of aortic cross-clamp placement. In addition to major bleeding and thromboembolic end points, bleeding times and platelet counts were monitored serially.. Forty-three patients were randomized to receive DDAVP, and 48 were assigned to a placebo. An equivalent proportion of patients with aneurysm and patients with occlusive disease was in each group. In spite of mild prolongation in the postoperative bleeding times and moderate thrombocytopenia, DDAVP had no beneficial effect on blood loss or transfusion requirements. Total blood transfusion amount (mean +/- standard deviation) for patients receiving DDAVP was 3.1 +/- 3.0 U compared with 2.7 +/- 3.0 U for those receiving placebo. For all patients the period associated with the greatest blood loss was the time between heparin administration with cross-clamp application and reversal of heparin with protamine sulfate. The incidence of major thromboembolic complications was similar in both groups.. Thrombocytopenia and mild platelet dysfunction are common after aortic operation, but DDAVP does not improve hemostasis or lessen transfusion requirements. This study does not rule out a beneficial effect of DDAVP in patients who are undergoing more complex aortic operations or who have major hemostatic aberrations.

Topics: Aged; Aorta; Bleeding Time; Blood Loss, Surgical; Blood Transfusion; Deamino Arginine Vasopressin; Double-Blind Method; Female; Hemostasis; Humans; Male; Middle Aged; Platelet Count; Postoperative Complications; Thromboembolism

Topics: Aged; Antithrombin III; Deamino Arginine Vasopressin; Female; Hip Joint; Hip Prosthesis; Humans; Male; Middle Aged; Postoperative Complications; Thromboembolism

There is a high degree of uncertainty regarding optimum care of patients with potential or known intake of oral anticoagulants and traumatic brain injury (TBI). Anticoagulation therapy aggravates the risk of intracerebral hemorrhage but, on the other hand, patients take anticoagulants because of an underlying prothrombotic risk, and this could be increased following trauma. Treatment decisions must be taken with due consideration of both these risks. An interdisciplinary group of Austrian experts was convened to develop recommendations for best clinical practice. The aim was to provide pragmatic, clear, and easy-to-follow clinical guidance for coagulation management in adult patients with TBI and potential or known intake of platelet inhibitors, vitamin K antagonists, or non-vitamin K antagonist oral anticoagulants. Diagnosis, coagulation testing, and reversal of anticoagulation were considered as key steps upon presentation. Post-trauma management (prophylaxis for thromboembolism and resumption of long-term anticoagulation therapy) was also explored. The lack of robust evidence on which to base treatment recommendations highlights the need for randomized controlled trials in this setting.

Topics: Administration, Oral; Anticoagulants; Austria; Brain Injuries, Traumatic; Consensus; Dabigatran; Deamino Arginine Vasopressin; Humans; Interdisciplinary Communication; Partial Thromboplastin Time; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Thiazoles; Thromboembolism; Tomography, X-Ray Computed; Tranexamic Acid; Treatment Outcome; Vitamin K

Topics: Blood Loss, Surgical; Cardiac Surgical Procedures; Deamino Arginine Vasopressin; Humans; Thromboembolism

Aa a plasma marker of an endothelial abnormality, the serum activity of angiotensin-converting enzyme (ACE) was investigated at rest and after stimulation either by local venostasis or infusion of an analogue of lysine-vasopressin (desmopressin acetate). Desmopressin acetate did not induce any significant change in ACE, in contrast to the effect of venostasis. Searching for an endothelial abnormality implicated in the genesis of deep vein thrombosis, we used the local venostasis test in patients affected by recurrent deep vein thrombosis. Patients, divided in three groups (group I, documented history of recurrent deep vein thrombosis; group II, only one deep vein thrombosis or recurrent superficial venous thrombosis; group III, history of arterial thromboembolism), and controls were screened for basal and stimulated levels of serum ACE, together with fibrinolytic activity and von Willebrand factor level. Two types of abnormalities of serum ACE activity were found: low basal level in group I, and low response to venostasis in groups I and III; group II did not differ from controls. Measures of fibrinolytic and ACE activities are not redundant because the two types of ACE abnormalities were not individually encountered in the same patients and were independent from abnormalities of the fibrinolytic system. These findings suggest that an endothelial lesion could participate in the pathogenesis of some forms of recurrent deep vein thrombosis and support interest in the measurement of serum ACE to discriminate some patients at high risk of deep vein thrombosis.

Topics: Adult; Aged; Biomarkers; Deamino Arginine Vasopressin; Endothelium; Factor VIII; Female; Fibrinolysis; Humans; Male; Middle Aged; Peptidyl-Dipeptidase A; Thromboembolism; von Willebrand Factor

A 22 year-old woman with diabetes insipidus on chronic therapy with desmopressin acetate (DDAVP) developed recurrent venous thromboembolism and transient thrombocytopenia temporally related to the administration of DDAVP. Large increases in plasma von Willebrand factor (vWF), vWF-activity, and relative increases in the concentrations of the larger multimeric forms of vWF-antigen were observed, as well as a plasma factor which sensitized normal platelets to undergo spontaneous aggregation in vitro. Additional studies showed that the patient's plasma retained the platelet aggregation inducing activity after selective removal of vWF by immunoabsorption. The nature of the platelet activating factor and the relationship of this factor and the excessively increased and transiently abnormal vWF to the recurrent venous thromboembolism in this patient remain uncertain. Although the findings do not implicate definitively DDAVP in the elevation of vWF in this patient, it is suggested that its use be considered with caution in patients with diabetes mellitus and increased levels of vWF.

Topics: Adult; Antithrombin III; Deamino Arginine Vasopressin; Diabetes Insipidus; Female; Fibrinogen; Humans; Platelet Aggregation; Staphylococcus aureus; Thrombocytopenia; Thromboembolism; von Willebrand Factor

Patients with hyperlipoproteinaemia or spontaneous thromboembolism, known to be poor responders to DDAVP or to venous occlusion with regard to the rise in fibrinolytic activity of the blood, appeared to show a normal increase in t-PA-antigen after the same procedure. In their plasma a higher than normal level of free, fast-acting t-PA-inhibitor was found as measured by titration with purified t-PA. This free t-PA-inhibitor level only decreased after the test, in contrast to its complete disappearance in normal responders. The same happened in a healthy volunteer who failed to exhibit a rise in fibrinolytic activity after exhaustive exercise. We suppose that the lack of response of the fibrinolytic activity in these cases is due to a high inhibitor level and not to impaired release of t-PA into the blood. In contrast, patients with terminal renal insufficiency showed only a slight increase in t-PA-antigen after DDAVP. The level of free fast-acting inhibitor was normal in most cases and did not change appreciably during DDAVP-infusion. In these patients, a true impairment of the release of t-PA appears to exist.

Topics: Antigens; Constriction; Deamino Arginine Vasopressin; Fibrinolysis; Humans; Hyperlipoproteinemias; Leg; Physical Exertion; Plasminogen Activators; Plasminogen Inactivators; Renal Dialysis; Thromboembolism; Veins

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