Willebrand Disease

Hematologic von Willebrand disease Idiopathic thrombocytopenic purpura Factor VII defect causing impaired platelet adhesion and increased bleeding time Decrease in circulating platelets—can be acute or chronic... 

Von Willebrand disease (vWD) is the most common inherited bleeding disorder caused by a deficiency or dysfunction of von Willebrand factor. The disease prevalence is estimated at 30 to 100 cases per million. In contrast to hemophilia, vWD is inherited as an autosomal dominant disorder (although autosomal recessive cases exist), ensuing equal frequency in male and females.16... 

FIGURE 64-3. Guidelines for the treatment of von Willebrand disease. aUse factor VIII concentrate for life-threatening bleeding. 6Some patients with type 2 or 3 von Willebrand disease may respond to desmopressin. 

Haemophilia A (classical haemophilia, often simply termed haemophilia) is an X-linked recessive disorder caused by a deficiency of factor VIII. Von Willebrand disease is a related disorder, also caused by a defect in the factor VIII complex, as discussed below. 

Federici, A. and Mannucci, P. 2002. Advances in the genetics and treatment of von Willebrand disease. Current Opinion in Pediatrics 14(1), 23-33. 

Leissinger C, Becton D, Cornell C Jr, Cox GUI J. High-dose DDAVP intranasal spray (stimate) for the prevention and treatment of bleeding in patients with mild haemophilia A, mild or moderate type 1 von Willebrand disease and symptomatic carriers of haemophilia A. Haemophilia 2001 7 258-66. 

Pathophysiologically, primary haemostatic defects, characteristically due to malfunction of vascular endothelial or platelets, are exemplified by von Willebrand disease and agents such as aspirin and non-steriodal anti-inflammatory drugs (NSAID) where there is a prolonged bleeding time or abnormality in closure using the laboratory equivalent of platelet function analyse the PEA-100. In contrast, secondary bleeding, follows a period of haemostasis... 

Von Willebrand Von Willebrand disease 30% Approximately 10 hours Intermediate purity factor VIII concentrates that contain von Willebrand factor. Some patients respond to DDAVP Cryoprecipitate1... 

Cryoprecipitate should be used to treat bleeding in the setting of factor VIII deficiency and von Willebrand disease only in an emergency in which pathogen-inactivated products are not available. 

Desmopressin acetate increases the factor VIII activity of patients with mild hemophilia A or von Willebrand disease. It can be used in preparation for minor surgery such as tooth extraction without any requirement for infusion of clotting factors if the patient has a documented adequate response. High-dose intranasal desmopressin (see Chapter 17) is available and has been shown to be efficacious and well tolerated by patients. 

Cryoprecipitate may also be used for patients with factor VIII deficiency and von Willebrand disease if desmopressin is not indicated and a pathogen-inactivated, recombinant, or plasma-derived product is not available. The concentration of factor VIII and von Willebrand factor in cryoprecipitate is not as great as that found in the concentrated plasma fractions. Moreover, cryoprecipitate is not treated in any manner to decrease the risk of viral exposure. For infusion, the frozen cryoprecipitate unit is thawed and dissolved in a small volume of sterile citrate-saline solution and pooled with other units. Rh-negative women with potential for childbearing should receive only Rh-negative cryoprecipitate because of possible contamination of the product with Rh-positive blood cells. 

Desmopressin Activates vasopressin V2 receptors much more than Vi Acts in the kidney to decrease the excretion of water acts on extrarenal V2 receptors Pituitary diabetes insipidus hemophilia A and von Willebrand disease Oral, IV, SC, or intranasal Toxicity Gastrointestinal disturbances, headache, hyponatremia, allergic... 

VIIIivWFA vascular, endothelial 18-24 1-1.5 60 von Willebrand disease, AD 12pter—pl2... 

Deficiency of the VIII C portion of the Factor VIII complex results in classic hemophilia or hemophilia A and is inherited as a sex-finked recessive disorder. Based on the degree of deficiency of the VIII C molecule three different forms of hemophilia A are recognized. Less than 1% VII I C activity equals severe hemophilia A. Two to 10% of normal VIII C activity equals moderately severe hemophilia A. Ten to 25% of normal VIII C activity equals minimal symptomatic disease. Deficiency of the VIIkvWFAg portion of the Factor VIII complex results in von Willebrand disease. There are at present five principal types of von Willebrand disease and numerous subtypes or variants. For the most part, von Willebrand disease is inherited as an autosomal dominant, and a few subtypes may be inherited as an autosomal recessive trait. 

At higher doses desmopressin also has significant hematological effects and can significantly boost concentrations of factor VIII and von Willebrand factor (VWF) in the blood. Desmopressin is therefore a valuable agent for the treatment of mild and moderate hemophilia A (congenital or acquired) and type 1 von Willebrand disease, in which the VWF protein structure is normal but... 

Facial flushing occurred in two of 25 children with either hemophilia or von Willebrand disease given high-dose intranasal desmopressin (150 micrograms) in a singledose open study (19). 

A 47-year-old woman with von Willebrand disease, who was given desmopressin and intravenous fluids perioperatively, developed hyponatremia and seizures, which resolved after water restriction (50). 

A 38-year-old man with von Willebrand disease type 2B developed severe thrombocytopenia after a single dose of desmopressin (66). 

In four patients with von Willebrand disease, desmopressin caused a significant but transient reduction in platelet count without an increase in plasma glycocalicin concentrations nor enhanced expression of P selectin, suggesting that acute thrombocytopenia after the administration of desmopressin in type 2B von Willebrand disease is not related to platelet activation and consumption (68). 

One report described adverse reactions in two pregnant women with von Willebrand disease (73). One went into premature labor after a single dose (attributed to the... 

Gill JC, Ottum M, Schwartz B. Evaluation of high concentration intranasal and intravenous desmopressin in pediatric patients with mild hemophilia A or mild-to-moderate type 1 von Willebrand disease. J Pediatr 2002 140(5) 595-9. 

Casonato A, Steffan A, Pontara E, Zucchetto A, Rossi C, De Marco L, Girolami A. Post-DDAVP thrombocytopenia in type 2B von Willebrand disease is not associated with platelet consumption failure to demonstrate glycocalicin increase or platelet activation. Thromb Haemost 1999 81(2) 224-8. 

Several disorders of coagulation and fibrinolysis have been identified that lead to thrombosis or bleeding. These include von Willebrand disease (vWD), hemophilia, coagulation factor deficiencies, acquired/congenital inhibitors of coagulation, and antiphospolipid syndrome. 

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