Von Willebrand disease medical therapy

The mainstay of management of VWD is medical therapy. Medical therapy of von Willebrand’s disease ( vWD) involves normalizing the von Willebrand factor and factor VIII levels. Endogenous factor levels can be increased by the use of desmopressin or by infusing exogenous coagulation factors example high-purity or low-purity von Willebrand factor concentrate. Medical therapy depends on the type of von Willebrand’s disease. Desmopressin is used for type 1 and 2 von Willebrand’s disease. von Willebrand factor–factor VIII or von Willebrand factor concentrate is used in some of type 2 von Willebrand’s disease and all of type 3 von Willebrand’s disease. Alternate or additional therapy involves the use of tranexamic acid or aminocaproic acid.

Pharmacologic medical therapies for VWD include desmopressin (DDAVP), recombinant VWF , von Willebrand factor/factor VIII (vWF/FVIII) concentrates and antifibrinolytic agents.^{[1][2][3][4][5]}

Desmopressin

• Desmopressin works by raising the patient’s own plasma levels of von Willebrand factor by inducing release of von Willebrand factor stored in the Weibel-Palade bodies in the endothelial cells.

• It is used to treat patients with mild to moderately severe type 1 and some cases of type 2A vWD
• Desmopressin is usually not effective in type 2B, 2N, and 3 disease.
• Desmopressin is contraindicated in patients with type 2B disease.
• A test dose is given by nasal spray (1.5 mg/mL) or intravenously or subcutaneously (0.3 µg/kg).
• Fluids are to be restricted for 24 hours following the dose to avoid hyponatremia.

• Preferred regimen (1) IV: 0.3 mcg/kg in 50 mL saline over 20 minutes

• Preferred regimen (2) Nasal spray: weight >50 kg: 300 mcg (1 spray in each nostril); <50 kg: 150 mcg (1 spray in one nostril)
• May repeat dose after 12 hours and 24 hours
• DDAVP should not be used along antifibrinolytic agents such as tranexamic acid or aminocaproic acid.

VWF concentrates containing all VWF multimers

• Patients with type 3 VWD, more severe type 1, and those with types 2A, 2B, and 2M disease will need replacement therapy with a VWF-containing product,.
• Patients with more serious bleeding when other measures have failed.
• In those patients who require more prolonged treatment like post-surgery
• Major bleeding or surgery: Preferred regimen : 40 to 60 ristocetin cofactor units/kg followed by 20 to 40 ristocetin cofactor units/kg every 12 to 24 hours to keep VWF level 50 to 100 international units/dL for 7 to 14 days,
• Minor bleeding or surgery: Preferred regimen: 30 to 60 ristocetin cofactor units/kg followed by 20 to 40 ristocetin cofactor units/kg every 12 to 48 hours to keep VWF level >30 international units/dL for 3 to 5 days,
• Cryoprecipitate can also be used to treat vWD, since cryoprecipitate contains factor I, factor VIII, and vWF.

Antifibrinolytic agents: Aminocaproic acid,Tranexamic acid

• Used alone or in conjunction with other therapy except DDAVP.
• Useful for mucosal bleeding specially for dental procedures.

• Use after trial of DDAVP or other measures in patients with acquired von Willebrand syndrome (aVWS), particularly when associated with autoimmune diseases.
• May be used in conjunction with VWF concentrates to increase the half-life of VWF.
• Preferred regimen (1) : Aminocaproic acid, 25 to 50 mg/kg PO, QID (maximum 5 g dose)
• Preferred regimen (2) : Tranexamic acid, 10 mg/kg, I/V TDS.

For women with heavy menstrual bleeding, the combined oral contraceptive pill may be effective in reducing bleeding or in reducing the length or frequency of periods.

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