Platelet Aggregation Induced by I-Desamino-8-D-Arginine Vasopressin (dDAVP) in Type IIb von Willebrand's Disease

Abstract

Type IIB von Willebrand's disease is a distinct form of this disorder, in which there are abnormal factor VIII/von Willebrand factor multimers in plasma (but normal multimers in platelets) and heightened interaction between the von Willebrand factor and platelets in the presence of ristocetin. We have found that infusion of desmopressin acetate (1-desamino-8-D-arginine vasopressin [DDAVP]), an agent used in the treatment of von Willebrand's disease, causes platelet aggregation and thrombocytopenia in patients with Type IIB disease. In vitro, platelets in normal plasma and those obtained from patients with Type IIB disease before DDAVP infusion aggregated upon the addition of platelet-poor plasma from Type IIB patients treated with DDAVP. Platelet aggregation was associated with adsorption of multimers of factor VIII/von Willebrand factor onto the platelets and was inhibited by EDTA. We conclude that in Type IIB von Willebrand's disease, DDAVP releases an abnormal factor with platelet-aggregating properties. DDAVP should not be used to treat patients with Type IIB disease, since the presence of platelet aggregates in the circulation may be harmful.

The obstetric and gynaecological management of women with inherited bleeding disorders – review with guidelines produced by a taskforce of UK Haemophilia Centre Doctors’ Organization

“…DDAVP can be used in women with type 1 VWD and in some with type 2A, as there is usually a good response to this treatment with no risk of viral transmission. DDAVP should generally be avoided in women with type 2B VWD because it can precipitate thrombocytopenia [69]; platelet transfusions have been given when the platelet count was <20 · 10 9 L in type 2B [60]. Management of type 2N VWD using recombinant FVIII has been reported [70].…”

Native multimer analysis of plasma and platelet von Willebrand factor compared to denaturing separation: Implication for the interpretation of satellite bands

“…In vWD type 2B it is generally contraindicated owing to a temporary thrombocytopenia after administering the drug (Holmberg et al 1983). In vWD type 3 administration of desmopressin is ineffective (Ruggeri et al 1982).…”

Management of Inherited Bleeding Disorders in Pregnancy

“…109 In type 2B VWD, a transient thrombocytopenia occurs frequently after DDAVP administration and the therapeutic response is poor, therefore, it is not usually recommended for type 2B. 110 In type 2N VWD, the abnormal binding of factor VIII to VWF shortens the response. DDAVP…”