Choroba von Willebranda typu 2M. Problemy klasyfikacyjne i diagnostyczne

Type 2M von Willebrand disease (type 2M VWD) is an autosomaly dominant inherited bleeding disorder characterized by a decrease in the affinity of the Willebrand factor (von Willebrand factor; VWF) for platelets in the absence of any deficiency of high molecular weight (HMW) VWF multimers. Type 2M VWD accounts for 5-10% of the general population of patients with von Willebrand disease and is frequently misdiagnosed with type 1 and type 2A VWD. The underlying cause of this bleeding disorder are missence mutations and deletions in WVD-A1 domain (binding site for glycoprotein Ib and collagen) and much rarely in WVD-A3 domain (binding site for collagen). Laboratory characteristics of type 2M VWD include: lower ristocetin cofactor activity (VWF:RCo), normal/decreased collagen binding, discrepancy between VWF antigen and ristocetin activity (VWF:RCo/VWF:Ag rate < 0,7) and normal multimer distribution. Diagnosis of type 2M VWD is particularily difficult as it should take into account not only defects in VWF binding with platelet receptor GPIbα (VWF:RCo) but also with epithelial collagen (VWF:CB). Furthermore, 2M VWD requires multimer analysis so it is predominantly recognized in high-tech laboratories. Correct recognition of 2M VWD may have impact on the choice of therapy. Literature reports present disparity in the evaluation of 2M VWD treatment. In some 2M VWD patients treatment with desmopressin (DDAVP) is often ineffective due to increased VWF clearance from plasma. However, replacement therapy with concentrates containing FVIII and VWF has proved as effective as in type 1 and 2A VWD.