RESUMO
Type 2B von Willebrand's disease (vWD) is associated with spontaneous binding of large von Willebrand factor (vWF) multimers to platelets in vivo, followed by clearance of both the large multimers and platelets resulting in thrombocytopenia, which may be intermittent, mild to severe, and may be exacerbated by stress such as infection or pregnancy. We report our experience in two kindreds (49 caucasian individuals) with type 2B vWD and discuss their varied clinical manifestations. The largest kindred (45 patients) was traced back five generations to a presumed index case. The genetic defect in this kindred was identified as a missense mutation, with a C to T transition at a CpG dinucleotide (nucleotide 3916) resulting in an amino acid substitution (Arg 543 to Trp) within the glycoprotein Ib binding domain of vWF. Ristocetin cofactor activity varied from < 10 to 28%, and factor VIII activity from 7 to 69%. Analysis of von Willebrand multimers consistently revealed loss of large molecular weight forms. Platelet counts in those with thrombocytopenia varied from 10 x 10(9) L(-1) to 120 x 10(9) L(-1). The severity of thrombocytopenia has also varied within the same individual during the period of follow-up. The clinical manifestations were varied and ranged from mild to moderate spontaneous bleeding episodes, including epistaxis, menorrhagia and gastro-intestinal haemorrhage. Severe bleeding episodes were observed in those undergoing surgery (both elective and non-elective), and in a few patients despite aggressive replacement with exogenous source of intact vWF, antifibrinolytics when indicated, and a near normal platelet count. Thrombotic disease may be a rare and unusual sequela of this disorder as was noted in one of our patients. Obtaining a platelet count at birth in infants of mothers with type 2B vWD who exhibit thrombocytopenia, may help in the earlier detection of infants at risk for thrombocytopenia.
