Dominant von Willebrand disease type 2A groups I and II due to missense mutations in the A2 domain of the von Willebrand factor gene: diagnosis and management.
Pertinent findings in patients with von Willebrand disease (VWD) type 2A include prolonged bleeding time (BT), consistently low von Willebrand factor (VWF):ristocetin cofactor activity (RCo)/antigen concentration (Ag) and VWF:collagen binding (CB)/Ag ratios, absence of high, and (depending on severity) intermediate and large VWF multimers, the presence of pronounced triplet structure of individual bands and increased VWF degradation products due to increased proteolysis caused by mutations in the A2 domain of VWF. Two categories of VWD type 2A can be distinguished: group I with severe and group II with mild VWD. A minority of VWD type 2A have mild VWD characterized by near normal to prolonged BT, normal factor VIII coagulant activity and VWF:Ag, low VWF:RCo and VWF:CB, a normal ristocetin-induced platelet aggregation and complete but transient correction of BT and functional VWF parameters to normal levels for only a few hours due to short half-lives for VWF:RCo and CWF:CB. Such transient complete responses to desmopressin (DDAVP) lasting only a few hours may facilitate treatment and prophylaxis of minor bleedings, but may not be able to prevent bleeding during minor and major surgery. Most VWD type 2A patients have pronounced VWD with very low VWF:RCo, prolonged BT, PFA-100 closure times >250 s, and response to DDAVP is only transient, minor, poor or absent, with no correction of the BT despite some increase in VWF:RCo, thus being candidates for factor VIII-VWF concentrate substitution for the acute and prophylactic treatment of bleeding symptoms.
Michiels
Jan Jacques
JJ
Hemostasis and Thrombosis Research Center, Antwerp University Hospital, Wilrijkstraat 10, Edegem, Belgium. postbus@goodheartcenter.demon.nl
van Vliet
Huub H D M
HH
D051722:ADAM Proteins / Q000378:metabolism; D000071120:ADAMTS13 Protein; D000328:Adult; D000368:Aged; D001760:Bleeding Time; D001797:Blood Protein Electrophoresis; D003094:Collagen / Q000378:metabolism; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D005091:Exons / Q000235:genetics; D005260:Female; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D020125:Mutation, Missense; D010974:Platelet Aggregation / Q000187:drug effects; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D014842:von Willebrand Diseases / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D014841:von Willebrand Factor / Q000032:analysis / Q000737:chemistry / Q000235:genetics*
D014841:von Willebrand Factor; D003094:Collagen; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human; D003894:Deamino Arginine Vasopressin