ABSTRACT
Platelet-type von Willebrand disease (PT-VWD) is an autosomal dominant rare bleeding
disorder characterized by hyperresponsive platelets. This inherent platelet function
defect is due to a gain-of-function mutation within the GP1BA gene coding for the platelet surface glycoprotein Ib alpha protein, the receptor
for the adhesive protein von Willebrand factor (VWF). The defect results in excessive
and unnecessary platelet–VWF interaction with subsequent removal of the hemostatically
efficient high molecular weight VWF as well as platelets from the circulation, leading
to thrombocytopenia and bleeding diathesis. Patients with PT-VWD present with mild
to moderate mucocutaneous bleeding, which becomes more pronounced during pregnancy
and following aspirin ingestion or drugs that have antiplatelet activity. Laboratory
testing shows low VWF:ristocetin cofactor and low or normal VWF:antigen and characteristically
an enhanced ristocetin-induced platelet agglutination (RIPA). These laboratory features
are also indicators of the closely similar and more common bleeding disorder type
2B VWD. Simplified RIPA mixing assays, cryoprecipitate challenge, and flow cytometry
can differentiate between the two disorders. However, the gold standard is to identify
mutations within the VWF gene (indicating type 2B VWD) or the platelet GP1BA gene ( confirming PT-VWD). Treatment is based on making a correct diagnosis of PT-VWD where
platelet concentrates instead of VWF/factor VIII preparations should be administered.
A recent fairly large retrospective/prospective registry-based international study
showed that PT-VWD is very rare, likely to be misdiagnosed as type 2B VWD or idiopathic
thrombocytopenic purpura, and represents 15% of type 2B VWD diagnoses.
KEYWORDS
Glycoprotein 1bα - type 2B VWD - registry - RIPA - PT-VWD mouse - platelet concentrate
REFERENCES
http://http//www.pt-vwd.org Accessed February 9, 2011
Othman@queensu.ca
