Background: The biological variability of von Willebrand factor and the variability in assays can make diagnosis and subclassification of von Willebrand disease (VWD) difficult. We describe a case series of four patients with a typical history of VWD and prolonged closure time in the platelet function analyser (PFA-100) but initially a normal ratio of ristocetin cofactor activity (VWF:RCo) to von Willebrand factor antigen levels (VWF:Ag) for whom further diagnostics verified VWD type 2A.
Methods: For the initial VWD diagnostics we measured VWF:Ag, VWF:RCo, platelet aggregation induced by ADP, ristocetin and collagen, closure time in the PFA-100 test, and platelet count. We used VWF multimer analysis and collagen binding capacity for extended diagnostics. VWD diagnostics were carried out as part of extensive laboratory screening to exclude other haemostatic defects.
Results: Multimer analysis revealed the absence of ultralarge multimers in all 4 patients. Ristocetin-induced platelet aggregation was consistently diminished in three patients with hereditary VWD 2A but not in a patient with essential thrombocythaemia. After repeat testing, diminished VWF:RCo and collagen binding capacity (VWF:CB) could be identified in all patients. However, all four cases would have been missed if the initial VWD assays had been performed only once.
Conclusions: A single measurement of a normal ratio of VWF:RCo/VWF:Ag does not exclude VWD 2A in patients with a typical history of VWD. The PFA-100 is suitable for screening. To ensure that no cases of VWD are missed, multimer analysis and repeat functional testing of platelet aggregation, VWF:RCo, and VWF:CB are necessary.