This study investigates the effect of pre-analytic storage conditions on the laboratory evaluation of von Willebrand disease (VWD) and haemophilia. Samples from healthy controls and patients with VWD were stored as whole blood and as separated plasma, both at room temperature and on crushed ice, for two different time periods (3 or 6 h). In samples from healthy individuals (n=10) and in patients with suspected type 1 VWD (n=10), storage of whole blood on ice caused a drastic time-dependent decrease in von Willebrand factor (VWF):ristocetin cofactor activity, in VWF:antigen activity and factor VIII activity (mean+/-SD) to 35+/-18, 55+/-23 and 53+/-15% of baseline levels after 6 h storage, respectively. Patients with type 2 VWD and non-detectable VWF:ristocetin cofactor activity did not demonstrate such drastic cold-induced losses in VWF and factor VIII levels. Storage of plasma caused only minor changes in VWF levels. The cold-induced loss in VWF might thus depend on the presence of platelets and of high molecular weight VWF. Chilling of platelets induces a clustering of the glycoprotein Ib subunit. We therefore hypothesize that cold-induced loss in VWF might be due to a cold-promoted binding of VWF to glycoprotein VWF receptor Ib alpha. These results suggest a serious potential for misdiagnosis of haemophilia or VWD due to inappropriate pre-analytical handling of blood.