S ubtype 2B von Willebrand disease (VWD) is a rare variant of VWD characterized by an increased and often spontaneous binding of von Willebrand factor (VWF) to platelet glycoproteinIbα (GPIbα)(1, 2). Thisresultsinaclearanceofthe most adhesive, high-molecular-weight VWF multimers (HMWM) from the circulation (3, 4). Since the remaining multimers in plasma are less haemostatically effective, patients suffer from a bleeding tendency. The diagnostic hallmark of subtype 2BVWD is the enhanced ristocetin-induced platelet aggregation (RIPA) in patient’s platelet-rich plasma (PRP) at low-dose of ristocetin (0.5 mg/ml), although the ristocetin cofactor activity (VWF: RCo) in patient’s plasma might be normal. The VWF antigen (VWF: Ag) and factor VIII procoagulant activity (FVIII: C) may range from low to normal, whereas the collagen binding activity (VWF: CB) is generally low, consistent with the loss of HMWM from the patient’s plasma (5–8). Thrombocytopenia can be an additional manifestation in subtype 2B VWD. This may be intermittent, mild to severe, and is related to the increased VWF-GPIbα interaction and subsequent platelet aggregation in vivo (9).

Over twenty mutations resulting in subtype 2B VWD have been described (database: www. sheffield. ac. uk/vwf). Most of them are clustered within the large disulfide loop of the A1-domain of VWF, between amino acid residues (aa) Cys1272-Cys1458 (10), a region known to play an important role in the regulation of VWF binding to GPIbα (11, 12). InthisstudywereportontheidentificationofaR1306Wmutation in six patients from two unrelated families with subtype 2BVWDanddiscusstheirvariousphenotypicabnormalities. We also report the presence of a R1306Q mutation in a Belgian patient with subtype 2B VWD.