Differentiation of patients with subtype IIb‐like von Willebrand's disease by means of perfusion experiments with reconstituted blood

Abstract

Four unrelated patients with a bleeding diathesis (bleeding time longer than 30 min), some spontaneous platelet aggregation, thrombocytopenia and large platelets, had decreased levels of factor VIII-von Willebrand factor (FVIII-VWF) related properties and impaired platelet adherence to human artery subendothelium. The largest multimers of plasma FVIII-VWF were absent and enhanced ristocetin induced platelet aggregation in platelet-rich plasma was observed. 'Pseudo-von Willebrand's disease' was excluded, because FVIII-VWF from normal subjects did not initiate platelet aggregation. Perfusion studies with reconstituted blood, consisting of respectively patient platelets in normal plasma or normal platelets in patient plasma, yielded evidence for an intrinsic platelet abnormality in two out of the four patients and a plasma defect in the other two patients. Similar experiments with platelets and plasma from four patients with von Willebrand's disease (VWD) subtype I and four patients with VWD subtype IIa showed that the impaired platelet adherence in blood from these patients was caused by a plasma defect. These experiments indicate that patients with laboratory findings in many respects similar to those originally reported for patients with VWD subtype IIb may represent a heterogeneous group of individuals. The data derived from our study imply that perfusion experiments with reconstituted blood offer a new approach in characterization of these patients, which may be more relevant for the treatment of the patients than characterization by ristocetin induced adsorption of FVIII-VWF to platelets.

Von Willebrand's disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor.

“…Takahashi (23), and one other study with SPA (24). In the latter study, two patients had defects oftheir platelets and two defects in their plasma when studied in perfusion experiments (24). Holmberg et al (5) Recent studies in platelet-type vWd in Japanese patients have shown an abnormality of the GPIb, possibly explaining why the platelets of these patients adsorbed normal vWf without any agonist (23).…”

“…We have previ- ously described a form of vWd similar to that described by Takahashi; however, in our binding studies we employed patients' platelets free of plasma proteins and used purified radiolabeled normal F.VIII/vWf (20). Takahashi (23), and one other study with SPA (24). In the latter study, two patients had defects oftheir platelets and two defects in their plasma when studied in perfusion experiments (24).…”

Laboratory Diagnosis of Congenital von Willebrand Disease

“…Thus, the only ex vivo tests that reflect vWF function are perfusion experiments with high shear forces over defined matrixes (denuded endothelium, collagen preparations). The most frequently used perfusion chambers of Baumgartner et al 38 or Sakariassen et al 39 are not suitable for routine diagnostic procedures and are therefore reserved for scientific work. With the cone and plate aggregometer, 40 defined shear forces can be applied; however, its use as a routine diagnostic instrument has not been thoroughly investigated.…”

Additional variant of type I von willebrand disease

“…They classified it as having a pathophysiologic mechanism in common with either platelet-type VWD or type IIb VWD. Sakariassen et a1 [35] described four patients with subtype IIb VWD, two with the specific defect of intrinsic platelet abnormality, and two with a plasma defect. They concluded that subtype IIb may represent a heterogeneous group.…”