Platelet von Willebrand factor: an important determinant of the bleeding time in type I von Willebrand's disease

Gralnick, Harvey R.; Rick, Margaret E.; McKeown, Laurie P.; Williams, Sybil B.; Parker, Robert I.; Maisonneuve, P.; Jenneau, Christine; Sultan, Yvette

doi:10.1182/blood.v68.1.58.58

Cited by 97 publications

(37 citation statements)

References 13 publications

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“…Two hypotheses may explain our findings. First, the concentrate infusion does not correct the platelet VWF defect, and many basic and clinical studies have emphasized the key role of platelet VWF in mediating platelet adhesion and aggregation to injured vessels especially at very high shear rates (Gralnick et al , 1986; Castillo et al , 1991, 1997; Fressinaud et al , 1994; Mannucci, 1995). Secondly, no concentrate today exhibits an intact multimeric structure (Mannucci et al , 1994) and the very large VWF multimers (like those contained in storage sites) are known to be the most effective in primary haemostasis.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic monitoring of von Willebrand disease: interest and limits of a platelet function analyser at high shear rates

et al. 1999

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We have evaluated the position of the Platelet Function Analyzer PFA‐100TM in the management of 41 patients with von Willebrand disease (VWD) receiving either desmopressin (23 patients with type 1, five with type 2M, three with type 2A and three with type 2B) or von Willebrand factor (VWF) concentrates (four patients with type 3, two with type 2M ‘type B’, two with type 2A and one type 1 ‘platelet low’). In all patients the following were studied before and 30 min after infusion of desmopressin and/or VWF concentrates: VWF ristocetin cofactor activity (VWFRCo), bleeding time (BT) and closure time with the PFA‐100 using ADP (CT‐ADP) as well as epinephrine (CT‐Epi) cartridges. After the infusion of desmopressin, the CT was modified in the same way as the VWFRCo levels, being always normalized in patients with type 1 and not constantly corrected in those with type 2. Thus, our results indicated that the measurement of the CT enabled a quick and accurate evaluation of the response to desmopressin which, in fact, measured the releasable VWF cellular compartment containing the highly multimerized forms of VWF. For patients with type 2 or 3 VWD who were non‐responsive to desmopressin, VWF concentrates corrected the VWFRCo defect but not the CT as none of these patients had a normal platelet VWF content and the VWF concentrates did not contain the ultralarge VWF multimers. In conclusion, the very high shear conditions in the PFA‐100 make it very sensitive to the contribution of platelet VWF and to the ultralarge VWF multimers, indicating that the evaluation of the CT is a very simple and rapid tool to discriminate between good and non‐responders to desmopressin.

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Section: Discussionmentioning

confidence: 99%

Therapeutic monitoring of von Willebrand disease: interest and limits of a platelet function analyser at high shear rates

et al. 1999

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“…On the other hand, patients belonging to the platelet low phenotype have consistently prolonged bleeding times, even when their plasma vWF is similar to or higher than that in the platelet normal patients (26). Finally, the correlation coefficient between platelet vWF activity and the bleeding time is high (r = +0.80), whereas there is little correlation between the latter and plasma vWF (r = +0.17) (43). Obviously, these observations are not meant to indicate that a defect of platelet vWF is the only or main determinant of the bleeding time prolongation, because the few individuals who carry the phenotype of low platelet/ normal plasma vWF have normal bleeding times and do not bleed excessively (25,27).…”

Section: Significance Of Platelet Vwf In Vwdmentioning

confidence: 95%

Platelet von Willebrand factor in inherited and acquired bleeding disorders.

Mannucci

1995

Proc. Natl. Acad. Sci. U.S.A.

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“…The concentration of platelet vWF can be measured as an additional parameter, although the lack of standardization makes it difficult to compare the results of this test with those from other laboratories. 45,46 The Laurell rocked electrophoresis, 47 which was previously most commonly used, has been replaced widely by the better standardized and much more sensitive enzyme-linked immunosorbent assay (ELISA) methods. 48 Routinely, polyclonal antibodies are preferred because they show no epitope restriction.…”

Section: Vwf Antigenmentioning

confidence: 99%

Laboratory Diagnosis of Congenital von Willebrand Disease

Budde¹,

Drewke²,

Mainusch³

et al. 2002

Semin Thromb Hemost

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Von Willebrand disease (vWD) is caused by quantitative or qualitative defects, or both, of the von Willebrand factor (vWF), a multimeric high-molecular glycoprotein (GP). Typically, it affects the primary hemostatic system, which is reflected by a mucocutaneous bleeding tendency simulating a platelet function defect. The vWF promotes its function in two ways: (1) by supporting platelet adhesion to the injured vessel wall under conditions of high shear forces and (2) by its carrier function for factor VIIIc (FVIIIc) in plasma. Because of the complexity of the disease, diagnosis of vWD is one of the most challenging of any coagulation disorder. The stepwise diagnosis of vWD includes patients and family history, screening procedures (bleeding time [BT], filter tests, platelet counts, activated partial thromboplastin time [aPTT]), confirmatory tests (vWF antigen [vWF:Ag], vWF ristocetin cofactor activity [vWF:RCo], vWF collagen-binding [vWF:CB] assay, ristocetin-induced platelet aggregation [RIPA], FVIIIc) and tests for final classification (multimeric analysis, FVIII binding capacity of vWF [vWF:FVIIIB], platelet vWF). In 1999, we classified 303 patients with congenital vWD as type 1 (n = 122), type 2 (n = 171), and type 3 (n = 10). Type 2 was further subdivided into type 2A (n = 126), type 2B (n = 17), type 2M (n = 22), and type 2N (n = 6). Type 2A showed a remarkable heterogeneity, with only 27.8% (n = 36) of the "classic" IIA pattern. The other high-frequency patterns were type IB (25.4% n = 32) and type IIE/F/H-like structural abnormalities (28.6% n = 36). The spectrum was completed with samples from patients with types 2D, 2C, 2C Miami, smeary structures, and other rare subtypes (together 18.9% n = 23).

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Platelet von Willebrand factor: an important determinant of the bleeding time in type I von Willebrand's disease

Cited by 97 publications

References 13 publications

Therapeutic monitoring of von Willebrand disease: interest and limits of a platelet function analyser at high shear rates

Therapeutic monitoring of von Willebrand disease: interest and limits of a platelet function analyser at high shear rates

Platelet von Willebrand factor in inherited and acquired bleeding disorders.

Laboratory Diagnosis of Congenital von Willebrand Disease

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