当前位置： SCI文献检索 > BRITISH JOURNAL OF HAEMATOLOGY期刊下所有文献 > The generation of thrombin in vivo induces the selective loss of high molecular weight multimers of von Willebrand factor and the reversible sequestration of platelets.

The generation of thrombin in vivo induces the selective loss of high molecular weight multimers of von Willebrand factor and the reversible sequestration of platelets.

Abstract：

:Various levels of thrombin generation were induced by the infusion of a combination of factor Xa (F.Xa) and phosphatidylcholine/phosphatidylserine (PCPS) vesicles into normal dogs and non-human primates. In the dog, an immediate loss of von Willebrand factor antigen (vWF:Ag) with a progressive recovery to normal levels by 45 min was observed. Multimeric assay demonstrated a selective loss of high molecular weight multimers (HMWM) with subsequent replacement. At low doses, in non-human primates (chimpanzees), identical changes to those seen in the dog were observed and this was associated with an equivalent loss of ristocetin co-factor activity (vWF:RCoF). At high dose a reversal of the wWF response occurred with levels increasing to twice that of baseline values by 2 min and multimeric analysis demonstrated the presence of abnormally large multimers and increased vWF:RCoF specific activity, suggesting that the response at each dosage reflected a net balance of consumption over release. This was supported by in vitro simulation where increasing thrombin generation was associated with a selective loss of HMWM without replacement. In both species, an immediate fall in platelet count occurred and this was directly correlated with the amount of thrombin generated. Full recovery occurred within 45 min and isotopic labelling studies demonstrated that platelet sequestration rather than consumption was occurring. These studies demonstrate that thrombin generation in vivo is associated with a selective loss of the multimeric forms of vWF known to interact with platelets and this may provide an in vivo model to characterize the physiology/pathophysiology of this primary event in haemostasis.

journal_name

Br J Haematol

journal_title

British journal of haematology

authors

Toh CH,Hoogendoorn H,Giles AR

doi

10.1111/j.1365-2141.1993.tb03219.x

subject

Has Abstract

pub_date

1993-12-01 00:00:00

pages

751-60

issue

eissn

0007-1048

issn

1365-2141

journal_volume

pub_type

杂志文章

在线工具

The generation of thrombin in vivo induces the selective loss of high molecular weight multimers of von Willebrand factor and the reversible sequestration of platelets.