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Thrombin-activatable fibrinolysis inhibitor antigen and TAFI activity in patients with APC resistance caused by factor V Leiden mutation.

Abstract：

:Thrombin-activatable fibrinolysis inhibitor (TAFI), also known as procarboxypeptidase U or plasma procarboxypeptidase B, is a relatively recently described plasma glycoprotein synthesised in the liver. It can be activated into active enzyme TAFIa (carboxypeptidase U or plasma carboxypeptidase B) by a complex of thrombin/thrombomodulin. TAFIa can potentially inhibit fibrinolysis by removing carboxyterminal lysine residues from partially degraded fibrin, decreasing plasminogen binding on the surface of fibrin, which thereby results in a decrease of the fibrinolytic activity. Since TAFI represents a connection between coagulation and fibrinolysis, it can be expected that TAFI levels are altered in different thrombotic and hemorrhagic diseases. Thrombin generation is increased in patients with activated protein C (APC) resistance, while it has been shown that APC has profibrinolytic effect. Therefore, changes in TAFI level should be found in patients with APC resistance due to factor V Leiden (FV Leiden) mutation. TAFI antigen (including TAFI, TAFIa and the inactive form TAFIai) and TAFI activity were determined in 17 female patients heterozygous for FV Leiden mutation while 13 healthy volunteers were controls. No statistically significant difference in levels of TAFI antigen was observed. TAFI activity was significantly reduced in APC resistance patients compared to control (P=.018). The nondifference in TAFI antigen, together with the decrease of TAFI activity level, can be explained by activation of TAFI to TAFIa and shifting of equilibrium towards an increase of the latter. This can be an indirect proof that TAFIa is increased in patients with APC resistance due to FV Leiden mutation, indicating that downregulation of fibrinolysis can be an additional risk factor for thrombosis in these patients.

journal_name

Thromb Res

journal_title

Thrombosis research

authors

Antovic JP,Blombäck M

doi

10.1016/s0049-3848(02)00072-5

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

59-62

issue

1

eissn

0049-3848

issn

1879-2472

pii

S0049384802000725

journal_volume

106

pub_type

杂志文章

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