Elsevier

Thrombosis Research

Volume 104, Issue 1, 1 October 2001, Pages 1-6
Thrombosis Research

REGULAR ARTICLE
Activity and Antigen Levels of Thrombin-Activatable Fibrinolysis Inhibitor in Plasma of Patients With Disseminated Intravascular Coagulation

https://doi.org/10.1016/S0049-3848(01)00331-0Get rights and content

Abstract

We measured the plasma levels of thrombin-activatable fibrinolysis inhibitor (TAFI) activity and antigen in patients with disseminated intravascular coagulation (DIC) to examine the relationship between hypofibrinolysis and the pathogenesis of DIC. TAFI activity and antigen levels in the plasma were both significantly low in patients with DIC. TAFI activity in plasma was correlated with TAFI antigen, indicating that activity and antigen correspond well. The decrease of TAFI activity in DIC may be due to enhanced consumption. Since the plasma thrombin–antithrombin III complex (TAT) level was found to be elevated in DIC, increase of thrombomodulin–thrombin complex generation is suggested in this state. TAFI activity and antigen levels were negatively correlated with TAT and D-dimer, suggesting that the plasma levels of TAFI are reduced by thrombin generation. Since TAFI was not correlated with fibrinogen, plasma–α2plasmin inhibitor complex (PPIC) and tissue type plasminogen activator/plasminogen activator inhibitor-1 (tPA/PAI-1) complex, TAFI might be a secondary modulator of fibrinolysis. The TAFI activity in plasma was significantly low in patients with infection and in those with organ failure, suggesting that TAFI may play an important role in the mechanism of organ failure in DIC-associated sepsis. In brief, TAFI may play an important role in the pathogenesis of DIC and organ failure.

Section snippets

Materials and Methods

We examined 36 patients with DIC, 15 with pre-DIC, 63 without DIC and 17 healthy volunteers. The underlying diseases of the patients were leukemia (23 patients), malignant lymphoma (17 patients), infection (18 patients), solid cancer (16 patients), and other diseases (40 patients) (Table 1). The diagnosis of DIC was based on a modified version of the criteria established by the Japanese Ministry of Health and Welfare [9]. Patients with high levels thrombin–antithrombin III complex (TAT),

Results

The plasma levels of TAT, PPIC, D-dimer, thrombomodulin and tPA/PAI-1 complex (P<.01) were significantly higher in patients with DIC than in those with non-DIC and healthy control; the plasma levels of fibrinogen were significantly lower (P<.01) in patients with DIC than in those with non-DIC. The plasma levels of TAT, D-dimer and tPA/PAI-1 complex were significantly (P<.01) higher in patients with DIC than in those with pre-DIC. Plasma levels of D-dimer and thrombomodulin were significantly

Discussion

The plasma levels of TAT, PPIC and D-dimer were significantly increased and the plasma levels of fibrinogen were significantly decreased in patients with DIC as compared to non-DIC patients, suggesting the occurrence of hypercoagulability and hyperfibrinolysis in DIC patients [10]. Bleeding tendency is frequently observed in DIC, particularly in case of acute promyelocytic leukemia. Previous studies [10], [11] have showed that significant changes in the plasma levels of fibrinogen, PPIC and

Acknowledgements

This work was supported in part by a Grant-In-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan.

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