Procarboxypeptidase U (TAFI) contributes to the risk of thrombosis in patients with hereditary thrombophilia

Heylen, Evelien; Miljic, Predrag; Willemse, Johan; Djordjevic, Valentina; Radojkovic, Dragica; Colovic, Milica; Elezovic, Ivo; Hendriks, Dirk

doi:10.1016/j.thromres.2009.01.005

« Previous Next »Thrombosis Research
Volume 124, Issue 4 , Pages 427-432, September 2009

Procarboxypeptidase U (TAFI) contributes to the risk of thrombosis in patients with hereditary thrombophilia

Evelien Heylen
- Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium
- Both authors contributed equally to this study.
- E. Heylen is a research assistant of the Fund for Scientific Research Flanders (FWO-Vlaanderen).
Predrag Miljic
- Institute of Hematology, University Clinical Centre of Serbia, Belgrade, Serbia
- Both authors contributed equally to this study.
Johan Willemse
- Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium
Valentina Djordjevic
- Institute of Molecular Genetics and Genetic Engineering, Belgrade, Serbia
Dragica Radojkovic
- Institute of Molecular Genetics and Genetic Engineering, Belgrade, Serbia
Milica Colovic
- Institute of Hematology, University Clinical Centre of Serbia, Belgrade, Serbia
Ivo Elezovic
- Institute of Hematology, University Clinical Centre of Serbia, Belgrade, Serbia
Dirk Hendriks
- Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium
- Corresponding author. Laboratory of Medical Biochemistry, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium. Tel.: +32 3 820 27 27; fax: +32 3 820 27 45.

Received 2 September 2008; received in revised form 8 January 2009; accepted 12 January 2009.

Abstract

Introduction

It is considered that high plasma levels of procarboxypeptidase U (proCPU or TAFI) can promote the development of thrombosis, but data comparing proCPU levels in thrombophilia carriers and healthy subjects are rather scarce. Moreover, the results of previous studies on the risk of thrombosis related to high proCPU concentration in this population were not consistent. Although the 325 polymorphism of proCPU has a significant effect on the CPU half-life, it's influence on the risk of thrombosis or spontaneous pregnancy loss in carriers of hereditary thrombophilia is not clear.

Materials and Methods

The study population consisted of 144 thrombophilic patients (94 heterozygous and 10 homozygous carriers of FV Leiden, 26 heterozygous carriers of the prothrombin G20210A variation and 14 double carriers of FV Leiden and FII variation) and 69 healthy controls.

Results

The results show that patients with inherited thrombophilia have a tendency toward lower mean proCPU plasma levels compared to healthy controls, however, this difference was only significant in carriers of FII G20210A (p=0.014). A higher frequency of the most stable Ile325Ile proCPU was seen among carriers of FII G20210A mutation compared to the control group (19% vs 7%; p=0.186).

In the second part of the study proCPU as a risk factor for thrombosis was evaluated. In heterozygous carriers of FV Leiden or FII G20210A high levels of proCPU conferred to an almost 4-fold increased risk for spontaneous onset thrombosis. The more stable Ile325Ile proCPU seems to impose a higher risk for clinical manifestation of the thrombophilic condition. Finally, a significant positive correlation between F1+2 and proCPU concentration was seen.

Conclusion

The increased risk of thrombosis in thrombophilia patients is not only ascribable to an increased thrombin generation, but also high levels of proCPU and the presence of the 325Ile genotype tip the balance towards thrombotic tendency even further.

Abbreviations: FV Leiden, Factor V Leiden, proCPU, procarboxypeptidase U, CPU, carboxypeptidase U, TAFI, Thrombin Activatable Fibrinolysis Inhibitor, TAFIa, activated Thrombin Activatable Fibrinolysis Inhibitor, IIa, thrombin, TM, thrombomodulin, PPACK, D-phenylalanyl-L-prolyl-arginyl chloromethylketone.