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

Heylen, Evelien; Miljić, Predrag; Willemse, Johan; Đorđević, Valentina; Radojković, Dragica; Colović, Milica; Elezović, Ivo; Hendriks, Dirk

(Pergamon-Elsevier Science Ltd, Oxford, 2009)

TY  - JOUR
AU  - Heylen, Evelien
AU  - Miljić, Predrag
AU  - Willemse, Johan
AU  - Đorđević, Valentina
AU  - Radojković, Dragica
AU  - Colović, Milica
AU  - Elezović, Ivo
AU  - Hendriks, Dirk
PY  - 2009
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/399
AB  - 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 I'll 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.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Thrombosis Research
T1  - Procarboxypeptidase U (TAFI) contributes to the risk of thrombosis in patients with hereditary thrombophilia
EP  - 432
IS  - 4
SP  - 427
VL  - 124
DO  - 10.1016/j.thromres.2009.01.005
ER  - 
@article{
author = "Heylen, Evelien and Miljić, Predrag and Willemse, Johan and Đorđević, Valentina and Radojković, Dragica and Colović, Milica and Elezović, Ivo and Hendriks, Dirk",
year = "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 I'll 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.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Thrombosis Research",
title = "Procarboxypeptidase U (TAFI) contributes to the risk of thrombosis in patients with hereditary thrombophilia",
pages = "432-427",
number = "4",
volume = "124",
doi = "10.1016/j.thromres.2009.01.005"
}
Heylen, E., Miljić, P., Willemse, J., Đorđević, V., Radojković, D., Colović, M., Elezović, I.,& Hendriks, D.. (2009). Procarboxypeptidase U (TAFI) contributes to the risk of thrombosis in patients with hereditary thrombophilia. in Thrombosis Research
Pergamon-Elsevier Science Ltd, Oxford., 124(4), 427-432.
https://doi.org/10.1016/j.thromres.2009.01.005
Heylen E, Miljić P, Willemse J, Đorđević V, Radojković D, Colović M, Elezović I, Hendriks D. Procarboxypeptidase U (TAFI) contributes to the risk of thrombosis in patients with hereditary thrombophilia. in Thrombosis Research. 2009;124(4):427-432.
doi:10.1016/j.thromres.2009.01.005 .
Heylen, Evelien, Miljić, Predrag, Willemse, Johan, Đorđević, Valentina, Radojković, Dragica, Colović, Milica, Elezović, Ivo, Hendriks, Dirk, "Procarboxypeptidase U (TAFI) contributes to the risk of thrombosis in patients with hereditary thrombophilia" in Thrombosis Research, 124, no. 4 (2009):427-432,
https://doi.org/10.1016/j.thromres.2009.01.005 . .
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