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


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.


CONCLUSIONS
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.
Heylen
Evelien
E
Laboratory of Medical Biochemistry, University of Antwerp, Antwerp, Belgium.
Miljic
Predrag
P
Willemse
Johan
J
Djordjevic
Valentina
V
Radojkovic
Dragica
D
Colovic
Milica
M
Elezovic
Ivo
I
Hendriks
Dirk
D
D000328:Adult; D025901:Carboxypeptidase B2 / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic / Q000235:genetics; D011516:Prothrombin / Q000235:genetics; D019851:Thrombophilia / Q000235:genetics*; D013927:Thrombosis / Q000235:genetics*
D011516:Prothrombin; D025901:Carboxypeptidase B2