High intrinsic coagulation activation may increase arterial thrombosis risk
MedWire News: High levels of activated intrinsic coagulation proteins are associated with an increased risk for arterial thrombosis in young women, study findings indicate.
The strength of this association is increased by oral contraceptive use, but differs for myocardial infarction (MI) and ischemic stroke (IS), report Ale Algra (Leiden University Medical Center, The Netherlands) and colleagues in the journal Circulation.
Recently, intrinsic coagulation proteins, especially factor (F)XII, have been implicated in the pathogenesis of arterial thrombosis, explain the researchers.
In the present study, Algra and team aimed to determine whether high levels of intrinsic coagulation activation are associated with different forms of arterial thrombosis in women aged 18-50 years, and whether oral contraceptive use further increases this risk.
Intrinsic coagulation protein activation was determined by measuring activated protein-inhibitor complexes in 205 women with MI, 175 women with IS, and 638 healthy controls.
The proteins assessed were in complex with C1 esterase inhibitor (FXIIa-C1-INH, FXIa-C1-INH, Kallikrein-C1-INH) or antitrypsin inhibitor (FXIa-AT-INH).
Women with high levels of protein activation, defined as being above the 90th percentile of the controls, had a significantly increased risk for IS compared with women with normal levels. Specifically, the risk was 2.1-, 2.8-, 2.3-, and 4.3-fold higher among women with raised FXIIa-C1-INH, FXIa-C1-INH, FXIa-AT-INH, and Kallikrein-C1-INH, respectively.
The risk for MI was only marginally increased by Kallikrein-C1-INH (odds ratio [OR]=1.5).
In addition, oral contraceptive use in the year before the thrombotic event further increased the risks in all patients regardless of protein activation levels.
However, the increases were more noticeable in the patients with high protein activation. Indeed, women who had high levels of activated Kallikrein-C1-INH and used oral contraceptives had a 23.0-fold increased risk for IS compared with women with neither risk factor.
Algra and co-authors note that their findings contrast with those from similar analyses among men in the Northwick Park Heart Study.
This, along with the fact that oral contraceptive use further increases the risks, raises the question of whether the role of intrinsic coagulation proteins in the pathogenesis of arterial thrombosis is gender-specific, they conclude.
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By Laura Dean