Elevated coagulation factor VIII and the risk for recurrent early pregnancy loss

Abstract

Inherited and acquired thrombophilia are associated with recurrent pregnancy loss. Recently, an increased risk for thromboembolic disease was described for patients with elevated coagulation factor VIII, but it is unknown whether there is also an association to early pregnancy loss. We therefore evaluated the relation between recurrent early pregnancy loss and levels of coagulation factor VIII. We enrolled 49 unrelated Caucasian women with a history of 2-6 early pregnancy losses and 48 healthy controls, who had delivered at least one term infant and had never experienced pregnancy loss. We determined factor V Leiden-, G20210A prothrombin-, MTHFR C677T- and A1298C-gene mutations, levels of antithrombin, protein C, protein S, factor VIII, C-reactive protein and antiphospholipid antibodies. There was a significantly higher rate of pregnancy losses in women with Antiphospholipid Syndrome (p = 0.043). Furthermore, plasma levels of coagulation factor VIII were significantly higher in cases than in controls (130.5 IU/dl +/- 25.4 vs 119.5 IU/dl +/- 24.1; p = 0.032) and appeared independent of C-reactive protein (R = 0.146, p = 0.323 in cases; R = -0.028, p = 0.850 in controls). The relative risk for recurrent pregnancy loss in women with factor VIII levels above 151 IU/dl (90(th) percentile of controls) was 2.5 (0.7 - 8.9, 95 percent confidence interval), for levels above 156 IU/dl (95(th) percentile of controls) 3.9 (0.8 - 20.0, 95 percent confidence interval). Elevated maternal plasma levels of coagulation factor VIII tend to be associated with an increased risk for recurrent early pregnancy loss.

Study of Thrombophilia in Recurrent Pregnancy Loss

“…The strongest association of thrombophilia with RPL was observed with protein S deficiency. These data seem to be in agreement with the results of several studies [7,14,17,18]. Marietta et al [18], in their study, evaluated statistically significant association (p = 0.0002) between elevated factor VIII level and early pregnancy failures.…”

“…A number of studies have reported an increased risk of RPL in women with inherited thrombophilia [5][6][7]. In the European prospective cohort study on thrombophilia (EP-COT), a significant association between thrombophilia and miscarriage was reported [8].…”

Recurrent Pregnancy Loss and Thrombophilia

“…On the other hand, new evidence seems to be available for the role of increased maternal plasma levels of clotting factor VIII and the risk of RPL [53]. Furthermore, acquired activated protein C resistance, which is not associated with …”

Coagulation and Fibrinolytic Indices During the First Trimester of Pregnancy in Women With Polycystic Ovary Syndrome: A Preliminary Study

“…Elevated levels of FVIII and FX could lead to hypercoagulability. Factor VIII is a component of the intrinsic coagulation pathway and is associated with the risk of venous thrombosis 13 and increases during a normal pregnancy. 7 Factor X is a vitamin K-dependent plasma glycoprotein that plays a pivotal role in the coagulation cascade, because it is the first enzyme in the common pathway of thrombin formation.…”