Summary
Coagulation activation in pregnancy is further enhanced in preeclampsia. We investigated
whether this results from increased thrombin generation by the plasma itself or its
cell-derived microparticles. Plasma samples were obtained from preeclamptic, normal
pregnant and nonpregnant women (each n = 10). Prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) concentrations were increased in pregnancy
and further increased in preeclampsia. In pregnancy and preeclampsia, increased activated
protein C resistance occurred (APC sensitivity ratio: 3.3 ± 0.8 and 2.5 ± 0.8, both
P < 0.001 vs. nonpregnant). In normal pregnant microparticle-free plasma the thrombin
generation correlated with TAT (r = 0.84, P = 0.005) and APC resistance correlated
with F1+2 (r = 0.68, P = 0.04). In preeclampsia thrombin generation by plasma was increased
(P = 0.005), independent of APC resistance. Thrombin generation by microparticles
was similar in all groups, although different coagulation activation pathways were
utilized, indicating that circulating microparticles are not directly involved in
coagulation activation in pregnancy and preeclampsia. In contrast, APC resistance
can explain coagulation activation in pregnancy, while enhanced coagulation activation
in preeclampsia results, in part, from an increased thrombin generating capacity of
plasma independent of APC resistance.
Keywords
Pregnancy - preeclampsia - coagulation - APC resistance - microparticles