S. Eichinger et al., Prospective evaluation of hemostatic system activation and thrombin potential in healthy pregnant women with and without factor V Leiden, THROMB HAEM, 82(4), 1999, pp. 1232-1236
Normal pregnancy is associated with alterations of the hemostatic system to
wards a hypercoagulable state and an increased risk of venous thromboemboli
sm. The risk of venous thrombosis is higher in pregnant women with factor V
Leiden (FVL) than in those with wildtype factor V. Routine laboratory assa
ys are not useful to detect hypercoagulable conditions. A prospective and s
ystematic evaluation of hemostatic system activation in women with and with
out FVL during an uncomplicated pregnancy employing more sensitive markers
of hypercoagulability, such as prothrombin fragment 1 + 2 (F1 + 2), thrombi
n-antithrombin complex (TAT), D-Dimer, or the endogenous thrombin potential
(ETP), an indicator of the plasma's potential to generate thrombin, has no
t been performed. We prospectively followed 113 pregnant women with (n = 11
) and without (n = 102) FVL and measured F1 + 2, TAT, D-Dimer and the ETP a
t the 12(th), 22(nd) and 34(th) gestational week as well as 3 months after
delivery (baseline) in each subject. None of the women developed clinical s
igns of venous thromboembolism during pregnancy or postpartum. Pregnant wom
en with and without FVL exhibited substantial activation of the coagulation
and Fibrinolytic system as indicated by a gradual increase of F1 + 2, TAT
and D-Dimer throughout uncomplicated pregnancy up to levels similar to thos
e found in acute thromboembolic events (p < 0.0001 by analysis of variance
for each parameters). Levels of F1 + 2 and TAT were comparable between wome
n with and without FVL, but levels of D-Dimer were significantly higher in
women with FVL than in those without the mutation (p = 0.0005). The ETP rem
ained unchanged in both women with and without FVL at all timepoints. Our d
ata demonstrate a substantial coagulation and fibrinolytic system activatio
n in healthy women with and without FVL during uncomplicated pregnancy. An
elevated F1 + 2, TAT or D-Dimer level during pregnancy is not necessarily i
ndicative for an acute thromboembolic event. The normal ETP in both women w
ith and without FVL suggests that the capacity of the plasma to generate th
rombin after in vitro activation of the clotting system is not affected by
pregnancy. Higher levels of D-Dimer in women with FVL than in women with wi
ldtype factor V at baseline as well as during pregnancy indicate increased
fibrinolytic system activation in carriers of the mutation.