Circulating pro- and anticoagulant levels in normal and complicated primigravid pregnancies and their relationship to placental pathology

Abstract

We aimed to compare the changes in factor VIII:C, antithrombin, protein C, protein S and fibrinogen in a cohort of low-risk primigravida who developed maternal or fetal complications to those who had uncomplicated pregnancies and to correlate these findings with placental pathology. This is a case-control study of 170 cases and 122 controls selected from a prospective cohort of 1,011 low-risk primigravida. Significantly elevated levels of factor VIII:C and significantly decreased levels of antithrombin were seen in women who developed pre-eclampsia (p <0.001), placental infarction (p < 0.001) or had infants with a birth weight < 3rd centile (p < 0.001). Placental villous dysmaturity was significantly associated with raised factor VIII:C (p < 0.001). Women who developed pre-eclampsia showed elevated fibrinogen at 14 weeks (p = 0.03). Significantly higher than normal pregnancy levels of factor VIII:C, in tandem with significantly lower antithrombin levels associated with certain adverse pregnancy outcomes, may be related to underlying placental insufficiency. This is supported by associated placental findings.

Increased contact activated endogenous thrombin potential in pregnant women with preeclampsia

“…Moreover, in agreement with other studies, we observed decreased antithrombin in women with preeclampsia compared with controls [34,35]. It has been suggested, that decreasing levels of antithrombin is associated with clinical worsening of preeclampsia [35].…”

Normal pregnancy is associated with an increase in thrombin generation from the very early stages of the first trimester

“…The prothrombotic state of pregnancy has previously been demonstrated using other laboratory markers [20][21][22]. Protein S and VIII are known to decrease and increase respectively in response to pregnancy although it is unknown exactly at what stage of pregnancy these changes occur.…”

Changes in laboratory markers of thrombotic risk early in the first trimester of pregnancy may be linked to an increase in estradiol and progesterone

“…There are some well recognised changes in coagulation factor concentrations that occur during pregnancy. The concentration of Protein S, both total and free (the latter being the active form), decreases during pregnancy, resulting in a decrease in the downregulation of activated factors V and VIII [8][9][10][11][12] . An increase in factor VIII also occurs, likely secondary to both reduced Protein S and increased VWF levels, the latter extending the half life of FVIII 8,9,12 .…”