Tissue factor‐dependent blood coagulation is enhanced following delivery irrespective of the mode of delivery

Abstract

Summary. Background: The risk of thrombosis is clearly increased in the postpartum period. Mice with a targeted deletion of the transmembrane domain of tissue factor (TF) develop serious activation of blood coagulation and widespread thrombosis after delivery. Objective and methods: We hypothesized that TF, abundantly present in placental tissue, is released during delivery, resulting in the activation of blood coagulation. We measured sensitive markers for TF-dependent activation of coagulation before and after induction of labor in two groups: a vaginal delivery (VAG) group and a cesarean section (CS) group. Results: One hour after delivery, soluble TF (sTF) significantly increased in both groups [VAG group (mean ± SD) 226 ± 42 to 380 ± 42 pg mL )1 and CS group 193 ± 17 to 355 ± 44 pg mL]. The day after delivery, sTF was somewhat less increased. Both groups also showed an increase in factor VIIa, indicating activation of the TF pathway of coagulation. Indeed, after delivery, TF-dependent coagulation, as measured by the TF clotting time assay, was significantly enhanced. Increased plasma levels of prothrombin fragment 1 + 2 and thrombin-antithrombin complexes demonstrated thrombin generation following delivery. TF pathwaydependent activation of coagulation upon delivery was not blocked by TF pathway inhibitor and was not dependent on the mode of delivery. Conclusion: The postdelivery increase in TFdependent activation of coagulation is likely to be a natural mechanism to prevent excessive blood loss during and after delivery, and may also indicate a novel mechanism by which puerperal women have an increased risk of venous thromboembolism.

Impact de l’âge maternel avancé sur les profils de coagulation thrombo-élastographique du péripatum: une étude observationnelle prospective exploratoire

“…Within the first postpartum week, factor II, factor VII, factor IX, C-reactive protein, fibrinogen, antithrombin, and markers of thrombin generation can remain at pre-delivery levels or increase after delivery. [31][32][33] In keeping with these observations, the incidence of postpartum VTE is highest during the first postpartum week. 6,34,35 It is unclear when peak hypercoagulable changes occur during the early postpartum period or whether the risk of postpartum VTE is influenced to a greater degree by dynamic changes in the maternal coagulation profile.…”

“…The median [IQR] ages of women were 38 [37][38][39][40][41] yr and 29 [25][26][27][28][29][30][31][32][33][34] yr in the AMA and non-AMA groups, respectively (Table 1). Other maternal demographic and obstetric characteristics were similar in both groups (Table 1).…”

“…Nous avons utilisé un modèle de régression linéaire d'effets mélangés (SAS Ò PROC MIXED) pour évaluer les différences entre les groupes concernant les résultats individuels des paramètres thrombo-élastographiques et de coagulation. Résultats Les âges médians (intervalle interquartile) des femmes étaient de 38 (37-41) ans et 29 (25)(26)(27)(28)(29)(30)(31)(32)(33)(34) ans pour, respectivement, les groupes AMA et non AMA (P \ 0,001). Nous n'avons observé aucun effet statistiquement significatif de groupe d'étude sur les paramètres thrombo-élastographiques ou sur les paramètres de laboratoire de la coagulation.…”

“…The aim of this prospective observational study was to compare peripartum thromboelastography parameters of AMA and non-AMA women undergoing elective Cesarean delivery (CD). [25][26][27][28][29][30][31][32][33][34] yr in the AMA and non-AMA groups, respectively (P \ 0.001). We observed no statistically significant effect of study group on any thromboelastographic or laboratory coagulation parameters.…”

Use of thromboelastography to guide thromboprophylaxis after caesarean section

“…Pregnancy-related pharmacokinetic changes cause increases in glomerular filtration rate, drug protein binding, volume of distribution and enhanced tissue factor dependent blood coagulation which in turn lead to relative heparin resistance. 20,21 The finding was surprising since the dose of UH used (7500 IU) was higher than that used in the non-obstetric population (typically 5000 IU), a choice based on the increased heparin requirement in pregnancy. 8,22 The current findings complement those of Stirrup et al, 23 who measured anti-factor Xa levels following UH injected subcutaneously at doses of 5000, 7500 and 10 000 IU after CS.…”