Acquired Activated Protein C Resistance, Thrombophilia and Adverse Pregnancy Outcomes: A Study Performed in an Irish Cohort of Pregnant Women

Abstract

The combination of thrombophilia and pregnancy increases the risk of thrombosis and the potential for adverse outcomes during pregnancy. The most significant common inherited risk factor for thrombophilia is activated protein C resistance (APCR), a poor anticoagulant response of APC in haemostasis, which is mainly caused by an inherited single-nucleotide polymorphism (SNP), factor V G1691A (FV Leiden) (FVL), referred as inherited APCR. Changes in the levels of coagulation factors: FV, FVIII, and FIX, and anticoagulant factors: protein S (PS) and protein C (PC) can alter APC function causing acquired APCR. Prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T are prothrombotic SNPs which in association with APCR can also increase the risk of thrombosis amongst Caucasians. In this study, a correlation between an acquired APCR phenotype and increased levels of factors V, VIII, and IX was demonstrated. Thrombophilic mutations amongst our acquired APCR pregnant women cohort are relatively common but do not appear to exert a severe undue adverse effect on pregnancy.

Factors contributing to APC-resistance in women with recurrent spontaneous miscarriages: Indian perspective

“…Nevertheless, the strength of association between recurrent miscarriages and various thrombophilic risk factors contributing to APCR still remains to be elucidated. In this prospective case-control study, the prevalence of APCR in Indian patients with recurrent pregnancy losses was found to be 17.4% which is similar to the observations of most other published studies [2,6,7].…”

“…Spontaneous abortion may take place in response to an increased coagulation imbalance. Balbas et al found a strong positive correlation of elevated FV and FVIII levels with an acquired APCR phenotype [6]. But we could demonstrate a statistically significant correlation of adverse pregnancy outcomes only with respect to FVIII levels in comparison to normal controls [6,12,13].…”

“…Balbas et al found a strong positive correlation of elevated FV and FVIII levels with an acquired APCR phenotype [6]. But we could demonstrate a statistically significant correlation of adverse pregnancy outcomes only with respect to FVIII levels in comparison to normal controls [6,12,13]. We also chose the 95th percentile of control population distribution as cut-off value for FV and FVIII levels, which corresponded to an absolute value of 145 IU/dL and 120 IU/dL respectively, which is still lower than the reference value of 150 IU/dL, previously reported as a thrombophilic risk factor.…”

Risk of Postoperative Venous Thromboembolism Among Pregnant Women

“…2 Despite the physiological increase in body fluid during the antepartum period as partly reflected by lower serum sodium levels, pregnancy was associated with postoperative VTE. These results suggested the involvement of other factors such as increased procoagulant factors (i.e., fibrinogen, factor VIII, and von Willebrand factor) 18 and reduced anticoagulant factors (i.e., protein C and protein S), 19 as well as venous compression by enlarged uterus. 2 The higher prevalence of emergent surgery among pregnant women may reflect an effort of physicians to avoid surgical complications.…”

Polimorfismos genéticos relacionados à hemostasia e a sua relação com abortos espontâneos recorrentes

“…No estudo BRATROS, a frequência desse polimorfismo em pacientes com TV foi de 6,6%, enquanto que em indivíduos saudáveis foi de 1,2% (Pieroni et al, 2007) Na gravidez, cerca de 17% da mulheres que apresentavam TEV eram heterozigotas para essa mutação (Middeldorp et al, 2001). Também foi descrito que a presença desse polimorfismo aumenta em cerca de dez vezes o risco de ocorrência de trombose durante a gestação, além de aumentar em cerca de quatro vezes a chance de eventuais complicações obstétricas (Kupferminc et al, 1999;Sedano-Balbás et al, 2011).…”