A possible role for activated protein C resistance in patients with first and second trimester pregnancy failure

Abstract

Thrombophilia was recently suggested as a possible factor in recurrent pregnancy losses. We studied prospectively 125 patients (mean age 31.4 +/- 5.6 years) with one or more first or second trimester pregnancy losses for the prevalence of activated protein C resistance (APCR). Proteins C and S antigens, antithrombin III, anticardiolipin, and lupus anti-coagulant were also evaluated. Patients with uterine malformations, hormonal abnormalities, chromosomal translocations and infectious causes were excluded. A control group of 125 women with no past fetal loss were matched with the study group. Whenever the APC-sensitivity ratio (APC-SR) was </=2.2, polymerase chain reaction for factor V mutation (Leiden) was performed. Heterozygosity for the mutation was found in 18 patients (14.4%) compared with seven heterozygous among 125 control group (5. 6%; P < 0.05). Acquired APCR (APC-SR 1.8 and Leiden negative) was revealed in seven patients (5.6%) in the study group and in three of the controls (2.4%; not significant). The rate of preclinical pregnancy losses (17/48) and second trimester miscarriages (10/48) in mutation carriers was significantly higher than in patients with no APCR (25/214) and (14/214) respectively (P < 0.001 and P < 0.01 respectively). Live birth rate was not different between the two groups. Occurrence of APCR with any kind of pregnancy loss calculated per patient, in our study group, was approximately 1/7, 1/4 and 1/5 with one, two and three or more pregnancy losses respectively. These findings suggest that assessment of APCR should be considered in a more extended evaluation of such patients.

Recurrent Pregnancy Loss and Thrombophilia

“…One or more unexplained deaths of a morphologically normal neonate before the 34th week of gestation because of eclampsia or severe eclampsia or placental insufficiency Anticardiolipin antibody (aCL) of IgG and/or IgM isotype in serum or in plasma present in medium or high titer on two or more occasions at least 12 weeks apart Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation Anti-β 2 glycoprotein-I antibody of IgG and/or IgM isotype in serum or in plasma present on two or more occasion at least 12 weeks apart the presence of FVL, has been described in several women with RPL, but also in this case, not all involved mechanisms are known [54].…”

Factor V Leiden thrombophilia

“…However, other evidence suggests that Factor V Leiden also increases the risk for early first-trimester loss. 70,66,96 Other obstetric complications Although preeclampsia, intrauterine growth restriction, and placental abruption may also involve impaired placental perfusion, their association with Factor V Leiden is controversial. The conflicting results reported in different studies may reflect the varying diagnostic and selection criteria, different ethnic groups, and small number of cases included.…”

Can Factor V Leiden and prothrombin G20210A testing in women with recurrent pregnancy loss result in improved pregnancy outcomes?: Results from a targeted evidence-based review

“…Among five studies (conducted in Israel, 95,100,110 Serbia, 80 and Spain 54 ), a phenotypic test, APCR, was used to determine which women would be tested for the F5 variant. The remaining 37 studies genotyped all women.…”