Anti-Phosphatidylserine/Prothrombin Antibodies in Healthy Women with Unexplained Recurrent Pregnancy Loss

Abstract

Recurrent pregnancy loss (RPL) affects up to 6% of couples. Although chromosomal aberrations of the embryos are considered the leading cause, 50% of cases remain unexplained. Antiphospholipid Syndrome is a known cause in a few cases. Antiphospholipid antibodies (aPL) anticardiolipin, anti-Beta-2-Glycoprotein-I and Lupus Anticoagulant (criteria aPL) are recommended studies in RPL workup. We tested healthy women with unexplained RPL for criteria aPL and anti-Phosphatidylserine/Prothrombin antibodies (aPS/PT). Patients were classified into three groups according to the number and pregnancy week of RPL: Extra-Criteria (EC), with 2 miscarriages, Early Miscarriage (EM), with ≥3 before pregnancy at week 10 and Fetal Loss (FL), with ≥1 fetal death from pregnancy at week 10. Circulating criteria aPL were absent in 98.1% of EM, 90.9% of FL and 96.6% of EC groups. In contrast, aPS/PT were positive in 15.4% of EM, 15.1% of FL, 16.6% of EC patients and 2.9% in controls. aPS/PT posed a risk for RPL, with an odds ratio of 5.96 (95% confidence interval (CI): 1.85-19.13. p = 0.002) for EM, 7.28 (95% CI: 2.07-25.56. p = 0.002) for FL and 6.56. (95% CI: 1.77-24.29. p = 0.004) for EC. A successful live birth was achieved in all pregnant patients positive for aPS/PT who received treatment with heparin, aspirin and/or hydroxychloroquine.

Keywords: anti-beta-2-glycoprotein-I; anti-phosphatidylserine/prothrombin; anticardiolipin; antiphospholipid syndrome; heparin; hydroxychloroquine; lupus anticoagulant; miscarriage; recurrent pregnancy loss; reproductive immunology.

Figure 1

Positivities of criteria aPL (aPL) and aPS/PT among groups of patients and controls are shown. While positivity of criteria aPL did not surpass 10% in each one of the groups, aPS/PT was positive in 15–18% of patients.

Figure 2

Venn diagrams of overlapping and isolated aPS/PT over criteria aPL. The number of women positive for aPS/PT, aCL and aB2GPI in each one of the groups in which patients were categorized is shown in this figure. LA is absent from this figure because none of our patients resulted in positive values. aPS/PT was mainly found in patients negative for criteria aPL.