Thrombophilia, Inflammation, and Recurrent Pregnancy Loss: A Case-Based Review

Abstract

Recurrent pregnancy loss (RPL) is defined as the loss of two or more pregnancies and is often multifactorial with the majority of miscarriages being due to aneuploidy and anatomic or physiological abnormalities. However, inherited or acquired thrombophilias have also been associated with RPL, albeit inconsistently. While inherited thrombophilias, such as factor V Leiden and prothrombin gene mutation, are relatively prevalent in women with RPL compared with the general population, a causal link has yet to be definitively established. Recently, systemic inflammation, as measured by high-sensitivity C-reactive protein, has also been hypothesized to play a role in infertility. Based on limited prospective trial data, antithrombotic therapy and antiplatelet agents have been proposed as possible tools for the prevention of RPL. Because of the multifactorial nature of RPL and infertility, various clinicians, as obstetricians and gynecologists, endocrinologists, hematologists, or vascular medicine specialists, may be requested to counsel these women. This, together with evidence gaps, frequently leads to distinctly different diagnostic and therapeutic recommendations, especially regarding thrombophilia testing and treatment. Using four case vignettes in this review, we critically appraise the literature and highlight how two clinicians from different subspecialties approach the relationship between RPL, inflammation, and thrombophilia.

The ART of Thromboprophylaxis in the Prevention of Gestational Venous Thromboembolism

“…This is based on the financial, physical, and psychological burden of the fertility treatments and the growing recognition of the thromboembolic complications associated with IVF. 7,26,29,42 Thrombophilia testing can be accomplished at a relatively low cost ($1,100-2,400) relative to an IVF cycle ($15,000-23,000) in the United States and may provide important insights into a patient's individual thromboembolic risk and possibly contributors to recurrent pregnancy loss (RPL), such as the presence of antiphospholipid antibodies. 42,43 As for thrombotic risk in severe thrombophilias (inherited or acquired), data are largely lacking, whereas there are systematic reviews and meta-analyses focusing on pregnancy outcome in women testing positive for antiphospholipid antibodies.…”

“…7,26,29,42 Thrombophilia testing can be accomplished at a relatively low cost ($1,100-2,400) relative to an IVF cycle ($15,000-23,000) in the United States and may provide important insights into a patient's individual thromboembolic risk and possibly contributors to recurrent pregnancy loss (RPL), such as the presence of antiphospholipid antibodies. 42,43 As for thrombotic risk in severe thrombophilias (inherited or acquired), data are largely lacking, whereas there are systematic reviews and meta-analyses focusing on pregnancy outcome in women testing positive for antiphospholipid antibodies. 44,45 Notably, there is paucity of data on thrombotic risk in women with antiphospholipid syndrome (APLA) or in those testing positive for antiphospholipid antibodies without diagnosis of APLA.…”

Low molecular weight heparin treatment reduced apoptosis and oxidative cytotoxicity in the thrombocytes of patients with recurrent pregnancy loss and thrombophilia: Involvements of TRPM2 and TRPV1 channels

“…Some pregnant women exposure to two or more consecutive spontaneous abortions before 20 weeks of gestation and the reproductive disease is called as recurrent pregnancy loss (RPL) 2 . About 2%–3% of couples are affected by the RPL 2 . Several factors such as oxidative toxicity, apoptosis, and thrombocytopenia are involved in the pathophysiology of RPL 3 …”

The postpartum uterine ultrasonographic scale in assessment of uterine involution after cesarean section in treated thrombophilia pregnant patients at term

“…Recurrent pregnancy loss is generated mainly by acquired thrombophilia (antiphospholipid antibody syndrome), according to Alecsandru, 7 while, according to Gandone, 8 inherited thrombophilia (factor V Leiden) is mostly involved.…”

“…[3][4][5] Therefore, antithrombotic treatment in pregnant patients with previous adverse fetal outcomes, and especially thrombophilia, is recommended. 6 Recurrent pregnancy loss is generated mainly by acquired thrombophilia (antiphospholipid antibody syndrome), according to Alecsandru, 7 while, according to Gandone, 8 inherited thrombophilia (factor V Leiden) is mostly involved.…”