Prevalence of Thrombophilia in Women with Recurrent Early Miscarriage, and a Systematic Review of the Literature

Abstract

Background: There are many studies reporting a disproportionally high prevalence of thrombophilia in women with a history of recurrent miscarriage, which has led to over diagnosis and treatment, without an improvement in clinical outcomes. Methods: This is a retrospective cohort study of 1155 women between 2012 and 2017. All patients had three or more first trimester miscarriages and a full thrombophilia screen. We reviewed all the available literature related to causes of recurrent miscarriages. We ascertained the prevalence of thrombophilia in the study population and compared it with historical and published prevalence in the general population. Findings: The overall prevalence of thrombophilia in our study population is 9.2% (106/1155) with the majority of cases positive for inherited thrombophilia, 8.1% (94/1155) which is similar to the general population; Factor V Leiden (FVL) (4.9%; 57/1155) and Prothrombin Gene Mutation (PGM) (2.9%; 34/1155) were the most common thrombophilias. Only 1% (12/1155) tested positive for acquired thrombophilia. Persistent positive lupus anticoagulant (LA) was found in 0.5% (6/1155) and persistent positive anticardiolipin (ACL) antibodies with a value ≥40 U/ml 0.5% (6/1155) of patients. Both tests were performed a minimum of 12 weeks apart; meeting the revised Sapporo criteria for a diagnosis of antiphospholipid syndrome. Interpretation: Women with recurrent miscarriage have a low prevalence of acquired thrombophilia, albeit higher than the general population, and a similar prevalence of inherited thrombophilia to the general population. Our findings of inherited thrombophilia are in agreement with the literature and we therefore do not recommend testing or treatment. When we applied the revised Sapporo criteria, we found a lower prevalence of acquired thrombophilia among miscarriage patients than what has previously been published. However, despite the low percentage, the prevalence is higher among the miscarriage population when compared to the general population. We therefore recommend screening for antiphospholipid antibodies and lupus anticoagulant, but it is important to adhere to the revised Sapporo criteria to define a diagnosis of antiphospholipid syndrome. Trial Registration: This study is registered with International Prospective Register of systematic Reviews PROSPERO 2020 CRD42020223554. Funding: None Declaration of Interest: None Ethical Approval: This study has been approved by NHS Health Research Authority (HRA) (IRAS ID: 281484, REC reference 20/HRA/6376)