What is the treatment for recurrent miscarriages with elevated dRVVT (dilute Russell's viper venom time) indicating lupus anticoagulants and potential antiphospholipid syndrome (APS)?

From the Guidelines

The treatment for recurrent miscarriages with elevated dRVVT indicating lupus anticoagulants and potential antiphospholipid syndrome (APS) should involve a combination of low-dose aspirin and prophylactic-dose heparin therapy, as recommended by the 2020 American College of Rheumatology guideline 1. The standard regimen consists of aspirin 81-100 mg daily, started before conception and continued throughout pregnancy, along with prophylactic-dose low molecular weight heparin (such as enoxaparin 40 mg subcutaneously once daily or dalteparin 5,000 units subcutaneously once daily) started once pregnancy is confirmed. Some key points to consider in the treatment of recurrent miscarriages with elevated dRVVT include:

• The importance of confirming a complete APS diagnosis with repeat testing of lupus anticoagulant 12 weeks after the initial positive result
• The need for regular monitoring with complete blood counts to check for heparin-induced thrombocytopenia
• The provision of appropriate calcium supplementation to prevent osteopenia from prolonged heparin use
• The consideration of adding hydroxychloroquine (HCQ) to prophylactic-dose heparin or low molecular weight heparin and low-dose aspirin therapy for patients with primary APS, as suggested by recent small studies 1 The mechanism behind this treatment is that aspirin inhibits platelet aggregation while heparin prevents clot formation, addressing the hypercoagulable state caused by antiphospholipid antibodies that can lead to placental thrombosis and subsequent pregnancy loss. It is worth noting that the 2012 American College of Chest Physicians evidence-based clinical practice guidelines also recommend low-molecular-weight heparin for the prevention and treatment of VTE in pregnant women, as well as antepartum administration of prophylactic or intermediate-dose unfractionated heparin or prophylactic low-molecular-weight heparin combined with low-dose aspirin for women who fulfill the laboratory criteria for antiphospholipid antibody (APLA) syndrome and meet the clinical APLA criteria based on a history of three or more pregnancy losses 1. However, the 2020 American College of Rheumatology guideline provides more recent and specific recommendations for the management of reproductive health in rheumatic and musculoskeletal diseases, including APS 1.

From the Research

Treatment for Recurrent Miscarriages with Elevated dRVVT

• The treatment for recurrent miscarriages with elevated dRVVT indicating lupus anticoagulants and potential antiphospholipid syndrome (APS) typically involves antithrombotic therapy using antiplatelet and anticoagulant agents 2, 3, 4.
• For patients with a history of thrombotic events, long-term anticoagulation is usually recommended, while those without previous thrombotic events may focus on reducing additional vascular risk factors 3.
• Pregnancy complications are often managed with low-dose aspirin in association with low molecular weight heparin 3, 4.
• In cases of refractory APS, adding hydroxychloroquine and/or intravenous immunoglobulin to anticoagulation therapy may be beneficial 3.
• The diagnosis of APS requires a persistently positive functional lupus anticoagulant (LA) assay and/or the presence of anti-b2GPI and/or anti-cardiolipin antibodies, together with clinical symptoms 2.

Diagnostic Considerations

• The detection of lupus anticoagulant (LA) requires a prolongation of a phospholipid-dependent clot-based screening assay, noncorrection upon adding normal pooled plasma, and a confirmatory phospholipid dependency test 5.
• Paired LA assays can help evaluate test results, and a reevaluation of laboratory criteria for LA detection may be needed, as negative low-phospholipid screens may not necessarily lack LA 5.

Clinical Implications

• Elevated dRVVT is more frequent in pregnancy, women, and younger age, and is associated with thromboembolic events 5.
• The presence of lupus anticoagulants and APS can increase the risk of recurrent miscarriages and pregnancy complications, highlighting the importance of proper diagnosis and treatment 2, 3, 4.