How to manage a patient with a positive lupus anticoagulant (LA)?

From the Guidelines

Patients with a positive lupus anticoagulant (LA) should be managed with prophylactic anticoagulation therapy with heparin or low molecular weight heparin (LMWH) during assisted reproductive technology (ART) procedures to prevent thrombotic complications. This approach is based on the increased risk of thrombosis associated with elevated estrogen levels during ovarian stimulation, as highlighted in the 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases 1.

Key considerations in managing patients with LA include:

• The use of prophylactic anticoagulation with heparin or LMWH in asymptomatic aPL-positive patients during ART procedures to mitigate the risk of thrombosis
• The recommendation for prophylactic dosing of enoxaparin, usually 40 mg daily, started at the beginning of ovarian stimulation, withheld 24–36 hours prior to oocyte retrieval, and resumed following retrieval 1
• The importance of consulting with a reproductive endocrinology and infertility specialist to determine the optimal duration of prophylactic LMWH for asymptomatic aPL-positive patients undergoing ovarian stimulation
• The consideration of ovarian stimulation protocols that yield lower peak serum estrogen levels, such as those incorporating aromatase inhibitors, to reduce the risk of thrombosis or ovarian hyperstimulation syndrome 1

In terms of specific anticoagulation regimens, prophylactic anticoagulation with heparin or LMWH is conditionally recommended for asymptomatic aPL-positive patients during ART procedures, with the goal of preventing thrombotic complications while minimizing the risk of bleeding or other complications 1. For patients with a history of thrombotic events or other high-risk features, more intensive anticoagulation regimens may be necessary, and should be individualized based on the patient's specific clinical circumstances and risk factors.

From the Research

Management of Patients with Positive Lupus Anticoagulant

• The management of patients with a positive lupus anticoagulant (LA) involves anticoagulation therapy, which is central to the treatment of antiphospholipid syndrome (APS) 2.
• The mainstay of anticoagulation in patients with thrombotic APS is warfarin or an alternative vitamin K antagonist (VKA) and, in certain situations, low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) 2.
• Accurate assessment of anticoagulation intensity is crucial for optimal anticoagulant dosing, and the international normalized ratio (INR) may not be representative of anticoagulation intensity in patients with APS on warfarin due to an interaction between LA and the thromboplastin reagent used in the INR determination 2.

Anticoagulant Therapy

• Antiaggregant and anticoagulant drugs, such as coumadin derivatives (warfarin and acenocumarol), heparin, and aspirin, are essential in the management of APS in patients with primary Hughes' syndrome or systemic lupus erythematosus 3.
• The use of direct oral anticoagulants (DOACs) can interfere with LA testing, and strategies to mitigate these interferences include avoidance of testing while patients are on such anticoagulants, temporarily switching to an anticoagulant with less assay interference, testing for LA at nadir levels of anticoagulants, and/or use of anticoagulant neutralizers 4.

Clinical Relevance of Isolated Lupus Anticoagulant Positivity

• Isolated LA positivity has been found to be strongly associated with vascular thrombosis, even better than triple-positive samples 5.
• The presence of anti-phosphatidylserine/prothrombin antibodies could not explain LA positivity in isolated LA, and isolated LA showed a weaker LA activity compared with triple-positive patients 5.

Pregnancy Outcome

• The use of LMWH and aspirin in women with systemic lupus erythematosus and antiphospholipid syndrome has been found to be associated with a higher risk of maternal and perinatal complications, despite anticoagulant treatment 6.
• Hypertensive disorders of pregnancy and preterm birth were found to be more frequent in women treated with LMWH and aspirin compared with those not receiving anticoagulant treatment 6.