Based on evidence from systematic literature reviews and expert opinions, a task force put together by the European League Against Rheumatism (EULAR) released overarching principles and recommendations for the management of antiphospholipid syndrome (APS) in adults.

This report was published in Annals of the Rheumatic Diseases.

Investigators performed a systematic review of articles focused on laboratory and clinical criteria used to define APS as well as treatment approaches for the management of APS. Recommendations on 12 topics and 3 overarching principles were prepared by the convener and co-convener, including level of evidence and grade of recommendations, and were reviewed and approved by the task force.

Overarching Principles

A high-risk antiphospholipid antibody (aPL) profile is defined as the presence of lupus anticoagulant, multiple aPL positivity (lupus anticoagulant, anticardiolipin antibodies, and/or antibeta2 glycoprotein I antibodies), or persistently high aPL titers. Additional APS risk factors include coexistence of other systemic autoimmune diseases, a history of thrombotic and obstetric APS, and presence of traditional cardiovascular risk factors.

For all aPL-positive individuals, EULAR recommends following general guidelines for the prevention of cardiovascular disease and screening for and management of venous thrombosis risk factors. In high-risk situations, such as surgery, hospitalization, prolonged immobilization, and puerperium, care providers should use low molecular weight heparin.

For all women with APS, counseling is recommended on the use of contraceptives, pregnancy planning, and postmenopausal hormone therapy. Dietary counseling and physical activity are recommended in all patients with APS, and patients receiving vitamin K antagonists should be counseled on treatment adherence, drug and food interactions, and receive close international normalized ratio (INR) monitoring, especially when initiating treatment or bridging therapy with heparin.

Recommendations for Primary Thromboprophylaxis in aPL-Positive Subjects

Prophylactic treatment with low-dose aspirin (75-100 mg/day) is recommended for asymptomatic individuals with a high-risk aPL profile (with or without traditional risk factors) and patients with systemic lupus erythematosus and no history of thrombosis or pregnancy complications. Low-dose aspirin may be recommended to treat non-pregnant women with a history of obstetric APS only after risk/benefit has been adequately evaluated.

Recommendations for Secondary Thromboprophylaxis in APS

Following initial heparin therapy, EULAR recommends that patients with APS and first venous thrombosis be treated with vitamin K antagonists with a target INR of 2 to 3. Patients unable to achieve target INR despite good adherence to vitamin K antagonists or who have contraindications to vitamin K antagonists may consider direct oral anticoagulants. Patients with triple aPL positivity (presence of lupus anticoagulant, anticardiolipin antibodies, and antibeta2 glycoprotein I antibodies) should not be treated with rivaroxaban due to high risk for recurrent thromboembolic events.

In patients with unprovoked first venous thrombosis, long-term anticoagulation therapy should be considered; patients who demonstrate high-risk aPL profiles in repeated measurements or who demonstrate risk factors for recurrence may also consider longer anticoagulation. Patients with provoked first venous thrombosis should continue therapy for the duration recommended for patients without APS.

The use of vitamin K antagonists are recommended over low-dose aspirin alone in patients with APS and first arterial thrombosis; based on the individual’s risk for recurrent thrombosis or major bleeding, a target INR of 2 to 3 or 3 to 4 is recommended. Alternatively, treatment with vitamin K antagonists with a target INR of 2 to 3 plus low-dose aspirin may be considered. In patients with arterial events and triple aPL positivity, both rivaroxaban and direct oral anticoagulants are recommended against.

In patients with APS and recurrent thrombosis, physicians should consider investigating vitamin K antagonist adherence, educating patients on treatment adherence, and perform frequent INR testing. If the target INR of 2 to 3 has been achieved, care providers may consider adding low-dose aspirin to the treatment regimen, increasing the INR target to 3 to 4, or changing to low molecular weight heparin.

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Recommendations for Obstetric APS

During pregnancy, treatment with low-dose aspirin (75-100 mg/day) should be considered in women with a high-risk aPL profile but no history of thrombosis or pregnancy complications. In pregnant women with a history of ≥3 recurrent miscarriages occurring before the 10th week of gestation, or those with a history of fetal loss in the 10th week of gestation or later, EULAR recommends a combination therapy of low-dose aspirin and heparin at prophylactic dosage.

In women with a history of delivery before the 34th week of gestation due to eclampsia severe pre-eclampsia, or placental insufficiency, treatment recommendations include low-dose aspirin alone or low-dose aspirin plus heparin at prophylactic dosage. Considering the patient’s risk profile, the same treatment of low-dose aspirin or combination low-dose aspirin and heparin may be considered in women with clinical “non-criteria” obstetric APS. Pregnant women with a history of thrombotic APS are also recommended by EULAR to receive combination low-dose aspirin and heparin therapy.

Women with obstetric APS treated with heparin should continue heparin at prophylactic dose for 6 weeks following delivery to reduce thrombosis risk. And women with “criteria” obstetric APS who experience recurrent pregnancy complications despite the recommended treatment, may consider increasing heparin dose to therapeutic dose or adding hydroxychloroquine or low-dose prednisolone in the first trimester. In highly selected cases, physicians may consider use of intravenous immunoglobulin.

Recommendations for Catastrophic APS

Early diagnosis and treatment of infections and minimizing interuptions in anticoagulation is recommended to prevent the development of catastrophic APS. EULAR recommends combination therapy with glucocorticoids, heparin and plasma exchange, or intravenous immunoglobulin as first-line treatment of patients with catastrophic APS, along with treating precipitating factors, like infection, gangrene, or malignancy. In patients with refractory catastrophic APS, care providers may consider B cell depletion (eg, rituximab) or complement inhibition (eg, eculizumab) therapies.

Disclosure: Multiple authors declared affiliations with the pharmaceutical companies. Please refer to reference for a complete list of authors’ disclosures.

Reference

Tektonidou MG, Andreoli L, Limper M, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults [published online May 15, 2019]. Ann Rheum Dis. doi:10.1136/annrhumdis-2019-215213