Antiphospholipid Syndrome Management

Diagnostic Considerations

Phosphatidylserine/Prothrombin antibodies are associated with Antiphospholipid Syndrome and have a high correlation with lupus anticoagulant positivity 1
A positive Phosphatidylserine/Prothrombin antibody IgM result should be confirmed with repeat testing after 12 weeks to establish persistence, as per Antiphospholipid Syndrome diagnostic criteria 2
Consider testing for other antiphospholipid antibodies, including Anti-β2-glycoprotein I antibodies, to establish a complete antibody profile 1

The American College of Chest Physicians recommends adjusted-dose vitamin K antagonist therapy with a target INR of 2.5 (range 2.0-3.0) for patients with confirmed Antiphospholipid Syndrome 3
Adjusted-dose vitamin K antagonist, such as warfarin, with target INR 2.5 (range 2.0-3.0) is recommended as first-line therapy for thrombotic Antiphospholipid Syndrome 3, 4
Direct oral anticoagulants are not recommended, especially in triple-positive patients, due to increased risk of thrombotic events 2
Low-dose aspirin (75-100mg daily) is recommended for patients with high-risk antiphospholipid antibody profile, including triple-positive antibodies, double-positive antibodies, and isolated lupus anticoagulant or persistently positive anticardiolipin at medium-high titers 5
Low-dose aspirin (75-100mg daily) is recommended for non-pregnant adults with a history of obstetric Antiphospholipid Syndrome 5
During pregnancy, low molecular weight heparin plus low-dose aspirin is recommended 6, 7
Prophylactic anticoagulation with low molecular weight heparin is recommended for antiphospholipid antibody-positive patients undergoing assisted reproductive technology procedures due to increased thrombosis risk from elevated estrogen levels 6, 7

Triple-positive patients are at highest risk for thrombotic events and should strictly avoid direct oral anticoagulants 2
Addition of antiplatelet therapy to anticoagulation may be considered for patients who fail standard therapy 2

The American College of Rheumatology recommends that obstetric APS patients be managed based on clinical presentation, including pregnancy complications 8

For patients with catastrophic APS, the Kidney International guidelines recommend aggressive treatment with a combination of anticoagulation, glucocorticoids, and plasma exchange 9
The American College of Rheumatology recommends that during pregnancy, combination therapy with low-dose aspirin and prophylactic low molecular weight heparin is strongly recommended for obstetric APS patients 8
The Kidney International guidelines recommend that hydroxychloroquine should be continued during pregnancy to reduce the risk of pregnancy complications 9

The American College of Rheumatology recommends that estrogen-containing contraceptives are strongly contraindicated in women with positive aPL due to increased thrombosis risk, and that intrauterine devices and progestin-only pills are recommended contraceptive options 10
The Kidney International guidelines recommend that patients with lupus nephritis and positive aPL should be co-managed with an experienced hematologist, and that long-term anticoagulation with warfarin is reasonable for APS nephropathy 9

The Blood journal guidelines recommend that direct oral anticoagulants should be avoided in triple-positive patients due to increased risk of thrombotic events, and that invasive procedures should be avoided during acute thrombotic episodes due to bleeding risk 11

The American Heart Association recommends warfarin with a target INR of 2.0-3.0 plus aspirin 75-100 mg/day for arterial thrombosis in Antiphospholipid Syndrome (APS) patients 12

Adjusted-dose vitamin K antagonist (warfarin) with a target INR of 2.5 (range 2.0-3.0) is the gold standard for venous thrombosis in APS, as recommended by the American College of Chest Physicians 13, 14
Lifelong anticoagulation with warfarin is required for APS patients with unprovoked venous thrombosis, not aspirin monotherapy 12

High-intensity anticoagulation (INR 3.0-4.0) does not provide additional benefit over moderate-intensity therapy and increases bleeding risk, according to the American College of Chest Physicians 14
The American College of Chest Physicians explicitly recommends against high-intensity warfarin, suggesting moderate-intensity INR 2.0-3.0 instead 14

Anticoagulation in APS with thrombotic events should be lifelong, not time-limited, due to high recurrence rates without vitamin K antagonist therapy 12