What is the management for patients with elevated anti-cardiolipin antibody (ACA) levels?

Management of Elevated Anti-Cardiolipin Antibody Levels

Patients with elevated anti-cardiolipin antibody (ACA) levels should receive anticoagulation with vitamin K antagonists (VKAs) as the cornerstone of therapy for thrombotic antiphospholipid syndrome (APS), with treatment decisions based on clinical manifestations and antibody profile. 1

Diagnosis and Risk Assessment

• Diagnosis of APS requires both clinical criteria (vascular thrombosis or pregnancy complications) and laboratory criteria (persistent detection of anticardiolipin antibodies, β2-glycoprotein I antibodies, and/or lupus anticoagulants for at least 12 weeks) 2
• Patients presenting with all three types of antibodies (triple positive) and vascular events are considered high-risk patients 2
• All three idiotypes (IgG, IgA, and IgM) should be assessed when evaluating for APS 3

Management Based on Clinical Presentation

For Patients with Thrombotic Events

• Venous Thrombosis:

  • Vitamin K antagonists (VKAs) with target INR 2-3 are the treatment of choice for patients with venous thrombosis 1, 2
  • Direct oral anticoagulants (DOACs) could be considered in patients with venous thrombosis who are negative for lupus anticoagulant, though more data are needed 2

• Arterial Thrombosis:

  • VKA with or without low-dose aspirin is the current treatment of choice 2
  • Target INR should be between 2 and 3, though in some cases keeping the target INR above 3 may be necessary 2
  • DOACs are not recommended in patients with arterial thrombosis 1

• Duration of Treatment:

  • Long-term anticoagulation is recommended for patients with thrombotic APS as long as antibodies persist 2
  • In rare cases where antibodies become persistently negative, discontinuation of anticoagulation might be considered in low-risk primary APS patients, though larger studies are needed to confirm this approach 4

For Asymptomatic Patients with Positive ACA

• Low-dose aspirin is the first option for primary thromboprophylaxis in asymptomatic aPL carriers 1
• This is particularly important when additional vascular risk factors are present 2

For Catastrophic APS

• Occurs in less than 1% of APS patients and presents as a thrombotic storm 2
• Early use of combined triple therapy (anticoagulation, plasma exchange, and steroids) with or without immunoglobulins is important to reduce mortality 2

Adjunctive Therapies

• Hydroxychloroquine and statins may be useful in complex settings such as thrombotic recurrences or high risk of bleeding 1
• Minimizing vascular risk factors is always necessary in APS patients 2

Special Considerations

• Patients with APS may have prolonged activated partial thromboplastin time (aPTT), but this is unreliable (prolonged in only about 40-50% of patients with lupus anticoagulant) 3
• Most patients with antiphospholipid thrombosis syndrome will fail warfarin therapy, and except for retinal vascular thrombosis, most will fail antiplatelet therapy alone 3
• In patients requiring long-term anticoagulation, oral anticoagulant therapy can be resumed within 24 hours after procedures like PCI, based on assessment of bleeding risk and post-procedure complications 5

Common Pitfalls and Caveats

• Crossing over between different anticoagulant therapies may increase bleeding risk 5
• For patients on low-molecular-weight heparin, activated clotting time (ACT) should not be used as a guide to anticoagulation therapy 5
• The presence of APS can complicate perioperative management and may be associated with increased risk of complications including disseminated intravascular coagulation and adult respiratory distress syndrome 6