Treatment for a patient who had a cerebral arterial clot and elevated levels of Antiphospholipid Antibodies

What is the treatment for a patient who had a cerebral arterial clot and elevated levels of aPL abs (secondary arterial thrombosis prevention)?

There is significant debate over how to manage patients following an arterial thrombosis associated with aPL abs. One area of controversy is the value of antiplatelet agents compared with warfarin as the best therapy. The one prospective trial (APASS–WARSS study) ( JAMA 291:576, 2004) had significant flaws making definitive recommendations difficult. Several retrospective studies and data from stroke studies not specifically including APS patients suggest the following for a patient with a stroke and aPL abs:

• Thrombolytic therapy as per expert guidelines.

• Evaluation for other causes of cerebral thrombosis: transthoracic echocardiogram with bubble study to rule out patent foramen ovale and a transesophageal echocardiogram to rule out valvular lesions and an intramural clot.

• Treatment during first 48 hours: low-dose ASA (81 mg daily) and prophylactic dose LMWH. If large stroke, may continue ASA therapy for 2 weeks and not start full anticoagulation to lessen chance of bleeding into the damaged area of the brain.

• If the patient’s stroke is due to a cardioembolic source (atrial fibrillation, heart valve, intracardiac thrombus), then the patient should be treated with warfarin maintaining an INR between 2 and 3 (some recommend INR 3 to 4).

• If the patient’s stroke is not cardioembolic and the patient is medium-risk for recurrence (negative LA, no prior clot, no cardiovascular risk factors, no SLE) and/or is a high-bleeding risk, then treatment can be combination antiplatelet agents (ASA [81 mg daily] plus dipyridamole [200 mg twice a day], clopidogrel [75 mg daily], or ticagrelor [90 mg twice a day]). Some experts feel that combination of antiplatelet agents (ASA plus clopidogrel or ticagrelor) is more effective than warfarin-based therapies for any arterial thrombosis.

• If the patient’s stroke is not cardioembolic and the patient is high-risk for recurrence (triple positive aPL abs, multiple lesions on brain MRI, previous arterial clot, active SLE, smoking), then treatment should be warfarin (INR 2 to 3) plus an antiplatelet agent, or high-dose warfarin (INR 3 to 4).

Because the risk of recurrent arterial thrombosis is over 50%, the patient should remain on lifelong therapy. Smoking must be discontinued and hypertension, hyperlipidemia, and diabetes should be controlled. The risk of major bleeding on therapy is <1% on antiplatelet therapy, 2.5% for warfarin therapy (INR 2 to 3), and 4% for combination of the two therapies. Ticagrelor causes more bleeding than clopidogrel. Patients should be assessed for clinical factors (age >65–70 years, systolic blood pressure >160 mm Hg, renal insufficiency [Cr >2 mg/dL], significant liver disease, labile INR, prior bleeding episode, prior stroke, >1 alcohol drink/day) and medications (nonsteroidal antiinflammatory drugs) that increase bleeding risk before choosing therapy.

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