Antiphospholipid Antibodies and Recurrent Thrombotic Events: Persistence and Portfolio

Abstract

Background: There are very limited prospective data on the significance of persistent antiphospholipid antibodies (aPL) and recurrent thrombo-occlusive events (TOEs). We investigated the prognostic value of (1) 2 newer aPL assays, (2) an aPL portfolio and (3) persistent aPL positivity following stroke. Methods: A total of 1,770 subjects from the APASS-WARSS study underwent further aPL testing for antibodies to phosphatidylserine (aPS) and anti-β₂-glycoprotein-I (anti-β₂GPI) from stored sera. Follow-up aPL status was also tested in a subset of subjects. Primary analysis was based on time to any TOE (ischemic stroke, myocardial infarction, transient ischemic attack, deep vein thrombosis, pulmonary embolism or systemic arterial occlusion)/death at 2 years. Cox proportional hazard analyses assessed whether aPL independently related to outcome. Results: Persistent anti-β₂GPI decreased the time to TOE/death after adjustment for potential confounders (hazards ratio (HR) 2.86, 95% CI 1.21-6.76, p = 0.017). When persistent anti-β₂GPI was combined with another persistently positive aPL, time to TOE/death was also reduced (HR 3.79, 95% CI 1.18-12.14, p = 0.025). Neither persistent anticardiolipin antibodies nor persistent aPS alone nor a single positive anti-β₂GPI nor aPS was associated with decreased time to TOE/death. No single positive aPL, portfolio of baseline aPL or any persistent aPL increased the rate of TOE/death. Conclusions: Rates of TOE/death were not influenced by aPL results at baseline or follow-up. Persistent anti-β₂GPI alone, and with persistent second aPL, was independently associated with decreased time to TOE/death. Persistent aPL, an aPL portfolio and newer aPL in ischemic stroke patients are not helpful in predicting an increased rate of recurrent TOEs.

Antiphosphatidylserine Antibodies and Clinical Outcomes in Patients With Acute Ischemic Stroke

“…The primary outcome was a combination of death and major disability (modified Rankin Scale score, [3][4][5][6]. 18 Secondary outcomes were death, major disability, recurrent fatal and nonfatal stroke, and vascular events (eg, vascular deaths, nonfatal stroke, nonfatal myocardial infarction, hospitalized and treated angina, hospitalized and treated congestive heart failure, and hospitalized and treated peripheral arterial disease).…”

“…3 Anticardiolipin antibodies (aCL) and lupus anticoagulant antibodies were the most frequently studied members and had been associated with an increased risk of recurrent thrombo-occlusive events and death after stroke in some but not in all studies. [4][5][6][7][8] Recently, studies suggest that antibodies directed against phosphatidylserine (antiphosphatidylserine antibodies [aPS]) may be a useful marker for the syndrome. [9][10][11][12] Population-based studies showed an independent association of aPS with ischemic stroke.…”

The impact of antibody profile in thrombosis associated with primary antiphospholipid syndrome

“…However, APS is a heterogeneous disease and the clinical relevance of the aPL profile, in particular TP, in the clinical course of PAPS has not yet been confirmed . A recent meta‐analysis demonstrated that each aPL (LAC, aCL, and aB2GP1) were independently associated with increased risk of thrombosis in PAPS, particularly LAC was associated with the highest risk .…”

The Role of Transcranial Doppler Monitoring in Patients with Multi‐Territory Acute Embolic Strokes: A Review

“…Ten‐year survival probability was 90.7% . Persistence of aPL positivity in patients with previous cerebrovascular events increases the risk of recurrence, whereas persistent anti‐b2GPI are associated with decreased time to thrombotic events and death . Interestingly, an association between patent foramen ovale with atrial septal aneurysm and APS has been reported, raising further risk of ischemic stroke …”

“…45 Persistence of aPL positivity in patients with previous cerebrovascular events increases the risk of recurrence, whereas persistent anti-b2GPI are associated with decreased time to thrombotic events and death. 46,47 Interestingly, an association between patent foramen ovale with atrial septal aneurysm and APS has been reported, raising further risk of ischemic stroke. 48 Even despite anticoagulation treatment, individuals with APS carry a substantial risk of future ischemic stroke, especially when positivity for IgM-type anti-B2GPI is persistent.…”