Antiphosphatidyl Serine Antibodies and Ischemic Stroke
abstract & commentary
Source: Tuhrim S, et al. Antiphosphatidyl serine antibodies are independently associated with ischemic stroke. Neurology 1999;53:1523-1527.
Anticardiolipin antibodies (acl) are associat-ed with an increased risk of thromboembolism and stroke, particularly in the young. Antibodies against phosphatidylserine (aPS), another phospholipid epitope, may pose a similar risk. In a recent cohort of young patients with cryptogenic stroke, 18% showed aPS positivity (Toschi V, et al. Stroke 1998;29:1759-1764). Tuhrim and colleagues now report on the strength of this association, comparing the incidence of aPS among stroke patients with that of the general population.
In a case-control study of 267 acute ischemic stroke patients (age > 45) and 653 community controls, aCL positivity was found in 15.7% and 5.7%, respectively. A positive titer was defined as an IgG aPS of more than 16 or an IgM aPS of more than 22 ELISA units. Adjusting for age, gender, ethnicity, and traditional stroke risk factors, the odds ratios (ORs) for stroke were 5.6 for aPS IgG, 2.9 for aPS IgM, and 3.2 for any positive aPS titer. Due to a low prevalence of aPS among Hispanic controls of only 1.8%, the OR for stroke among this group was particularly high, 22.9.
APS represents an important addition to standard antiphospholipid antibody testing. Although the major-ity of aPS positive patients (9/15) were also found to have aCL antibodies, the remainder were negative for aCL. These patients would, therefore, have been misclassified as antiphospholipid antibody negative if aPS were not included in serologic testing.
The mechanism by which aCL or aPS antibodies induce thrombosis is not well understood. Cofactors such as B2-glycoprotein I, annexin-V, or other antiphospholipid antibodies, discussed briefly by Tuhrim et al, may ultimately distinguish between patients with benign versus malignant syndromes.
Young patients with unexplained stroke should be exhaustively tested for these antibodies. Broader testing depends on whether management decisions would be affected by these results. Pending controlled trials, treatment options remain controversial. Many experts, including this author, recommend chronic, high-intensity anticoagulation with warfarin (Khamastha MA, et al. N Eng J Med 1995;332:993-997). —azs (Dr. Alan Z. Segal is Assistant Professor, Department of Neurology, Weill-Cornell Medical College, Attending Neurologist, New York Hospital.)