Thrombophilic Patients with Migraines Have a High Incidence of Antiphospholipid Antibodies.
Authors: Zeigler Zella Rose , Cortese Hassett Andrea L. 
Published: April 2020

Migraines are associated with an increased risk of stroke and are recognized as a non-stroke neurologic complicaton in the antiphospholipid syndrome (aPls). Traditional tests for antiphospholipid antibodies (APA) include PTT assays [aPTT, dRVV, and Hexagonal phospholipid (Hex PL)], a dilute PT assay (Tissue Thromboplastin Inhibition) for lupus anticoagulants (LAC), and ELISA assays for anticardiolipin antibodies (ACA). These assays have not correlated with migraines. It is now recognized that antibodies to a phospholipid binding protein called beta-2-GPI are important in autoimmune aPls. Some patients (pts) with aPls are sero-negative, eg. negative in the routine assays, but have + anti-beta-2-GPI antibodies. Animal studies have shown an association of the latter antibodies to neurologic dysfunction. This study is a clinical retrospective medical record methodology, examining the relationship between migraines and APA results in pts referred to the Hemostasis & Thrombosis Clinic at the Institute for Transfusion Medicine from 7/1/03-7/15/05. Inclusion criteria were any pt. referred to the PI, who had a LAC screening panel and anti-beta-2-GPI testing. Exclusion criteria were any pt who did not have this testing or were + without repeat testing &gt;2 mos later. Abstracted data included history of migraines (with or without aura), opthalmic migraines, referral reason, age, sex and APA results. Results were considered to be + (in non-anticoagulated pts), if any of the clotting assays were repeatedly +, did not correct on a mix, and shortened with phospholipid. Patients with only a + clotting assay, were taken off coumadin (OAC) and retested. Patients with + ELISA assays on OAC Rx, required an abnormal dRVV mix and/or a + Hex PL assay to be considered as + for a LAC. ELISA results were considered as +, if they were low titer or higher, e.g. ≥ mean ± 3 SD. The cohort consisted of 258 pts (69M: 189F) with a median age of 48 (range=13–85). Of these, 76 (29%) had migraines. Thirty-five/258 (13.6%) of the pts were referred for risk assessment and 10/35 (28.6%) had migraines. The remaining 223 pts were referred for clinical events: arterial or venous thrombosis [n= 133/233 (59.6%)], neurologic reasons [n=62/223 (28.2%)] and other [n=27/233 (12.1%)]. Of this group, migraines were present in 66 (29.6%). None of the 10 risk pts with migraines had + results. One of the 25 risk pts had a + anti-beta-2-GPI antibody (1/25=4.0%). Positive APA were detected in 58/233 (24.9%) pts with clinical events. Table 1 is a breakdown of the APA results vs migraines in pts with events vs those evaluated for risk issues. It appears that pts with thrombotic events with migraines have a higher incidence of +APA than those who do not have migraines. This data supports the suspected association between migraines and APA in the thrombphilic pt population. The same does not appear to be true in pts (without a thrombotic event) undergoing risk assessment.

Incidence of Positive APA in Patients with regard to Migraine Status Group Total Pos Total Neg P OR CI APA = LAC/ACA and/or anti-beta-2-GPI Risk-no migraine 1/25 (4%) 24/25 (96%) Risk-migraines 0/10 (0%) 10/10 (100%) 1.00 0.810 0.03–21.5 Events-ALL pts 58/233 (25%) 175/233 (75%) 0.002 11.27 1.51 to 84.2 Events-no migraine 30/157 (19%) 127/157 (81%) 0.058 5.83 0.77 to 44.22 Events-migraines 28/66 (42%) 38/66 (58%) &lt;0.001 25.05 3.23 to 194.2