Study Selection

Two authors (T.C., E.D.) independently searched the literature, screened titles and abstracts, and reviewed full texts to identify potentially eligible studies. Disagreements were resolved by consensus or a third reviewer (A.C.) when necessary.

The primary outcome of interest was arterial ischemic stroke. Eligible studies included case‐control or cohort studies of adults, aged ≥15 years, that reported the prevalence of at least one of the inherited thrombophilias of interest (FVL, PTM, PCD, PSD, or ATD) in both subjects with a history of arterial ischemic stroke and subjects without arterial ischemic stroke. Both prospective and retrospective studies were included. Studies were required to have ≥10 subjects in each group. Studies that enrolled patients with transient ischemic attack, hemorrhagic stroke, cerebral venous sinus thrombosis, and other arterial thromboses were excluded unless data for arterial ischemic stroke could be disaggregated. Studies that included neonates or children were also excluded.

If multiple studies used the same or overlapping samples, we included only the one with the largest sample size in the quantitative analysis. Cohen's κ coefficient was calculated to evaluate interobserver agreement for study selection.

We did not attempt to control for method used to diagnose thrombophilia, nor did we limit how the control population was constituted, assuming it appeared to be a valid comparator group.