Prothrombotic conditions are associated with ischemic stroke in young women. In particular, the combination of oral contraceptive use and prothrombotic genetic variants appears to increase the risk of ischemic stroke. We performed a population-based case-control study in 190 women aged 20 to 49 years with ischemic stroke and 767 women without cardiovascular disease stratified for age, calendar year of the index event, and residence. A total of 4 variants of coagulation factor XIII subunit A and B genes (F13A1 and F13B) were investigated. The Phe allele of the F13A1 Tyr204Phe variant was present in 59 (31%) patients and 43 (6%) controls; the odds ratio for ischemic stroke was 9.1 for Phe/Phe and Phe/Tyr versus Tyr/Tyr genotype; the 95% confidence interval was 5.5 to 15. Homozygous genotypes (Phe/Phe) conferred a higher risk (odds ratio, 77; 95% confidence interval, 7.0-848) than heterozygous (Tyr/Phe) genotypes (odds ratio, 8.2; 95% confidence interval, 4.9-14). The risk of ischemic stroke was further increased in carriers of the 204Phe allele using oral contraceptives (odds ratio, 20; 95% confidence interval, 9-46) compared with nonusers with Tyr/Tyr genotype. In conclusion, the F13A1 204Phe allele was strongly associated with ischemic stroke in young women. Oral contraceptive use further increased the risk of ischemic stroke. IntroductionProthrombotic conditions are associated with ischemic stroke in young women. For example, oral contraceptive use approximately doubles the risk of ischemic stroke. 1 Genetic factors also appear to play a role as is indicated by familial aggregation of ischemic stroke in young women. 2 Two prothrombotic genetic variants, the prothrombin G20210A variant and the methylenetetrahydrofolate (MTHFR) C677T variant, have been associated with ischemic stroke in young women. 3 Previous studies also found evidence of a combined effect of oral contraceptive use and prothrombotic gene variation on ischemic stroke risk. [3][4][5][6] Coagulation factor XIII (FXIII) is a protransglutaminase that circulates as a heterotetramer composed of 2 A and 2 B subunits. Activated FXIII is involved in cross-linking of the fibrin clot by transglutaminase reactions between glutamine and lysine residues on fibrin. The effect of a specific change in FXIII plasma level or activity on clot structure and thrombotic risk appears to depend upon several other factors, including the concentrations of thrombin, prothrombin, fibrinogen, and fibronectin. 7-9 A twin study showed a clear genetic influence on fibrin clot structure. 10 Several variants in the FXIII subunit A and B genes (F13A1 and F13B) change the FXIII level or activity and may therefore affect clot structure and the risk of thrombotic disease. Some of these variants have also been previously associated with myocardial infarction or ischemic stroke. The Leu allele of the F13A1 Val34Leu variant (Ref SNP ID no.: rs5985) increases the rate of FXIII activation and alters fibrin clot structure, 11 and has been associated with a decreased risk of myocardial in...

Our results support a change of practice wherein a lumbar puncture can be withheld in patients with a head CT scan performed <6 hours after headache onset and reported negative for the presence of SAH by a staff radiologist in the described nonacademic setting.