Natural anticoagulants deficiencies and transient ischemic attacks

Cerebrovascular ischemic disorders are caused by the release of various materials into the arteries that supply the brain. Recent findings have reported an association between familial hemostatic abnormalities and ischemic stroke. The aim of our study was to investigate the role of protein C (PC) and protein S (PS) in juvenile Transient Ischemic Attacks (TIAs). Sixty-eight patients (s 45 years old) with a diagnosis of TIA in anterior or posterior brain territory were admitted into the study. One hundred and three healthy subjects acted as a control group Subjects on oral anticoagulation and oral contraceptives were not studied. All patients and control subjects had a physical examination, clinical chemestry and radiologic work-up We defined as deficiency of PC and PS activity or antigen levels below 60% (<2.5th centile) and as activated protein C (APC) -resistance an APC ratio below 2.20. The number of patients with PC or PS deficiency was higher in cases than in controls (8 vs 2, p< 0.01; 10 vs 2, p< 0.002 respectively, Fisher Exact Test). However, there was no difference in the distribution of APC-resistance between cases and controls. The levels of PC and PS activity, PC and PS antigens and APC-resistance were significantly lower in cases than in controls. No differences in fibrinogen concentrations, antithrombin III (either antigen or activity) and plasminogen activity were found After multivariate analysis the number of subjects with a family history of TIA and stroke or with hypertension was significantly higher in the group of patients as compared to controls. TIA patients showed significantly higher levels of tryglicerides compared to controls. PC and PS were both positively correlated with HDL and negatively correlated with total cholesterol, LDL and tryglicerides plasma levels. The association between PC/PS deficiency and TIA persisted in multivariate analysis controlling for age, sex, smoke, hypertension, diabetes and tryglicerides. Our findings suggest that PC and PS deficiencies are risk factors for TIAs and are strongly associated with a family history of cerebrovascular ischemic disease.