Protein S deficiency in middle‐aged women with stroke

Abstract

We examined the relationship between free protein S deficiency and cerebrovascular disease by reviewing the records of all patients with the diagnoses of cerebral thrombosis, cerebral embolism, and cerebral vascular occlusion who were referred for coagulation studies over a 12-month period. We assayed for free protein S antigen, protein C antigen, and antithrombin III and tested for lupus-like anticoagulant and anticardiolipin antibody. Twenty-two of 267 patients (8.2%) admitted with thrombotic strokes were referred for coagulation studies. Free protein S antigen was significantly lower in women than in men (62 +/- 25% versus 88 +/- 24%, p = 0.03; n = 11 in each group). Six women had free protein S antigen levels below the range recorded for a contemporary group of 24 age-matched normal women (17 to 59% versus 70 to 102%, p less than 0.001); four of these women had cerebral arterial thrombosis and two had venous dural sinus thrombosis. The six women were aged 29 to 55 at the time of their first strokes; two had family members with protein S deficiency, and one of these had died of a stroke at age 52. Other abnormalities in this population included a positive test for lupus-like anticoagulant or anticardiolipin in five patients, a modest decrease in protein S in two men, and one patient with an isolated deficiency of antithrombin III. We conclude that protein S deficiency may be an important risk factor for stroke in middle-aged women but this requires confirmation by prospective studies in unselected patients.

Natural Coagulation Inhibitor Proteins in Young Patients with Cerebral Ischemia

“…More detailed laboratory screening of stroke patients for recently identified prothrombotic states increased the rate of stroke attributed to disturbances of the coagulation system [19, 20, 21, 22, 23, 24, 25, 26, 27, 38]. In ischemic stroke, routine coagulation tests are usually normal, even if they are examined immediately after stroke [38].…”

“…However, it seems that the association of a prothrombotic condition with secondary hypercoagulable states (cigarette smoking, pregnancy, puerperium, oral contraceptive use, alcohol consumption, surgery, inflammation, malignancy) may significantly elevate the risk of cerebral ischemia [18]. It has recently been shown that not only venous but arterial thrombosis is also associated with abnormalities of natural coagulation inhibitor activities, and/or decreased fibrinolytic activity [19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30]. …”

Human protein S inhibits the uptake of AcLDL and expression of SR-A through Mer receptor tyrosine kinase in human macrophages

“…The critical antithrombotic role of protein S is revealed by the massive thrombotic complications suffered by infants homozygous for protein S deficiency. 3 Adult patients with mild heterozygous deficiencies in protein S are associated with risk for venous and arterial thrombosis, 4,5 ischemic stroke, 6 cerebral thrombophlebitis, 7 myocardial infarction, and vascular calcification. 8,9 Protein S infused in a murine model of ischemic stroke decreases infarction and edema volumes.…”

Protein S Confers Neuronal Protection During Ischemic/Hypoxic Injury in Mice

“…[1][2][3][4][5][6][7] The critical physiological antithrombotic role of protein S is revealed by the massive thrombotic complications suffered by infants homozygous for protein S deficiency. 8,9 In adults, mild heterozygous deficiencies in protein S are associated with risk for venous and arterial thrombosis, 10 -13 ischemic stroke, 14,15 and cerebral thrombophlebitis. 16,17 Protein S binds to vascular cells and is a potent mitogen.…”