PB2435 PROTEIN S DEFICIENCY AND ISCHAEMIC STROKE
Authors: A. Kazantzi, F. Girtovitis, V. Voulgaridou, C. Savopoulos, E. Hassapopoulou-Matami, A. Hatzitolios
Journal: HemaSphere (2019)

Background: The incidence of stroke in young adults is around 10%. The majority is due to known risk factors (dyslipidemia, smoking, hypertension, diabetes mellitus, heart disease, etc). Nevertheless, in around 30% no identifiable cause is found, despite extensive diagnostic work up. Protein S is a vitamin K-dependent glycoprotein, which serves as a natural coagulation inhibitor by acting as a cofactor to Protein C, in order to deactivate factor V and VIII. Hereditary protein S deficiency is an independent risk factor for venous thromboembolism. However, whether it is a risk factor for arterial thrombotic events remains unclear. Aims: To identify whether hereditary protein S deficiency could be a risk factor for stroke in adults, aged below 59, without cardiovascular risk factors. Methods: We evaluated patients with a diagnosis of ischaemic stroke who were referred to the Haemostasis and Thrombosis Clinic during the last 8 years. Only patients less than 59 years old, without any known risk factors for stroke were included in the study: 83 patients in total, 29 men and 54 women. The mean age was 42,8 years (range 17-59). They were all subjected to the specific blood tests of our thrombophilia panel, which included APA testing (lupus anticoagulant (LA), anticardiolipin antibody (ACL) and anti-β2 glycoprotein 1 (anti-β2GPI), antithrombin III levels, free protein S and C levels, serum homocysteine levels. They also had vasculitis screening done. Furthermore, they underwent transesophageal echocardiogram, Holter monitoring and carotid duplex scan. Results: In most cases (31/83, 37.3%) antiphospholipid syndrome was identified. Decreased levels of protein S were found in 9 (10.8%) without any other abnormal tests. One patient (1.2%) had low levels of protein C. From the group of the patients with low levels of protein S, 8 were female with mean age 47,8 (range 30-58) and 1 was male, 47 years old. The mean value of protein S was 35,2% (range 6-54%) (normal range 60-140%). The abnormal blood tests were confirmed on repeat testing a few months later. Patent foramen ovale was found in 8 patients (9.6%) and carotid dissection in 3 (3.6%). Two patients were diagnosed with chronic atrial fibrillation and 4 patients with vasculitis. High levels of serum homocysteine >200 μmol/L were found in only one patient. In 12 patients (14,4%), no cause could be identified. Summary/Conclusion: As expected, the most frequent cause for ischaemic stroke identified was antiphospholipid syndrome. Low levels of protein S was the second cause. The role of protein S deficiency in patients with ischaemic stroke remains controversial. Although a wide prospective study is needed, we believe that it is essential to identify those patients early. As they have a relatively high life expectancy, it is crucial to avoid recurrent thrombotic events in the future, which will have significant impact on their quality of life. Therefore we suggest that protein S should be part of the screening tests in every patient with stroke.