Protein C, protein S, Factor V Leiden mutation and antithrombin deficiency as a cause of hereditary thrombophilia in patients of venous thromboembolism and cerebrovascular accident.

Abstract

Objectives: To determine the frequency of Protein C, Protein S (PC & PS), antithrombin deficiency (AT III) and Factor V Leiden mutation (FVL) as a cause of thrombophilia in the patients with venous thromboembolism (VTE) and cerebrovascular accident (CVA). Methods: It was an observational study conducted at Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan. All patients referred for thrombophilia screening from July 2009 to June 2012 were screened. Patients with evidence of VTE or CVA were screened for PC & PS, AT III deficiency, and FVL. Results: Total 404 patients of age between 1-71 years mean 33 ± 14 with male to female ratio of 2.4:1 had evidence of thrombophilia. Two hundred eighteen (54%) patients presented with CVA, 116 (29%) with deep vein thrombosis (DVT), 42 (10.5%) with pulmonary embolism (PE), and 28 (7.5%) with portal or mesenteric vein thrombosis (PV). Protein C & S deficiency was detected in 35/404 (8.7%), ATIII in 9/404 (2%), and FVL in 25/173 patients (14.5%). The findings were suggestive of a significant association of FVL mutation for developing DVT (OR=11.0, 95% C I 4.6-26.3), CVA (OR=5.7, 95% C I 2.1-15.1), and PV (OR=5.4, 95% C I 1.3-21.9). PC & PS deficiency was a significant risk factor for developing PE (OR=3, 95% C I 0.8-11.4). Conclusion: FVL mutation and Protein C & S are the leading causes of thrombophilia with strong association of Factor V Leiden mutation as risk for developing DVT.

Analysis of PROC and PROS1 single nucleotide polymorphisms in a thrombophilia family

“…Protein S deficiency is an important risk factor for venous thrombosis, accounting for approximately 5% of thrombophilic cases and 1%‐2% of cases with a first DVT . The prevalence of thrombophilia in the general population is approximately 0.3% for protein C deficiency . A mutation in PROS1 may cause a genetic predisposition to venous thromboembolic disorders in humans …”

Osteonecrosis of the Femoral Head in Patients with Hypercoagulability—From Pathophysiology to Therapeutic Implications

“…The highest frequency of heritable thrombophilia was recorded in individuals with ancestry from northern Europe [26] and some parts of the Middle East [27]. The most common and important thrombophilic states are: the factor V Leiden mutation, the prothrombin gene G20210A mutation, antithrombin III deficiency, protein C and protein S deficiency [28] and the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism [29]. It has also been noted that thrombosis may occur due to either a single dominant abnormality or to a combination of milder but multiple defects-as by association, their prothrombotic effects are potentiated.…”

Enfoque diagnóstico de la tromboembolia pulmonar

“…5 Es bien sabido que ciertos trastornos genéticos predisponen a estados protrombóticos; los más frecuentes están representados por las mutaciones del factor V de Leiden (FVL) y del gen de protrombina 20210. 6 Se calcula que la prevalencia de trombofilias hereditarias en la población general es del 0.2-0.4% por deficiencia de proteína C (PC), 0.2% por déficit de proteína S (PS), 0.02% por déficit de antitrombina III (AT-III) y, por último, 4-5% por mutaciones en el FVL. 7 Se estima que un 11-29% de los sujetos con ETV presentan la mutación del FVL; asimismo, los portadores heterocigotos de dicha mutación poseen un riesgo 3-8 veces mayor de presentar ETV.…”

“…Entre los factores de riesgo reversibles más destacables se encuentran cirugía, traumatismos, fracturas en miembros pélvicos, inmovilización prolongada, viajes largos en aeronaves, tabaquismo, obesidad, hipercolesterolemia, embarazo, uso de anticonceptivos orales y terapia de reemplazo hormonal durante la menopausia. 6,7 Diversas situaciones clínicas actúan también como factores predisponentes en la EP; por ejemplo, Stojanovich y sus colaboradores observaron en un estudio clínico prospectivo que la tasa de prevalencia de EP en personas con síndrome antifosfolípido era del 12.3-13.2%; dicha variación dependía de la subclase de anticuerpos antifosfolípidos expresados. 8 Asimismo, la EP es una de las complicaciones más frecuentes y peligrosas en pacientes con lesión de médula espinal en fase aguda, presentándose en un 10-30% de los casos.…”