Role of inherited thrombophilic profile on survival of patients with sepsis

Abstract

The existence of various coagulation and/or fibrinolytic system disorders (such as inherited thrombophilia) in patients with sepsis could possibly modify host response to infection as well as patient outcome. The aim of the study is to investigate inherited thrombophilic profile in patients with sepsis. Eighty-three patients with sepsis admitted at the Department of Internal Medicine of the University General Hospital of Patras, Greece were included. Thrombophilic profile (factor V G1691A (Leiden), factor V H1299R (R2), prothrombin G20210A, MTHFR C677T, MTHFR A1298C, factor XIII V34L, β-fibrinogen-455 G-A and plasminogen activator inhibitor (PAI)-1 4G/5G) was evaluated using the cardiovascular diseases (CVD) StripAssay based on DNA isolation, PCR and reverse hybridisation. Data were collected from patients' chart reviews. Seventy patients (84.3%) of the 83 enrolled had at least one thrombophilic mutation. The most common mutations were heterozygous for β-fibrinogen-455 G-A (43.4%), heterozygous for factor XIII V34L (32.5%), PAI-1 4G/4G (26.5%), homozygous MTHFR C677T (22.9%), heterozygous factor V H1299R (R2) (13.3%) and homozygous MTHFR A1298C (12.0%). A 30-day mortality was 14.5%. Multivariate analysis revealed that mortality was independently associated with Simplified Acute Physiology Score II score on admission, pneumonia and fibrinogen on admission. Nine patients (10.8%) developed septic shock. Coagulation disorders on admission, bacteraemia and PAI-1 genotype 5G/5G were independently associated with development of septic shock. The presence of thrombophilic mutations in patients with sepsis may affect their clinical response, and future studies are needed in order to elucidate the role of isolated thrombophilic mutations in patients with sepsis or septic shock.

Keywords: inherited thrombophilia; plasminogen activator inhibitor-1 (PAI-1); sepsis; septic shock; thrombophilic profile.