Increased plasma level of vascular endothelial glycoprotein thrombomodulin as an early indicator of endothelial damage in bone marrow transplantation

Abstract

We investigated the nature of hemostatic alterations occurring after bone marrow transplantation. In 45 patients, we evaluated the coagulation parameters, naturally occurring anticoagulants and thrombomodulin at days +15 and +22 after conditioning therapy. It was observed that endothelial cell damage is a central pathogenetic mechanism in some BMT complications. The increased plasma level of thrombomodulin after conditioning therapy is therefore discussed as a marker of endothelial cell injury. At day +15 a significant increase of fibrinogen from 276.1 mg/dI to 389.1 mg/dI was observed, while the natural anticoagulants all decreased significantly. Eleven patients with clinical complications related to endothelial damage had a significant thrombomodulin increase which, in uncomplicated patients, remained unchanged or resulted in lower than baseline values. Analysis of the data shows a strong correlation between clinical findings, reflecting endothelial cell injury and thrombomodulin increase when the increment is > or = 30%. We found a significant elevation in thrombomodulin in 70% of clinical complications related to endothelial cell damage namely: septicemia, GVHD, VOD. There were four cases (or 9%) of false positive data, and only two (or 4.5%) of false negative results. We therefore propose thrombomodulin assessment as a valid parameter to monitor chemotherapy toxicity-related complications.