Plasma Fibrin Clot Properties as Determinants of Bleeding Time in Human Subjects: Association with Histidine-Rich Glycoprotein

Abstract

Aims. Fibrin formation and histidine-rich glycoprotein (HRG) are involved in primary hemostasis and wound healing. Little is known regarding the relationship of clot characteristics, bleeding time, and wound healing. Methods and Results. We studied 154 patients with coronary artery disease (CAD) and 154 subjects free of CAD matched for age, obesity, and current smoking. We evaluated bleeding time (BT) using standardized skin incisions on a forearm, along with plasma clot permeability (Ks), clot lysis time (CLT), and histidine-rich glycoprotein (HRG). Compared with controls, BT was 45% shorter in CAD cases. CAD patients had 32% lower Ks and 17% longer CLT as well as 50% lower HRG compared with controls (all p<0.001). After adjusting for potential confounders, Ks and HRG levels were independent predictors of prolonged BT in CAD patients (OR 23.70, 95% CI 4.65-120.8 and OR 10.27, 95% CI 2.05-51.31, respectively) and controls (OR 10.89, 95% CI 2.31-51.11 and OR 4.54, 95% CI 1.07-19.27, respectively). Scar formation (n=79, 25.6%) was independently predicted by both short and prolonged BT in CAD cases (OR 21.87, 95% CI 7.41-64.55 and OR 10.17, 95% CI 2.88-35.97) and controls (OR 5.94, 95% CI 2.29-15.41 and OR 14.76, 95% CI 4.29-50.77, respectively). Conclusions. The study shows that plasma fibrin clot density and HRG may influence BT and that appropriate skin wound healing is associated with medium BT. Translational Perspective. Elucidation of the complex relationships between plasma fibrin clot phenotype and wound healing might have important practical implications.