Type 2 diabetes as a modifier of fibrin clot properties in patients with coronary artery disease

Abstract

Altered fibrin clot structure has been reported both in patients with coronary artery disease (CAD) and those with type 2 diabetes mellitus (DM2). The aim of the present study was to evaluate plasma fibrin clot permeability and susceptibility to lysis in patients with DM2 and CAD. We studied 132 consecutive CAD patients, including 67 subjects with DM2, scheduled for elective coronary artery bypass grafting surgery. Ex vivo plasma fibrin clot permeability (K(s)) and lysis time (t(50%)) induced by 1 μg/mL recombinant tissue plasminogen activator (tPA), along with plasma levels of plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), tPA, von Willebrand factor (vWF), P-selectin, soluble CD40 ligand (sCD40L), were measured. Diabetic and non-diabetic patients did not differ in regard to demographics and remaining cardiovascular risk factors. Concomitant DM2 was associated with higher glucose (+24.3%, p < 0.001), fibrinogen (+9.0%, p = 0.037), PAI-1 (+58.7%, p < 0.001), tPA (+24.0%, p < 0.001) and P-selectin (+12.2%, p < 0.001). Compared with the non-diabetic group, the CAD patients with DM2 had lower K(s) (-6.1%, p = 0.02) and prolonged t(50%) (+5.1%, p = 0.04). Multiple regression analysis of the whole study group showed that vWF, PAI-1, fibrinogen and DM2 were the independent predictors of t(50%) (R(2) = 0.58, p < 0.001), while only vWF was an independent predictor of K(s) (R(2) = 0.22, p < 0.001). This study indicates that DM2 is potent enough to unfavorably affect plasma fibrin clot characteristics despite abnormal clot phenotype typically observed in CAD. Of note, platelet and endothelial markers appear to contribute to fibrin clot properties in CAD concomitant with DM2.

Fig. 1

Clot lysis time (t_50%) and permeation coefficient (K_s) in relation to different therapy of diabetes. Abbreviations: box plot shows median and interquartile range (IQR) (Q3 to Q1). Q1 and Q3 are the first and third quartiles. Whiskers are drawn at Q3 + 1.5 × IQR, Q1 − 1.5 × IQR. Extreme values are omitted

Fig. 2

Correlation between permeation coefficient (K_s) and von Willebrand factor (vWF) and P-selectin in diabetic patients

Fig. 3

Correlation between clot lysis time (t_50%) and von Willebrand factor (vWF) and P-selectin in diabetic patients