Hyperglycemia is associated with enhanced thrombin formation, platelet activation and fibrin clot resistance to lysis in patients with acute coronary syndrome

Abstract

Objective: Acute hyperglycemia on admission for acute coronary syndrome (ACS) worsens the prognosis in patients with and without known diabetes mellitus. Postulated mechanisms of this observation include prothrombotic effects. The aim of this study was to evaluate the effect of elevated glucose levels on blood clotting in ACS patients.

Research Design and Methods: We studied 60 ACS patients within the first 12 hours after pain onset, including 20 subjects with type 2 diabetes, 20 with no diagnosed diabetes but with glucose levels above 7.0 mmol/L, and 20 with glucose levels below 7.0 mmol/L. We determined generation of thrombin-antithrombin complexes (TAT) and soluble CD40 ligand (sCD40L), a platelet activation marker, at the site of microvascular injury, together with ex vivo plasma fibrin clot permeability and lysis time.

Results: The ACS patients with no prior diabetes but elevated glucose levels had increased maximum rates of formation and total production of TAT (by 42.9%, p<0.0001 and 25%, p<0.0001, respectively) as well as sCD40L release (by 16.2%, p=0.0011 and 16.3%, p<0.0001, respectively) compared with those with normoglycemia, while DM patients had the highest values of the TAT and sCD40L variables (p<0.0001 for all comparisons). Patients with hyperglycemia, with no previously diagnosed diabetes, had longer clot lysis time (by ∼18%, p<0.0001) similarly to diabetic subjects, but not lower clot permeability, compared with normoglycemic subjects.

Conclusions: Hyperglycemia in ACS is associated with enhanced local thrombin generation and platelet activation, as well as unfavorably altered clot features in patients with and without a previous history of diabetes.