Hypercoagulability in patients with type 2 diabetes mellitus detected by a thrombin generation assay.
Diabetes is a risk factor for the development of atherothrombosis and venous thromboembolism (VTE). We investigated whether plasma from patients with type 2 diabetes has an imbalance of pro- versus anti-coagulation resulting in hypercoagulability despite normal conventional coagulation tests. We analyzed blood samples from 60 patients with type 2 diabetes and 60 gender- and age-matched healthy subjects (controls) for the levels of pro- and anti-coagulant factors, for thrombin generation and for the numbers of cell-derived circulating microparticles bearing such pro-coagulant triggers as tissue factor and negatively charged phospholipids. The levels of pro- or anti-coagulants as measured with conventional coagulation tests or single factor measurements were similar to those of the control population. In contrast, the median (range) of the height of the thrombin peak (taken as an index of thrombin generation) was higher in patients [205 nM (126-352)] than controls [151 nM (41-289)], P < 0.001. The median numbers of circulating microparticles were higher for patients [5,041/μl (1,821-13,132)] than for controls [1,753/μl (554-13,308)], P < 0.001 and their values were correlated with the height of the thrombin peak (ρ = 0.66, P < 0.001). In conclusion, plasma from patients with type 2 diabetes possesses an imbalance of pro- versus anti-coagulation resulting in hypercoagulability that can be detected by thrombin generation tests, but not by the measurement of the single pro- or anti-coagulant factors. This hypercoagulability is associated with increased numbers of circulating microparticles bearing endogenous pro-coagulant triggers. These findings might explain the relatively high risk of atherothrombosis and VTE described in these patients.
Tripodi
Armando
A
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine and Medical Specialties, IRCCS Cà Granda Ospedale Maggiore Policlinico Foundation and Università degli Studi di Milano, Via Pace 9, 20122 Milan, Italy. armando.tripodi@unimi.it
Branchi
Adriana
A
Chantarangkul
Veena
V
Clerici
Marigrazia
M
Merati
Giuliana
G
Artoni
Andrea
A
Mannucci
Pier Mannuccio
PM
D000328:Adult; D000368:Aged; D001780:Blood Coagulation Tests; D055252:Cell-Derived Microparticles / Q000378:metabolism; D048909:Diabetes Complications / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D013917:Thrombin / Q000032:analysis*; D019851:Thrombophilia / Q000097:blood*; D054556:Venous Thromboembolism / Q000097:blood
D013917:Thrombin