Platelet-dependent thrombin generation in patients with diabetes mellitus: Effects of glycemic control on coagulability in diabetes

Objectives. This study sought to assess the usefulness of platelet-dependent thrombin generation as an index of coagulability in diabetes and to determine the effect of glycemic control on coagulability in diabetes. Background. It is important to investigate the interaction of platelets and the coagulation factors to clarify the processes of the coagulation system in detail. Methods. Platelet rich plasma (150 x 10(9)/liter), 0.5 mi, was prepared, and 40 mmol/liter of calcium chloride was added to initiate clotting, S-2238 was added to each sample in a microtiter plate every 10 min, and the absorbance of the released color product at 2 min was measured spectrophotometrically at a wavelength of 405 nm using a microtiter plate reader as thrombin generation. We measured the platelet dependent thrombin generation in patients with non-insulin-dependent diabetes mellitus grouped according to glycemic control. Results. Platelet-dependent thrombin generation at 30 min after calcium chloride addition was significantly higher in 23 patients with poorly glycemic controlled non-insulin-dependent diabetes mellitus without complications, such as diabetic retinopathy, nephropathy and neuropathy (hemoglobin [Hb] A(1c) greater than or equal to 9.0%) than in 46 healthy normal subjects (448 +/- 75 vs. 165 +/- 28 mU/min, p <0.001). Thrombin generation in 31 well controlled diabetic patients without complications (Hb A(1c) <9.0%) was intermediate (240 +/- 72 mU/min) between those of the poorly controlled group and healthy normal subjects. Platelet-poor plasma from diabetic patients increased platelet-dependent thrombin generation in normal subjects. Conclusions. Coagulability is evidently enhanced in patients with non-insulin-dependent diabetes mellitus compared with that in healthy normal subjects on the basis of assessments of the platelet dependent thrombin generation, and good glycemic control may help to correct a hypercoagulable state in diabetic patients.