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

Second Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.

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 ml, 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-independent 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] A1c >/= 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 A1c < 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.

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