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-dep endent thrombin generation as an index of coagulability in diabetes an d to determine the effect of glycemic control on coagulability in diab etes. Background. It is important to investigate the interaction of pl atelets and the coagulation factors to clarify the processes of the co agulation system in detail. Methods. Platelet rich plasma (150 x 10(9) /liter), 0.5 mi, was prepared, and 40 mmol/liter of calcium chloride w as added to initiate clotting, S-2238 was added to each sample in a mi crotiter plate every 10 min, and the absorbance of the released color product at 2 min was measured spectrophotometrically at a wavelength o f 405 nm using a microtiter plate reader as thrombin generation. We me asured the platelet dependent thrombin generation in patients with non -insulin-dependent diabetes mellitus grouped according to glycemic con trol. 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 wi thout complications, such as diabetic retinopathy, nephropathy and neu ropathy (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) b etween those of the poorly controlled group and healthy normal subject s. Platelet-poor plasma from diabetic patients increased platelet-depe ndent thrombin generation in normal subjects. Conclusions. Coagulabili ty is evidently enhanced in patients with non-insulin-dependent diabet es mellitus compared with that in healthy normal subjects on the basis of assessments of the platelet dependent thrombin generation, and goo d glycemic control may help to correct a hypercoagulable state in diab etic patients.