Changes of platelet function and blood clotting in diabetes mellitus

We investigated some aspects of blood clotting and of platelet function in 48 diabetics (12 affected by preclinical diabetes, 15 by clinical diabetes, 21 with complications of diabetes, peripheral vascular disease, ischaemic heart disease or diabetic nephropathy with or without hypertension) and compared them with those from 35 age matched controls and 7 prediabetics. Blood clotting was investigated by gel-chromatography of fibrin soluble complexes, by factor VIII(COAG) two stage assay, by factor VIII(AGN) electroimmunodiffusion assay and by factor VIII(vWF)assay. Platelet function was investigated by the determination of the circulating platelet aggregates associated with megathrombocytes count and by the malondialdehyde formation after thrombin and after arachidonic acid. In order to clarify some mechanisms responsible for platelet aggregating plasmatic activity (PAPA) this activity was investigated by plasma-platelet cross-matches. Our results indicate early changes of platelet function in diabetics, already demonstrable in preclinical diabetes. Platelets are hyperaggregable and produce increased amounts of malondialdehyde after stimulation by thrombin and arachidonic acid, thus suggesting an increased activity of the intraplatelet endoperoxide-thromboxane forming metabolic pathway. An increased concentration of fibrin-soluble complexes can be shown in clinical and complicated diabetes whereas in preclinical diabetes the fibrogen complexes concentration is within the normal range. Factor VIII(vWF) results significantly increased in all groups of diabetics, and even in the subjects with prediabetes. Factor VIII(COAG) and Factor VIII(AGN), besides factor VIII(vWF), were significantly increased in clinical and in complicated diabetes. The increased concentration of factor VIII(COAG) and of soluble fibrinogen complexes suggest the existence of a hypercoagulable condition in patients with clinical and above all with complicated diabetes. In these patients a platelet aggregating plasmatic activity can be frequently found. The indication is that platelet hyperaggregation in diabetes is due to various mechanisms. In preclinical diabetes and in some patients with clinical diabetes platelet hyperaggregability is mainly due to a primary platelet hypersensitivity whereas in complicated diabetes, especially when hypercoagulability occurs, platelet hyperaggregation is due to a plasmatic factor related to blood clotting activation.