Changes of Platelet Function and Blood Clotting in Diabetes Mellitus

Abstract

We investigated some aspects of blood clotting and of platelet functions 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) in 35 age matched controls and in 7 prediabetics. Blood clotting has been 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 functions have been investigated by the determination of circulating platelet aggregates associated with megathrombocytes count, by the malondial- dehyde formation after thrombin and after arachidonic acid. In order to clarify some mechanisms responsible for platelet aggregating plasmatic activity (PAPA) has been investigated by plasmaplatelet cross-matches. Our results indicate early changes of platelet functions 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 VHICoag 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, specially when hypercoagulability occurs, platelet hyperaggregation is due to a plasmatic factor related to blood clotting activation.