title: Coagulation activation in diabetes mellitus: the role of hyperglycaemia and therapeutic prospects.
abstract: Numerous studies have shown that coagulation abnormalities occur in the course of diabetes mellitus, resulting in a state of thrombophilia. These observations are supported by epidemiological studies which demonstrate that thromboembolic events are more likely to occur in diabetic patients. The coagulation abnormalities observed in diabetic patients seem to be caused by the hyperglycaemia, which also constitutes the distinguishing feature of this disease. These data are also supported by in vitro studies which demonstrate how glucose can directly determine alterations in the coagulation system. The abnormalities observed involve all stages of coagulation, affecting both thrombus formation and its inhibition, fibrinolysis, platelet and endothelial function. The final result is an imbalance between thrombus formation and dissolution, favouring the former. Hyperglycaemia probably determines the onset of these abnormalities through three mechanisms which are, respectively, non-enzymatic glycation, the development of increased oxidative stress and a decrease in the levels of heparan sulphate. The first seems to affect the functionality of key molecules of coagulation in a negative sense. Oxidative stress constitutes an important pro-thrombotic stimulus, while the decrease in heparan sulphate determines a reduction in antithrombotic defenses. Good metabolic control could play a key role in controlling the coagulation irregularities in diabetes. However, considering the difficulties in achieving such an objective, it is possible that the use of drugs may represent a valid alternative. In fact, several drugs exist which are of potential interest. It is, however, necessary to perform long-term studies which demonstrate unequivocably that by controlling the coagulation abnormalities in diabetic patients, prolongation of life is possible.
authors.affiliation: Department of Experimental and Clinica Pathology, University of Udine, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ceriello
mesh_terms: D000419:Albuminuria; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000378:metabolism; D001791:Blood Platelet Disorders / Q000209:etiology* / Q000628:therapy; D001792:Blood Platelets / Q000502:physiology*; D003920:Diabetes Mellitus / Q000097:blood* / Q000628:therapy / Q000652:urine; D004730:Endothelium, Vascular / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D017270:Lipoprotein(a) / Q000097:blood; D010974:Platelet Aggregation
chemical_list: D001779:Blood Coagulation Factors; D017270:Lipoprotein(a)