Summary
The frequent occurrence of vascular complications in diabetes mellitus has prompted extensive research into possible mechanisms which may relate to these complications. Recently, most emphasis has been directed towards the platelet and there is now good evidence of disordered platelet function, platelet biochemistry and platelet vessel wall interaction in many diabetic patients. In addition to these disturbances of platelet behaviour, other haemostatic abnormalities are not uncommon in the diabetic patient. These include evidence of coagulation activation, impaired fibrinolysis and altered blood viscosity. All of these changes could theoretically predispose to a thrombotic state, but the precise relationship between the observed abnormalities and the development and progression of the vascular complications remains to be established.
References
Abrahamsen A. F.: Platelet survival studies in man, with special reference to thrombosis and atherosclerosis — Scand. J. Haemat.5 (Suppl.), 3, 1968.
Almer L.-O., Nilsson I. M.: On fibrinolysis in diabetes mellitus — Acta med. scand.198, 101, 1975.
Almer L.-O., Pandolfi M., Nilsson I. M.: Diabetic retinopathy and the fibrinolytic system — Diabetes24, 529, 1975.
Barnes A. J.: Blood viscosity in diabetes mellitus. In:Lowe G. D. O., Barbenel J. C., Forbes C. D. (Eds): Clinical aspects of blood viscosity and cell deformability. Springer-Verlag, Berlin-Heidelberg-New York, 1981; p. 151.
Bedi H. K., Vyas B. R., Bomb B. S., Agarwal M. L., Bedi T.: Fibrinogen content and fibrinolytic activity of blood in diabetics before and after antidiabetic drugs — J. Ass. Phycns India25, 181, 1977.
Begg G. S., Pepper D. S., Chesterman C. N., Morgan F. J.: Complete covalent structure of human β-thromboglobulin — Biochemistry17, 1739, 1978.
Bensoussan D., Levy-Toledano S., Passa P., Caen J., Canivet J.: Platelet hyperaggregation and increased plasma level of von Willebrand factor in diabetics with retinopathy — Diabetologia11, 307, 1975.
Bern M. M.: Platelet functions in diabetes mellitus — Diabetes27, 342, 1978.
Best L. C., Jones P. B., Preston F. E.: Effect of glucose on platelet thromboxane biosynthesis — Lancetii, 790, 1979.
Bridges J. M., Dalby A. M., Millar J. H., Weaver J. A.: An effect of D-glucose on platelet stickiness — Lanceti, 75, 1965.
Burrows A. W., Chavin S. I., Hockaday T. D.: Plasma thromboglobulin concentrations in diabetes mellitus — Lanceti, 235, 1978.
Butkus A., Skrinska V. A., Schumacher O. P.: Thromboxane production and platelet aggregation in diabetic subjects with clinical complications — Thrombos. Res.19, 211, 1980.
Campbell I. W., Dawes J., Fraser D. M., Pepper D. S., Clarke B. F., Duncan L. J., Cash J. D.: Plasma beta-thromboglobulin in diabetes mellitus — Diabetes26, 1175, 1977.
Coller B. S., Frank R. N., Milton R. C., Gralnick H. R.: Plasma cofactors of platelet function: correlation with diabetic retinopathy and haemoglobins\(A_{1_{a \cdot c} } \) — Ann. intern. Med.88, 311, 1978.
Colwell J. A., Halushka P. V., Sarji K. E., Lopes-Virella M. F., Sagel J.: Vascular complications in diabetes — Arch. intern. Med.139, 225, 1979.
Cooper R. A.: Abnormalities of cell-membrane fluidity in the pathogenesis of disease — New Engl. J. Med.297, 371, 1977.
Corbella E., Miragliotta G., Masperi R., Villa S., Bini A., de Gaetano G., Chiumello G.: Platelet aggregation and antithrombin III levels in diabetic children — Haemostasis8, 30, 1979.
Creter D., Pavlotzky F., Savir H.: Platelet aggregation in diabetic retinopathy — Acta haemat. (Basel)60, 53, 1978.
Crofford D. B.: Report of the National Commission on Diabetes. The long-range plan to combat diabetes. NIH publication no. 76-1018, US Department of Health, Education and Welfare. Public Health Service National Institute of Health, 1976; vol. 1.
Dassin E., Najean Y., Poirier O., Passa P., Bensoussan D.:In vivo platelet kinetics in 31 diabetic patients. Correlation with the degree of vascular impairment — Thrombos. Haemost.40, 83, 1978.
Davis T. M., Bown E., Finch D. R., Mitchell M. D., Turner R. C.:In vitro venous prostacyclin production, plasma 6-keto-prostaglandin F1α concentrations and diabetic retinopathy — Brit. med. J.282, 1259, 1981.
Davis T. M., Mitchell M. D., Turner R. C.: Prostacyclin and thromboxane metabolites in diabetes — Lancetii, 789, 1979.
Dawes J., Borsey D. Q., Fraser D. M., Prowse C. V., Elton R. A., Clarke B. F.: Plasma beta-thromboglobulin in diabetes mellitus — Diabetologia18, 353, 1980.
Dintenfass L.: Blood viscosity factors in severe non-diabetic and diabetic retinopathy — Biorheology14, 151, 1977.
Dollery C. T., Friedman L. A., Hensby C. N., Kohner E., Lewis P. J., Porta M., Webster J.: Circulating prostacyclin may be reduced in diabetes — Lancetii, 1365, 1979.
Editorial: Platelets, beta-thromboglobulin and diabetes mellitus — Lanceti, 250, 1978.
Egeberg O.: The blood coagulability in diabetic patients — Scand. J. clin. Lab. Invest.15, 533, 1963.
Fagerberg S. E.: Diabetic neuropathy, a clinical and histological study on the significance of vascular affections — Acta med. scand.164 (Suppl. 345), 1, 1959.
Ferguson J. C., Mackay N., Philip J. A.: Determination of platelet and fibrinogen half-life with (75 Se) selenomethionine: studies in normal and diabetic subjects — Clin. Sci. molec. Med.49, 115, 1975.
Fuller J. H., Keen H., Jarrett R. J., Omer T., Meade T. W., Chakrabarti R., North W. R., Stirling Y.: Haemostatic variables associated with diabetes and its complications — Brit. med. J.ii, 964, 1979.
Fuster V., Bowie E. J. W., Lewis J. C., Fass D. N., Owen C. A.: Resistance to arteriosclerosis in pigs with von Willebrand’s disease. Spontaneous and high cholesterol diet-induced — J. clin. Invest.61, 722, 1978.
Gensini G. F., Abbate R., Favilla S., Neri Serneri G. G.: Changes of platelet function and blood clotting in diabetes mellitus — Thrombos. Haemost.42, 983, 1979.
Graves J. M., Colwell J. A., Nair R. M. G., Sarji K. E.: The effect of oral glucose on von Willebrand factor activity in normal and diabetic subjects — Clin. Endocr.6, 437, 1977.
Greaves M., Preston F. E.: Plasma 6-keto prostaglandin F1α, fact or fiction — Thrombos. Res. (In press).
Halushka P. V., Rogers R. C., Loadholt C. B., Colwell J. A.: Increased platelet thromboxane synthesis in diabetes mellitus — J. Lab. clin. Med.97, 87, 1981.
Hamberg M., Svensson J., Samuelsson B.: Thromboxanes; a new group of biologically active compounds derived from prostaglandin endoperoxides — Proc. nat. Acad. Sci. (Wash.)72, 2994, 1975.
Harrison H. E., Reece A. H., Johnson M.: Effect of insulin treatment on prostacyclin in experimental diabetes — Diabetologia18, 65, 1980.
Hassanein A. A., El-Garf T. A., El-Baz A.: Platelet aggregation in diabetes mellitus and the effect of insulinin vivo on aggregation — Thrombos. Diathes. haemorrh. (Stuttg.)27, 114, 1972.
Heath H., Brigden W. D., Canever J. V., Pollock J., Hunter P. R., Kelsey J., Bloom A.: Platelet adhesion and aggregation in relation to diabetic retinopathy — Diabetologia7, 308, 1971.
Hockaday T. D. R.: Direct animal and indirect human evidence of altered platelet function in diabetics — Mctabolism28, 415, 1979.
Honour A. J., Hockaday T. D. R.: Increased sensitivity ofin vivo platelet aggregation in rabbits after alloxan or streptozotocin — Brit. J. exp. Path.57, i, 1976.
Jones R. L., Peterson C. M.: Reduced fibrinogen survival in diabetes mellitus: a reversible phenomenon — J. clin. Invest.63, 485, 1979.
Kelsey J., Bloom A.: Platelet adhesion and aggregation in relation to diabetic retinopathy — Diabetologia7, 308, 1971.
Khosla P. K., Mahabaleswara M., Tiwari H. K., Saraya A. K.: Platelet aggregation and retinal microangiopathy in diabetes and hypertension — Acta haemat. (Basel)61, 161, 1979.
Kwaan H. C., Colwell J. A., Cruz S., Suwanwela N., Dobbie J. G.: Increased platelet aggregation in diabetes mellitus — J. Lab. clin. Med.80, 236, 1972.
Lecrubier C., Scarabin P. Y., Grauso F., Samama M.: Platelet aggregation related to age in diabetes mellitus — Haemostasis9, 43, 1980.
Lufkin E. G., Fass D. N., O’Fallon W. M., Bowie E. J.: Increased von Willebrand factor in diabetes mellitus — Metabolism28, 63, 1979.
McMillan D. E.: Disturbance of serum viscosity in diabetes mellitus — J. clin. Invest.53, 1071, 1974.
McMillan D. E., Utterback N. G., La Puma J.: Reduced erythrocyte deformability in diabetes — Diabetes27, 895, 1978.
Malmsten C.: Prostaglandins, thromboxanes and platelets — Brit. J. Haemat.41, 453, 1979.
Mayne E. E., Bridges J. M., Weaver J. A.: Platelet adhesiveness, plasma fibrinogen and factor VIII levels in diabetes mellitus — Diabetologia6, 436, 1970.
Meade T. W., North W. R., Chakrabarti R., Stirling Y., Haines A. P., Thompson S. G., Brozovic M.: Haemostatic function and cardiovascular death: early results of a prospective study — Lanceti, 1050, 1980.
Moncada S., Gryglewski R., Bunting S., Vane J. R.: An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation — Nature (Lond.)263, 663, 1976.
Moncada S., Vane J. R.: Arachidonic acid metabolites and the interactions between platelets and blood-vessel walls — New Engl. J. Med.300, 1142, 1979.
Needleman P., Minkes M., Raz A.: Thromboxanes: selective biosynthesis and distinct biological properties — Science193, 163, 1976.
O’Malley B. C., Ward J. D., Timperley W. R., Porter N. R., Preston F. E.: Platelet abnormalities in diabetic peripheral neuropathy — Lancetii, 1274, 1975.
Oppenheimer E. H., Esterly J. R.: Thrombosis in the newborn: comparison between infants of diabetic and non-diabetic mothers — J. Pediat.67, 549, 1965.
Pepper D. S., Ludlam C. A.: β-thromboglobulin — a new approach to the diagnosis of thrombosis. In:Mills D. C. B., Pareti F. I. (Eds): Platelets and thrombosis. Serono Symposium no. 10, London. Academic Press, New York, 1977; p. 145.
Peterson C. M., Jones R. L., Koenig R. J., Melvin E. T., Lehrman M. L.: Reversible haematologic sequelae of diabetes mellitus — Ann. intern. Med.86, 425, 1977.
Preston F. E., Ward J. D., Marcola B. H., Porter N. R., Timperley W. R., O’Malley B. C.: Elevated β-thromboglobulin levels and circulating platelet aggregates in diabetic microangiopathy — Lanceti, 238, 1978.
Sagel J.: Platelet adhesion and aggregation in diabetes mellitus — Metabolism28, 394, 1979.
Sagel J., Colwell J. A., Crook L., Laimins M.: Increased platelet aggregation in early diabetes mellitus — Ann. intern. Med.82, 733, 1975.
Sarji K. E., Nair R. M. G., Schraibman H. B., Chambers A. L., Laimins M., Barnes M., Colwell J. A.: Relation between growth hormone and von Willebrand factor activity — Circulation52, 144, 1975.
Schmid-Schönbein H., Volger E.: Red cell aggregation and red cell deformability in diabetes — Diabetes25 (Suppl. 2), 897, 1976.
Silberbauer K., Schernthaner G., Sinzinger H., Piza-Katzer H., Winter M.: Decreased vascular prostacyclin in juvenile-onset diabetes — New Engl. J. Med.300, 366, 1979.
Smith J. B., Ingerman G. B., Silver M. J.: Effects of arachidonic acid and some of its metabolites on platelets. In:Silver M. J., Smith J. B., Kocas J. J. (Eds): Prostaglandins in haematology. Spectrum, New York, 1977.
Stuart M. J., Elrad H., Graeber J. E., Hakanson D. O., Sunderji S. G., Barvinchak M. K.: Increased synthesis of prostaglandin endoperoxides and platelet hyperfunction in infants of mothers with diabetes mellitus — J. Lab. clin. Med.94, 12, 1979.
Takeuchi A., Benirschke K.: Renal vein thrombosis of the newborn and its relation to maternal diabetes — Biol. Neonat. (Basel)3, 237, 1961.
Timperley W. R., Preston F. E., Ward J. D.: Cerebral intravascular coagulation in diabetic ketoacidosis — Lanceti, 952, 1974.
Timperley W. R., Ward J. D., Preston F. E., Duckworth T., O’Malley B. C.: A reassessment of vascular factors in relation to intravascular coagulation — Diabetologia12, 237, 1976.
Tindall H., Paton R. C., Zuzel M., McNicol G. P.: Platelet life-span in diabetics with and without retinopathy — Thrombos. Res.21, 641, 1981.
Weiss H. J., Lages B. A.: Possible congenital defect in platelet thromboxane synthetase — Lanceti, 760, 1977.
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Preston, F.E. Disorders of haemostasis in diabetes mellitus. La Ricerca Clin. Lab. 12, 425–438 (1982). https://doi.org/10.1007/BF02909394
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DOI: https://doi.org/10.1007/BF02909394