PDF herunterladen
Thromb Haemost 1979; 42(03): 983-993
DOI: 10.1055/s-0038-1656989
Original Article
Schattauer GmbH Stuttgart

Changes of Platelet Function and Blood Clotting in Diabetes Mellitus

G F Gensini
The Istituto di Patologia Medica II – Universitä di Firenze (Direttore: Prof. G. G. Neri Serneri) Consiglio Nazionale delle Ricerche – Rome – Italy. Program of Preventive Medicine (Project Atherosclerosis)
,
R Abbate
The Istituto di Patologia Medica II – Universitä di Firenze (Direttore: Prof. G. G. Neri Serneri) Consiglio Nazionale delle Ricerche – Rome – Italy. Program of Preventive Medicine (Project Atherosclerosis)
,
S Favilla
The Istituto di Patologia Medica II – Universitä di Firenze (Direttore: Prof. G. G. Neri Serneri) Consiglio Nazionale delle Ricerche – Rome – Italy. Program of Preventive Medicine (Project Atherosclerosis)
,
G G Neri Serneri
The Istituto di Patologia Medica II – Universitä di Firenze (Direttore: Prof. G. G. Neri Serneri) Consiglio Nazionale delle Ricerche – Rome – Italy. Program of Preventive Medicine (Project Atherosclerosis)
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 22. August 1978

Accepted 25. September 1978

Publikationsdatum:
23. August 2018 (online)

Auch verfügbar auf
  als PDF herunterladen  Lizenzen und Reprints

Summary

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 VIIICOAG two stage assay, by factor VIIIAGN electroimmunodiffusion assay and by factor VIIIvWF 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 VIIIvWF results significantly increased in all groups of diabetics, and even in the subjects with prediabetes. Factor VHICoag and Factor VIIIAGN, besides factor VIIIvWF, were significantly increased in clinical and in complicated diabetes. The increased concentration of factor VIIICOAG 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.

 

  • References

  • 1 Almer LO, Nilsson IM. 1975; On fibrinolysis in diabetes mellitus. Acta Medica Scandinavica 198: 101
    PubMedGoogle Scholar
  • 2 Almer LO, Pandolfi M, Aberg M. 1975; The plasminogen activator activity of arteries and veins in diabetes mellitus. Thrombosis Research 6: 177
    CrossrefPubMedGoogle Scholar
  • 3 Amherdt M, Scherrer JR, Rufener C, Pometta D. 1971; Early capillary changes in diabetes mellitus. Acta Diabetologica Latina 8: 88
    PubMedGoogle Scholar
  • 4 Badawi H, El-Sawy M, Mikhail M. 1970; Platelets, coagulation and fibrinolysis in diabetic and non-diabetic patients with quiescent coronary heart disease. Angiology 21: 511
    CrossrefPubMedGoogle Scholar
  • 5 Bensoussan D, Levy-Toledano S, Passa P. 1975; Platelet hyperaggregation and increased plasma level of von Willebrand Factor in diabetics with retinopathy. Diabetologia 11: 307
    CrossrefPubMedGoogle Scholar
  • 6 Bloodworth Jr JM, Molitor DL. 1965; Ultrastructural aspects of human and canine diabetic retinopathy. Investigations in Ophthalmology 4: 1037
    PubMedGoogle Scholar
  • 7 Boneu B, Corberand J, Plante J, Bierme R. 1977; Evidence that platelet density and volume are not related to aging. Thrombosis Research 10: 475
    CrossrefPubMedGoogle Scholar
  • 8 Bridges JM, Dalby AM, Millar JH, Weaver JA. 1965; An effect of D-glucose on platelet stickness. Lancet 1: 75
    PubMedGoogle Scholar
  • 9 Campbell IW, Dawes J, Fraser DM, Pepper DS, Clarke BF, Duncan LJ F, Cash JD. 1977; Plasma β-Thromboglobulin in diabetes mellitus. Diabetes, 26 12: 1175
    PubMedGoogle Scholar
  • 10 Colwell A, Halushka PV, Sarji K, Levine J, Sagel J, Nair RM G. 1976; Altered Platelet Function in Diabetes Mellitus. Diabetes 25: 826
    PubMedGoogle Scholar
  • 11 Denson KW E. 1976. In Biggs R. (Ed.) Human Blood Coagulation, Haemostasis and Thrombosis. Blackwell Scientific Publications; Oxford and Edinburgh:
  • 12 Dobbie JG, Kwann HC, Colwell J, Suwanwela N. 1973; The role of platelets in the pathogenesis of diabetic retinopathy. Transactions American Academy Ophthalmology Otoryngology 77: 43
    PubMedGoogle Scholar
  • 13 Fearnley GR, Chakrabarti R, Avis PR D. 1963; Blood fibrinolytic activity in diabetes mellitus and its bearing on heart disease and obesity. British Medical Journal 1: 921
    CrossrefPubMedGoogle Scholar
  • 14 Fearnley GR, Chakrabarti R, Hocking ED. 1967; Fibrinolytic effects of diguanides plus ethynoestrenol in occlusive vascular disease. Lancet 2: 1008
    PubMedGoogle Scholar
  • 15 Fleischman AI, Marvin L, Bierenbaum AS, Somol SL, Watson PB. 1976; In vivo platelet function in diabetes mellitus. Thrombosis Research 9: 467
    CrossrefPubMedGoogle Scholar
  • 16 Garg SK, Amorosi EL, Karpatkin S. 1971; Use of the megathrombocytes as an index of megakariocyte number. New England Journal Medicine 284: 11
    CrossrefPubMedGoogle Scholar
  • 17 Garg SK, Lackener H, Karpatkin S. 1972; The increased percentage of megathrombocytes in various clinical disorders. Annals of Internal Medicine 77: 361
    CrossrefPubMedGoogle Scholar
  • 18 Hafter R, Graeff H. 1975; Molecular aspects of defibrination: in a reptilase-treated case of »dead fetus syndrome«. Thrombosis Research 7: 391
    CrossrefPubMedGoogle Scholar
  • 19 Hathorn M, Gilmann T, Campbell GD. 1961; Blood lipids, mucoproteins, and fibrinolytic activity in diabetic Indians and Africans in Natal. Lancet 1: 1314
    PubMedGoogle Scholar
  • 20 Heath H, Bridgen WD, Canever JV, Pollock J, Hunter PR, Kelsey J, Bloom A. 1971; Platelet adhesiveness and aggregation in relation to diabetic retinopathy. Diabetologia 7: 308
    CrossrefPubMedGoogle Scholar
  • 21 Hallem AJ. 1971; Adenosinediphosphate induced platelet adhesiveness in diabetes mellitus with complications. Acta Medica Scandinavica 190: 291
    PubMedGoogle Scholar
  • 22 Hellem AJ, Skalhegg BA, Odegaard AE. 1964; The platelet adhesiveness in plasma from diabetic and lipemic patients. Sangre 9: 175
    PubMedGoogle Scholar
  • 23 Karpatkin S, Garg SK, Siskind GW. 1971; Autoimmune thrombocytopenic purpura and the compensated thrombocytolytic state. American Journal of Medicine 51: 1
    CrossrefPubMedGoogle Scholar
  • 24 Kraytman M. 1973; Platelet size in thrombocytopenias and thrombocytosis of various origin. Blood 41: 587
    PubMedGoogle Scholar
  • 25 Kwaan HC, Colwell JA, Cruz S, Suwanwela N, Dobbie JC. 1972; Increased platelet aggregation in diabetes mellitus. Journal of Laboratory and Clinical Medicine 80: 236
    PubMedGoogle Scholar
  • 26 Kwaan HC, Colwell JA, Suwanwela N. 1972; Disseminated intravascular coagulation in diabetes mellitus, with reference to the role of increased platelet aggregation. Diabetes 21: 108
    CrossrefPubMedGoogle Scholar
  • 27 Laurell CB. 1966; Quantitative estimation of proteins by electrophoresis in agarose gel containing antibody. Analytical Biochemistry 15: 45
    CrossrefPubMedGoogle Scholar
  • 28 Leone G, Bizzi B, Accorra F, Boni P. 1974. Functional aspects of platelets in diabetes mellitus. In Caprino L, Rossi FC. (Eds.) Platelet Aggregation and Drugs. New York: Academic Press; pages 49
    Google Scholar
  • 29 MacFarlane DE, Stibbe J, Kirby EP, Zucker MB, Grant RA, Mcpherson J. 1975; A method for assaying von Willebrand factor (ristocetin cofactor). Thrombosis et Diathesis Haemorrhagica 34: 306
    PubMedGoogle Scholar
  • 30 Malone JI, Van Cader TC, Edwards WC. 1977; Diabetic vascular changes in children Diabetes. 26: 673
    PubMedGoogle Scholar
  • 31 Matsuo T, Ohki Y. 1977; Classification of platelet aggregation patterns with two ADP solutions (the double-ADP method) and its clinical application to diabetes mellitus. Thrombosis research 11: 453
    CrossrefPubMedGoogle Scholar
  • 32 Mayne EE, Bridges JM, Weaver JA. 1970; Platelet adhesiveness, plasma fibrinogen and factor VIII levels in diabetes mellitus. Diabetologia 6: 436
    CrossrefPubMedGoogle Scholar
  • 33 Moolten SE, Jiennings PB, Solden A. 1963; Dietary fat and platelet adhesiveness in arteriosclerosis and diabetes. American Journal of Cardiology 11: 290
    CrossrefPubMedGoogle Scholar
  • 34 Neri Serneri GG, Abbate R, Gensini GF, Mugnaini C, Lagi A. 1976. Occurrence of a plasmatic aggregating activity in some patients with increased platelet aggregation. European Symposium on Platelet Aggregation, Coagulation, Fibrinolysis and Atherosclerosis. Palermo: 1976
    Google Scholar
  • 35 Neri Serneri GG, Gensini GF, Abbate R, Prisco D, Mugnaini C. 1976. Soluble fibrinogen complexes and platelet aggregates in patients with history of myocardial infarction and chronic cerebrovascular disorders. A rationale for prophylactic therapy. European Symposium on Platelet Aggregation, Coagulation, Fibrinolysis and Atherosclerosis. Palermo: 1976
    Google Scholar
  • 36 Neri Serneri GG, Silvestrini E, Gensini GF, Abbate-Gensini R. 1977. Platelet hyperreactivity and decreased survival in chronic cerebrovascular patients. Chronic defibrination syndrome. In Platelet Aggregation in the pathogenesis of cerebrovascular disorders. Proceedings of the Round Conference, Rome 30.10.1974. Springer Verlag: 1977
    Google Scholar
  • 37 Neri Serneri GG, Gensini GF, Abbate R, Favilla S. 1978 Feature of platelet aggregating plasmatic activity. In press
    PubMedGoogle Scholar
  • 38 Okuma M, Steiner M, Baldini GM. 1971; Studies on lipid peroxides in platelets. II. Effect of aggregating agents and platelet antibody. Journal of Laboratory and Clinical Medicine 77: 728
    PubMedGoogle Scholar
  • 39 O’malley BC, Ward JD, Timperly WR, Porter NR, Preston FR. 1975; Platelet abnormalities in diabetic peripheral neuropathy. Lancet 2: 1274
    PubMedGoogle Scholar
  • 40 Palmberg PF. 1977; Diabetic retinopathy. Diabetes 26: 703
    CrossrefPubMedGoogle Scholar
  • 41 Pandolfi M, Nilsson IM, Robertson B, Isacson S. 1967; Fibrinolytic activity of human veins. Lancet 2: 127
    PubMedGoogle Scholar
  • 42 Pandolfi M, Holmberg L, Turesson I. 1975; Coagulation and platelet adhesion-inducing factor in the endothelium of the retinal vessels. American Journal of Ophthalmology 80: 47
    CrossrefPubMedGoogle Scholar
  • 43 Preston FE, Ward JD, Mazzola B, Portez NR, Timperley WR, O’malley BC. 1978; Elevated β-thromboglobulin levels and circulating platelet aggregates in diabetic microangiopathy. Lancet 1: 238
    PubMedGoogle Scholar
  • 44 Sagel J, Colwell JA, Crook L, Laimins M. 1975; Increased platelet aggregation in early diabetes mellitus. Annals of Internal Medicine 82: 733
    CrossrefPubMedGoogle Scholar
  • 45 Shaw S, Pegrum GD, Wolff S, Ashton WL. 1967; Platelet adhesiveness in diabetes mellitus. Journal of Clinical Pathology 20: 845
    CrossrefPubMedGoogle Scholar
  • 46 Siperstein MD. 1971; Quantitation of diabetic microangiopathy: practical implications. Acta Diabetologica Latina 8: 391
    PubMedGoogle Scholar
  • 47 Szirtes M. 1970; Platelet aggregation in diabetes mellitus. Advances in Cardiology 4: 179
    PubMedGoogle Scholar
  • 48 Timperley WR, Ward JD, Preston FE, Duckworth T, O’malley BC. 1975; A reassesment of small vessel disease in diabetic neuropathy. Diabetologia 11: 379
    PubMedGoogle Scholar
  • 49 Waitzman MB, Colley AM, Nardelli-Olkowska K. 1977; Metabolic approaches to studies on diabetic microangiopathy. Diabetes 26 5: 510
    PubMedGoogle Scholar
  • 50 Wu KK, Hoak JC. 1974; A new method for the quantitative detection of platelet aggregates in patients with arterial insufficiency. Lancet 2: 924
    PubMedGoogle Scholar