Zusammenfassung
Gefäßerkrankungen und damit verbundene Akutkomplikationen stellen unverändert die Haupttodesursache des Diabetikers dar. Die Entwicklung der letztlich lebensterminierenden thrombotischen Akutereignisse an endothelialen Läsionsstellen des Gefäßsystems ist verstärkt. Morbidität und Mortalität des Diabetikers hängen damit von den gefäßvermittelten Komplikationen schicksalhaft ab.
Die Integrität des Blutflusses als Voraussetzung einer bedarfsgerechten Organperfusion resultiert aus Vasomotion, Plasmazusammensetzung, Eigenschaften zellulärer Blutelemente, der Gefäßstruktur sowie v. a. aus der ungestörten Interaktion dieser Komponenten an der endothelialen Grenzfläche. Die funktionelle Thromboresistenz des Endothels ist beim Diabetiker vermindert. Neben gesteigerter intravasaler Thrombinbildung und verminderter re-parativer Fibrinolyse führen v. a. primär funktionsgesteigerte Thrombozyten zu einem präthrombotischen Zustand. Im Gegensatz zu hämorrheologischen Mechanismen kann eine thrombotische Diathese zur akuten Strombahnobstruktion führen. Aktivierte Thrombozyten sind dabei dreifach schädigend: 1) primäre Mikroembolisierung der Kapillarstrombahn, 2) lokale Progression von Gefäßwandläsionen durch Sekretion vasokonstriktiver, mitogener und oxydativ wirksamer Substanzen, 3) Auslösung einer arteriellen Akutthrombose.
Aus diesen Gründen liegt eine ergänzende thrombozytenfunktionshemmende Präventionsmedikation bei Diabetikern nahe. Voraussetzung für eine weitere Verbesserung der Nutzen-Risiko-Abwägung solcher Therapieansätze ist die Analyse des individuellen Risikos eines aktivierten zellulären Hämostasesystems z. B. mit der durchflußzytometrischen Aktivierungsmarkeranalyse nach dem Düsseldorf-III-Protokoll („thrombotic risk assessment“).
Auszug aus dem Übersichtsartikel „Rheologische Veränderungen und diabetische Folgeschäden“. Veröffentlicht in: Diabetes und Stoffwechsel, Heft 1, 2/1992. Mit freundlicher Genehmigung des Herausgebers, Prof. Willms, Bad Lauterberg.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Literatur
Abrams CHS, Ellison N, Budzynski AZ, Shattil SJ (1990) Direct detection of activated platelets and platelet-derived microparticles in humans. Blood 75:128–138
Alessandrini P, McRae J, Feman S, Fitzgerald GA (1988) Thromboxane biosynthesis and platelet function in type I diabetes mellitus. New Engl J Med 319/4:208–212
Antiplatelet Trialist Collaboration (1988) Secondary prevention of vascular disease by prolonged antiplatelet treatment. Br Med J 296:310
Auwerx J, Bouillon R, Collen D, Geboers J (1972) Tissue-type Plasminogen activator antigen and Plasminogen activator inhibitor in diabetes mellitus. Arteriosclerosis 8:68–72
Banga JD, Sixma JJ (1986) Diabetes mellitus, vascular disease and thrombosis. Clin Haematol 15:465–492
Bauer KA, Rosenberg RD (1987) The pathophysiology of the prethrombotic state in humans: insights gained from studies using markers of hemostatic system activation. Blood 70:343–350
Baumgartner HR, Sakariassen KS (1987) Factors controlling thrombus formation on arterial lesions. Ann NY Acad Sci: 162-177
Bennett PH (1990) Epidemiology of Diabetes Mellitus, in: Rifkin H, Prts D jr (eds) Diabetes mellitus. Elsevier, New York Amsterdam London, p 249–256
Berndt MC (1986) The Molecular Mechanism of Platelet Adhesion, in: Fidge NH, Nestel PJ (eds) Athersclerosis VII. Springer, Berlin Heidelberg New York, p 467–471
Betteridge DJ, Zahavi J, Jones NAG, Shine B, Kakkar VV, Galton DJ (1981) Platelet function in diabetes mellitus in relationship to complications, glycosylated haemoglobin. and serum lipoproteins. Eur J Clin Invest 11:273–277
Betteridge DJ, El Tahir KEH, Reckless JPD, Williams KI (1982) Platelets from diabetic subjects show diminished sensitivity to prostacyclin. Eur J Clin Invest 12:395–398
Boeri D, Almus F, Maiello M, Cagliero E, Vijaya Mohan Rao L, Lorenzi M (1989) Modification of tissue factor mRNA and protein response to thrombin and interleukin 1 by high glucose in cultured human endothelial cells. Diabetes 38:212–218
Brand FN, Abbott RD, Kannel WB (1989) Diabetes, intermittent claudication, and risk of cardiovascular events. The Framingham Study. Diabetes 38:504–509
Bransome ED (1992) Financing the Care of Diabetes Mellitus in the U.S. Diab Care 15 Supplement 1:1–5
Breddin HK, Kryzwanek HJ, Althoff P, Kirchmaier CM, Rosak C, Schepping M, Weichert W, Ziemen M, Schöffling K, Überla K (1986) Spontaneous platelet aggregation and coagulation parameters as risk factors for arterial occlusions in diabetics. Results of the PARD-study. Int Angiol 5:181–195
Brownlee M, Cerami A, Vlassara H (1988) Advanced glycosylation end products and the biochemical basis of diabetic vascular complications. N Engl J Med 318:1315–1321
Burrows AW, Chavin SI, Hockaday TDR (1978) Plasma-thromboglobulin concentrations in diabetes mellitus. Lancet 2/4:235–237
Ceriello A, Giugliano D, Quatraro A, Stante A, Dello Russo P, D’Onofrio P (1987) Induced hyperglycemia alters antithrombin III activity but not its plasma concentration in healthy normal subjects. Diabetes 36:320–323
Ceriello A, Marchi E, Barbanti M, Milani MR, Giuliano D, Quatraro A, Lefebre P (1990) Non-enzymatic glycation reduces heparin cofactor II antithrombin activity. Diabetologia 33:205–207
Ceriello A, Quatraro A, Marchi E, Barbanti M, Dello Russo P, Lefebvre P (1990) The role of hyperglycemia-induced alterations of anti-thrombin III and factor X activation in the thrombin hyperactivity of diabetes mellitus. Diab Med 7:343–348
Cho NH, Becker D, Dorman JS, Wolfson S, Kuller LH, Drash AL, Follansbee WF, Kelsey SF, Orchard TJ (1989) Spontaneous whole blood platelet aggregation in insulin-dependent diabetes mellitus: an evaluation in an epidemiologic study. Thromb Haemost 61:127–130
Colwell JA (1991) Clinical Trials of Antiplatelet Agents in Diabetes Mellitus: Rationale and Results. Sem Thromb Hemostas 17:439–444
Colwell JA (1991) Platelet-active drugs in diabetes mellitus, in: Mogensen CE, Standl E (eds) Pharmacology of Diabetes. de Gruyter, Berlin, p 193–209
Colwell JA et al. (1989) Consensus Statement. Role of cardiovascular risk factors in prevention and treatment of macrovascular disease in diabetes. Diab Care 12:573–579
Colwell JA, Lopes-Virella MF (1988) A review of the development of large-vessel disease in diabetes mellitus. Am J Med 85:113–118
Colwell JA, Lopes-Virella, Halushka PV (1981) Pathogenesis of atherosclerosis in diabetes mellitus. Diabetes Care 4:121–133
Colwell JA, Winocour PD, Halushka PV (1983) Do platelets have anything to do with diabetic microvascular disease? Diabetes 32:14–19
Colwell JA, Winocour PD, Lopes-Virella MF (1990) Platelet interactions in atherosclerosis and diabetes mellitus, in: Rifkin H, Prts D jr (eds) Diabetes mellitus. Elsevier, New York Amsterdam London, p 249–256
Corash L, Chen HY, Levin J, Baker G, Lu H, Mok Y (1987) Regulation of thrombopoiesis: effects of the degree of thrombocytopenia on megakaryocyte ploidy and platelet volume. Blood 70:177–185
D’Angelo A, Micossi P, Mannucci PM, Garimberti B, Franchi F, Pozza G (1984) Increased production of platelet thromboxane B2 in non-insulin-dependent diabetes. Relationship to vascular complications. Eur J Clin Invest 14:83–86
Davi G, Catalano I, Averna M, Notarbartolo A, Strano A, Ciabattoni G, Patrono C (1990) Thromboxane biosynthesis and platelet function in type II diabetes mellitus. N Engl J Med 21:1769–1774
Di Minno G, Thiagarajan P, Perussia B, Martinez J, Shapiro S, Trinchieri G, Murphy S (1983) Exposure of platelet fibrinogen-binding sites by collagen, arachidonic acid, and ADP: inhibition by a monoclonal antibody to the glycoprotein IIb-IIIa complex. Blood 61:140–148
Diabetes Epidemiology Research International Mortality Study Group (1991) International evaluation of cause-specific mortality and IDDM. Diabetes Care 14:55–60
Diabetes Epidemiology Research International Mortality Study Group (1991) Major crosscountry differences in risk of dying for people with IDDM. Diabetes Care 14:49–54
Esposito C, Gerlach H, Brett J, Stern D, Vlassara H (1989) Endothelial receptor-mediated binding of glucose modified albumin is associated with increased monolayer permeability and modulation of cell surface coagulant properties. J Exp Med 170:1387–1407
Fitzgerald DJ, Roy L, Catella F, Fitzgerald GA (1986) Platelet activation in unstable coronary disease. N Engl J Med 315:983–989
Frade LJG, de la Calle H, Alava I, Navarro JL, Creighton LJ, Gaffney PJ (1987) Diabetes Mellitus as a hypercoagulable state: its relationship with fibrin fragments and vascular damage. Thromb Res 47:533–540
Frazier WA (1987) Thrombospondin: a modular adhesive glycoprotein of platelets and nucleated cells. J Cell Biol 105:625–632
Fritschi J, Christe M, Lämmle B, Marbet GA, Berger W, Duckert F (1984) Platelet aggregation, β-thromboglobulin and platelet factor 4 in diabetes mellitus and in patients with vasculopathy. Thromb Hameostas 52/3:236–239
Fristma G, Engelmann G, Yousuf M (1981) Control mechanisms in platelet activation. Am J Med Tech 47:813–817
George JN, Pickett EB, Saucerman S, McEver R, Kunicki TJ, Kieffer N, Newman PJ (1986) Platelet surface glycoproteins. Studies on resting and activated platelets and platelet membrane microparticles in normal subjects and observations in patients during adult respiratory distress syndrome and cardiac surgery. J Clin Invest 78:340–348
Guillausseau PJ, Dupuy E, Bryckaert MC, Timsit J, Chanson P, Tobelem G, Caen JP, Lubetzki J (1989) Platelet-derived growth factor (PDGF) in type 1 diabetes mellitus. Eur J Clin Invest 19:172–175
Halushka PV, Rogers RC, Loadholt CB, Colwell JA, Charleston SC (1981) Increased platelet thromboxane synthesis in diabetes mellitus. J Lab Clin Med 97:87–96
Hawiger J, Kloczewiak M, Timmons S (1985) Platelet Receptor Mechanisms for Adhesive Macromolecules, in: Oates JA, Hawiger J, Ross R (eds) Interaction of Platelets with the Vessel Wall. American Physiological Society, Bethesda, Maryland: 1–20
Jarrett RJ (1984) The epidemiology of coronary heart disease and related factors in the context of diabetes mellitus and impaired glucose tolerance. In: Jarrett RJ (ed). Elsevier, Amsterdam
Jarrett RJ, Keen H (1975) Die Epidemiologie des Diabetes. In: Handbuch der Inneren Medizin Bd 7, Teil 2 A: Diabetes mellitus. Springer, Berlin, p 679–694
Johnston GI, Pickett EB, McEver RP, George JN (1987) Heterogeneity of platelet secretion in response to thrombin demonstrated by fluorescence flow cytometry. Blood 69:1401–1403
Landgraf-Leurs MMC, Ladik T, Smolka B, Bock T, Schramm W, Spannagl M, Landgraf R (1987) Increased thromboplastic potential in diabetes: A multifactorial phenomenon. Klin Wochenschr 65/13:600–606
Levin E, Loskutoff DG (1978) Comparative studies of the fibrinolytic activity of cultured vascular cells. Thromb Res 15:869–878
Localzo J, Melnick B, Hardin RI (1985) Interactions of platelet factor 4 and the glycosaminoglycanes. Arch Biochem Biophys 240:446–455
Lorenzi M, Cagliero E, Roy S, Roth T (1989) The diabetic milieu and endothelial cell replication. In: Molinatti GM, Bar RS, Belfiore F, Porta M (eds) Endothelial cell function in diabetic microangiopathy: Problems in methodology and clinical aspects. Karger, Basel, p 64–74
Lorenzi M, Cagliero E (1991) Pathobiology of endothelial and other vascular cells in diabetes mellitus. Diabetes 40:653–659
Maiello M, Boeri D, Bonadonna R, Odetti P, Sacarello A (1988) Platelet and Clotting Activities after Cold Stress in Diabetic Patients. Thromb Res 50:885–894
Marks HH, Krall LP (1971) Onset, course, prognosis and mortality in diabetes mellitus, in: Marble A, White P, Bradley RF, Krall LP (eds) Joslin’s Diabetes Mellitus, 11th edn. Lea and Febiger, Philadelphia, p 209–254
Marshall M (1986) Ultrastructural findings on platelet depositions in initial atherogenesis. Wien Klin Wochenschr 98:212–214
Martin JF, Bath PM, Burr ML (1991) Influence of platelet size on outcome after myocardial infarction. Lancet 338:1409–1411
Martin JF, Booth RFG, Moncada S (1991) Arterial wall hypoxia following thrombosis of the vasa vasorum is an initial lesion in atherosclerosis. Eur J Clin Invest 21:355–359
McEver RP (1990) Properties of GMP-140, an inducible granule membrane protein of platelets and endothelium. Blood Cells 16:73–83
McEver RP (1992) Leukocyte Interactions Mediated by GMP140, in: Cochrane CG, Gimbrone MA (eds) Cellular and Molecular Mechanisms of Inflammation. Academic Press Inc, San Diego New York Boston Sydney Tokyo Toronto, p 15–29
Micossi P, Gallus G, Pozza G (1987) Excess Mortality in Diabetes, in: Andreani D, Crepaldi G (eds) Diabetic Complications. Early Diagnosis and Treatment. John Wiley & Sons Ltd, p 13-23
Mizuno K, Satomura K, Miyamoto A, Arakawa K, Shibuya T, Tsunenori A, Kurita A, Nakamura H, Ambrose J (1992) Angioscopic Evaluation of Coronary-Artery Thrombi in Acute Coronary Syndromes. New Engl J Med 326:287–291
Niiya K, Hodson E, Bader R, Byers-Ward V, Koziol JA, Plow EF, Ruggeri ZM (1987) Increased surface expression of the membrane glycoprotein IIb/IIIa complex induced by platelet activation. Relationship to the binding of Fibrinogen and platelet aggregation. Blood 70:475–483
Nurden AT (1987) Platelet membrane glycoproteins and their clinical aspects, in: Verstraete M, Vermylen J, Lijnen R, Arnout J (eds) Thrombosis and Haemostasis. Leuven University Press, p 93-125
Ostermann H, van de Loo J (1986) Factors of the hemostatic system in diabetic patients — A survey of controlled studies. Haemostasis 16/6:386–416
Panzram G (1987) Mortality and survival in Type 2 (non-insulin dependent) diabetes mellitus. Diabetologia 30:123–131
Parker RI, Gralnick HR (1986) Identification of platelet glycoprotein Ilb/IIIa as the major binding site for released platelet-von Willebrand factor. Blood 68:732–736
Pennington DG, Streatfield K (1975) Heterogeneity of Megakaryocytes and Platelets. Ser Haematol 8:22–47
Pirart J (1978) Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973. Diabetes Care 1:168–188
Preston FE, Ward JD, Marcola BH, Porter NR, Timperley WR (1978) Elevated β-thromboglobulin levels and circulating platelet aggregates in diabetic microangiopathy. Lancet: 238-239
Rodgers GM, Shuman MA (1983) Prothrombin is activated on vascular endothelial cells by factor Xa and calcium. Proc Natl Acad Sci 80:7001–7005
Roy S, Gala R, Cagliero E, Lorenzi M (1990) Overexpression of fibronectin induced by diabetes of high glucose: phenomenon with a memory. Proc Natl Acad Sci 87:404–408
Ross R (1986) The pathogenesis of atherosclerosis — an update. N Engl J Med 314:488–498
Rösen P, Hohl C (1984) Prostaglandins and diabetes. Ann Clin Res 16:300–313
Rösen P, Hohl C, Tschöpe D, Körner A, Halfmann U, Berger M (1987) Thromboxane and 6-Oxo-PGFla in the plasma of patients with diabetes type I and II. Prostaglandins in Clinical Research. Alan R Liss Inc 300:247–252
Rösen P, Tschöpe D, Kayser S, Kaufmann L (1989) Platelet activation and cyclo-and lipoxygenase-activities in diabetics type II. Prostaglandins in Clinical Research: Cardiovascular System. Alan R Liss Inc: 359-363
Rösen P, Tschöpe D (1991) Chronische Hyperglykämie als Ursache endothelialer Dysfunktion im Diabetes. Berichte der ÖGKC 14:124–131
Sagel J, Colwell JA, Crook L, Laimins M (1975) Increased platelet aggregation in early diabetes mellitus. Ann Intern Med 82:733–738
Schafer AI (1985) The hypercoagulable States. Ann Int Med 102:814–828
Schmid-Schönbein H (1981) Physiologie und Pathophysiologie der Mikrozirkulation sowie Konsequenzen für deren pharmakologische Behandlung, in: Messmer K, Fagrell B (eds) Mikrozirkulation und arterielle Verschlußkrankheiten. Karger, Basel München Paris London New York Sydney, p 22–38
Schmitz G, Hankowitz J, Kavacs EM (1991) Cellular aspects of the antiatherogenic properties of Ca++-channel blockers and their potential role in risk factor intervention. Atherosclerosis 88:109–132
Sevitt S (1986) Platelets and foam cells in the evolution of atherosclerosis. Atherosclerosis 61:107–115
Shattil SJ, Cunningham M, Hoxiw JA (1987) Detection of activated platelets in whole blood using activation-dependent monoclonal antibodies and flow cytometry. Blood 70:307–315
Singer DE, Moulton AW, Nathan DM (1989) Interaction of diabetes with other preinfarction risk factors. Diabetes 38:350–357
Sinzinger H (1986) Role of platelets in atherosclerosis. Sem Thromb Hemostas 12:124–133
Sixma J (1987) Platelet Adhesion in Health and Disease, in: Verstraete M, Vermylen J, Lijnen R, Arnout J (eds) Thrombosis Haemostasis. Leuven University Press: 127-146
Songer TJ, DeBerry K, LaPorte RE, Tuomilehto J (1992) International Comparisons of IDDM Mortality. Diab Care 15 Supplement 1:15–21
Sprafka JM, Burke GL, Folsom RA, McGovern PG, Hahn PL (1991) Trends in prevalence of diabetes mellitus in patients with myocardial infarction and effect of diabetes on survival. Diabetes Care 14:537–543
Stamler J (1987) Epidemiology, established major risk factors, and the primary prevention of coronary heart disease. In: Parmley W, Chatterjee K (eds) Cardiology. Lippincott JB, Philadelphia, p 1–41
Stout RW (1987) The endothelial cell in diabetes, in Belfiore F (ed) Front Diabetes. Karger, Basel, p 116–124
Thompson CB, Jakubowski JA, Quinn PG, Deykin D, Valeri CR (1983) Platelet size as determinant of platelet function. J Lab Clin Med 101:205–213
Tsibashi T, Tanaka K, Tanigushi Y (1981) Platelet aggregation and coagulation in the pathogenesis of diabetic retinopathy. Diabetes 20:601–606
Tschoepe D, Schwippert B, Schettler B, Kiesel U, Rothe H, Roesen P, Gries FA (1992) Increased GPIIB/IIIA Expression and Altered DNA-Ploidy Pattern in Megakaryocytes of Diabetic BB-Rats. Eur J Clin Invest 22:591–598
Tschöpe D, Esser J, Schwippert B, Rösen P, Kehrel B, Nieuwenhuis HK, Gries FA (1991) Large platelets circulate in an activated state in diabetes mellitus. Sem Thromb Haemostas 17:433–439
Tschöpe D, Langer E, Schauseil S, Rösen P, Kaufmann L, Gries FA (1989) Increased platelet volume — sign of impaired thrombopoiesis in diabetes mellitus. Klin Wochenschr 67:253–259
Tschöpe D, Ostermann H, Hübinger A, Ziegler D, Wiefels K, Gries FA (1990) Elevated platelet activation in type I diabetics with chronic complications under long term near normoglycemic control. Haemostasis 20:93–98
Tschöpe D, Rösen P, Gries FA (1989) Increased platelet function as risk factor for diabetic microangiopathy. In: Thromboembolic risk and dysbalance of haemostasis. Spannuth E, Pindur G, Wenzel E (eds). Schattauer, Stuttgart, p 1.22–1.30
Tschöpe D, Rösen P, Kaufmann L, Schauseil S, Kehrel B, Ostermann H, Gries FA (1990) Evidence for abnormal platelet glycoprotein expression in diabetes mellitus. Eur J Clin Invest 20:166–170
Tschöpe D, Spangenberg P, Esser J, Schwippert B, Kehrel B, Rösen P, Gries FA (1990) Flowcytometric detection of surface membrane alterations and concomitant changes in the cytoskeletal actin status of activated platelets. Cytometry 11:652–656
Tschoepe D, Rösen P, Schwippert B, Kehrel B, Schauseil S, Esser J, Gries FA (1990) Platelet Analysis Using Flowcytometric Procedures. Platelets 1/3:127–133
Tschoepe D, Schultheiß HP, Kolarov P, Nieuwenhuis HK, Danehl K, Strauer B, Gries FA (1993) Platelet Activation is predictive for an increased PTCA-risk. Circulation 88:1–6
Tschoepe D, Roesen P, Gries FA (1992) The Role of the Megakaryocyte-Platelet System for Diabetic Angiopathy: Is Metabolic Control Preventive Therapy Enough? Thromb Haemorr Disorders 6:1–8
Tuszynski GP, Rothman VL, Murphy A, Siegler K, Knudsen KA (1988) Thrombospondin promotes platelet aggregation. Blood 72:109–115
Ulvenstam G, Aberg A, Bergstrand R, Johansson S, Pennert K, Vedin A, Wilhelmsen L, Wilhelmsson C (1985) Long-term prognosis after myocardial infarction in men with diabetes. Diabetes 34:787–792
Voisin PJ, Rousselle D, Streiff F, Debry G, Stoltz JF, Drouin P (1983) Reduction of betathromboglobulin levels in diabetics controlled by artificial pancreas. Metabolism 32:138–141
West KM (1978) Epidemiology of Diabetes and its Vascular Lesions. Elsevier, New York, p170
Wolff R, Plow EF, Ginsberg MH (1986) Interaction of thrombospondin with resting and stimulated human platelets. J Biol Chem 261:6840–6846
Zatz R, Brenner BM (1986) Pathogenesis of Diabetic Microangiopathy. Am J Med 80:443–453
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1993 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Tschöpe, D., Rösen, P., Schwippert, B. (1993). Aktivierte zelluläre Hämostase und diabetische Angiopathie. In: Hasslacher, C., Spanuth, E. (eds) Diabetes und Angiopathie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-47621-1_6
Download citation
DOI: https://doi.org/10.1007/978-3-642-47621-1_6
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-56721-9
Online ISBN: 978-3-642-47621-1
eBook Packages: Springer Book Archive