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Thromb Haemost 1967; 18(03/04): 674-685
DOI: 10.1055/s-0038-1655077
Originalarbeiten — Original Articles — Travaux Originaux
Schattauer GmbH

Zum Mechanismus der Thrombozytenaggregation[*]

II Erhöhung der Klebrigkeit durch geladene Makromoleküle
Th Pfleiderer   **
1   Aus der Medizinischen Universitätsklinik (Ludolf Krehl-Klinik) Heidelberg (Direktor: Prof. Dr. G. Schettler) und dem Max-Planck-Institut für Medizinische Forschung, Institut für Chemie, Heidelberg (Direktor: Prof. Dr. R. Kuhn)
,
R Brossmer
1   Aus der Medizinischen Universitätsklinik (Ludolf Krehl-Klinik) Heidelberg (Direktor: Prof. Dr. G. Schettler) und dem Max-Planck-Institut für Medizinische Forschung, Institut für Chemie, Heidelberg (Direktor: Prof. Dr. R. Kuhn)
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Publication Date:
26 June 2018 (online)

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Zusammenfassung

Bestimmungen der Thrombozytenklebrigkeit in vitro zeigen, daß Zusatz von positiv und negativ geladenen Makromolekülen zu einer Verklumpung von menschlichen Blutplättchen führt. Substanzen mit der gleichen Grundstruktur, aber ohne geladene Gruppen besitzen keine derartige Wirkung. Die Ladung ist für die Aggregation also von entscheidender Bedeutung. Die Verklumpung von Thrombozyten durch geladene Makromoleküle ist nicht wesentlich temperaturabhängig, d.h. sie erfolgt bei 37° C und bei 4° C in gleicher Weise. Es scheint fraglich, ob Stoffwechselprozesse oder enzymatische Vorgänge für den Ablauf der Aggregation von Bedeutung sind. Zwischen der Wirkung positiv und negativ geladener Makromoleküle läßt sich ein prinzipieller Unterschied nach weisen : negativ geladene Substanzen sind in kalziumfreiem Milieu (EDTA-Plasma) nicht mehr wirksam; DEAE-Dextran und Polylysin als Vertreter von positiv geladenen Makromolekülen steigern dagegen in EDTA- und Zitratmilieu gleichermaßen die Klebrigkeit. Das bedeutet, daß Kalziumionen und ADP an diesem Effekt nicht beteiligt sind. Anhand der Befunde werden Vorstellungen zum Mechanismus der Aggregation menschlicher Blutplättchen in vitro entwickelt und deren Bedeutung für Verhältnisse in vivo diskutiert.

* Herrn Prof. Dr. H. Schaefer zum 60. Geburtstag.


** Mit Unterstützung der Deutschen Forschungsgemeinschaft.


 

  • Literatur

  • 1 Astrup T, Piper J. Interaction between fibrinogen and polysaccharide polysulfuric acids. Acta physiol, scand. 11: 211 1946;
    CrossrefPubMedSearch in Google Scholar
  • 2 Bangham A. D, Pethica B. A, Seaman G. V. P. The charged groups at the interface of some blood cells. Biochem. J. 69: 12 1958;
    CrossrefPubMedSearch in Google Scholar
  • 3 Bettex-Galland M, Lüscher E. Induction of viscous metamorphosis in human blood platelets by means other than by thrombin. Nature (Lond) 200: 1109 1963;
    CrossrefPubMedSearch in Google Scholar
  • 4 Born G. V. R. Aggregation of blood platelets by ADP and its reversal. Nature (Lond) 194: 927 1962;
    PubMedSearch in Google Scholar
  • 5 Born G. V. R, Cross M. J. The aggregation of blood platelets. J. Physiol. (Lond) 168: 178 1963;
    CrossrefPubMedSearch in Google Scholar
  • 6 Born G. V. R, Gross M. J. Effects of inorganic ions and of plasma proteins on the aggregation of blood platelets by adenosine diphosphate. J. Physiol. (Lond) 170: 397 1964;
    CrossrefPubMedSearch in Google Scholar
  • 7 Brossmer R, Pfleiderer T. h. Zum Mechanismus der Thrombocytenaggregation. I. Die Bedeutung der Ladung hochmolekularer Substanzen, insbesondere von Dextranen für die Aggregation in vitro. Naturwissenschaften 53: 464 1966;
    PubMedSearch in Google Scholar
  • 8 Bryant M. F, Bloom W. L, Brewer SSp. Experimental study of the antithrombotic properties of dextrans of low molecular weight. Amer. Surg. 29: 256 1963;
    PubMedSearch in Google Scholar
  • 9 Bryant M. F, Bloom W. L, Brewer SSp. Study of the anti-thrombotic properties of dextrans of large molecular weight. J. cardiovasc. Surg. 04: 48 1964;
    PubMedSearch in Google Scholar
  • 10 Constantine J. W. Temperature and the aggregation of rabbit platelets by ADP. Nature (Lond) 205: 1075 1965;
    CrossrefPubMedSearch in Google Scholar
  • 11 Feissly R, Lüdin H. Microscopie par constrates de phase. Rev. Hémat. 04: 401 1949;
    PubMedSearch in Google Scholar
  • 12 Fischer A. Die Bindung von Heparin an Eiweiß. Biochem. Z. 278: 133 1935;
    PubMedSearch in Google Scholar
  • 13 Gaardner A, Jonson J, Laland S, Hellem A, Owren P. A. ADP in red cells as a factor in the adhesiveness of human blood platelets. Nature (Lond) 192: 531 1961;
    CrossrefPubMedSearch in Google Scholar
  • 14 Gaardner A, Laland S. Hypothesis for the aggregation of platelets by nucleotides. Nature (Lond) 202: 909 1964;
    CrossrefPubMedSearch in Google Scholar
  • 15 Hampton J. R, Mitchell J. R. A. Effect of aggregating agents on the electrophoretic mobility of human platelets. Brit. Med. J. I: 1074 1966;
    PubMedSearch in Google Scholar
  • 16 Hellem A. J. The adhesiveness of human blood platelets in vitro. Scand. J. clin. Lab. Invest 12 Suppl. 51) 117 1960;
    PubMedSearch in Google Scholar
  • 17 Hellem A. J, Ödegaard A. E, Skalhegg B. A. Investigations on ADP-induced platelet adhesiveness in vitro. Part. I. The ADP platelet reaction in various experimental conditions. Thrombos. Diathes. haemorrh. (Stuttg) 10: 61 1963;
    PubMedSearch in Google Scholar
  • 18 Hovig T. Release of a platelet-aggregating substance (ADP) from rabbit blood platelets induced by saline “extract” of tendons. Thrombos. Diathes. haemorrh. (Stuttg) 09: 264 1963;
    PubMedSearch in Google Scholar
  • 19 Hovig T. The effect of calcium and magnesium ob rabbit blood platelet aggregation in vitro. Thrombos. Diathes. haemorrh. (Stuttg) 12: 179 1964;
    PubMedSearch in Google Scholar
  • 20 Kaullav K. N, Husemann E. The relation of molecular size and shape to physiological activity. Experientia (Basel) 02: 222 1946;
    PubMedSearch in Google Scholar
  • 21 Kerby G. P. The role of chelators in surface metabolism of adenosine nucleotides added to native human blood platelets in vitro. Thrombos. Diathes. haemorrh. (Stuttg) 15: 457 1966;
    PubMedSearch in Google Scholar
  • 22 Kopéc M, Budzynski A, Stachorska J, Wegrzynowicz Z, Kowalski E. Studies on the mechanism of interference by fibrinogen degradation products (FDP) with the platelet function. Role of fibrinogen in the platelet atmosphere. Thrombos. Diathes. haemorrh. (Stuttg) 15: 476 1966;
    PubMedSearch in Google Scholar
  • 23 McLean J. R, Maxwell R. E, Hertler D. Fibrinogen and ADP-induced aggregation of platelets. Nature (Lond) 202: 605 1964;
    CrossrefPubMedSearch in Google Scholar
  • 24 Mustard J. F, Rowsell H. G, Murphy E. A. Platelet economy (platelet survival and turnover). Brit. J. Hematol. 12: 1 1966;
    CrossrefPubMedSearch in Google Scholar
  • 25 Nilsson J. M, Eiken O. Further Studies on the effect of Dextran of various Mol weight on the coagulation mechanism. Thrombos. Diathes. haemorrh. (Stuttg) 11: 38 1964;
    PubMedSearch in Google Scholar
  • 26 O’Brien J. R. The adhesiveness of nativ platelets and its prevention. J. clin. Pathol. 14: 140 1961;
    CrossrefPubMedSearch in Google Scholar
  • 27 O’Brien J. R. Platelet aggregation: Part I. Some effects of the adenosine phosphates, thrombin and cocaine upon platelet adhesiveness. Part. II. Some results from a new method of study. J. clin. Path. 15: 446 1962;
    PubMedSearch in Google Scholar
  • 28 O’Brien J. R. Some possible enzyme systems in volved in platelet aggregation. J. Atheroscler. Res. 05: 262 1963;
    PubMedSearch in Google Scholar
  • 29 O’Brien J. R. A comparison of platelet aggregation produced by seven compounds and their inhibitors. J. clin. Path. 17: 275 1964;
    CrossrefPubMedSearch in Google Scholar
  • 30 Oellgaard E. Macroscopic studies of platelet aggregation. Nature of an aggregating factor in red blood cells and platelets. Thrombos. Diathes. haemorrh. (Stuttg) 06: 86 1961;
    PubMedSearch in Google Scholar
  • 31 Pfleiderer T. h, Brossmer R. Unveröffentlichte Befunde..
    PubMed
  • 32 Piper J. Toxicology of synthetic polysaccharide polysulfuric acid esters. Acta pharmacol. (Kbh) 02: 317 1946;
    PubMedSearch in Google Scholar
  • 33 Ponder E. Revêtement des plaquettes humaines et des globules rouges par les dextranes. Rev. Hémat. 12: 11 1957;
    PubMedSearch in Google Scholar
  • 34 Robinson G. W, Kress S. C, Wagner R. H, Brinkhous K. M. Platelet agglutination and deagglutination with a sulfhydryl inhibitor, methyl mercuric nitrate: relationship to platelet ATPase. Exp. molec. Path. 04: 457 1965;
    CrossrefPubMedSearch in Google Scholar
  • 35 Ross W. S, Ebert R. V. Microelectrophoresis of blood platelets and the effects of dextran. J. clin. Invest 38: 155 1959;
    CrossrefPubMedSearch in Google Scholar
  • 36 Salzman E. W, Chambers D. A, Neri L. L. Incorporation of labelled nucleotides and aggregation of human blood platelets. Thrombos. Diathes. haemorrh. (Stuttg) 15: 52 1966;
    PubMedSearch in Google Scholar
  • 37 Salzman E. W. Studies on the mechanism of platelet aggregation by ADP. Thrombos. Diathes. haemorrh. (Stuttg) 15: 628 1966;
    PubMedSearch in Google Scholar
  • 38 Sasaki S, Noguchi H. Interaction of fibrinogen with dextran sulfate. J. gen. Physiol. 43: 1 1959;
    CrossrefPubMedSearch in Google Scholar
  • 39 Sasaki S, Takemoto T, Oka S. Toxicity of heparinoids, with special reference to the precipitation of fibrinogen. Thrombos. Diathes. haemorrh. (Stuttg) 12: 232 1964;
    PubMedSearch in Google Scholar
  • 40 Sawyer P, Harshaw D. Possible relationship of ionic structure of the blood intimai interface to intravascular thrombosis. Surgery. 56: 846 1964;
    PubMedSearch in Google Scholar
  • 41 Sawyer R. B, Moncrief G. J. A. Dextran specifity in thrombus inhibition. Arch. Surg 90: 562 1965;
    CrossrefPubMedSearch in Google Scholar
  • 42 Spaet HTh. The platelets in hemostasis : a morphological and biochemical study. Thrombos. Diathes. haemorrh. (Stuttg) 11: 303 1964;
    PubMedSearch in Google Scholar
  • 43 Spaet HTh, Lejnieks J. Studies on the mechanism whereby platelets are clumped by adenosine diphosphate. Thrombos. Diathes. haemorrh. (Stuttg) 15: 36 1966;
    PubMedSearch in Google Scholar
  • 44 Walton K. W. The biological behavior of a new synthetic anticoagulant (dextran sulfat) posessing heparin-like properties. Brit. J. Pharmacol. 07: 370 1952;
    PubMedSearch in Google Scholar
  • 45 Weber E, Pfleiderer T. h, Brossmer R. Unveröffentlichte Befunde..
    PubMed
  • 46 Zucker M. B, Levine R. U. Microelectrophoresis of washed and unwashed human blood platelets with additional studies of platelets from patients with von Willebrand’s disease and Thrombasthenia. Thrombos. Diathes. haemorrh. (Stuttg) 10: 1 1963;
    PubMedSearch in Google Scholar