PDF herunterladen
Thromb Haemost 1975; 33(01): 066-072
DOI: 10.1055/s-0038-1647812
Meeting of the International Committee on Thrombosis and Haemostasis — Symposium on Heparin, Basel, Switzerland, September, 1974
Schattauer GmbH

Platelet Heparin-Neutralizing Factor[*] (Platelet Factor 4)

E. F Lüscher
1   Theodor Kocher Institute, University of Berne, Switzerland
,
R Käser-Glanzmann
1   Theodor Kocher Institute, University of Berne, Switzerland
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
02. Juli 2018 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Summary

The heparin-neutralizing platelet factor (PF4) is released from platelets under the influence of inducers of aggregation and nucleotide-release in the form of a high-molecular weight complex. The heparin-neutralizing activity is carried by a basic protein of molecular weight 29,700, four of which combine with a proteoglycan carrier, which in turn consists of 4 chondroitin sulfate A residues and a peptide moiety.

The carrier-PF4-complex dissociates at higher ionic strength into proteoglycan and PF4 proper ; both forms (bound and free) are active in the inactivation of heparin, which displaces PF4 from its natural mucopolysaccharide carrier.

PF4 is localized in human platelets in storage organelles, most likely in the α-granules and not in the adenine nucleotide and serotonin containing dense bodies. It is released simultaneously with the contents of these latter organelles.

The physiological significance of PF4 is mainly seen in the interference with the inhibition of the clotting system by heparin within and in the vicinity of platelet aggregates. Released in circulation in the course of intravascular platelet damage, it may contribute to a facilitation of thrombin formation and action, by removing heparin.

Adequately purified PF4 does not interact with fibrinogen and its derivatives and therefore is not directly involved in the induction of intravascular coagulation or platelet aggregation.

* Presented at the Symposium on Heparin, Basel, Switzerland, September, 1974.


 

  • References

  • 1 Ǻborg C. H, Uvnäs B. A mucopolysaccharide-protein complex with amine binding properties in rat thrombocytes. Acta Physiologica scandinavica 1971; 81: 568.
    CrossrefPubMedSuche in Google Scholar
  • 2 Barber A. J, Käser-Glanzmann R, Jakábová M, Lüscher E. F. Characterization of a chondroitin 4-sulfate proteoglycan carrier for heparin neutralizing activity (platelet factor 4) released from human blood platelets. Biochimica et Biophysica Acta 1972; 286: 312.
    CrossrefPubMedSuche in Google Scholar
  • 3 Barber A. J, Käser-Glanzmann R, Lüscher E. F. Characterization of the carbohydrate moiety of a proteoglycan-protein complex with heparin-neutralizing activity (Platelet factor 4) released from human blood platelets. In Gerlach Moser, Deutsch and Wiemanns (eds.)., Erythrocytes, Thrombocytes, Leukocytes. Thieme, Stuttgart 211. 1973;
    PubMedSuche in Google Scholar
  • 4 Barkhan P, Youssef A. Effect of salicylates on human platelets. Lancet 1968; II: 359.
    PubMedSuche in Google Scholar
  • 5 Chmielewski J, Farbiszewski R. Platelet Factor 4 (PF4) release during human platelet aggregation in diabetic patients. Thrombosis et Diathesis Haemorrhagica 1970; 24: 203.
    PubMedSuche in Google Scholar
  • 6 Conley L. O, Hartmann R. C, Lalley J. S. The relationship of heparin activity to platelet concentration. Proceedings of the Society for Experimental Biology N. Y. 1948; 69: 284.
    PubMedSuche in Google Scholar
  • 7 van Creveld S, Paulssen M. M. P. Significance of clotting factors in blood platelets in normal and pathological conditions. Lancet 1951; II: 242.
    PubMedSuche in Google Scholar
  • 8 van Creveld S, Paulssen M.M.P. Isolation and properties of the third clotting factor in blood platelets. Lancet 1952; I: 23.
    PubMedSuche in Google Scholar
  • 9 Cronberg S, Kubisz P, Caen J. P. Demonstration of a plasmatic cofactor different from fibrinogen necessary for platelet release by ADP and adrenaline. Thrombosis et Diathesis Haemorrhagica 1970; 24: 409.
    PubMedSuche in Google Scholar
  • 10 Da Prada M, von Berlepsch K, Pletscher A. Storage of biogenic amines in blood platelets and adrenal medulla. Lack of evidence for direct involvement of glycosamino glycans. Archiv für experimentelle Pathologie und Pharmakologie 1972; 275: 315.
    PubMedSuche in Google Scholar
  • 11 Day H. J, Stormorken H, Holmsen H. Subcellular localization of platelet factor 3 and platelet factor 4. Scandinavian Journal of Haematology 1973; 10: 254.
    PubMedSuche in Google Scholar
  • 12 Deutsch E, Wawersich E, Franke G. Über das Vorkommen eines Antiheparinfaktors in Thrombozyten und Geweben I. Mitt. : Antiheparinaktivität der Thrombozyten.. Thrombosis et Diathesis Haemorrhagica 1957; 1: 397.
    PubMedSuche in Google Scholar
  • 13 Deutsch E, Kain W. Studies on platelet factor 4. In Johnson Monto, Bebuck and Horn (eds.). Blood Platelets; Henry Ford Hospital Symposium Little, Brown: Boston; 1961: 337.
    Suche in Google Scholar
  • 14 Deutsch E, Lechner K. Platelet clotting factors. In: Kowalski and Niewiarowski (eds.). Biochemistry of Blood Platelets Acad. Press; London.: 1967: 23
    Suche in Google Scholar
  • 15 Evensen S. A, Jeremic M. Platelets and triggering mechanism of intravascular coagulation. British Journal of Haematology 1970; 19: 33.
    CrossrefPubMedSuche in Google Scholar
  • 16 Farbiszewski R, Niewiarowski S, Poplawski A. Purification and separation of platelet factor 2 (fibrinogen activating factor) and of platelet factor 4 (antiheparin factor). Biochimica et Biophysica Acta 1966; 115: 397.
    CrossrefPubMedSuche in Google Scholar
  • 17 Farbiszewski R, Lipinski B, Niewiarowski S, Poplawski A. Hypercoagulability and thrombocytopenia after platelet factor 4 infusion into rabbits. Experientia (Basel) 24: 578. 1968; a
    CrossrefPubMedSuche in Google Scholar
  • 18 Farbiszewski R, Niewiarowski S, Worowski K, Lipinski B. Release of platelet factor 4 in vivo during intravascular coagulation and in thrombotic states. Thrombosis et Diathesis Haemorrhagica 19: 578. 1968; b
    PubMedSuche in Google Scholar
  • 19 Fuster V, Bowie E. J. W, Kazmier F. J, Owen jr. C. A. Platelet consumption in chronically induced plasma platelet factor 4-like activity reflecting rate of intravascular coagulation. Thrombosis Research 1974; 4: 247.
    CrossrefPubMedSuche in Google Scholar
  • 20 Gjesdal K. Platelet factor 4 (PF-4). A study on methodology and physiology. Scandinavian Journal of Haematology 1974; 12: 51.
    PubMedSuche in Google Scholar
  • 21 Harada K, Zucker M. B. Simultaneous development of platelet 4 activity and release of 14C-serotonin. Thrombosis et Diathesis Haemorrhagica 1971; 25: 41.
    PubMedSuche in Google Scholar
  • 22 Jürgens R. Funktion der Thrombocyten bei Blutung und Thrombose. Wiener klinische Wochenschrift 1954; 66: 850.
    PubMedSuche in Google Scholar
  • 23 Käser-Glanzmann R, Jakábová M, Lüscher E. F. Isolation and some properties of the heparin-neutralizing factor (PF4) released from human blood platelets. Experientia (Basel) 1972; 28: 1221.
    CrossrefPubMedSuche in Google Scholar
  • 24 Käser-Glanzmann R, Jakábová M, Lüscher E. F. Heparin-neutralizing factor (PF4) from human blood platelets and its reactivity with fibrinogen and soluble fibrin-monomer complexes. Haemostasis 1972; 73 1: 136.
    PubMedSuche in Google Scholar
  • 25 Kubisz P, Sultan Y, Delobel J, Caen J. Mesure de la libération du facteur plaquettaire 4 (PF4) dans les thrombopathies constitutionnelles et acquises. Revue européenne d’Etudes cliniques et biologiques 1970; 15: 698.
    PubMedSuche in Google Scholar
  • 26 Kubisz P, Suranowa J. Further variant of the thrombocytopathy with abnormalities in platelet release reaction. Thrombosis Research 1974; 4: 119.
    CrossrefPubMedSuche in Google Scholar
  • 27 Lipinski B, Worowski K, Jeljaszewicz J, Niewiarowski S, Rejniak L. Participation of soluble fibrin monomer complexes and platelet factor 4 in the generalized Shwartzman reaction. Thrombosis et Diathesis Haemorrhagica 1968; 20: 285.
    PubMedSuche in Google Scholar
  • 28 Moriau M. Have the platelet antiheparin and antiplasmin activities the same support ?. Thrombosis et Diathesis Haemorrhagica 1969; 22: 403
    PubMedSuche in Google Scholar
  • 29 Moskowitz R. W, Schwartz H. J, Michel B, Ratnoff O. D, Astrup T. Generation of kinin-like agents by chondroitin sulfate, heparin, chitin sulfate, and human articular cartilage : Possible pathophysiological implications. Journal of Laboratory and Clinical Medicine 1970; 76: 790.
    PubMedSuche in Google Scholar
  • 30 Niewiarowski S, Farbiszewski R, Poplawski A. Neutralization of anti-thrombin VI (fibrinogen breakdown products) with platelet antiheparin factor (platelet factor 4). Thrombosis et Diathesis Haemorrhagica 1965; 14: 490.
    PubMedSuche in Google Scholar
  • 31 Niewiarowski S, Farbiszewski R, Poplawski A. Studies on platelet factor 2 (PF2-fibrinogen activating factor) and platelet factor 4 (PF4-antiheparin factor); In : Kowalski and Niewiarowski. Biochemistry of Blood Platelets. Acad. Press; London: 35. 1967
    Suche in Google Scholar
  • 32 Niewiarowski S, Farbiszewski R, Poplawski A, Lipinski B. Further investigations on the role of platelet factor 4 (PF4) in the mechanism of platelet aggregation. In Deutsch Gerlach, Moser, Stoffwechsel und Membranpermeabilität von Erythrocyten und Thrombozyten; Thieme Stuttgart: 1968. a 314.
    Suche in Google Scholar
  • 33 Niewiarowski S, Lipinski B, Farbiszewski R, Poplawski A. The release of platelet factor 4 during platelet aggregation and the possible significance of this reaction in hemostasis. Experientia (Basel) 24: 343. 1968; b
    CrossrefPubMedSuche in Google Scholar
  • 34 Niewiarowski S, Poplawski A, Lipinski B, Farbiszewski R. The release of platelet clotting factors during aggregation and viscous metamorphosis. Experimental Biology and Medicine 1968; c 3: 121 (Karger, Basel/New York)
    PubMedSuche in Google Scholar
  • 35 Niewiarowski S, Thomas D. P. Platelet factor 4 and adenosine diphosphate release during human platelet aggregation. Nature Lond 1969; 222: 1269.
    CrossrefPubMedSuche in Google Scholar
  • 36 O’Brien J. R. Cell membrane damage, platelet stickiness and some effects of aspirin. British Journal of Haematology 1969; 17: 610.
    PubMedSuche in Google Scholar
  • 37 O’Brien J. B, Finch W, Clark E. Platelet-bound and soluble platelet factor 4: Effects of aggregating agents, of aggregation, and of aspirin. Proceedings of the Society of Experimental Biology N. Y 1970; 134: 1128.
    PubMedSuche in Google Scholar
  • 38 Pepper D. S, Moore S, Cash J. D. Preliminary studies on the isolation and characterization of human platelet anti-heparin activity (PF4). 2nd Congress International Society on Thrombosis and Haemostasis, Oslo Abstract 244. 1971
    Suche in Google Scholar
  • 39 Poplawski A, Niewiarowski S. Dissociation of platelet antiheparin factor (platelet factor 4) from lipoprotein lipase inhibitor. Biochimica et Biophysica Acta 1964; 90: 403.
    CrossrefPubMedSuche in Google Scholar
  • 40 Schulz H, Hiepler E. Über die Lokalisierung von gerinnungsphysiologischen Aktivitäten in submikroskopischen Strukturen der Thrombocyten. Klinische Wochenschrift 1959; 37: 273.
    CrossrefPubMedSuche in Google Scholar
  • 41 Thomas D. P, Niewiarowski S, Ream V. J. Release of adenine nucleotides and platelet factor 4 from platelets of man and four other species. Journal of Laboratory and Clinical Medicine 1970; 75: 607.
    PubMedSuche in Google Scholar
  • 42 Weiss H. J, Rogers J. Platelet factor 4 in platelet disorders – Storage location and the requirement of endogenous ADP for its release. Proceedings of the Society for Experimental Biology N. Y 1973; 142: 30.
    PubMedSuche in Google Scholar
  • 43 Youssef A, Barkhan P. Release of platelet factor 4 by adenosine diphosphate and other platelet aggregating agents. British Medical Journal I 1968; I: 746.
    PubMedSuche in Google Scholar