Studies on the Mechanism of Interference by Fibrinogen Degradation Products (FDP) with the Platelet Function Role of Fibrinogen in the Platelet Atmosphere

Summary

1. Blood platelets can be aggregated by solutions of fibrinogen preparations of different origins. Fibrinogen degradation products (FDP) obtained by plasmin digestion do not aggregate platelets.

2. Preparations of FDP added to platelet suspension inhibit aggregation induced by fibrinogen,.

3. FDP when added to platelet suspensions, inhibit the release of adenine nucleotides induced by thrombin, connective tissue extract, kaolin or the contact factor.

4. Platelet suspensions pretreated with SKPL loose partly the ability to release adenine nucleotides after the action of inducing agents.

5. Washed platelet suspensions possess the capacity to adsorb fibrinogen and FDP, the latter being adsorbed in greater amounts and bound stronger than fibrinogen.

6. An attempt was undertaken to explain the observed phenomena on the basis of a general view on the molecular mechanism of platelet function.

It is postulated that fibrinogen is an integral part of the platelet surface and that it is one of the determinants of the platelet surface properties. Fibrinogen is necessary for platelet aggregation by ADP and for the adequate action of the agents which initiate metabolic changes and induce the release reaction. FDP act antagonistically to fibrinogen. They inhibit ADP aggregation as well as the access to the susceptible sites on. the surface of the platelet of the agents inducing release.

• References

• 1 Bettex-Galland M, Lüscher E. F, Simon G, Vassalli P. Induction of viscous metamorphosis in human blood platelets by means other than by thrombin. Nature (Lond) 200: 1109 1963;
• 2 Blombäck B, Blombäck M. Purification of human and bovine fibrinogen. Arkiv kemi 10: 415 1956;
• 3 Born G. V. R, Gross M. I. Effects of inorganic ions and of plasma proteins on the aggregation of blood platelets by adenosine diphosphate. J. Physiol. (Lond) 170: 397 1964;
• 4 Brinkhous K, Read M, Mason R. Plasma thrombocyte agglutinating activity and fibrinogen: synergism with adenosine diphosphate. Information Exchange Group Nr. 2 IEG 2. Scientific Nemo, 56.
• 5 Buckingham S, Maynert E. W. The release of 5-hydroxytryptamine, potassium and amino- acids from platelets. J. Pharmacol, exp. Ther 143: 332 1964;
• 6 Caen J, Castaldi P, Inceman S. Le role du fibrinogène dans l’hémostase primaire. Nouv. Rev. Franc. Hemat 05: 327 1965;
• 7 Caen J, Inceman S. Considerations sus l’allongement du temps de saignement dans l’afi- brinogènèmie congenitale. Nouv. Rev. franç. Hémat 03: 614 1963;
• 8 Castaldi P. A, Gaen J. Platelet fibrinogen, Information Exchange Group No 2 IEG 2. Scientific Memo 45..
• 9 Castaldi P. A, Firkin B. G, Blackwell P. M, Clifford K. I. An electron microscopic study of the changes in platelets during viscous metamorphosis. Blood 20: 566 1962;
• 10 Gaarder A, Laland S. Hypothesis for the aggregation of platelets by nucleotides. Nature (Lond) 202: 909 1964;
• 11 Glynn M. F, Movat H. Z, Murphy E. A, Mustard J. F. Study of platelet adhesiveness and aggregation with latex particles. J. Lab. Clin. Med 65: 179 1965;
• 12 Gocke D. J, Osler A. G. In vitro damage of rabbit platelets by an unrelated antigen - ant ib o dy reaction. I General characteristic of the reaction. J. Immunol 94: 236 1965;
• 13 Gokoen M, Yunis E. Fibrinogen as a part of platelet structure. Nature (Lond) 200: 590 1963;
• 14 Grette K. The mechanism of thrombin catalysed hemostatic reactions in blood platelets. Norvegian University Press; Oslo: 1962
• 15 Gugler E, Lüscher E. Die kongenitale Afibrinogenämie. Ann. paediat. (Basel) 200: 125 1963;
• 16 Hagan J. J, Ablondi F. B, Renso E. C. Purification and biochemical properties of human plasminogen. J. Biol. Chem 235: 1005 1960;
• 17 Hardisty R. M, Dormady K. M, Hutton R. A. Thrombastenia : studies on three cases. Brit. J. Haemat 10: 371 1964;
• 18 Haslam R. I. Role of adenosine diphosphate in the aggregation of human blood-platelets by thrombin and by fatty acids. Nature (Lond) 202: 765 1964;
• 19 Hovig T. Release of a platelet aggregating substance (Adenosine diphosphate) from rabbit blood platelets induced by saline “extract” of tendons. Thrombos. Diathes. haemorrh. (Stuttg) 09: 264 1963;
• 20 Hovig T. The effect of various enzymes on the ultrastructure, aggregation and clot retraction ability of rabbit blood platelets. Thrombos. Diathes. haemorrh. (Stuttg) 13: 84 1965;
• 21 Jackson D. P, Morse E. E, Zieve P. D, Conley C. L. Thrombocytopathic purpura associated with defective clot retraction and absence of platelet fibrinogen. Blood 22: 827 1963;
• 22 Kaser-Glanzmann Lüscher E. F. The mechanism of platelet aggregation in relation to hemo- stasis. Thrombos. Diathes. haemorrh. (Stuttg) 07: 480 1962;
• 23 Kekwick R. A, Mac Kay M. E, Nance M. H, Record B. R. The purification of human fibrinogen. Biochem. J 60: 67 1965;
• 24 Kline D. L. The purification and cristallisation of plasminogen (profibrinolysin). J. biol. Chem 204: 949 1953;
• 25 Kowalski E, Budzynski A. Z, Kopec M, Latallo Z. S, Lipiński B, Węgrzynowicz Z. Studies on the molecular pathology and pathogenesis of bleeding in severe fibrinotytic states in dogs. Thrombos. Diathes. haemorrh. (Stuttg) 12: 69 1964;
• 26 Kowalski E, Budzyński A. Z, Kopeć M, Latallo Z. S, Lipiński B, Węçgrzynowicz Z. Circulating fibrinogen degradation products (FDP) in dog blood after intravenous thrombin infusion. Thrombos. Diathes. haemorrh. (Stuttg) 13: 12 1965;
• 27 Kowalski E, Kopeć M, Węgrzynowicz Z. Influence of fibrinogen degradation products (FDP) on platelet aggregation, adhesiveness and viscous metamorphosis. Thrombos. Diathes. haemorrh. (Stuttg) 10: 406 1964;
• 28 Morse E. E, Jackson D. P, Conley C. L. Role of platelet fibrinogen in the reaction of platelet to thrombin J. clin. Invest 44: 809 1965;
• 29 Larrieu M. J, Faur Y, Caen J, Bernard J. Syndrome biologique de F afibrinogénémie congenitale. Nouv. Rev. franç. Hémat 05: 368 1965;
• 30 Latallo Z, Budzynski A. Z, Lipinski B, Kowalski E. Inhibition of thrombin and of fibrin polymerisation, two activities derived from plasmin digested fibrinogen. Nature (Lond) 203: 1184 1964;
• 31 Latallo Z, Fletcher A. P, Alkjaersig N, Sherry S. Inhibition of fibrin polymerization by fibrinogen proteolysis products. Amer. J. Physiol 202: 681 1962;
• 32 Mc Lean J. R, Maxwell R. E, Hertler D. Fibrinogen and adenosine dipnosphate induced aggregation of platelets. Nature (Lond) 202: 605 1964;
• 33 Nachman R. L, Marcus A. J, Zucker-Franklin D. orothea. Subcellular localization of platelet fibrinogen. Blood 24: 853 1964;
• 34 Niewiarowski S, Kozlowska J, Gulmantowicz A, Pelczarska-Kasperska E. Afibrinogénémie congenitale. Etude biologique de deux cas. Hémostase 02: 191 1962;
• 35 Niewiarowski S, Stachurska J, Wçgrzynoivicz Z. Arginine esterase activity of the contact (Hageman)factor. Thrombos. Diathes. haemorrh. (Stuttg) 07: 514 1962;
• 36 Parmeggiani A. Elektronenoptische Beobachtungen an menschlichen Blutplättchen während der viskosen Metamorphose. Thrombos. Diathes. haemorrh. (Stuttg) 06: 517 1961;
• 37 Pinniger J. L, Prunty F. T. Some observations on the blood clotting mechanism. The role of fibrinogen and platelets with reference to a case of congenital afibrinogenemie. Brit. J. exp. Path 27: 200 1964;
• 38 Rodman Jr. N. F, Mason R. G, Brinkhous K. M. Some pathogenic mechanism of white thrombus formation: agglutination and self destruction of the platelet. Fed. Proc 22: 1356 1963;
• 39 Salmon J. Y. Bounameaux Situation du fibrinogène décelé dans le thrombocytes bovins isolés et lavés. Arch, intern. Physiol. Biochim 65: 502 1957;
• 40 Salmon J, Bounameaux Y. Etude des antigenes plaquettaires et en particulier, du fibrinogène. Thrombos. Diathes. haemorrh. (Stuttg) 02: 93 1958;
• 41 Salmon J, Verstraete M, Bounameaux Y. Fibrinogène plaquettaire et afibrinogénémie. Arch intern. Physiol. Biochim 65: 632 1957;
• 42 Schmid H. J, Jackson D. P, Conley C. L. Mechanism of action of thrombin on platelets. J. clin. Invest 41 3 543 1962;
• 43 Seligman M, Goudemand M, Janin A, Bernard J, Grabar P. Etudes immunochimiques sur la presence du fibrinogène dans les extraits de plaquettes humaines lavées et dans certains extraits leucocytaires. Rev. Hémat 12: 302 1957;
• 44 Sharp A. A. Platelet (Viscous) metamorphosis. In Henry Ford Hospital Intern. Symposium. Blood Platelets. P. 67. Little Brown and Co; Boston: 1961
• 45 Shore P. A, Alpers H. S. Platelet damage induced in plasma by certain fatty acids. Nature (Lond) 200: 1331 1963;
• 46 Sokal G. Etude morphologique des plaquettes sanguines et de la metamorphose visqueuse an moyen d’anti-serums fluorescent antifibrinogène et antiplaquettes. Acta haemat. (Basel) 28: 313 1962;
• 47 Spaet T. H, Citron J, Spivack M. Some properties of the platelet-connective tissue mixed agglutination reaction. Proc. soc. exp. Biol. (N. Y.) 111: 292 1962;
• 48 Spaet T. H, Zucker M. B. Mechanism of platelet plug formation and role of adenosine diphosphate. Amer. J. Physiol 206: 1267 1964;
• 49 Westerholm B. Observations on 5-hydroxytryptamine and histamine release from rabbit platelets. Acta physiol. scand 63: 257 1965;
• 50 Ware A, Fahey J, Seegers W. Platelet extracts, fibrin formation and interaction of purified prothrombin and thromboplastin Amer. J. Physiol 154: 140 1948;
• 51 Zieve P. D, Gamble J. L, Jackson D. P. Effects of thrombin on the potassium and ATP content of platelets. J. clin. Invest 43: 2063 1964;
• 52 Zucker M. B. Platelet adhesion, release and aggregation. In Fibrinogen and fibrin. Turnorer of clotting factors. Ed. Koller F. 301 Schattauer; Stuttgart.:
• 53 Zucker M. B, Marcus A. J. Unanswered questions concerning functions of platelets Informational Exchange Group Nr. 2. IEG 2 Scientific Memo 54.