Download PDF
Thromb Haemost 1974; 31(02): 188-203
DOI: 10.1055/s-0038-1649157
Original Article
Schattauer GmbH

Arterial and Venous Thromboembolism: Kinetic Characterization and Evaluation of Therapy[*]

Laurence A Harker
1   Department of Medicine, University of Washington School of Medicine, Harborview Medical Center and the King County Central Blood Bank Seattle, Washington 98104
,
Sherrill J Slichter
1   Department of Medicine, University of Washington School of Medicine, Harborview Medical Center and the King County Central Blood Bank Seattle, Washington 98104
› Author Affiliations
Further Information

Publication History

Received 02 February 1974

Accepted 03 February 1974

Publication Date:
29 June 2018 (online)

    Permissions and Reprints

Summary

Survival and turnover measurements of platelets, fibrinogen and plasminogen have been studied in eight patients with arterial and twelve patients with venous thromboembolism, and six patients with advanced, stable atherosclerotic peripheral vascular disease.

Venous thrombosis is characterized by combined and equivalent consumption of platelets, fibrinogen and plasminogen. This process, the result of activation of the coagulation system, is completely reversed by heparin or warfarin anticoagulation but remains unaltered by dipyridamole. The removal of circulating plasminogen is directly reflected as fibrinogen-fibrin related antigen in the blood and is regulated by the rate of fibrin formation as evidenced by the reversal of fibrinogen and plasminogen consumption to normal following heparin therapy.

In contrast, arterial thromboembolism involves selective platelet consumption presumably in the formation of platelet thrombus on non-endothelialized end-arterial surfaces. This process is interrupted by dipyridamole inhibition of platelet function but not by heparin anticoagulation. Although acetylsalicylic acid itself has little capacity to correct platelet consumption, it has a potentiating effect on dipyridamole.

Stable, severe, widespread arteriosclerotic disease only minimally increases platelet consumption and produces no change in fibrinogen and plasminogen kinetics from normal. The minimal decrease in platelet survival in these patients is not corrected by dipyridamole therapy.

The results of these studies demonstrate the potential usefulness of platelet and fibrinogen kinetic measurements in the differentiation of ongoing venous and arterial thromboembolism and in identifying potentially effective antithrombotic therapy.

* Presented at the International Conference on “Platelets in Thrombosis: Their Clinical Significance and the Evaluation of Potential Drugs” in Titisee, Germany, October, 1973.


 

  • References

  • 1 Abrahamsen A. F. Platelet survival studies in man: with special reference to thrombosis and atherosclerosis. Scandinavian Journal of Haematology (Supplement) 1968; 3: 1
    PubMedGoogle Scholar
  • 2 Adelson E, Rheingold J. J, Parker O. et al. Platelet and fibrinogen survival in normal and abnormal states of coagulation. Blood 1961; 17: 267
    PubMedGoogle Scholar
  • 3 Aster R. H. Effect of anticoagulant and ABO incompatibility on recovery of transfused human platelets. Blood 1965; 26: 732
    PubMedGoogle Scholar
  • 4 Aster R. H. Pooling of platelets in the spleen: role in the pathogenesis of "hyper-splenic" thrombocytopenia. Journal of Clinical Investigation 1966; 45: 645
    CrossrefPubMedGoogle Scholar
  • 5 Bonchek L. I, Anderson B. P, Starr A. Mitral valve replacement with cloth-covered, composite seat prostheses : the case for early operation. Journal of Thoracic and Cardiovascular Surgery, (in press) 1973
    Google Scholar
  • 6 Born G. V. B, Cross J. J. The aggregation of blood platelets. Journal of Physiology 1963; 168: 173
    PubMedGoogle Scholar
  • 7 Bowie E. J. W, Owen Jr. C. A, Thompson J. H. et al. A test of platelet adhesiveness. Mayo Clinic Proceedings 1969; 44: 306
    PubMedGoogle Scholar
  • 8 Browse N. L, Hall J. H. Effect of dipyridamole on the incidence of clinically detectable deep-vein thrombosis. Lancet 1969; 2: 718
    PubMedGoogle Scholar
  • 9 Bull B. S, Schneiderman M. A, Brecher G. Platelet counts with the Coulter counter. American Journal of Clinical Pathology 1965; 44: 678
    CrossrefPubMedGoogle Scholar
  • 10 Deutsch D, Mertz E. T. Plasminogen: purification from human plasma by affinity chromatography. Science 1970; 170: 1095
    CrossrefPubMedGoogle Scholar
  • 11 Hardisty R. M, Hutton B. A. The kaolin clotting time of platelet-rich plasma: a test of platelet factor-3 availability. British Journal of Haematology 1965; 11: 258
    CrossrefPubMedGoogle Scholar
  • 12 Harker L. A, Finch C. A. Thrombokinetics in man. Journal of Clinical Investigation 1969; 48: 963
    CrossrefPubMedGoogle Scholar
  • 13 Harker L. A, Slichter S. J. Studies of platelet and fibrinogen kinetics in patients with prosthetic heart valves. New England Journal of Medicine 1970; 283: 1302
    CrossrefPubMedGoogle Scholar
  • 14 Harker L. A, Slichter S. J. Platelet and fibrinogen consumption in man. New England Journal of Medicine 1972; a 287: 999
    CrossrefPubMedGoogle Scholar
  • 15 Harker L. A, Slichter S. J. The bleeding time as a screening test for evaluation of platelet function. New England Journal of Medicine 1972; b 287: 155
    CrossrefPubMedGoogle Scholar
  • 16 Harker L. A, Schmer G, Slichter S. J. 1972. Plasminogen kinetics in man. In: Proceedings of the Third Congress of the International Society on Thrombosis and Haemostasis (abstract) 294
    Google Scholar
  • 17 Harker L. A, Slichter S. J, Scott R. Platelet thromboembolism and its prevention in homocystinuria. Blood (abstract) 1972; 40: 938
    PubMedGoogle Scholar
  • 18 Izak G, Galewski K, Eyal Z. Studies on hypercoagulable state II. The application of 131I-labelled fibrinogen for the estimation of intravascular coagulation in human subjects. Thrombosis et Diathesis Haemorrhagica 1967; 18: 544
    PubMedGoogle Scholar
  • 19 Jacobsson K. 1955; Studies on the determination of fibrinogen in human blood plasma. Scandinavian Journal of Clinical Laboratory Investigation, 7 Supplement 14: 3
    PubMedGoogle Scholar
  • 20 Johnson A. J, Kline D. L, Alkjaersig N. Assay methods and standard preparations for plasmin, plasminogen, and urokinase in purified systems. Thrombosis et Diathesis Haemorrhagica 1969; 21: 259
    PubMedGoogle Scholar
  • 21 Kakkar V. V, Field E. S, Nicolaides A. N. Low doses of heparin in prevention of deep-vein thrombosis. Lancet 1970; 2: 669
    PubMedGoogle Scholar
  • 22 McConahey P. J, Dixon F. J. A method of trace iodination of proteins for immunologic studies. International Archives of Allergy and Applied Immunology 1966; 29: 185
    CrossrefPubMedGoogle Scholar
  • 23 Merskey C, Lalezari P, Johnson A. J. A rapid, simple, sensitive method for measuring fibrinolytic split products in human serum. Proceedings of the Society of Experimental Biological Medicine 1969; 131: 871
    PubMedGoogle Scholar
  • 24 Merskey C, Johnson A. J, Lalezari P. Increase in fibrinogen and fibrinrelated antigen in human serum due to in vitro lysis by thrombin. Journal of Clinical Investigation 1972; 51: 903
    CrossrefPubMedGoogle Scholar
  • 25 Mielke Jr. C. H, Kaneshiro M. M, Maher I. A. The standardized normal Ivy bleeding time and its prolongation by aspirin. Blood 1969; 34: 204
    PubMedGoogle Scholar
  • 26 Mills J. N. The life-span of the erythrocyte. Journal of Physiology (London) 1946; 105: 16P
    CrossrefPubMedGoogle Scholar
  • 27 Murphy E. A, Mustard J. F. Coagulation tests and platelet economy in atherosclerotic and control subjects. Circulation 1962; 25: 114
    CrossrefPubMedGoogle Scholar
  • 28 Mustard J. F, Hegardt B, Rowsell H. C. et al. Effect of adenosine nucleotides on platelet aggregation and clotting time. Journal of Laboratory Clinical Medicine 1964; 64: 548
    PubMedGoogle Scholar
  • 29 Paulus J. M. Platelet kinetics: Radioisotopic, cytological, mathematical and clinical aspects. New York: American Elsevier Publishing Co.; 1971
    Google Scholar
  • 30 Schmer G, Kriss J. Solid phase radioassay for the measurement of plasminogen in normal human plasma. Journal of Laboratory Clinical Medicine 1973. (in press)
    Google Scholar
  • 31 Sevitt S. Venous thrombosis and pulmonary embolism: their prevention by oral anticoagulants. American Journal of Medicine 1962; 33: 703
    CrossrefPubMedGoogle Scholar
  • 32 Sharnoff J. G. Results in the prophylaxis of postoperative thromboembolism. Surgery Gynecology Obstetrics 1966; 123: 303
    PubMedGoogle Scholar
  • 33 Sherry S, Fletcher A. P, Alkjaersig N. Fibrinolysis and fibrinolytic activity in man. Physiology Review 1959; 39: 343
    CrossrefPubMedGoogle Scholar
  • 34 Slichter S. J, Leandoer J. L, Funk D. D, Harker L. A. Platelet and fibrinogen consumption with surgery. Clinical Research (abstract) 1971; 19: 431
    PubMedGoogle Scholar
  • 35 Slichter S. J, Harker L. A. Studies of platelet and fibrinogen consumption in cancer patients. Clinical Research (abstract) 1972; 20: 194
    PubMedGoogle Scholar
  • 36 Slichter S. J, Harker L. A, Sauvage L. R. Platelet consumption as a measure of endothelization of aorto-femoral grafts. Blood (abstract) 1972; 40: 938
    PubMedGoogle Scholar
  • 37 Spaet T. H, Lejnieks I. A technique for estimation of platelet-collagen adhesion. Proceedings of the Society of Experimental Biological Medicine 1969; 132: 1038
    PubMedGoogle Scholar
  • 38 Sullivan J. M, Harken D. E, Gorlin R. Pharmacologic control of thromboembolic complications of cardiac-valve replacement. New England Journal of Medicine 1971; 284: 1391
    CrossrefPubMedGoogle Scholar
  • 39 Takeda Y. Studies of the metabolism and distribution of fibrinogen in healthy men with autologous 125I-labelled fibrinogen. Journal of Clinical Investigation 1966; 45: 103
    CrossrefPubMedGoogle Scholar
  • 40 Van der Maas A. P. C, Teulings F. A. G, den Ottolander G. J. H. The use of labelled fibrinogen in the diagnosis of venous thrombosis. Thrombosis et Diathesis Haemorrhagica 1971; 26: 1
    PubMedGoogle Scholar
  • 41 Weiley H. S, Steele P. P, Davies H, Genton E. Platelet studies in patients with substitute heart valves. New England Journal of Medicine; 1973. (in press)
    Google Scholar
  • 42 Weiss H. J, Aledort L. M, Kochwa S. The effect of salicylates on the hemostatic properties of platelets in man. Journal of Clinical Investigation 1968; 47: 2169
    CrossrefPubMedGoogle Scholar