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. 1963 Nov;16(6):558–568. doi: 10.1136/jcp.16.6.558

Activation of coagulation and fibrinogen loss after using an extracorporeal circulation

A L Bloom 1
PMCID: PMC480640  PMID: 14076375

Abstract

Alterations of the coagulation potential of heparinized blood after using an extracorporeal circulation have been studied by means of a toluidine blue-calcium chloride reagent. This technique was originally used to detect the effect of activation by contact on the coagulation mechanism in heparinized blood. It has been shown that it also detects, in the presence of heparin, the clotpotentiating effect of blood cell contents liberated in vitro by mechanical trauma to blood.

Variable destruction of platelets, red cells, and white cells occurred in heparinized sheep blood recirculated in a heart-lung machine in vitro. This was accompanied by increased clotting potential. Complete coagulation was prevented by heparin and fibrinogen levels remained unaltered.

Similar enhancement of the coagulation potential and destruction of blood cells were detected in the blood of heparinized patients and sheep after perfusion for open-heart surgery. The coagulation changes were usually transient, and impaired coagulation associated with significant fibrinogen loss was detected in most samples taken after the neutralization of heparin.

It is suggested that the coagulation changes are due to activation by contact of the coagulation mechanism during perfusion and to the clot-accelerating effect of blood cell contents. The results support the hypothesis that coagulation defects and fibrinogen loss after using an extracorporeal circulation are due, at least in part, to intravascular coagulation. This is thought to occur, especially during neutralization of heparin, while the coagulation mechanism is hyperactive.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ABLONDI F. B., HAGAN J. J., PHILIPS M., DE RENZO E. C. Inhibition of plasmin, trypsin and the streptokinase-activated fibrinolytic system by 6-aminocaproic acid. Arch Biochem Biophys. 1959 May;82(1):153–160. doi: 10.1016/0003-9861(59)90100-6. [DOI] [PubMed] [Google Scholar]
  2. BELL W. N., ALTON H. G. A brain extract as a substitute for platelet suspensions in the thromboplastin generation test. Nature. 1954 Nov 6;174(4436):880–881. doi: 10.1038/174880a0. [DOI] [PubMed] [Google Scholar]
  3. BRAYTON R. G., ZUCKER M. B. Bleeding syndrome in thrombin-injected rats deficient in fibrinogen and antihemophilic factor. Proc Soc Exp Biol Med. 1957 Nov;96(2):418–421. doi: 10.3181/00379727-96-23496. [DOI] [PubMed] [Google Scholar]
  4. Baar H. S. The Enumeration of Blood Platelets. J Clin Pathol. 1948 May;1(3):175–176. [PMC free article] [PubMed] [Google Scholar]
  5. Bloom A. L. Changes in Blood After Using an Extracorporeal Circulation. Br Med J. 1961 Jul 1;2(5243):16–20. doi: 10.1136/bmj.2.5243.16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CLOWES G. H., Jr, NEVILLE W. E., HOPKINS A., ANZOLA J., SIMEONE F. A. Factors contributing to success or failure in the use of a pump oxygenator for complete by-pass of the heart and lung, experimental and clinical. Surgery. 1954 Sep;36(3):557–579. [PubMed] [Google Scholar]
  7. COON W. W., DUFF I. F. Effects of intravenous human plasmin on the blood clotting mechanism of the dog. J Lab Clin Med. 1958 Mar;51(3):381–385. [PubMed] [Google Scholar]
  8. DENNIS C., KARLSON K. E., EDER W. P., NELSON R. M., EDDY F. D., SANDERSON D. Pump-oxygenator to supplant the heart and lungs and brief periods. A method applicable to dogs. Surgery. 1951 May;29(5):697–713. [PubMed] [Google Scholar]
  9. DESMET V., VERSTRAETE M., VANDENBROUCKE J. Propriétés coagulantes d'hémolysats erythrocytaires. Thromb Diath Haemorrh. 1957 Dec 15;1(3-4):459–470. [PubMed] [Google Scholar]
  10. DEUTSCH E., JOHNSON S. A., SEEGERS W. H. Differentiation of certain platelet factors related to blood coagulation. Circ Res. 1955 Jan;3(1):110–115. doi: 10.1161/01.res.3.1.110. [DOI] [PubMed] [Google Scholar]
  11. DIDISHEIM P., HATTORI K., LEWIS J. H. Hematologic and coagulation studies in various animal species. J Lab Clin Med. 1959 Jun;53(6):866–875. [PubMed] [Google Scholar]
  12. DUBOURG G., TRARIEUX M., FONTAN F., MOULINIER J., BRICAUD H., BROUSTET P. [Neutralization of heparin by protamine during interventions using extracorporeal circulation]. Rev Fr Etud Clin Biol. 1960 Aug-Sep;5:691–696. [PubMed] [Google Scholar]
  13. EGERTON W. S., ROBINSON C. L. The anti-heparin, anticoagulant and hypotensive properties of hexadimethrine and protamine. Lancet. 1961 Sep 16;2(7203):635–637. doi: 10.1016/s0140-6736(61)90311-7. [DOI] [PubMed] [Google Scholar]
  14. FANTL P., WARD H. A. Blood coagulation problems in openheart surgery. Thorax. 1960 Dec;15:292–298. doi: 10.1136/thx.15.4.292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. FIELDING H. E., LANGLEY P. E. A simple method for measurement of hemoglobin in serum and urine. Am J Clin Pathol. 1958 Dec;30(6):528–529. doi: 10.1093/ajcp/30.6.528. [DOI] [PubMed] [Google Scholar]
  16. FLETCHER A. P., ALKJAERSIG N., SHERRY S. The maintenance of a sustained thrombolytic state in man. I. Induction and effects. J Clin Invest. 1959 Jul;38(7):1096–1110. doi: 10.1172/JCI103886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. GANS H., KRIVIT W. Problems in hemostasis during openheart surgery. IV. On the changes in the blood clotting mechanism during cardiopulmonary bypass procedures. Ann Surg. 1962 Mar;155:353–359. doi: 10.1097/00000658-196203000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. GANS H., LILLEHEI C. W., KRIVIT W. Problems in hemostasis during open-heart surgery. I. On the release of plasminogen activator. Ann Surg. 1961 Dec;154:915–924. [PMC free article] [PubMed] [Google Scholar]
  19. GANS H., SIEGAL D. L., LILLEHEI C. W., KRIVIT W. Problems in hemostasis during open-heart surgery. II. On the hypercoagulability of blood cardiac bypass. Ann Surg. 1962 Jul;156:19–23. doi: 10.1097/00000658-196207000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. GERBODE F., HURT R., MACKENZIE R., OSBORN J. J., PERKINS H., SHAW A. Cause and prevention of hemorrhage following extracorporeal circulation. Surg Forum. 1956;6:96–100. [PubMed] [Google Scholar]
  21. GODAL H. C. A comparison of two heparin-neutralizing agents: protamine and polybrene. Scand J Clin Lab Invest. 1960;12(4):446–457. doi: 10.3109/00365516009065409. [DOI] [PubMed] [Google Scholar]
  22. HARDAWAY R. M., WATSON H. E., WEISS F. H. Alterations in blood coagulation mechanism after intra-aortic injection of thrombin. Arch Surg. 1960 Dec;81:983–991. doi: 10.1001/archsurg.1960.01300060129025. [DOI] [PubMed] [Google Scholar]
  23. HOLEMANS R., AMERY A., VERSTRAETE M. Clotting deviations during complete cardiac by-pass in dogs with a heart-lung apparatus Crafoord-Senning. Cardiologia. 1960;37:193–205. doi: 10.1159/000167095. [DOI] [PubMed] [Google Scholar]
  24. MARGOLIS J. Initiation of blood coagulation by glass and related surfaces. J Physiol. 1957 Jun 18;137(1):95–109. doi: 10.1113/jphysiol.1957.sp005799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mellanby J. The Coagulation of blood: Part II. The actions of snake venoms, peptone and leech extract. J Physiol. 1909 Jul 2;38(6):441–503. doi: 10.1113/jphysiol.1909.sp001316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. NIEWIAROWSKI S., PROU-WARTELLE O. [Role of the contact factor (Hageman factor) in fibrinolysis]. Thromb Diath Haemorrh. 1959 Sep 1;3:593–603. [PubMed] [Google Scholar]
  27. NILSSON I. M., SWEDBERG J. Coagulation studies in cardiac surgery with extracorporeal circulation using a bubble-oxygenator. Acta Chir Scand. 1959 May 31;117(1-2):47–54. [PubMed] [Google Scholar]
  28. O'BRIEN J. R. Some effects on blood coagulation of erythrocytes and other cells. J Clin Pathol. 1959 Jan;12(1):45–47. doi: 10.1136/jcp.12.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. OLLENDORFF P. Estimation of the activation of the thromboplastic system in blood during extracorporeal circulation. Scand J Clin Lab Invest. 1962;14:303–306. [PubMed] [Google Scholar]
  30. PENICK G. D., AVERETTE H. E., Jr, PETERS R. M., BRINKHOUS K. M. The hemorrhagic syndrome complicating extracorporeal shunting of blood: an experimental study of its pathogenesis. Thromb Diath Haemorrh. 1958 Sep 1;2(3-4):218–225. [PubMed] [Google Scholar]
  31. QUICK A. J., GEORGATSOS J. G., HUSSEY C. V. The clotting activity of human erythrocytes: theoretical and clinical implications. Am J Med Sci. 1954 Aug;228(2):207–213. doi: 10.1097/00000441-195408000-00009. [DOI] [PubMed] [Google Scholar]
  32. RATNOFF O. D., ROSENBLUM J. M. Role of Hageman factor in the initiation of clotting by glass; evidence that glass frees Hageman factor from inhibition. Am J Med. 1958 Aug;25(2):160–168. doi: 10.1016/0002-9343(58)90023-8. [DOI] [PubMed] [Google Scholar]
  33. ROTHNIE N. G., NORMAN A. G., STEELE M., KINMONTH J. B. Changes in blood-coagulation due to perfusion for cardiac surgery. Br J Surg. 1960 Nov;48:272–281. doi: 10.1002/bjs.18004820907. [DOI] [PubMed] [Google Scholar]
  34. SHANBERGE J. N., REGAN E. E., TALARICO L., BUSIEK B. The effect of Polybrene on blood coagulation. In vitro. J Lab Clin Med. 1961 Jul;58:23–33. [PubMed] [Google Scholar]
  35. STOKES T. L., GIBBON J. H., Jr Experimental maintenance of life by a mechanical heart and lung during occlusion of the venae cavae followed by survival. Surg Gynecol Obstet. 1950 Aug;91(2):138–156. [PubMed] [Google Scholar]
  36. VAN CREVELD S., PAULSSEN M. M., VONK R. Isolation and properties of the third clotting factor in blood-platelets. Lancet. 1952 Jan 5;1(6697):23–25. doi: 10.1016/s0140-6736(52)90992-6. [DOI] [PubMed] [Google Scholar]
  37. VON KAULLA K. N., SWAN H. Clotting deviations in man during cardiac bypass: fibrinolysis and circulating anticoagulant. J Thorac Surg. 1958 Oct;36(4):519–530. [PubMed] [Google Scholar]
  38. WRIGHT T. A., DARTE J. M., MUSTARD W. T. Apparent increase in blood-prothrombin during extracorporeal bypass and during slow coagulation in siliconed containers. Lancet. 1958 May 31;1(7031):1157–1158. doi: 10.1016/s0140-6736(58)91954-8. [DOI] [PubMed] [Google Scholar]

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