Thromb Haemost 1970; 24(01/02): 055-067
DOI: 10.1055/s-0038-1654211
Originalarbeiten – Original Articles – Travaux Originaux
Schattauer GmbH

Acidosis Induced Disseminated Intravascular Microthrombosis and its Dissolution by Streptokinase[*]

R. J Broersma
1   Departments of Physiology and Pharmacology and Pathology, Wayne State University School of Medicine, Detroit, Michigan 48207
,
G. D Bullemer
1   Departments of Physiology and Pharmacology and Pathology, Wayne State University School of Medicine, Detroit, Michigan 48207
,
E. F Mammen
1   Departments of Physiology and Pharmacology and Pathology, Wayne State University School of Medicine, Detroit, Michigan 48207
› Author Affiliations
Further Information

Publication History

Publication Date:
28 June 2018 (online)

Summary

To elucidate the mechanisms triggering disseminated intravascular coagulation (DIC) in shock, acidosis was produced in dogs by intravenous infusions of lactic acid over a period of 4 h. As the pH of the blood dropped, the blood pressure increased and the heart rate fell. The platelet counts dropped and whole blood clotting times shortened. The partial thromboplastin times and prothrombin times decreased as did the r-times and maximal amplitudes of the thrombelastograms. Simultaneously, the levels of prothrombin, fibrinogen, factors V and VIII decreased with time in acidosis. There was no evidence of a systemic activation of the fibrinolytic system. The euglobulin lysis times increased as did the thrombin times and there was no lysis observed in the thrombelastograms.

Thrombi in the lungs, liver, spleen and kidneys, together with the coagulation changes indicated that the infusion of acid produced DIC, with the changes being similar to those produced in shock. The glomeruli were especially affected and the pictures were identical to those described in kidneys of animals having experienced a generalized Sanarelli-Shwartzman phenomenon.

A pH value of 7.20 or lower appeared to be a potent trigger of intravascular coagulation. The lower the pH, the more thrombi were found in the tissues. The consumption of clotting factors and thrombus formation thus corresponded to the degree of acidosis.

A generalized fibrinolytic state was induced using Streptokinase, after a 4 h period of acidosis and 1 h of compensation with sodium bicarbonate. Streptokinase was infused along with human euglobulin fractions on the basis of the streptokinase tolerance test of each dog’s blood and plasma. Thrombolysis was maintained for 3-4 h and this was reflected in the reduction of fibrin deposits in the tissues. Of 100 glomeruli counted/dog’s kidney, the average containing fibrin was 44 ± 11% after acidosis and 0.4 ± 0.3% after thrombolysis.

* Supported by the Michigan Heart Association Authors' Address: 1400 Chrysler Freeway, Detroit, Michigan 48207, USA


 
  • References

  • 1 Attar S, Kirby W. H, Masaitis G, Mansberge A. R, Gowely R. A. Coagulation changes in clinical shock: I. Effect of hemorrhagic shock on clotting times in humans. Ann. Surg 164: 34 1966;
  • 2 Growell J. W, Read W. L. In vivo coagulation — a probable cause of irreversible shock. Amer. J. Physiol 183: 565 1955;
  • 3 Hardaway R. M. Syndromes of disseminated intravascular coagulation. Charles C. Thomas; Springfield: 111 1966
  • 4 McKay D. G. Disseminated intravascular coagulation. An intermediary mechanism of disease. Hoeber Medical Publications. Harper and Row; New York: 1965
  • 5 Turjpini R, Stefanini M. The nature and mechanism of the hemostatic breakdown in the course of experimental hemorrhagic shock. J. clin. Invest 38: 53 1959;
  • 6 Lasch H, Heene D. L, Huth K, Sandritter W. Pathophysiology, clinical manifestation and therapy of consumption coagulopathy (“Verbrauchskoagulopathie”). Amer. J. Cardiol 20: 381 1967;
  • 7 Mosesson M. W, Golman R. W, Sherry S. Chronic intravascular coagulation syndrome. New Engl. J. Med 278: 815 1968;
  • 8 Mammen E. F, Anderson G. F, Barnhart M. I. (eds.): Disseminated intravascular coagulation. Thrombos. Diathes. haemorrh. (Stuttg). Suppl. 36 159-171 1969
  • 9 Huckabee W. E. Relationship of pyruvate and lactate during aerobic metabolism. I. Effects of infusion of pyruvate or glucose and of hyperventilation. J clin. Invest 37: 244 1958;
  • 10 Hardaway R. M, Brewster W. R, Glovitz M. J. The influence of vasoconstriction and acidosis on disseminated intravascular coagulation. Surgery 59: 804 1966;
  • 11 Baue A. E, Tragus E. T, Parkins W. M. Effects of sodium chloride and bicarbonate in shock with metabolic acidosis. Amer. J. Physiol 212: 54 1967;
  • 12 Hardaway R. M, Glovitz M. J, Brewster W. R, Houchin D. N. Clotting time of heparinized blood. Arch. Surg 89: 701 1964;
  • 13 Growell J. W, Houston B. Effect of acidity on blood coagulation. Amer. J. Physiol 201: 379 1961;
  • 14 Anderson M. N, Mouritzen G. Effect of acute respiratory and metabolic acidosis on cardiac output and peripheral resistance. Ann. Surg 163: 161 1966;
  • 15 Paar D, Heimsoth V, Werner M, Bocki K. D. Verbrauchskoagulopathie als Ursache haemorrhagischer Diathesis bei akuter Essigsäureintoxikation. Dtsch. med. Wschr 93: 206 1968;
  • 16 Huber G, Mason R, Pegg G, Norman J. Production, reversal and prevention of experimental hyaline membrane disease following disseminated intravascular coagulation. Clin. Res 17: 415 1969;
  • 17 Shepard F. M, Johnston R. B, Klatte E. G, Burko N, Stahlman M. Residual pulmonary findings in clinical hyaline membrane disease. New Engl. J. Med 279: 1063 1968;
  • 18 Stark G. R, Abramson D, Erkan V. Intravascular coagulation and hyaline membrane disease of the newborn. Lancet II: 1180 1968;
  • 19 Deutsch E, Fisher M. Die Wirkung intravenös applizierter Streptokinase auf Fibrinolyse und Blutgerinnung. Thrombos. Diathes. haemorrh. (Stuttg) 04: 482 1960;
  • 20 Brecher G, Cronkite E. P. Morphology and enumeration of human platelets. J. appl. Physiol 03: 365 1950;
  • 21 Lee R. I, White P. D. A clinical study of the coagulation time of blood. Amer. J. med. Sci 145: 495 1913;
  • 22 Langdell R. D, Wagner R. H, Brinkhous K. M. Effects of antihemophilic factor on one-stage clotting tests. J. Lab. clin. Med 41: 637 1953;
  • 23 Quick A. J. The thromboplastin reagent for the determination of prothrombin. Science 92: 112 1940;
  • 24 Seegers W. H, Gole E. R, Aoki N. Functions of Ac-globulin and lipid in blood clotting. Canad. J. Biochem 41: 2441 1963;
  • 25 Langdeil R. D, Wagner R. H, Brinkhous K. M. Estimation of antihemophilic activity by the partial thromboplastin time technique. In: Blood Coagulation, Hemorrhage and Thrombosis. Tocantins L. M, Kazall L. (Eds.) 107 Grune and Stratton; New York: 1964
  • 26 Ware A. G, Seegers W. H. Two stage procedure for the quantitative determination of prothrombin concentration. Amer. J. clin. Path 19: 471 1949;
  • 27 Ware A. G, Guest M. M, Seegers W. H. Fibrinogen: With special reference to its preparation and certain properties of the product. Arch. Biochem 13: 231 1947;
  • 28 Ingram G. I. G, Matchett M. O. The serial thrombin time method for measuring fibrinolytic activity of plasma. Nature (Lond) 188: 674 1960;
  • 29 Buckell M. The effect of citrate on euglobulin methods of estimating fibrinolytic activity. J. clin. Path 11: 403 1958;
  • 30 Gelander D. R, Guest M. M. Assay of canine profibrinolysin (plasminogen). Amer. J. Physiol 197: 391 1959;
  • 31 Broersma R. J, Bullemer G. D, Mammen E. F. Blood coagulation changes in hemorrhagic shock and acidosis. Thrombos. Diathes. haemorrh. (Stuttg.) Suppl. 36: 171 1969;
  • 32 Silberschmid M, Saito S, Smith L. L. Circulatory effects of acute lactic acidosis in dogs prior to and after hemorrhage. Amer. J. Surg 112: 175 1966;
  • 33 Kittle C. F, Aoki H, Brown E. B. The role of pH and C02 in the distribution of blood flow. Surgery 57: 139 1965;
  • 34 Connolly J. E, Kountz S. L, Guernsey J. M, Stemmer E. A. Acidosis as a cause of renal shutdown during extracorporeal circulation: Its correction by the use of THAM. J. thor. card. Surg 46: 680 1963;
  • 35 Barnhart M. I, Cress D. C, Henry R. L, Riddle J. M. Influence of fibrinogen split products on platelets. Thrombos. Diathes. haemorrh. (Stuttg) 17: 78 1967;
  • 36 Kowalski E, Kopec M, Wegrzynowiçz M. Influence of fibrinogen degradation produts (FDP) on platelet aggregation, adhesiveness, and viscous metamorphosis. Thrombos. Diathes. haemorrh. (Stuttg) 10: 406 1964;
  • 37 Zucker M. B, Jerushalmy Z. Elucidation of platelet function by use of inhibitors. Thrombos. Diathes. haemorrh. (Stuttg) 15: 631 1966;
  • 38 Brain M. C. Microangiopathic hemolytic anemia. New Engl. J. Med 281: 833 1969;
  • 39 Heilige Thrombelastograph System Hartert (Model 2601 D) Freiburg, Germany. 1959
  • 40 Mallory F. B. Pathological Technique. 76 & 86 W. B. Saunders; Philadelphia: 1938
  • 41 Broesma R. J. An experimental investigation into the causes of disseminated intravascular coagulation in hemorrhagic shock. Doctoral Thesis. Wayne State University Library; 1969
  • 42 Fenner F. Immune mechanisms in viral infections, viral and rickettsial infections of man. Fourth edition.. Horsfall F. L, Tamm I. (Eds.) 356-384 J. B. Lippincott; Philadelphia: 1965
  • 43 Kowalski E, Budzynski A, Kopec M, Latallo Z, Lipinski B, Wegrzynowiçz Z. Circulating fibrinogen degradation products (FDP) in dog blood after intravenous thrombin infusion. Thrombos. Diathes. haemorrh. (Stuttg) 13: 12 1965;
  • 44 Schmutzler R, Koller F. Die Thrombolyse-Therapie. Ergebn. inn. Med. Kinderheilk 22: 158 1965;