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Chymotrypsin Dissolution of Intra-Arterial Thrombi by Perfusion of Isolated Extremity

Chymotrypsin Dissolution of Intra-Arterial Thrombi by Perfusion of Isolated Extremity Abstract Acute arterial obstruction must be relieved immediately to prevent gangrene. Obstruction in major vessels can be relieved surgically; however, distal thrombus propagation obstructs circulation. Small arterial thrombosis is resistant to current therapy, namely, anticoagulants to limit thrombosis and more recently enzymatic lysis of the clot.37,49 Streptokinase,3,22,32,48,49 plasmin ( fibrinolysin),6,13,14,49,61 and chymotrypsin34,48,49 have been used to lyse intravascular thrombi. Objective evidence that thrombi are lysed and that clinical improvement follows is frequently lacking. The thrombolytic ability of enzymes decreases after three days as the aging clot is covered with endothelium and organizes.3,6,49 In very fresh thrombi lysis has been reported in 5 to 20 minutes.3,14,67 Clinically this is rare and fortuitous. The maximum safe systemic dose must be defined for each enzyme. The range between effective therapy and toxicity may be nil. Immunological phenomenon, fever, chills, hypotension, nausea, vomiting, and abnormalities of the hemopoietic and coagulation References 1. Upjohn Company. 2. Formerly the sclerosing material was injected into the femoral artery. This procedure was abandoned because perfusion caused hemorrhage through the needle arteriotomy. 3. Winthrop Laboratories. 4. One unit of activity is that amount which upon incubation with the hemoglobin substrate, (urea-denatured bovine hemoglobin) will release substances that, when reacted with Folin-Ciocalteau phenol reagent, will result in the formation of a colored solution of equal intensity to that produced from the reaction of 5.52×10-6 mM. of tyrosine. This assay is subject to a maximum error of ±8%. 5. Difco. 6. Protrol, Knickerbocker. 7. Dog plasma approximates 40 u/ml. Human plasma 53±5 u/ml. 8. Test system: 1 ml. bishydroxycoumarin plasma; 1 ml. serum diluted with saline; 1 ml. thromboplastin; 1 ml. 0.02 M CaCl2. Longer therapy with bishydroxycoumarin depresses not only prothrombin and Factor VII,25,26 but the clotting factors, plasma thromboplastin component, (P.T.C.),20,25,39,40 and Stuart factor as well.19,25 9. Good agreement was obtained with the above dilutions in normal samples. With a low concentration of Factor VII only the 1:10 and 1:20 dilutions of serum gave reproducible results. 10. Armour Pharmaceutical Fibrinogen contains only 50% clottable fibrinogen. 11. Parke, Davis & Company. 12. Since the prothrombin time of dogs' blood is normally 6-7 seconds, a few seconds difference from this value has considerable significance. 13. The amount of residual plasminogen12 and plasminogen activator38 or systemic proteolytic effect against casein44 was not specifically measured in our experiments. 14. References 6, 24, 34, 76, 56, 19, 43, 2. 15. Adams, E.: The Enzymatic Synthesis of Histidine from Histidinol , J. Biol. Chem. 209:829, 1954. 16. Adelson, E., and Roeder, W. H.: Studies on Fibrinolysin Using a Clinically Practical Method of Quantitative Determination , J. Clin. Path. 11:82, 1958.Crossref 17. Ambrus, J. L.; Ambrus, C. M.; Back, N.; Sokal, J. E., and Collins, G. L.: Clinical and Experimental Studies on Fibrinolytic Enzymes , Ann. New York Acad. Sc. 68:97, 1957.Crossref 18. Anson, M. L.: The Estimation of Pepsin, Trypsin, Papain, and Cathepsin with Hemoglobin , J. Gen. Physiol. 22:79, 1938.Crossref 19. Astrup, T., and Alkjaersig, N.: Classification of Proteolytic Enzymes by Means of Inhibitors , Nature 169:314, 1952.Crossref 20. Back, N.; Ambrus, J. L.; Simpson, C. L., and Shulman, S.: Study on the Effect of Streptokinase-Activated Plasmin (Fibrinolysin) on Clots in Various Stages of Organization , J. Clin. Invest. 37:864, 1958.Crossref 21. Bell, A. L. L.; Fitzpatrick, H. F.; Andreae, E.; Shimomura, S., and Pingeon, R.: The Influence of the Rats of Perfusion on Physiologic Responses During Cardiac Bypass , Ann. Surg. 148:968, 1958.Crossref 22. Biggs, R. P., and Macfarlane, R. G.: Human Blood Coagulation and Its Disorders , Springfield, Ill., Charles C Thomas, Publisher, 1953. 23. Brambel, C. E.: Proteases in the Clotting Mechanism , Ann. New York Acad. Sc. 68:70, 1957.Crossref 24. Brown, I. W., and Smith, W. W.: Hematologic Problems Associated with the Use of Extracorporeal Circulation for Cardiovascular Surgery , Ann. Int. Med. 49:1035, 1958.Crossref 25. Carroll, B. J.: Clinical Observations in the Treatment of Phlebothrombosis with Fibrinolysis , Angiology 10:308, 1959.Crossref 26. Christensen, L. R.: Methods for Measuring the Activity of Components of the Streptococcal Fibrinolytic System, and Streptococcal Desoxyribonuclease , J. Clin. Invest. 28:163, 1949.Crossref 27. Cliffton, E. E.; Grossi, C. E., and Cannamela, D.: Lysis of Thrombi Produced by Sodium Morrhuate in the Femoral Vein of Dogs by Human Plasmin (Fibrinolysin) , Ann. Surg. 139:52, 1954.Crossref 28. Cliffton, E. E.: Early Experience with Fibrinolysin , Angiology 10:244, 1959.Crossref 29. Creech, O.; Krementz, E. T.; Ryan, R. F., and Winblad, J. N.: Chemotherapy of Cancer: Regional Perfusion Utilizing an Extracorporeal Circuit , Ann. Surg. 148:616, 1958.Crossref 30. Creech, O.; Krementz, E. T.; Ryan, R. F.; Reemtsma, K., and Winblad, J. N.: Experiences with Isolation-Perfusion Techniques in the Treatment of Cancer , Ann. Surg. 149:627, 1959.Crossref 31. Creech, O.; Krementz, E. T.; Reemtsma, K.; Ryan, R. F.; Winblad, J. N., and Elliott, J. L.: The Treatment of Cancer by Perfusion , A.M.A. Arch. Surg. 79:963, 1959.Crossref 32. Damaskus, C. E.: Personal communication to the authors. 33. Dische, F. E.: Blood Clotting Substances with Factor VII Activity: A Comparison of Some Congenital and Acquired Deficiencies , Brit. J. Hemat. 4:201, 1958.Crossref 34. Douglas, A. S.: Mode of Action of Coumarin Drugs , Brit. M. Bull. 11:39, 1955. 35. Engler, H.; Christopher, P., and Moretz, W. H.: The Use of Fibrinolysin in the Prevention of Thrombus Formation in Small Artery Anastomoses , Angiology 10:259, 1959.Crossref 36. Fletcher, A. P.; Alkjaersig, N.; Smyrniotis, F. E., and Sherry, S.: The Treatment of Patients Suffering from Early Myocardial Infarction with Massive and Prolonged Streptokinase Therapy , Tr. A. Am. Physicians 71:287, 1958. 37. Ferguson, J. H., and Erickson, B. N.: Coagulant Action of Crystalline, Trypsin, Cefhalin and Lung Extracts , Am. J. Physiol. 126:661, 1939. 38. Grossi, C. E.; Cliffton, E. E., and Cannamela, D. A.: The Lysis of Intravascular Thrombi in Rabbits with Human Plasmin (Fibrinolysin) , Blood 9:310, 1954. 39. Hougie, C.; Barrow, E. M., and Graham, J. B.: Stuart Clotting Defect: I. Segregation of an Hereditary Hemorrhagic State from the Heterogeneous Group Heretofore Called a Stable Factor (S.P.C.A. Pro Convertin, Factor VII) Deficiency , J. Clin. Invest. 36:485, 1957.Crossref 40. Hunter, R. B., and Tudhope, G. R.: Mode of Action of Tromexan , Lancet 1:821, 1953.Crossref 41. Innerfield, T.; Angrist, A., and Schwarz, A.: Fibrinolytic and Anticoagulant Effects of Intravenous Crystalline Trypsin , Bull. New York Acad. Med. 28:537, 1952. 42. Innerfield, I.; Schwarz, A., and Angrist, A.: Intravenous Trypsin: Its Anticoagulant, Fibrinolytic and Thrombolytic Effects , J. Clin. Invest. 31:1049, 1952.Crossref 43. Innerfield, T.; Angrist, A., and Schwarz, A.: Parenteral Administration of Trypsin, Clinical Effect in 538 Patients , J.A.M.A. 152:597, 1953.Crossref 44. Jansen, E. F.; Nutting, R. J., and Balls, A. K.: Inhibition of the Proteinase and Esterase Activities of Trypsin and Chymotrypsin by Diisopropyl Fluorophosphate: Crystallization of Inhibited Chymotrypsin , J. Biol. Chem. 179:189, 1949. 45. Jensen, H.; Chamovitz, D. L.; Volkringer, E.; Gray, E.; Gosney, J. E., and Kocholaty, W.: Antifibrinolytic Activity in Plasma After Exposure to Cold and After Chymotrypsin Administration , Blood 8:324, 1953. 46. Johnson, A. J., and Tillett, W. S.: The Lysis in Rabbits of Intravascular Blood Clots by the Streptococcal Fibrinolytic System (Streptokinase) , J. Exper. Med. 95:449, 1952.Crossref 47. Loomis, E. C.; Ryder, A., and George, C.: Fibrinolysin and Antifibrinolysin; Biochemical Concentration of Antifibrinolysin , Arch. Biol. Chem. 20:444, 1949. 48. Martin, G. J., Editor: Clinical Enzymology , Boston, Little, Brown & Company, 1958. 49. Mindrum, G., and Glueck, H. I.: Plasma Prothrombin in Liver Disease; Its Clinical and Prognostic Significance , Ann. Int. Med. 50:1370, 1959.Crossref 50. Moser, K. M.: Thrombolysis with Fibrinolysin (Plasmin)—New Therapeutic Approach to Thromboembolism , J.A.M.A. 167:1695, 1958.Crossref 51. Moser, K. M.: Intravenous Administration of Fibrinolysin: Its Systemic Toxicity and Effect upon Components of the Coagulation Mechanism , Angiology 10:255, 1959. 52. Müllertz, S.: Activation of Plasminogen , Ann. New York Acad. Sc. 68:38, 1957.Crossref 53. Naeye, R. L.: Plasma Thromboplastin Component: Influence of Coumarin Compounds and Vitamin K on Its Activity in Serum , Proc. Soc. Exper. Biol. & Med. 91:101, 1956. 54. Owren, P. A., in New Clotting Factors, Blood Clotting and Allied Problems, Transactions of the Fifth Conference , edited by J. E. Flynn, New York, The Josiah Macy, Jr. Foundation, 1952. 55. Phillips, L. L., and Skrodelis, V.: The Fibrinolytic Enzyme System in Normal Hemorrhagic and Disease States , J. Clin. Invest. 37:965, 1958. 56. Quick, A. J.: Hemorrhagic Diseases , Philadelphia, Lea & Febiger, 1957. 57. Ratnoff, O. D., and Menzie, C.: A New Method for the Determination of Fibrinogen in Small Samples of Plasma , J. Lab. & Clin. Med. 37:316, 1951. 58. Remmert, L. F., and Cohen, P.: Partial Purification and Properties of Proteolytic Enzymes of Human Serum , J. Biol. Chem. 181:431, 1949. 59. Ryan, R. F.; Krementz, E. T.; Creech, O.; Winblad, J. N.; Chambler, W., and Check, H.: Selected Perfusion of Isolated Viscera with Chemotherapeutic Agents Using an Extracorporeal Circuit , S. Forum 8:58, 1958. 60. Ryan, R. F.; Winblad, J. N.; Krementz, E. T., and Creech, O.: Treatment of Malignant Neoplasms with Chemotherapeutic Agents Utilizing a Pump-Oxygenator: Techniques and Early Results , Bull. Tulane M. Fac. 17:133, 1958. 61. Sheard, C., and Sanford, A.: The Photometer and Its Use in the Clinical Laboratory , Am. J. Clin. Path. 3:412, 1933. 62. Sherry, S.; Titchener, A.; Gottesman, L.; Wasserman, P., and Troll, W.: The Enzymatic Dissolution of Intravascular Clots , J. Lab. & Clin. Med. 49:952, 1953. 63. Sherry, S.; Titchener, A.; Gottesman, L.; Wasserman, P., and Troll, W.: The Enzymatic Dissolution of Experimental Arterial Thrombi in the Dog by Trypsin, Chymotrypsin, and Plasminogen Activators , J. Clin. Invest. 33:1054, 1954. 64. Sherry, S.; Fletcher, A. P.; Alkjaersig, N., and Smyrniotis, F. E.: An Approach to Intravascular Fibrinolysis in Man , Tr. A. Am. Physicians 70:288, 1957. 65. Sherry, S.; Fletcher, A. P., and Alkjaersig, N.: Developments in Fibrinolytic Therapy for Thrombo-Embolic Disease , Ann. Int. Med. 50:560, 1959. 66. Sherry, S.; Lindemeyer, R. I.; Fletcher, A. P., and Alkjaersig, N.: Studies on Enhanced Fibrinolytic Activity in Man , J. Clin. Invest. 38:810, 1959. 67. Sherry, S.; Fletcher, A. P., and Alkjaersig, N.: Fibrinolysis and Fibrinolytic Activity in Man , Physiol. Rev. 39:343, 1959. 68. Shulman, N. R.: Studies on the Inhibition of Proteolytic Enzymes by Serum: I. The Mechanism of the Inhibition of Trypsin, Plasmin, and Chymotrypsin by Serum Using Fibrin Tagged with I131 as Substrate , J. Exper. Med. 95:571, 1952. 69. Shulman, N. R.: Studies on the Inhibition of Proteolytic Enzymes by Serum: Demonstration That Separate Proteolytic Inhibitors Exist in Serum: Their Distinctive Properties and Specificity of Action , J. Exper. Med. 95:593, 1952. 70. Shulman, N. R.: A Proteolytic Inhibitor with Anticoagulant Activity Separated from Human Urine and Plasma , J. Biol. Chem. 213:655, 1955. 71. Singher, H. O., and Chapple, R. V.: A Therapeutic Approach to Thrombo-Embolic Disease , Clin. Med. 6:3, 1959. 72. Stefanini, M.: Mechanism of Blood Coagulation in Normal and Pathologic Conditions , Am. J. Med. 14:64, 1953. 73. Stitt, E. R.; Clough, P. W., and Clough, M. C.: Practical Bacteriology, Hematology and Animal Parasitology , Ed. 10, Philadelphia, The Blakiston Company, 1948. 74. Sussman, B. J., and Fitch, T. S. P.: Thrombolysis with Fibrinolysin in Cerebral Arterial Occlusion , J.A.M.A. 167:1705, 1958. 75. Sussman, B. J., and Fitch, T. S. P.: Thrombolysis with Fibrinolysin in Cerebral Arterial Occlusion: The Role of Angiography , Angiology 10:269, 1959. 76. Tagnon, H. J.; Weinglass, A. R., and Goodpastor, W. E.: The Nature and Mechanism of Shock Produced by the Intravenous Injection of Chymotrypsin , Am. J. Physiol. 143:644, 1945. 77. Tagnon, J.: Enzymes in Clinical Medicine: Recent Developments in the Practical Application of Enzymes to Clinical Medicine , New England J. Med. 249:650, 1953. 78. Taylor, A., and Wright, I. S.: Intravenous Trypsin , Circulation 10:331, 1954. 79. Troll, W., and Sherry, S.: The Activation of Human Plasminogen by Streptokinase , J. Biol. Chem. 213:881, 1955. 80. Villavicencio, J. L., and Warren, R.: The Use of Plasmin for the Intra-Operative Lysis of Clots Occurring During Experimental Arterial Surgery , S. Forum 9:123, 1959. 81. Villavicencio, J. L., and Warren, R.: Experience with the Use of Human Fibrinolysin , Angiology 10:263, 1959.Crossref 82. Von Kaulla, K. N., and McDonald, T. S.: Effect of Heparin on Components of the Human Fibrinolytic System , Blood 13:811, 1958. 83. Walker, W., and Hunter, R. B.: Action of Coumarin Anticoagulants on Possible New Serum Clotting Factor , Nature, London 173:1192, 1954.Crossref 84. Welch, C.: Personal communication to the authors. 85. Wessler, S.: Experimental Intravascular Thrombosis Induced by Serum Fractions Containing Serum Prothrombin Conversion Accelerator , Federation Proc. 12:744, 1953. 86. Woodhall, B.; Hall, K.; Mahaley, S., and Jackson, J.: Chemotherapy of Brain Cancer , Ann. Surg. 150:640, 1959.Crossref 87. Wright, H. P.; Kubik, M. M., and Hayden, M.: Influence of Anticoagulant Administration on the Rate of Recanalization of Experimentally Thrombosed Veins , Brit. J. Surg. 40:1, 1952.Crossref 88. Wright, H. P.; Kubik, M. M., and Hayden, M.: Recanalization of Thrombosed Arteries Under Anticoagulant Therapy , Brit. M.J. 1:1021, 1953.Crossref 89. Wright, H. P.: Factors Influencing the Recanalization of Experimentally Thrombosed Blood Vessels , in Proceedings of the First International Conference on Thrombosis and Embolism , Basel, Benno, Schwabe & Co., 1954. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

Chymotrypsin Dissolution of Intra-Arterial Thrombi by Perfusion of Isolated Extremity

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Copyright © 1960 American Medical Association. All Rights Reserved.
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0004-0010
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Abstract

Abstract Acute arterial obstruction must be relieved immediately to prevent gangrene. Obstruction in major vessels can be relieved surgically; however, distal thrombus propagation obstructs circulation. Small arterial thrombosis is resistant to current therapy, namely, anticoagulants to limit thrombosis and more recently enzymatic lysis of the clot.37,49 Streptokinase,3,22,32,48,49 plasmin ( fibrinolysin),6,13,14,49,61 and chymotrypsin34,48,49 have been used to lyse intravascular thrombi. Objective evidence that thrombi are lysed and that clinical improvement follows is frequently lacking. The thrombolytic ability of enzymes decreases after three days as the aging clot is covered with endothelium and organizes.3,6,49 In very fresh thrombi lysis has been reported in 5 to 20 minutes.3,14,67 Clinically this is rare and fortuitous. The maximum safe systemic dose must be defined for each enzyme. The range between effective therapy and toxicity may be nil. Immunological phenomenon, fever, chills, hypotension, nausea, vomiting, and abnormalities of the hemopoietic and coagulation References 1. Upjohn Company. 2. Formerly the sclerosing material was injected into the femoral artery. This procedure was abandoned because perfusion caused hemorrhage through the needle arteriotomy. 3. Winthrop Laboratories. 4. One unit of activity is that amount which upon incubation with the hemoglobin substrate, (urea-denatured bovine hemoglobin) will release substances that, when reacted with Folin-Ciocalteau phenol reagent, will result in the formation of a colored solution of equal intensity to that produced from the reaction of 5.52×10-6 mM. of tyrosine. This assay is subject to a maximum error of ±8%. 5. Difco. 6. Protrol, Knickerbocker. 7. Dog plasma approximates 40 u/ml. Human plasma 53±5 u/ml. 8. Test system: 1 ml. bishydroxycoumarin plasma; 1 ml. serum diluted with saline; 1 ml. thromboplastin; 1 ml. 0.02 M CaCl2. Longer therapy with bishydroxycoumarin depresses not only prothrombin and Factor VII,25,26 but the clotting factors, plasma thromboplastin component, (P.T.C.),20,25,39,40 and Stuart factor as well.19,25 9. Good agreement was obtained with the above dilutions in normal samples. With a low concentration of Factor VII only the 1:10 and 1:20 dilutions of serum gave reproducible results. 10. Armour Pharmaceutical Fibrinogen contains only 50% clottable fibrinogen. 11. Parke, Davis & Company. 12. Since the prothrombin time of dogs' blood is normally 6-7 seconds, a few seconds difference from this value has considerable significance. 13. The amount of residual plasminogen12 and plasminogen activator38 or systemic proteolytic effect against casein44 was not specifically measured in our experiments. 14. References 6, 24, 34, 76, 56, 19, 43, 2. 15. Adams, E.: The Enzymatic Synthesis of Histidine from Histidinol , J. Biol. Chem. 209:829, 1954. 16. Adelson, E., and Roeder, W. H.: Studies on Fibrinolysin Using a Clinically Practical Method of Quantitative Determination , J. Clin. Path. 11:82, 1958.Crossref 17. Ambrus, J. L.; Ambrus, C. M.; Back, N.; Sokal, J. E., and Collins, G. L.: Clinical and Experimental Studies on Fibrinolytic Enzymes , Ann. New York Acad. Sc. 68:97, 1957.Crossref 18. Anson, M. L.: The Estimation of Pepsin, Trypsin, Papain, and Cathepsin with Hemoglobin , J. Gen. Physiol. 22:79, 1938.Crossref 19. Astrup, T., and Alkjaersig, N.: Classification of Proteolytic Enzymes by Means of Inhibitors , Nature 169:314, 1952.Crossref 20. Back, N.; Ambrus, J. L.; Simpson, C. L., and Shulman, S.: Study on the Effect of Streptokinase-Activated Plasmin (Fibrinolysin) on Clots in Various Stages of Organization , J. Clin. Invest. 37:864, 1958.Crossref 21. Bell, A. L. L.; Fitzpatrick, H. F.; Andreae, E.; Shimomura, S., and Pingeon, R.: The Influence of the Rats of Perfusion on Physiologic Responses During Cardiac Bypass , Ann. Surg. 148:968, 1958.Crossref 22. Biggs, R. P., and Macfarlane, R. G.: Human Blood Coagulation and Its Disorders , Springfield, Ill., Charles C Thomas, Publisher, 1953. 23. Brambel, C. E.: Proteases in the Clotting Mechanism , Ann. New York Acad. Sc. 68:70, 1957.Crossref 24. Brown, I. W., and Smith, W. W.: Hematologic Problems Associated with the Use of Extracorporeal Circulation for Cardiovascular Surgery , Ann. Int. Med. 49:1035, 1958.Crossref 25. Carroll, B. J.: Clinical Observations in the Treatment of Phlebothrombosis with Fibrinolysis , Angiology 10:308, 1959.Crossref 26. Christensen, L. R.: Methods for Measuring the Activity of Components of the Streptococcal Fibrinolytic System, and Streptococcal Desoxyribonuclease , J. Clin. Invest. 28:163, 1949.Crossref 27. Cliffton, E. E.; Grossi, C. E., and Cannamela, D.: Lysis of Thrombi Produced by Sodium Morrhuate in the Femoral Vein of Dogs by Human Plasmin (Fibrinolysin) , Ann. Surg. 139:52, 1954.Crossref 28. Cliffton, E. E.: Early Experience with Fibrinolysin , Angiology 10:244, 1959.Crossref 29. Creech, O.; Krementz, E. T.; Ryan, R. F., and Winblad, J. N.: Chemotherapy of Cancer: Regional Perfusion Utilizing an Extracorporeal Circuit , Ann. Surg. 148:616, 1958.Crossref 30. Creech, O.; Krementz, E. T.; Ryan, R. F.; Reemtsma, K., and Winblad, J. N.: Experiences with Isolation-Perfusion Techniques in the Treatment of Cancer , Ann. Surg. 149:627, 1959.Crossref 31. Creech, O.; Krementz, E. T.; Reemtsma, K.; Ryan, R. F.; Winblad, J. N., and Elliott, J. L.: The Treatment of Cancer by Perfusion , A.M.A. Arch. Surg. 79:963, 1959.Crossref 32. Damaskus, C. E.: Personal communication to the authors. 33. Dische, F. E.: Blood Clotting Substances with Factor VII Activity: A Comparison of Some Congenital and Acquired Deficiencies , Brit. J. Hemat. 4:201, 1958.Crossref 34. Douglas, A. S.: Mode of Action of Coumarin Drugs , Brit. M. Bull. 11:39, 1955. 35. Engler, H.; Christopher, P., and Moretz, W. H.: The Use of Fibrinolysin in the Prevention of Thrombus Formation in Small Artery Anastomoses , Angiology 10:259, 1959.Crossref 36. Fletcher, A. P.; Alkjaersig, N.; Smyrniotis, F. E., and Sherry, S.: The Treatment of Patients Suffering from Early Myocardial Infarction with Massive and Prolonged Streptokinase Therapy , Tr. A. Am. Physicians 71:287, 1958. 37. Ferguson, J. H., and Erickson, B. N.: Coagulant Action of Crystalline, Trypsin, Cefhalin and Lung Extracts , Am. J. Physiol. 126:661, 1939. 38. Grossi, C. E.; Cliffton, E. E., and Cannamela, D. A.: The Lysis of Intravascular Thrombi in Rabbits with Human Plasmin (Fibrinolysin) , Blood 9:310, 1954. 39. Hougie, C.; Barrow, E. M., and Graham, J. B.: Stuart Clotting Defect: I. Segregation of an Hereditary Hemorrhagic State from the Heterogeneous Group Heretofore Called a Stable Factor (S.P.C.A. Pro Convertin, Factor VII) Deficiency , J. Clin. Invest. 36:485, 1957.Crossref 40. Hunter, R. B., and Tudhope, G. R.: Mode of Action of Tromexan , Lancet 1:821, 1953.Crossref 41. Innerfield, T.; Angrist, A., and Schwarz, A.: Fibrinolytic and Anticoagulant Effects of Intravenous Crystalline Trypsin , Bull. New York Acad. Med. 28:537, 1952. 42. Innerfield, I.; Schwarz, A., and Angrist, A.: Intravenous Trypsin: Its Anticoagulant, Fibrinolytic and Thrombolytic Effects , J. Clin. Invest. 31:1049, 1952.Crossref 43. Innerfield, T.; Angrist, A., and Schwarz, A.: Parenteral Administration of Trypsin, Clinical Effect in 538 Patients , J.A.M.A. 152:597, 1953.Crossref 44. Jansen, E. F.; Nutting, R. J., and Balls, A. K.: Inhibition of the Proteinase and Esterase Activities of Trypsin and Chymotrypsin by Diisopropyl Fluorophosphate: Crystallization of Inhibited Chymotrypsin , J. Biol. Chem. 179:189, 1949. 45. Jensen, H.; Chamovitz, D. L.; Volkringer, E.; Gray, E.; Gosney, J. E., and Kocholaty, W.: Antifibrinolytic Activity in Plasma After Exposure to Cold and After Chymotrypsin Administration , Blood 8:324, 1953. 46. Johnson, A. J., and Tillett, W. S.: The Lysis in Rabbits of Intravascular Blood Clots by the Streptococcal Fibrinolytic System (Streptokinase) , J. Exper. Med. 95:449, 1952.Crossref 47. Loomis, E. C.; Ryder, A., and George, C.: Fibrinolysin and Antifibrinolysin; Biochemical Concentration of Antifibrinolysin , Arch. Biol. Chem. 20:444, 1949. 48. Martin, G. J., Editor: Clinical Enzymology , Boston, Little, Brown & Company, 1958. 49. Mindrum, G., and Glueck, H. I.: Plasma Prothrombin in Liver Disease; Its Clinical and Prognostic Significance , Ann. Int. Med. 50:1370, 1959.Crossref 50. Moser, K. M.: Thrombolysis with Fibrinolysin (Plasmin)—New Therapeutic Approach to Thromboembolism , J.A.M.A. 167:1695, 1958.Crossref 51. Moser, K. M.: Intravenous Administration of Fibrinolysin: Its Systemic Toxicity and Effect upon Components of the Coagulation Mechanism , Angiology 10:255, 1959. 52. Müllertz, S.: Activation of Plasminogen , Ann. New York Acad. Sc. 68:38, 1957.Crossref 53. Naeye, R. L.: Plasma Thromboplastin Component: Influence of Coumarin Compounds and Vitamin K on Its Activity in Serum , Proc. Soc. Exper. Biol. & Med. 91:101, 1956. 54. Owren, P. A., in New Clotting Factors, Blood Clotting and Allied Problems, Transactions of the Fifth Conference , edited by J. E. Flynn, New York, The Josiah Macy, Jr. Foundation, 1952. 55. Phillips, L. L., and Skrodelis, V.: The Fibrinolytic Enzyme System in Normal Hemorrhagic and Disease States , J. Clin. Invest. 37:965, 1958. 56. Quick, A. J.: Hemorrhagic Diseases , Philadelphia, Lea & Febiger, 1957. 57. Ratnoff, O. D., and Menzie, C.: A New Method for the Determination of Fibrinogen in Small Samples of Plasma , J. Lab. & Clin. Med. 37:316, 1951. 58. Remmert, L. F., and Cohen, P.: Partial Purification and Properties of Proteolytic Enzymes of Human Serum , J. Biol. Chem. 181:431, 1949. 59. Ryan, R. F.; Krementz, E. T.; Creech, O.; Winblad, J. N.; Chambler, W., and Check, H.: Selected Perfusion of Isolated Viscera with Chemotherapeutic Agents Using an Extracorporeal Circuit , S. Forum 8:58, 1958. 60. Ryan, R. F.; Winblad, J. N.; Krementz, E. T., and Creech, O.: Treatment of Malignant Neoplasms with Chemotherapeutic Agents Utilizing a Pump-Oxygenator: Techniques and Early Results , Bull. Tulane M. Fac. 17:133, 1958. 61. Sheard, C., and Sanford, A.: The Photometer and Its Use in the Clinical Laboratory , Am. J. Clin. Path. 3:412, 1933. 62. Sherry, S.; Titchener, A.; Gottesman, L.; Wasserman, P., and Troll, W.: The Enzymatic Dissolution of Intravascular Clots , J. Lab. & Clin. Med. 49:952, 1953. 63. 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Journal

Archives of SurgeryAmerican Medical Association

Published: Aug 1, 1960

References