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THROMBOPLASTIC REAGENT: DEVELOPMENT OF A MORE SUITABLE PREPARATION FOR MEASURING ACCELERATED CLOTTING TENDENCY AND FOR USE FOLLOWING ADMINISTRATION OF DICOUMARIN (3,3′-METHYLENE-BIS-[4-HYDROXYCOUMARIN])

THROMBOPLASTIC REAGENT: DEVELOPMENT OF A MORE SUITABLE PREPARATION FOR MEASURING ACCELERATED... Abstract It is a well established fact that in certain clinical conditions, especially those following surgical procedures and trauma, the equilibrium of the coagulation elements of the blood is shifted to a state favorable to clotting.1 A laboratory procedure is needed for detecting this tendency to intravascular clotting before the appearance of thrombotic phenomena. If such a procedure were available to the clinician, in vivo anticoagulants, such as heparin or dicoumarin (3,3′-methylene-bis [4-hydroxycoumarin] ), could be administered to patients having indications of such a tendency. Serious consequences and long periods of hospitalization could be averted in many instances. The introduction of dicoumarin,2 however, has posed another problem, that of maintaining a precise control of the mechanism for blood coagulation in order to avoid hemorrhagic consequences following the use of this drug. Difficulty in maintaining a given clotting level, as well as undesirable results, including death, has been reported.3 A References 1. (a) Bancroft, F. W.; Kugelmass, I. N., and Stanley-Brown, M.: Evaluation of Blood Clotting Factors in Surgical Diseases with Special Reference to Thrombosis and Embolism and Certain Bleeding Conditions , Ann. Surg. 90:161, 1929.Crossref 2. (b) Bancroft, F. W., and Stanley-Brown, M.: Postoperative Thrombosis, Thrombophlebitis and Embolism , Surg., Gynec. & Obst. 54: 898, 1932. 3. (c) de Takáts, G.: Thrombosis and Embolism , in Chrostopher, F.: Textbook of Surgery , ed. 3, Philadelphia, W. B. Saunders Company. 1941. 4. (d) Wright, H. P.: Adhesiveness of Blood Platelets in Normal Subjects with Varying Concentrations of Anticoagulants , J. Path. & Bact. 53:255, 1941 5. (e) Changes in Adhesiveness of Blood Platelets Following Parturition and Surgical Operations , Wright J. Path. & Bact. 54:461, 1942. 6. (f) Homans, J.: Diseases of the Veins , New England J. Med. 231:51, 1944. 7. Link, K. P.: The Anticoagulant from Spoiled Sweet Clover Hay , in Harvey Lectures , Lancester, Pa., Science Press, 1944, vol. 39, p. 162. 8. (a) Cahan, A.: Hemorrhage and Purpura Caused by Dicoumarin , New England J. Med. 228: 820, 1943. 9. (b) Evans, J. A.: Dicoumarol Therapy in Thrombotic Emergencies , New England J. Med. 230:131, 1944. 10. (c) Barker, N. W.: The Use of Dicoumarol in Surgery , Minnesota Med. 27:102, 1944. 11. (d) De Bakey, M.: Dicoumarin and Prophylactic Anticoagulants in Intravascular Thrombosis , Surgery 13:456, 1943. 12. (e) Schlevin, E. L., and Lederer, M.: Uncontrollable Hemorrhage After Dicoumarol Therapy with Autopsy Findings , Ann. Int. Med. 21:332, 1944. 13. Brambel, C. E., and Loker, F. F.: Significance of Variations of Prothrombin Activity of Dilute Plasma , Proc. Soc. Exper. Biol. & Med. 53:218, 1943. 14. (a) de Takáts, G.: Heparin Tolerance: A Test of the Clotting Mechanism , Surg., Gynec. & Obst. 77: 31, 1943. 15. (b) Waugh, T. R., and Ruddick, D. W.: A Test for Increased Coagulability of the Blood , Canad. M. A. J. 50:547, 1944. 16. Brambel, C. E., and Loker, F. F.: (a) Application of Dicoumarin (3,3′-Methylene-Bis-4-Hydroxycoumarin) in Trauma and Gangrene , Arch. Surg. 48:1 ( (Jan.) ) 1944 17. (b) footnote 4. 18. Howell W. H.: The Condition of the Blood in Hemophilia, Thrombosis and Purpura , Arch. Int. Med. 13:76 ( (Jan.) ) 1914. 19. Quick, A. J.: The Nature of the Bleeding in Jaundice , J. A. M. A. 110:1658 ( (May 14) ) 1938. 20. Warner, E. D.; Brinkhous, K. M., and Smith, H. P.: A Quantitative Study on Blood Clotting: Prothrombin Fluctuations Under Experimental Conditions , Am. J. Physiol. 114:667, 1936. 21. Dam, H., and Glavind, J.: Determination of Vitamin K by the Curative Blood-Clotting Method , Biochem. J. 32:1018, 1938. 22. Quick, A. J.: The Hemorrhagic Diseases and the Physiology of Hemostasis , Springfield, Ill., Charles C Thomas, Publisher, 1942. 23. Quick, A. J.: On the Various Properties of Thromboplastin (Aqueous Tissue Extracts) , Am. J. Physiol. 114:282, 1936; footnote 8. 24. Chargaff, E.: Lipoproteins, in Advances in Protein Chemistry I , New York, Academic Press, 1944. 25. Bingham, Meyer and Pohle.20a Brambel and Loker.4 Butsch and Stewart.20c Page and Russell.20d Quick (footnotes 8 and 19 b). Stats and Bullowa.20f 26. Barker.3c Davidson and MacDonald.20k Magath.20l Shapiro and others.20m Souter and Kark.20n 27. Hause and Tocantins.20g Lucia and Aggeler.20h Quick.19a Ziffren and others.20i 28. Quick.19a Ziffren and others.20i 29. (b) Page, R. C.; de Beer, E. J., and Orr, M. L.: Prothrombin Studies Using Russell Viper Venom: III. Effect of Lecithinized Venom on Prothrombin Clotting Time , J. Lab. & Clin. Med. 27: 830, 1942. 30. (a) Quick, A. J.: The Thromboplastin Reagent for the Determination of Prothrombin , Science 92:113, 1940Crossref 31. (b) Calcium Factor in Quantitative Determination of Prothrombin , Proc. Soc. Exper. Biol. & Med. 40:206, 1939. 32. (c) Pohle, F. J., and Stewart, J. K.: A Study of the Quick Method for the Quantitative Determination of Prothrombin with Suggested Modifications , Am. J. M. Sc. 198:622, 1939. 33. (a) Bingham, J. B.; Meyer, O. O., and Pohle, F. J.: Studies on the Hemorrhagic Agent 3,3′-Methylenebis (4-Hydroxycoumarin): I. Its Effect on the Prothrombin and Coagulation Time of the Blood of Dogs and Humans , Am. J. M. Sc. 202:563, 1941. 34. (c) Butsch, W. F., and Stewart, J. D.: Administration of Dicoumarin Compound for Prophylaxis and Postoperative Thrombosis and Embolism: A Preliminary Report , Arch. Surg. 45:551 ( (Oct.) ) 1942. 35. (d) Page, R. C., and Russell, H. K.: Prothrombin Estimation Using Russell Viper Venom: I. Simple Modification of Quick's Method , J. Lab. & Clin. Med. 26:1366, 1941. 36. (e) Quick (footnotes 8 and 19 b). 37. (f) Stats, D., and Bullowa, J. G. M.: Effect of a Single Dose of 3,3′-Methylenebis (4-Hydroxycoumarin) upon Blood Coagulation in Humans , Proc. Soc. Exper. Biol. & Med. 50:66, 1942. 38. (g) Hause, W. A., and Tocantins, L. M.: Determinations of Plasma Prothrombin Variations in Normal Men and Women , Am. J. Clin. Path. 11:54, 1941. 39. (h) Lucia, S. P., and Aggeler, P. M.: The Influence of Liver Damage on the Plasma Prothrombin Concentration and the Response to Vitamin K , Am. J. M. Sc. 201:326, 1941. 40. (i) Ziffren, S. E.; Owen, C. A.; Hoffman, G. R., and Smith, H. P.: Control of Vitamin K Therapy: Compensatory Mechanisms of Low Prothrombin Levels , Proc. Soc. Exper. Biol. & Med. 40:595, 1939. 41. (k) Davidson, C. S., and MacDonald, H.: A Critical Study of the Action of 3,3′-Methylenebis (4-Hydroxycoumarin) (Dicoumarin) , Am. J. M. Sc. 205:24, 1943. 42. (l) Magath, T. B.: Technic of Prothrombin Time Determination , Am. J. Clin. Path. (Tech. Supp.) 3:187, 1939. 43. (m) Shapiro, S.; Sherwin, B.; Redish, M., and Campbell, H. A.: Prothrombin Estimation: A Procedure and Clinical Interpretations , Proc. Soc. Exper. Biol. & Med. 50:85, 1942. 44. (n) Souter, A. W., and Kark, R.: Quick's Prothrombin Test Simplified by the Use of a Stable Thromboplastin , Am. J. M. Sc. 200:603, 1940. 45. (o) Wright, I. S., and Prandoni, A.: The Dicoumarin 3,3′-Methylene bis-(4-Hydroxycoumarin): Its Pharmacologic and Therapeutic Action in Man , J. A. M. A. 120:1015 ( (Nov. 28) ) 1942. 46. (p) Fullerton, H. W.: Estimation of Prothrombin: A Simplified Method , Lancet 2:195, 1940. 47. Campbell, H. A.; Smith, W. K.; Roberts, W. L., and Link, K. P.: Studies on the Hemorrhagic Sweet Clover Disease: II. The Bioassay of Hemorrhagic Concentrates by Following the Prothrombin Level in the Plasma of Rabbit Blood , J. Biol. Chem. 138:1, 1941. 48. (a) de Takáts.1c (b) Homans.1f 49. Sturm, E.: The Prothrombin Concentration in the Plasma of Normal and Leukemic Rats , Cancer Research 4:35, 1944. 50. Richards, R. K.: Influence of Fever upon the Action of 3,3′-Methylene-Bis-(4-Hydroxycoumarin) (Dicoumarol) , Science 97:313, 1943. 51. Allen, E. V.; Barker, N. W., and Waugh. J. M.: A Preparation from Spoiled Sweet Clover [3,3′-Methylene-Bis-(Hydroxycoumarin)] Which Prolongs Coagulation and Prothrombin Time of the Blood: A Clinical Study , J. A. M. A. 120:1009 ( (Nov. 28) ) 1942. 52. Evans, J. A.: Problems of Postoperative Thrombophlebitis and Pulmonary Embolism , Connecticut M. J. 8:71, 1944. 53. Wasserman, L. R., and Stats, D.: Clinical Observations on the Effect of 3,3′-Methylenebis (4-Hydroxycoumarin) , Am. J. M. Sc. 206:466, 1943.Crossref 54. Zucker, H. D.: Clinical Experiences with Dicoumarol , J. A. M. A. 124:217 ( (Jan. 22) ) 1944.Crossref 55. Evans, J. A.: Dicoumarol Therapy in Thrombotic Emergencies , New England J. Med. 230:131, 1944.Crossref 56. (a) Davidson and Mac Donald.20k (b) Barker, N. W.: Personal communication to the author. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

THROMBOPLASTIC REAGENT: DEVELOPMENT OF A MORE SUITABLE PREPARATION FOR MEASURING ACCELERATED CLOTTING TENDENCY AND FOR USE FOLLOWING ADMINISTRATION OF DICOUMARIN (3,3′-METHYLENE-BIS-[4-HYDROXYCOUMARIN])

BRAMBEL, CHARLES E.
Archives of Surgery , Volume 50 (3) – Mar 1, 1945
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References (53)

Publisher
American Medical Association
Copyright
Copyright © 1945 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1945.01230030143003
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Abstract

Abstract It is a well established fact that in certain clinical conditions, especially those following surgical procedures and trauma, the equilibrium of the coagulation elements of the blood is shifted to a state favorable to clotting.1 A laboratory procedure is needed for detecting this tendency to intravascular clotting before the appearance of thrombotic phenomena. If such a procedure were available to the clinician, in vivo anticoagulants, such as heparin or dicoumarin (3,3′-methylene-bis [4-hydroxycoumarin] ), could be administered to patients having indications of such a tendency. Serious consequences and long periods of hospitalization could be averted in many instances. The introduction of dicoumarin,2 however, has posed another problem, that of maintaining a precise control of the mechanism for blood coagulation in order to avoid hemorrhagic consequences following the use of this drug. Difficulty in maintaining a given clotting level, as well as undesirable results, including death, has been reported.3 A References 1. (a) Bancroft, F. W.; Kugelmass, I. N., and Stanley-Brown, M.: Evaluation of Blood Clotting Factors in Surgical Diseases with Special Reference to Thrombosis and Embolism and Certain Bleeding Conditions , Ann. Surg. 90:161, 1929.Crossref 2. (b) Bancroft, F. W., and Stanley-Brown, M.: Postoperative Thrombosis, Thrombophlebitis and Embolism , Surg., Gynec. & Obst. 54: 898, 1932. 3. (c) de Takáts, G.: Thrombosis and Embolism , in Chrostopher, F.: Textbook of Surgery , ed. 3, Philadelphia, W. B. Saunders Company. 1941. 4. (d) Wright, H. P.: Adhesiveness of Blood Platelets in Normal Subjects with Varying Concentrations of Anticoagulants , J. Path. & Bact. 53:255, 1941 5. (e) Changes in Adhesiveness of Blood Platelets Following Parturition and Surgical Operations , Wright J. Path. & Bact. 54:461, 1942. 6. (f) Homans, J.: Diseases of the Veins , New England J. Med. 231:51, 1944. 7. Link, K. P.: The Anticoagulant from Spoiled Sweet Clover Hay , in Harvey Lectures , Lancester, Pa., Science Press, 1944, vol. 39, p. 162. 8. (a) Cahan, A.: Hemorrhage and Purpura Caused by Dicoumarin , New England J. Med. 228: 820, 1943. 9. (b) Evans, J. A.: Dicoumarol Therapy in Thrombotic Emergencies , New England J. Med. 230:131, 1944. 10. (c) Barker, N. W.: The Use of Dicoumarol in Surgery , Minnesota Med. 27:102, 1944. 11. (d) De Bakey, M.: Dicoumarin and Prophylactic Anticoagulants in Intravascular Thrombosis , Surgery 13:456, 1943. 12. (e) Schlevin, E. L., and Lederer, M.: Uncontrollable Hemorrhage After Dicoumarol Therapy with Autopsy Findings , Ann. Int. Med. 21:332, 1944. 13. Brambel, C. E., and Loker, F. F.: Significance of Variations of Prothrombin Activity of Dilute Plasma , Proc. Soc. Exper. Biol. & Med. 53:218, 1943. 14. (a) de Takáts, G.: Heparin Tolerance: A Test of the Clotting Mechanism , Surg., Gynec. & Obst. 77: 31, 1943. 15. (b) Waugh, T. R., and Ruddick, D. W.: A Test for Increased Coagulability of the Blood , Canad. M. A. J. 50:547, 1944. 16. Brambel, C. E., and Loker, F. F.: (a) Application of Dicoumarin (3,3′-Methylene-Bis-4-Hydroxycoumarin) in Trauma and Gangrene , Arch. Surg. 48:1 ( (Jan.) ) 1944 17. (b) footnote 4. 18. Howell W. H.: The Condition of the Blood in Hemophilia, Thrombosis and Purpura , Arch. Int. Med. 13:76 ( (Jan.) ) 1914. 19. Quick, A. J.: The Nature of the Bleeding in Jaundice , J. A. M. A. 110:1658 ( (May 14) ) 1938. 20. Warner, E. D.; Brinkhous, K. M., and Smith, H. P.: A Quantitative Study on Blood Clotting: Prothrombin Fluctuations Under Experimental Conditions , Am. J. Physiol. 114:667, 1936. 21. Dam, H., and Glavind, J.: Determination of Vitamin K by the Curative Blood-Clotting Method , Biochem. J. 32:1018, 1938. 22. Quick, A. J.: The Hemorrhagic Diseases and the Physiology of Hemostasis , Springfield, Ill., Charles C Thomas, Publisher, 1942. 23. Quick, A. J.: On the Various Properties of Thromboplastin (Aqueous Tissue Extracts) , Am. J. Physiol. 114:282, 1936; footnote 8. 24. Chargaff, E.: Lipoproteins, in Advances in Protein Chemistry I , New York, Academic Press, 1944. 25. Bingham, Meyer and Pohle.20a Brambel and Loker.4 Butsch and Stewart.20c Page and Russell.20d Quick (footnotes 8 and 19 b). Stats and Bullowa.20f 26. Barker.3c Davidson and MacDonald.20k Magath.20l Shapiro and others.20m Souter and Kark.20n 27. Hause and Tocantins.20g Lucia and Aggeler.20h Quick.19a Ziffren and others.20i 28. Quick.19a Ziffren and others.20i 29. (b) Page, R. C.; de Beer, E. J., and Orr, M. L.: Prothrombin Studies Using Russell Viper Venom: III. Effect of Lecithinized Venom on Prothrombin Clotting Time , J. Lab. & Clin. Med. 27: 830, 1942. 30. (a) Quick, A. J.: The Thromboplastin Reagent for the Determination of Prothrombin , Science 92:113, 1940Crossref 31. (b) Calcium Factor in Quantitative Determination of Prothrombin , Proc. Soc. Exper. Biol. & Med. 40:206, 1939. 32. (c) Pohle, F. J., and Stewart, J. K.: A Study of the Quick Method for the Quantitative Determination of Prothrombin with Suggested Modifications , Am. J. M. Sc. 198:622, 1939. 33. (a) Bingham, J. B.; Meyer, O. O., and Pohle, F. J.: Studies on the Hemorrhagic Agent 3,3′-Methylenebis (4-Hydroxycoumarin): I. Its Effect on the Prothrombin and Coagulation Time of the Blood of Dogs and Humans , Am. J. M. Sc. 202:563, 1941. 34. (c) Butsch, W. F., and Stewart, J. D.: Administration of Dicoumarin Compound for Prophylaxis and Postoperative Thrombosis and Embolism: A Preliminary Report , Arch. Surg. 45:551 ( (Oct.) ) 1942. 35. (d) Page, R. C., and Russell, H. K.: Prothrombin Estimation Using Russell Viper Venom: I. Simple Modification of Quick's Method , J. Lab. & Clin. Med. 26:1366, 1941. 36. (e) Quick (footnotes 8 and 19 b). 37. (f) Stats, D., and Bullowa, J. G. M.: Effect of a Single Dose of 3,3′-Methylenebis (4-Hydroxycoumarin) upon Blood Coagulation in Humans , Proc. Soc. Exper. Biol. & Med. 50:66, 1942. 38. (g) Hause, W. A., and Tocantins, L. M.: Determinations of Plasma Prothrombin Variations in Normal Men and Women , Am. J. Clin. Path. 11:54, 1941. 39. (h) Lucia, S. P., and Aggeler, P. M.: The Influence of Liver Damage on the Plasma Prothrombin Concentration and the Response to Vitamin K , Am. J. M. Sc. 201:326, 1941. 40. (i) Ziffren, S. E.; Owen, C. A.; Hoffman, G. R., and Smith, H. P.: Control of Vitamin K Therapy: Compensatory Mechanisms of Low Prothrombin Levels , Proc. Soc. Exper. Biol. & Med. 40:595, 1939. 41. (k) Davidson, C. S., and MacDonald, H.: A Critical Study of the Action of 3,3′-Methylenebis (4-Hydroxycoumarin) (Dicoumarin) , Am. J. M. Sc. 205:24, 1943. 42. (l) Magath, T. B.: Technic of Prothrombin Time Determination , Am. J. Clin. Path. (Tech. Supp.) 3:187, 1939. 43. (m) Shapiro, S.; Sherwin, B.; Redish, M., and Campbell, H. A.: Prothrombin Estimation: A Procedure and Clinical Interpretations , Proc. Soc. Exper. Biol. & Med. 50:85, 1942. 44. (n) Souter, A. W., and Kark, R.: Quick's Prothrombin Test Simplified by the Use of a Stable Thromboplastin , Am. J. M. Sc. 200:603, 1940. 45. (o) Wright, I. S., and Prandoni, A.: The Dicoumarin 3,3′-Methylene bis-(4-Hydroxycoumarin): Its Pharmacologic and Therapeutic Action in Man , J. A. M. A. 120:1015 ( (Nov. 28) ) 1942. 46. (p) Fullerton, H. W.: Estimation of Prothrombin: A Simplified Method , Lancet 2:195, 1940. 47. Campbell, H. A.; Smith, W. K.; Roberts, W. L., and Link, K. P.: Studies on the Hemorrhagic Sweet Clover Disease: II. The Bioassay of Hemorrhagic Concentrates by Following the Prothrombin Level in the Plasma of Rabbit Blood , J. Biol. Chem. 138:1, 1941. 48. (a) de Takáts.1c (b) Homans.1f 49. Sturm, E.: The Prothrombin Concentration in the Plasma of Normal and Leukemic Rats , Cancer Research 4:35, 1944. 50. Richards, R. K.: Influence of Fever upon the Action of 3,3′-Methylene-Bis-(4-Hydroxycoumarin) (Dicoumarol) , Science 97:313, 1943. 51. Allen, E. V.; Barker, N. W., and Waugh. J. M.: A Preparation from Spoiled Sweet Clover [3,3′-Methylene-Bis-(Hydroxycoumarin)] Which Prolongs Coagulation and Prothrombin Time of the Blood: A Clinical Study , J. A. M. A. 120:1009 ( (Nov. 28) ) 1942. 52. Evans, J. A.: Problems of Postoperative Thrombophlebitis and Pulmonary Embolism , Connecticut M. J. 8:71, 1944. 53. Wasserman, L. R., and Stats, D.: Clinical Observations on the Effect of 3,3′-Methylenebis (4-Hydroxycoumarin) , Am. J. M. Sc. 206:466, 1943.Crossref 54. Zucker, H. D.: Clinical Experiences with Dicoumarol , J. A. M. A. 124:217 ( (Jan. 22) ) 1944.Crossref 55. Evans, J. A.: Dicoumarol Therapy in Thrombotic Emergencies , New England J. Med. 230:131, 1944.Crossref 56. (a) Davidson and Mac Donald.20k (b) Barker, N. W.: Personal communication to the author.

Journal

Archives of Surgery – American Medical Association

Published: Mar 1, 1945

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