Conclusion
This article has reviewed some of the more important aspects of anticoagulant therapy relevant to the anaesthetist. We hope that it will enable a rational approach to the management of the patient receiving anticoagulant therapy, and to the management of acute anticoagulation.
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References
Howell WH, Holt E. Two new factors in blood coagulation-heparin and pro-antithrombin. Am J Physiol 1918; 47: 328–41.
Schofield FW. Damaged sweet clover: the cause of a new disease in cattle simulating hemorrhagic septicemia and blackleg. J Am Vet Med Assoc 1924; 64: 553–75.
Roderick LM. The pathology of sweet clover disease in cattle. J Am Vet Med Assoc 1929; 74: 314–26.
Link KP. The anticoagulant from spoiled sweet clover hay. The Harvey Lectures 39: 162–216.
Ikawa M, Stahman MA, Link KP. Studies on 4-hydroxycoumarins. V. Condensation of alpha, beta unsaturated ketones with 4-hydroxycoumarin. J Am Chem Soc 1944; 66: 902–6.
Link KP. The discovery of dicumarol and its sequels. Circulation 1959; 19: 97–107.
Whitehead MI, McArthy TG. A comparative trial of sub-cutaneous sodium and calcium heparin as assessed by local haematoma formation and pain.In: Kakkar VV, Thomas DP, eds. Heparin: Chemistry and Clinical Use. London: Academic Press, 1976: 361.
Winter JA, Fenech A, Ridley W et al. Familial antithrombin III deficiency. Q J Med 1982; 51: 373–395.
Carlström A-S, Liedén K, Björk I. Decreased binding of heparin to antithrombin following the interaction between antithrombin and thrombin. Throm Res 1977; 11: 785–97.
Tollefsen DM, Majerus DW, Blank MK. Heparin co-factor II. Purification and properties of a heparin-dependent inhibitor of thrombin in human plasma. J Biol Chem 1982; 257: 2162–9.
Marciniak E, Farley CH, DeSimone PA. Familial thrombosis due to antithrombin III deficiency. Blood 1974; 43:219–31.
Fagerhol MK, Abildgaard U. Immunological studies on human antithrombin. 3. Influence of age, sex and use of oral contraceptives on serum concentrations. Scand J Haematol 1970; 7: 10–7.
Aberg M, Nilsson IM, Hedner U. Antithrombin III after operation. Lancet 1973; 2: 1337 (letter).
Zaidan JR, Johnson S, Brynes R, Monroe S, Guffin AV. Rate of protamine administration: its effect on heparin reversal and antithrombin recovery after coronary artery surgery. Anesth Analg 1986; 65: 377–80.
Abildgaard G, Fagerhol ME, Egeberg O. Comparison of progressive antithrombin activity and the concentrations of these thrombin inhibitors in human plasma. Scand J Clin Lab Invest 1970; 26: 349–54.
Rosenberg RD. Actions and interactions of antithrombin and heparin. N Engl J Med 1975; 292: 146–51.
Abildgaard U. Antithrombin and related inhibitors of coagulation.In: Poller L (Ed). Recent Advances in Blood Coagulation. New York: Churchill Livingstone, 1981: 162.
Wessler S. Heparin as an antithrombotic agent. JAMA 1976; 236: 389–91.
Davies JA. Anticoagulants and fibrinolytics.In: Losowsky MS, Bolton RP, eds. Advanced Medicine. London: Pitman Books, 1983: 217–27.
Kakkar VV, Lawrence D, Bentley PG, de Haas HA, Ward VP, Scully MF. A comparative study of low doses of heparin and a heparin analogue in the prevention of postoperative deep vein thrombosis. Thromb Res 1978; 13: 111–22.
Kakkar VV, Djazaeni B, Fok K, Fletcher M, Scully MF, Westwick J. Low-molecular-weight heparin and prevention of postoperative deep vein thrombosis. Br Med J 1982; 284: 375–9.
O’Reilly RA. Anticoagulant, antithrombotic and thrombolytic drugs.In: Gilman AG, Goodman LS, Rall TW, Murad F. (Eds). The Pharmacological Basis of Therapeutics, 7th edition, Chap 58. New York: Macmillan, 1985: 1338–59.
Wessler S, Gitel SN. Pharmacology of heparin and warfarin. J Am Coll Cardiol 1986; 8: 10B-20B.
Hirsh J, Gallus AS. Heparin.In: Hoffbrand AV, Brain MC, Hirsh J (Eds). Recent Advances in Haematology, Chap. 22. New York: Churchill Livingstone, 1977: 453–66.
Mann KG, Fass DN. Calcium and prothrombin activation. Mayo Clinic Proceedings 1974; 49: 929–32.
Hemker HC, Veltkamp JJ, Loeliger EA. Kinetic aspects of the interaction of blood clotting enzymes. III. Demonstration of an inhibitor of prothrombin conversion in vitamin K deficiency. Throm Diath Haemorrh 1968; 19: 346–63.
Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. Lancet 1960; 1: 1309–12.
Esmon CT. Protein-C: biochemistry, physiology, and clinical implications. Blood 1983; 62: 1155–8.
Ellison N, Ominsky AJ. Clinical considerations for the anesthesiologist whose patient is on anticoagulant therapy. Anesthesiology 1973; 39: 328–36.
Kakkar VV, Howe CT, Flanc C, Clarke MB. Natural history of postoperative deep-vein thrombosis. Lancet 1969; 2: 230–3.
Kakkar VV, Adams PC. Preventive and therapeutic approach to venous thromboembolic disease and pulmonary embolism — can death from pulmonary embolism be prevented? J Am Coll Cardiol 1986; 8: 146B-158B.
Hirsh J, Salzman E. Prevention of venous thromboembolism.In: Coleman RW, Hirsh J, Marder VE (Eds). Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Philadelphia: JB Lippincott and Co., 1982; 986–99.
Hirsh J, Genton E, Hull R. A practical approach to the prophylaxis of venous thrombosis.In: Hirsh J, Genton E, Hull R (Eds). Venous Thromboembolism. New York: Grune and Stratton, Inc., 1981: 108–21.
Bell WR, Simon TL. Current status of pulmonary thromboembolic disease: pathophysiology, diagnosis, prevention, and treatment. Am Heart J 1982; 103: 239–62.
35National Heart and Lung Institute Cooperative Study. Urokinase pulmonary embolism trial: phase 1 results. JAMA 1970; 214: 2163–72.
Chitwood WR Jr, Sabiston DC Jr, Wechsler AS. Surgical treatment of chronic unresolved pulmonary embolism. Clin Chest Med 1984; 5: 507–36.
Gurewich V, Thomas DP, Stuart RK. Some guidelines for heparin therapy of venous thromboembolic disease. JAMA 1967; 199: 152–4.
Crane C, Hartsuck J, Birtch A et al. The management of major pulmonary embolism. Surg Gynecol Obstet 1969; 128: 27–36.
Bomalaski JS, Martin GJ, Hughes RL, Yao JST. Interior vena cava interruption in the management of pulmonary embolism. Chest 1982; 82: 767–74.
Olovson T. Blutjodstudien. Acta Chir Scand 1944; 90: 469–481.
Sharnoff JG. Results in the prophylaxis of postoperative thromboembolism. Surg Gynecol Obstet 1966; 123: 303–7.
Kakkar VV, Field ES, Nicolaides AN, Flute PT, Wessler S, Yin ET. Low doses of heparin in prevention of deep-vein thrombosis. Lancet 1971; 2: 669–71.
Gallus AS, Hirsh J, Tuttle RJ et al. Small subcutaneous doses of heparin in prevention of venous thrombosis. N Engl J Med 1973; 288: 545–51.
Kakkar VV, Howe CT, Nicolaides AN, Renney JTG, Clarke MB. Deep vein thrombosis of the leg. Is there a “high risk” group? Am J Surg 1970; 120: 527–30.
Hirsh J. Prevention of deep venous thrombosis. Br J Hosp Med 1981; 26: 143–7.
Gallus AS, Hirsh J. Prevention of venous thromboembolism. Semin Thromb Haemost 1976; 2: 232–90.
Editorial. Prevention of deep-vein thrombosis: the way ahead? Lancet 1971; 2: 693–4.
Kakkar VV, Corrigan TP, Fossard DP, Sutherland I, Shelton MG, Thirwall J. Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial. Lancet 1975; 2: 45–51.
Calnan JS, Hills NH. Prevention of deep-vein thrombosis. Lancet 1971; 301: 870 (letter).
Kiil J, Axelsen F, Kill J, Andersen D. Prophylaxis against postoperative pulmonary embolism and deep-vein thrombosis by low-dose heparin. Lancet 1978; 1: 1115–6.
Bergqvist D. Postoperative thromboembolism. New York: Springer-Verlag, 1983: 89–112.
The Multicenter Trial Committee. Dihydroergotamine-heparin prophylaxis of postoperative deep vein thrombosis. A multicenter trial. JAMA 1984; 251: 2960–6.
Kakkar VV, Stamatakis JD, Bentley PG, Lawrence D, de Haas HA, Ward VP. Prophylaxis for postoperative deep-vein thrombosis: synergistic effect of heparin and dihydroergotamine. JAMA 1979; 241: 39–42.
Kakkar VV, Spindler J, Flute PT et al. Efficacy of low doses of heparin in prevention of deep-vein thrombosis after major surgery: a double-blind, randomized trial. Lancet 1972; 2: 101–6.
Morris GK, Mitchell JRA. Warfarin sodium in prevention of deep venous thrombosis and pulmonary embolism in patients with fractured neck of femur. Lancet 1976; 2: 869–72.
Sevitt S, Gallagher NG. Prevention of venous thrombosis and pulmonary embolism in injured patients. Lancet 1959; 2: 981–9.
Davies JA, McNicol GP. Thrombosis and antithrombotic therapy.In: Hardisty RM, Weatherall DJ (Eds). Blood and its Disorders. Oxford: Blackwell Scientific, 1982; 1207.
Mitchell JRA. Can we really prevent postoperative pulmonary emboli? Br Med J 1979; 1: 1523–4.
Hayes SP, Bone RC. Pulmonary emboli with respiratory failure. Med Clin North Am 1983; 67: 1179–91.
Pitt A, Anderson ST, Habersberger PG, Rosengarten DS. Low dose heparin in the prevention of deep-vein thromboses in patients with acute myocardial infarction. Am Heart J 1980; 99: 574–8.
de Vries WA, Tijssen JGP, de Jonge H, Loeliger EA, Roos J. Het effect van het staken van langdurige anti-stollingbehandeling wegens myocardinfarct bij ouderen; een dubbelblind onderzoek. Ned Tijdschr Geneesk 1979; 123: 1211–2.
Cade JF. High risk of the critically ill for venous thromboembolism. Crit Care Med 1982; 10: 448–50.
Pingleton SK, Bone RC, Pingleton WW, Ruth WE. Prevention of pulmonary emboli in a respiratory intensive care unit. Efficacy of low dose heparin. Chest 1981; 79: 647–50.
Bergqvist D. Prophylaxis of postoperative thromboembolic complications with low-dose heparin. Acta Chir Scand 1979; 145: 7–14.
Negus D. Low-dose heparin in prevention of postoperative deep vein thrombosis. J Royal Soc Med 1985; 78: 603–4 (letter).
Day TK. Low-dose heparin in prevention of postoperative deep vein thrombosis. J Royal Soc Med 1985; 78: 604 (reply to letter).
Salzman EW, Deykin D, Shapiro RM, Rosenberg R. Management of heparin therapy: controlled perspective trial. N Engl J Med 1975; 292: 1046–50.
Duxbury BM. Oral anticoagulant therapy. Hosp Update 1985; 2: 85–98.
Ellison N, Jobes DR, Schwartz AJ. Implications of anticoagulant therapy. Int Anesthesiol Clin 1982; 20: 121–35.
Cohen JA. Activated coagulation time method for the control of heparin is reliable during cardiopulmonary bypass. Anesthesiology 1984; 60: 121–4.
Quick AJ, Leu M. Quantitative determination of prothrombin. J Biol Chem 1937; 119: lxxxi.
Loeliger EA. The optimal therapeutic range in oral anticoagulation: history and proposal. Thromb Haemost 1979; 42: 1141–52.
Pachter HL, Riles TS. Low dose heparin: bleeding and wound complications in the surgical patient. Ann Surg 1977; 186: 669–74.
Brozovic M, Stirling Y, Klenerman L, Lowe L. Subcutaneous heparin and postoperative thromboembolism. Lancet 1974; 2: 99–100.
Moore FD, Jr, Osteen RT, Karp DD, Steele G, Jr, Wilson RE. Anticoagulants, venous thromboembolism, and the cancer patient. Arch Surg 1981; 116: 405–7.
Schwartz KA, Royer G, Kaufman DB, Penner JA. Complications of heparin administration in normal individuals. Am J Hematol 1985; 19: 355–63.
Carreras LO. Thrombosis and thrombocytopenia induced by heparin. Scand J Haematol 1980; 25: 64–80 (Suppl 36).
Anderson EF. Heparin resistance prior to cardiopulmonary bypass. Anesthesiology 1986; 64: 504–7.
Kubacz GJ. Femoral and sciatic compression neuropathy. Br J Surg 1971; 58: 580–2.
Duggan ML, Morgan C Jr. Heparin: a cause of priapism? South Med J 1970; 63: 1131–4.
Thompson RC Jr, Ludewig RM, Wangensteen SL, Rudolf LM. Effect of heparin on wound healing. Surg Gynecol Obstet 1972; 134: 22–6.
Becker MH, Genieser NB, Finegold M, Miranda D, Spackman T. Chondrodysplasia punctata. Is maternal warfarin therapy a factor? Am J Dis Child 1975; 129: 356–9.
Pennock JL. Perioperative management of drug therapy. Surg Clin North Am 1983; 63: 1049–56.
Defalque RJ. Percutaneous catheterization of the internal jugular vein. Anesth Analg 1974; 53: 116–21.
Klineberg PL, Greenkow DE, Ellison N. Haematoma following internal jugular cannulation. Anaesth Intensive Care 1980; 3: 94–5.
Moore DC. Regional Block. 4th edition. Springfield: CC Thomas, 1978: 218.
Bromage PR. Epidural Analgesia. Philadelphia: W.B. Saunders, 1978: 240.
De Angelis J. Hazards of subjural and epidural anesthesia during anticoagulant therapy: a case report and review. Anesth Analg 1972; 51: 676–9.
Stanley TH, Lunn JK. Anticoagulants and continuous epidural anesthesia. Anesth Analg 1980; 59: 394–5 (letter).
Cunningham FO, Egan JM, Inahara T. Continuous epidural anesthesia in abdominal vascular surgery. Am J Surg 1980; 139: 624–7.
Fuchs JCA, Fagraeus L, Lumb PD. The emerging role of epidural anesthesia in arteriography and in vascular operations. Ann Surg 1982; 195: 781–5.
Mathews ET, Abrams LD. Intrathecal morphine in open heart surgery. Lancet 1980; 2: 543 (letter).
Rao TLK, El-Etr AA. Anticoagulation following placement of epidural and subarachnoid catheters: an evaluation of neurologic sequelae. Anesthesiology 1981; 55: 618–20.
Odoom JA, Sih IL. Epidural anaesthesia and anticoagulant therapy. Experience with one thousand cases of continuous epidurals. Anaesthesia 1983; 38: 254–9.
Molnar I, Rø JS. Epidural analgesia and anticoagulant therapy. Anaesthesia 1984; 39: 602 (letter).
Odoom JA. Epidural analgesia and anticoagulant therapy. Anaesthesia 1984; 39: 602–3 (reply to letter).
Justins DM. Relief of pain in labour.In: Churchill-Davidson HC, ed. A Practice of Anaesthesia, 5th edition. Chicago: Yearbook Medical Publishers, 1984:1035.
Lee JA, Atkinson RS, eds. Sir Robert Macintosh’s Lumbar Puncture and Spinal Analgesia, 4th edition. Edinburgh: Churchill Livingstone, 1978: 201.
Atkinson RS, Rushman GB, eds. Synopsis of Anaesthesia, 9th edition. Bristol: Wright, 1982: 458.
Bull BS, Korpman RA, Huse WM, Briggs BD. Heparin therapy during extracorporeal circulation. I. Problems inherent in existing heparin protocols. J Thorac Cardiovasc Surg 1975; 69: 674–84.
Bull MH, Huse WM, Bull BS. Evaluation of tests used to monitor heparin therapy during extracorporeal circulation. Anesthesiology 1975; 43: 346–53.
Hattersley PG. Activated coagulation time of whole blood. JAMA 1966; 196: 436–40.
Kamatk BSK, Fozard JR. Control of heparinisation during cardiopulmonary bypass. Anaesthesia 1980; 35: 250–6.
Bull BS, Huse WM, Brauer FS, Korpman RA. Heparin therapy during extracorporeal circulation. II. The use of a dose-response curve to individualize heparin and protamine dosage. J Thorac Cardiovasc Surg 1975; 69: 685–9.
Umlas J, Taff RH, Gauvin G, Swierk P. Anticoagulant monitoring and neutralization during open heart surgery — a rapid method for measuring heparin and calculating safe reduced protamine doses. Anesth Analg 1983; 62: 1095–9.
Barrowcliffe TW, Johnson EA, Thomas D. Antithrombin III and heparin. Br Med Bull 1978; 34:143–50.
Sabbagh AH, Chung GKT, Shuttleworth P, Applegate BJ, Gabrhel W. Fresh frozen plasma: a solution to heparin resistance during cardiopulmonary bypass. Ann Thorac Surg 1984; 37: 466–8.
Toomasian JM, Helmer GA, Zeme MI, Oltean JN, Oran AD, Bartlett RH. Control of thrombosis in extracorporeal circulation: variations of anticoagulation. Trans Am Soc Artif Intern Organs 1983; 24: 206–9.
Langer R, Linhardt RJ, Hoffberg G et al. An enzymatic system for removing heparin in extracorporeal therapy. Science 1982; 217: 261–3.
Bell WR. Defibrinogenating enzymes.In: Hemostasis and Thrombosis, Colman RW, Hirsch J, Marder VJ, Salzman EW (Eds). Philadelphia, Lippincott, 1982, 1013–27.
Berglin E, Hansson H-A, Teger-Nilsson A-C, William-Olsson G. Defibrinogenation as an alternative to heparinization during prolonged extracorporeal circulation in the dog. Thromb Res 1976; 9: 81–93.
Thomson WH. Die physiologische wirkung der protamine und ihrer spaltunsprodukte. Hoppe-Seyler’s Zeitschrift fr Physiologische Chemie 1901; 29: 1–19.
Chargaff E, Olson KB. Studies on the chemistry of blood coagulation. VI. Studies on the action of heparin and other anticoagulants. The influence of protamine on the anticoagulant effect in vivo. J Biol Chem 1937; 122: 153–67.
Goldman BS, Joison J, Austin WG. Cardiovascular effects of protamine sulfate. Ann Thorac Surg 1969; 7: 459–71.
Fadali MA, Ledbetter M, Papacostas CA, Duke LJ, Lemole GM. Mechanism responsible for the cardiovascular depressant effect of protamine sulfate. Ann Surg 1974; 180: 232–5.
Masone R, Oka Y, Hong YW, Santos H, Frater RW. Cardiovascular effects of right atrial injection of protamine sulfate as compared to left atrial injection. Anesthesiology 1982; 57: 196 (abstract).
Jones RM, Hill AB, Nahrwold ML, Tait AR. Effect of protamine on plasma ionized calcium in the dog. Can Anaesth Soc J 1982; 29: 65–7.
Moorthy SS, Pond W, Rowland RG. Severe circulatory shock following protamine (an anaphylactic reaction). Anesth Analg 1980; 59: 77–8.
Lowenstein E, Johnston WE, happas DG et al. Catastrophic pulmonary vas constriction associated with protamine reversal of heparin. Anesthesiology 1983; 59: 470–3.
Fehr J, Rohr H. In vivo complement activation by polyanion-polycation complexes: evidence that C5a is generated intravascularly during heparin-protamine interaction. Clin Immunol Immunopathol 1983; 29: 7–14.
Sharath MD, Metzger WJ, Richerson HB et al. Protamine-induced fatal anaphylaxis. J Thorac Cardiovasc Surg 1985; 90: 86–90.
Michaels IAL, Barash PG. Hemodynamic changes during protamine administration. Anesth Analg 1983; 62: 831–5.
Aris A, Solanes H, Bonnin JO, Garin R, Carolos JM. Intraaortic administration of protamine: method for heparin neutralization after cardiopulmonary bypass. Cardiovascular Diseases. Bull Texas Heart Institute 1981; 8: 23–8.
Rogers K, Milne B, Salerno TA. The hemodynamic effects of intra-aortic versus intravenous administration of protamine for reversal of heparin in pigs. J Thorac Cardiovasc Surg 1983; 85: 851–5.
Bjoraker DG, Ketcham TR. In vivo platelet response to clinical protamine sulfate infusion. Anesthesiology 1982; 57: A7.
Lakin JD, Blocker TJ, Strong DM, Yocum MW. Anaphylaxis to protamine sulfate mediated by a complement dependent IgG antibody. J Allergy Clin Immunol 1978; 61: 102–7.
Doolan L, McKenzie I, Krafchek J, Parsons B, Buxton B. Protamine sulfate hypersensitivity. Anaesth Intensive Care 1981; 9: 147–9.
Chung F, Miles J. Cardiac arrest following protamine administration. Can Anaesth Soc I 1984; 31: 314–8.
Caplan SN, Berkman EM. Protamine sulfate and fish allergy. N Engl J Med 1976; 295: 172 (letter).
Samuel T, Kolk AHJ, Rümke P, Van Lis JMJ. Autoimmunity to sperm antigens in vasectomized men. Clin Exp Immunol 1975; 21: 65–74.
Dutton DA, Hothersall AP, McLaren AD, Taylor KM, Turner MA. Protamine titration after cardiopulmonary bypass. Anaesthesia 1983; 38: 264–8.
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Stow, P.J., Burrows, F.A. Continuing Medical Education Article Anticoagulants in anaesthesia. Can J Anaesth 34, 632–649 (1987). https://doi.org/10.1007/BF03010526
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DOI: https://doi.org/10.1007/BF03010526