Advertisement
Research Article| Volume 7, ISSUE 3, P533-554, July 1991

Anticoagulants and Thrombolytics

Risks and Benefits
      This paper is only available as a PDF. To read, Please Download here.
      The increased use of anticoagulation agents in critical care is associated with both hemorrhagic and thromboembolic sequelae. Bleeding is associated with thrombolytic agents, heparin, and warfarin; serious hemorrhage may require the administration of antifibrinolytic drugs, protamine sulfate, or vitamin K1, respectively. Recognition of early signs and symptoms of bleeding such as pain, neurologic symptoms, and metabolic abnormalities enable one to make an early diagnosis and institute treatment promptly. Heparin administration is associated with a delayedonset thrombocytopenia with thrombosis and may lead to amputation. Warfarin depletes proteins C and S causing thromboembolic episodes, including a rare skin necrosis, which may be prevented by administering both heparin and warfarin for 4 to 5 days.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Critical Care Clinics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Aarskog D.
        • Aksnes L.
        • Lehmann V.
        Low 1,25-dihydroxy vitamin D in heparin-induced osteopenia.
        Lancet. 1980; 2: 650
        • Ainsley E.J..
        • Mackie I.G.
        • McArthur D.
        Adverse reaction to chlorocresol-preserved heparin.
        Lancet. 1977; 1: 705
        • Amerena J.
        • Mashford M.L.
        • Wallace S.
        Adverse effects of anticoagulants.
        Adverse Drug Reactions Acute Poisoning Rev. 1990; 9: 1
        • Andersen P.
        • Godal H.C.
        Predictable reduction in anticoagulant activity of warfarin by small amounts of vitamin K.
        Acta Med Scand. 1975; 198: 269
        • Ansell J.E.
        • Price J.M.
        • Shah S.
        • et al.
        Heparin-induced thrombocytopenia.
        Chest. 1985; 88: 878
        • Aull L.
        • Chao H.
        • Coy K.
        Heparin-induced hyperkalemia.
        Drug Intelligence and Clinical Pharmacy. 1990; 24: 244
        • Babb R.R.
        • Spittell J.A.
        • Bartholomew L.G.
        Hematoma of the rectus adominus muscle complicating anticoagulant therapy.
        Mayo Clin Proc. 1965; 40: 760
        • Baker R.N.
        An evaluation of anticoagulant therapy in the treatment of cerebrovascular disease: Report of the Veterans Administration cooperative study of atherosclerosis.
        Neurology. 1961; 11: 132
        • Baker R.N.
        • Broward J.A.
        • Fang H.C.
        • et al.
        Anticoagulant therapy in cerebral infarction; report on cooperative study.
        Neurology. 1962; 12: 823
        • Battey P.M.
        • Salam A.A.
        Venous gangrene associated with heparin-induced thrombocytopenia.
        Surgery. 1985; 97: 618
        • Becker P.S.
        • Miller V.T.
        Heparin-induced thrombocytopenia.
        Stroke. 1989; 20: 1449
        • Becker R.C.
        • Corrao J.M.
        • Bovill E.G.
        • et al.
        Intravenous nitroglycerin resistance: A qualitative antithrombin III abnormality.
        Am Heart J. 1990; 119: 1254
        • Bell W.R.
        • Royall R.M.
        Heparin-associated thrombocytopenia; a comparison of three heparin preparations.
        N Engl J Med. 1980; 303: 902
        • Bell W.R.
        • Tomasulo P.A.
        • Duffy T.P.
        Thrombocytopenia occurring during the administration of heparin.
        Ann Intern Med. 1976; 85: 155
        • Bern M.M.
        • Lokich J.J.
        • Wallach S.R.
        • et al.
        Very low doses of warfarin can prevent thrombosis in central venous catheters.
        Ann Intern Med. 1990; 112: 423
        • Berridge D.C.
        • Makin G.S.
        • Hopkinson B.R.
        Local low-dose intra-arterial thrombolytic therapy: The risk of stroke or major hemorrhage.
        Br J Surg. 1989; 76: 1230
        • Bett J.H.N.
        • Bunce I.H.
        • Cade J.F.
        • et al.
        Initial experience with a new fibrinolytic agent (APSAC) in patients with major pulmonary embolism.
        Aust NZ J Med. 1987; 17: 77
        • Boster S.R.
        • Bergin J.J.
        Upper airway obstruction complicating warfarin therapy—with a note on reversal of warfarin toxicity.
        Ann Emerg Med. 1983; 12: 711
        • Brennan R.W.
        • Bergland R.M.
        Acute cerebellar hemorrhage.
        Neurology. 1977; 27: 527
        • Cairns J.A.
        • Collins R.
        • Fuster V.
        • et al.
        Coronary thrombolysis.
        Chest. 1989; 95: 73S
        • Califf R.M.
        • Topol E.J.
        • George B.S.
        • et al.
        Characteristics and outcome of patients in whom reperfusion with intravenous tissue-type plasminogen activator fails: Results of the thrombolysis and angioplasty in myocardial infarction (TAMI) I trial.
        Circulation. 1988; 77: 1090
        • Chakraborty A.K.
        • Dreisin R.B.
        Pulmonary hematoma secondary to anticoagulant therapy.
        Ann Intern Med. 1982; 96: 67
        • Chiu W.S.
        The syndrome of retroperitoneal hemorrhage and lumbar plexus neuropathy during anticoagulant therapy.
        South Med J. 1976; 69: 595
        • Chong B.H.
        • Fawaz I.
        • Chesterman N.
        • et al.
        Heparin-induced thrombocytopenia: Mechanism of interaction of the heparin-dependent antibody with platelets.
        Br J Haematol. 1989; 73: 235
        • Cimo P.L.
        • Moake J.L.
        • Weinger R.S.
        • et al.
        Heparin-induced thrombocytopenia: Association with a platelet-aggregating factor and arterial thrombosis.
        Am J Hematol. 1979; 6: 125
        • Cines D.B.
        • Kaywin P.
        • Bina M.
        • et al.
        Heparin-associated thrombocytopenia.
        N Engl J Med. 1980; 303: 788
        • Cipolle R.J.
        • Rodvold K.A.
        • Seifert R.
        • et al.
        Heparin-associated thrombocytopenia: A prospective evaluation of 211 patients.
        Ther Drug Monit. 1983; 5: 205
        • Cipolle R.J.
        • Seifert R.D.
        • Neilan B.A.
        • et al.
        Heparin kinetics: Variables related to disposition and dosage.
        Clin Pharmacol Ther. 1981; 29: 387
        • Cohen A.F.
        • Warman S.P.
        Upper airway obstruction secondary to warfarin-induced sublingual hematoma.
        Arch Otolaryngol Head Neck Surg. 1989; 115: 718
        • Cole M.S.
        • Minifee P.K.
        • Wolma F.J.
        Coumarin necrosis—a review of the literature.
        Surgery. 1988; 10: 271
        • Conlan M.G.
        • Bridges A.
        • Williams E.
        • et al.
        Familial type II protein C deficiency associated with warfarin-induced skin necrosis and bilateral adrenal hemorrhage.
        Am J Hematol. 1988; 9: 226
        • Conn J.W.
        • Rovner D.R.
        • Cohen E.L.
        • et al.
        Inhibition by heparinoid of aldosterone biosynthesis in man.
        J Clin Endocrinol. 1966; 26: 527
      1. Consensus Confeience: Fresh-frozen plasm?.
        JAMA. 1985; : 53-551
        • Conway E.M.
        • Bauer K.A.
        • Barzegar S.
        • et al.
        Suppression of hemostatic system ectivstion by oral anticoagulants in the blood of patients vdth thrombotic diatheses.
        J Clin Invest. 1987; 80: 535
        • Coon W.W.
        • Willis P.W.
        Hemorrhagic complications of anticoagulant therapy.
        Arch Intern Med. 1974; 133: 386
        • Cover D.E.
        • Torres V.E.
        • Hattery R.R.
        • et al.
        Bilateral hemorrhagic parapelvic pseudocysts.
        Am J Kidney Dis. 1988; 11: 343
        • Crabbe S.J.
        • Grimm A.M.
        • Hopkins L.E.
        Acylated plasminogen-streptokinase activator complex: A new approach to thrombolytic therapy.
        Pharmacotherapy. 1990; 10: 115
        • Cuttino J.T.
        • Clark R.L.
        • Feaster S.H.
        • et al.
        The evaluation of gross hematuria in anticoagulated patients.
        AJR. 1987; 149: 527
      2. Second ACCP conference on antithrombotic therapy.
        Chest. 1989; 95 (suppl): 1-1615
        • Doyle D.J.
        • Turpie G.G.
        • Hirsh J.
        • et al.
        Adjusted subcutaneous heparin or continuous intravenous heparin in patients with acute deep vein thrombosis: A randomized trial.
        Ann Intern Med. 1987; 107: 441
        • Duckert F.
        • Burkart F.
        • Hecker S.
        • et al.
        Controlled trial of urokinase myocardial infarction: A European collaborative study.
        Lancet. 1975; 2: 624
        • Earnshaw J.J.
        • Westby J.C.
        • Gregson R.H.S.
        • et al.
        Local thrombolytic therapy of acute peripheral arterial ischemia with tissue plasminogen activator: A dose ranging study.
        Br J Surg. 1988; 75: 1196
        • Edes T.E.
        • Sunderrajan E.V.
        Heparin-induced hyperkalemia.
        Arch Intern Med. 1985; 145: 1070
      3. Editorial Non-coronary thrombolysis.
        Lancet. 1990; 335: 691
        • Ellison M.J.
        • Sawyer W.T.
        • Mills T.C.
        Calculation of heparin dosage in a morbidly obese woman.
        Clin Pharm. 1989; 8: 65
        • Enger E.
        • Boyesen S.
        Long-term anticoagulant therapy in patients with cerebral infarction.
        Acta Med Scand. 1965; 178 ((suppl): 7
        • Feder W.
        • Auerbach R.
        “Purple toes”: an uncommon sequela of oral coumarin drug therapy.
        Ann Intern Med. 1961; 55: 911
        • Fell S.C.
        • Rubin I.L.
        • Enselberg C.D.
        • et al.
        Anticoagulant-induced hemopericardium with tamponade.
        N Engl J Med. 1965; 272: 670
        • Fennerty A.G.
        • Levine M.N.
        • Hirsh J.
        Hemorrhagic complications of thrombolytic therapy in the treatment of myocardial infarction and venous thromboembolism.
        Chest. 1989; 95: 88S
        • Fischer C.M.
        Anticoagulant therapy in cerebral thrombosis and cerebral embolism.
        Neurology. 1961; 11: 119
        • Franke C.L.
        • de Jonge J.
        • van Swieten J.C.
        • et al.
        Intracerebral hematomas during anticoagulant treatment.
        Stroke. 1990; 21: 726
        • Fraschini G.
        • Jadeja J.
        • Lawson M.
        • et al.
        Local infusion of urokinase for the lysis of thrombosis associated with permanent central venous catheters in cancer patients.
        J Clin Oncol. 1987; 5: 672
        • Glazier R.L.
        • Crowell E.B.
        Randomized prospective trial of continuous versus intermittent heparin therapy.
        JAMA. 1976; 236: 1365
        • Goa K.L.
        • Henwood J.M.
        • Stolz J.F.
        • et al.
        Intravenous streptokinase: A reappraisal of its therapeutic use in acute myocardial infarction.
        Drugs. 1990; 39: 693
        • Goldhaber S.Z.
        • Heit J.
        • Sharma G.V.RK.
        • et al.
        Randomized controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism.
        Lancet. 1988; 2: 293
        • Goldhaber S.Z.
        • Meyerovitz M.F.
        • Green D.
        • et al.
        Randomized controlled trial of tissue plasminogen activator in proximal deep venous thrombosis.
        Am J Med. 1990; 88: 235
        • Griffin P.H.
        • Schnure F.W.
        • Chopra S.
        • et al.
        Intramural gastrointestinal hemorrhage.
        JClin Gastroenterol. 1986; 8: 389
        • Gunnar R.M.
        • Bourdillon P.D.V.
        • Dixon D.W.
        • et al.
        AHA medical scientific statement special report: ACC/AHA guidelines for the early management of patients with acute myocardial infarction.
        Circulation. 1990; 82: 664
        • Habbab M.A.
        • Haft J.I.
        Heparin resistance induced by intravenous nitroglycerin.
        Arch Intern Med. 1987; 147: 857
        • Hall J.G.
        • Pauli R.M.
        • Wilson K.M.
        Maternal and fetal sequelae of anticoagulation during pregnancy.
        Am J Med. 1980; 68: 122
        • Hansten P.D.
        • Horn J.R.
        Oral anticoagulant drug interactions.
        Drug Interactions. 1989; : 710
        • Hartman A.R.
        • Hood R.M.
        • Anagnostopoulos C.E.
        Phenomenon of heparin-induced thrombocytopenia associated with skin necrosis.
        J Vase Surg. 1988; 7: 781
        • Hess H.
        • Mietaschk A.
        • Bruckl R.
        Peripheral arterial occlusions: A six-year experience with local low-dose thrombolytic therapy.
        Radiology. 1987; 163: 753
        • Hill J.
        • Caprini J.A.
        • Robins J.L.
        An unusual complication of minidose heparin therapy.
        Clin Orthop. 1976; 118: 130
        • Hirsh J.
        Mechanisms of action and monitoring of anticoagulants.
        Semin Thromb Hemost. 1986; 12: 1
        • Hirsh J.
        • Levine M.
        Confusion over the therapeutic range for monitoring anticoagulant therapy in North America.
        Thromb Haemost. 1988; 59: 129
        • Hirsh J.
        • Poller L.
        • Deykin D.
        • et al.
        Optimal therapeutic range for oral anticoagulants.
        Chest. 1989; 95 ((suppl): 5
        • Hochberg M.S.
        • Merrill W.H.
        • Gruber M.
        • et al.
        Delayed cardiac tamponade associated with prophylactic anticoagulation in patients undergoing coronary bypass grafting.
        J Thorac Cardiovasc Surg. 1978; 75: 777
        • Hodin E.
        • Dass T.
        Spontaneous retroperitoneal hemorrhage complicating anticoagulant therapy.
        Ann Surg. 1969; 170: 848
        • Hollander G.
        • Rothenberg R.
        • Greengart A.
        • et al.
        Full dose subcutaneous heparin therapy.
        NY State J Med. 1989; 89: 387
        • Horn J.R.
        • Danziger L.H.
        • Davis R.J.
        Warfarin-induced skin necrosis: Report of four cases.
        Am J Hosp Pharmacol. 1981; 38: 1763
        • Hrushesky W.J.
        Subcutaneous heparin-induced thrombocytopenia.
        Arch Intern Med. 1978; 138: 1489
        • Hull R.
        • Delmore T.
        • Carter C.
        • et al.
        Adjusted subcutaneous heparin versus warfarin sodium in the long-term treatment of venous thrombosis.
        N Engl J Med. 1982; 306: 189
        • Hull R.
        • Hirsh J.
        • Jay R.
        • et al.
        Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis.
        N Engl J Med. 1982; 307: 1676
        • Hull R.D.
        • Raskob G.E.
        • Rosenbloom D.
        • et al.
        Heparin for 5 days compared with 10 days in the initial treatment of proximal venous thrombosis.
        N Engl J Med. 1990; 322: 1260
        • Hurtubise M.R.
        • Bottino J.C.
        • Lawson M.
        • et al.
        Restoring patency of occluded central venous catheters.
        Arch Surg. 1980; 115: 212
        • Hyman B.T.
        • Landas S.K.
        • Ashman R.F.
        • et al.
        Warfarin-related purple toes syndrome and cholesterol microembolization.
        Am J Med. 1987; 82: 1233
        • Jaffin B.W.
        • Bliss C.M.
        • Lamont J.T.
        Significance of occult gastrointestinal bleeding during anticoagulation therapy.
        Am J Med. 1987; 83: 269
        • Jaques L.B.
        Heparins-anionic polyelectrolyte drugs.
        Pharmacol Rev. 1980; 31: 99
        • Johnson E.S.
        • Cregeen R.J.
        An interim report of the efficacy and safety of anisoylated plasminogen streptokinase activator complex (APSAC.
        Drugs. 1987; 33 ((suppl 3): 298
        • Kakkar V.V.
        • Lawrence D.
        Hemodynamic and clinical assessment after therapy for acute deep vein thrombosis: A prospective study.
        Am J Surg. 1985; 150 ((suppl 4A): 54
        • Kaplinsky N.
        • Thaler M.
        • Militianu J.
        • et al.
        Transient pulmonary infiltrates associated with warfarin [letter].
        JAMA. 1980; 243: 513
        • Kappa J.R.
        • Fisher C.A.
        • Berkowitz H.D.
        • et al.
        Heparin-induced platelet activation in 16 surgical patients: Diagnosis and management.
        J Vase Surg. 1987; 5: 101
        • Kappa J.R.
        • Fisher C.A.
        • Todd B.
        • et al.
        Intraoperative management of patients with heparin-induced thrombocytopenia.
        Ann Thorac Surg. 1990; 49: 714
        • Kase C.S.
        • Robinson R.K.
        • Stein R.W.
        • et al.
        Anticoagulant-related intracerebral hemorrhage.
        Neurology. 1985; 35: 943
        • Kazmier F.J.
        Current practice with vitamin K antagonist therapy.
        Mayo Clin Proc. 1974; 49: 918
        • Kelton J.G.
        • Sheridan D.
        • Santos A.
        • et al.
        Heparin-induced thrombocytopenia: Laboratory studies.
        Blood. 1988; 72: 925
        • King D.J.
        • Kelton J.G.
        Heparin-associated thrombocytopenia.
        Ann Intern Med. 1984; 100: 535
        • Klatte E.C.
        • Becker G.J.
        • Holden R.E.
        • et al.
        Fibrinolytic therapy.
        Radiology. 1986; 159: 619
        • Landefeld C.S.
        • Cook E.F.
        • Flatley M.
        • et al.
        Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy.
        Am J Med. 1987; 82: 703
        • Landefeld C.S.
        Major bleeding in outpatients treated with warfarin: Incidence and prediction by factors known at the start of outpatient therapy.
        Am j Med. 1989; 87: 144
        • Landefeld C.S.
        • Rosenblatt M.W.
        • Goldman L.
        Bleeding in outpatients treated with warfarin: Relation to the prothrombin time and important remediable lesions.
        Am J Med. 1989; 87: 153
        • Laster J.
        • Silver D.
        Heparin-coated catheters and heparin-induced thrombocytopenia.
        J Vase Surg. 1988; 7: 667
        • Lepor N.E.
        • Amin D.K.
        • Berberian L.
        • et al.
        Does nitroglycerin induce heparin resistance?.
        Clin Cardiol. 1989; 12: 432
        • Levesque H.
        • Verdier S.
        • Cailleux N.
        • et al.
        Low molecular weight heparins and hypoaldosteronism.
        Br Med J. 1990; 300: 1437
        • Levine E.L.
        • Bernstein J.E.
        • Soltani K.
        • et al.
        Heparin-induced cutaneous necrosis unrelated to injection sites.
        Arch Dermatol. 1983; 119: 400
        • Levine M.N.
        • Raskob G.
        • Hirsh J.
        Hemorrhagic complications of long-term anticoagulant therapy.
        Chest. 1989; 95: 26s
        • Lew A.S.
        • Laramee P.
        • Cercek B.
        • et al.
        The hypotensive effect of intravenous streptokinase in patients with acute myocardial infarction.
        Circulation. 1985; 72: 1321
        • Leyvraz P.F.
        • Jacques R.
        • Bachman F.
        • et al.
        Adjusted versus fixed-dose subcutaneous heparin in the prevention of deep vein thrombosis after hip replacement.
        N Engl J Med. 1983; 309: 954
        • Loeliger E.A.
        Progress in the control of oral anticoagulant therapy.
        Thromb Haemost. 1972; 28: 109
        • Loeliger E.A.
        • Broekmans A.W.
        Drugs affecting blood clotting, fibrinolysis, and hemostasis.
        Meyler’s Side Effects of Drugs. 1988; : 733
        • Makhoul R.G.
        • McCann R.I.
        • Aurtin P.H.
        • et al.
        Management of patients with heparin-associated thrombocytopenia requiring cardiac surgery.
        Ann Thorac Surg. 1987; 43: 617
        • Mant M.J.
        • Thong K.L.
        • Birtwhistle R.V.
        • et al.
        Hemorrhagic complications of heparin therapy.
        Lancet. 1977; 1: 1133
        • Marder V.J.
        • Sherry S.
        Thrombolytic therapy: Current status (first of two parts.
        N Engl J Med. 1988; 318: 1512
        • Marder V.J.
        • Sherry S.
        Thrombolytic therapy: Current status (second of two parts.
        N Engl J Med. 1988; 318: 1585
        • Mattie H.
        • Kohler S.
        • Huber P.
        • et al.
        Anticoagulation-related intracranial extracerebral hemorrhage.
        J Neurol Neurosurg Psych. 1989; 52: 829
        • McGehee W.G.
        • Klotz T.A.
        • Epstein D.J.
        • et al.
        Coumadin necrosis associated with hereditary protein C deficiency.
        Ann Intern Med. 1984; 101: 59
        • McLean M.R.
        • Hause L.L.
        The effect of bovine lung heparin on normal human platelets as measured by electronic particle size analysis.
        Thromb Haemost. 1982; 47: 5
        • Moldveen-Geronimus M.
        • Merriam J.C.
        Cholesterol embolization.
        Circulation. 1967; 35: 946
        • Monk J.P.
        • Heel R.C.
        Anisoylated plasminogen streptokinase activator complex (APSAC): A review of its mechanism of action, clinical pharmacology and therapeutic use in acute myocardial infarction.
        Drugs. 1987; 34: 25
        • Mosley D.H.
        • Schatz I.J.
        • Breneman G.M.
        • et al.
        Long-term anticoagulant therapy.
        JAMA. 1963; 186: 914
        • Moss J.
        • Jarchow R.C.
        Laryngeal complication of warfarin sodium therapy.
        Otolaryngol Head Neck Surg. 1988; 98: 354
        • Munger M.A.
        • Forrence E.A.
        Anistreplase: A new thrombolytic for the treatment of acute myocardial infarction.
        Clin Pharm. 1990; 9: 530
        • Myers T.M.
        • Hull R.D.
        • Weg J.G.
        Antithrombotic therapy for venous thromboembolic disease.
        Chest. 1989; 95
        • Nalbandian R.M.
        • Beller F.K.
        • Kamp A.K.
        • et al.
        Coumarin necrosis of skin treated successfully with heparin.
        Obstet Gynecol. 1971; 38: 395
        • Nidorf M.
        • Thompson P.L.
        Coronary Thrombolysis: An important therapy for myocardial infarction.
        Med J Aust. 1988; 149: 376
        • O’Reilly R.A.
        • Aggeler P.M.
        Covert anticoagulant ingestion: Study of 25 patients and review of world literature.
        Medicine. 1976; 55: 389
        • O’Toole R.D.
        Heparin: Adverse reaction (letter.
        Ann Intern Med. 1973; 79: 159
        • Olinger G.N.
        • Hussey C.V.
        • Olive J.A.
        • et al.
        Cardiopulmonary bypass for patients with previously documented heparin-induced platelet aggregation.
        J Thorac Cardiovasc Surg. 1984; 87: 673
        • Poller L.
        A simple nomogram for the derivation of international normalised ratios for the standardisation of prothrombin times.
        Thromb Haemost. 1988; 60: 18
        • Poller L.
        • McKernan A.
        • Thomson J.M.
        • et al.
        Fixed minidose warfarin: A new approach to prophylaxis against venous thrombosis after major surgery.
        Br Med J [Clin Res]. 1987; 295: 1309
        • Rao R.H.
        • Vagnucci A.H.
        • Amico J.A.
        Bilateral massive adrenal hemorrhage: Early recognition and treatment.
        Ann Intern Med. 1989; 110: 227
        • Reussi C.
        • Schiave J.E.
        • Altman R.
        • et al.
        Unusual complications in the course of anticoagulant therapy.
        Am J Med. 1969; 46: 460
        • Rogers L.Q.
        • Lutcher C.L.
        Streptokinase therapy for deep vein thrombosis: A comprehensive review of the English literature.
        Am J Med. 1990; 88: 389
        • Ruckley C.V.
        • Boulton F.E.
        • Redhead D.
        The treatment of venous thrombosis of the upper and lower limbs with APSAC (p-anisoylated streptokinase-plasminogen complex.
        Eur J Vase Surg. 1987; 1: 107
        • Sadjadpour K.
        Hazards of anticoagulation therapy shortly after lumbar puncture [letter].
        JAMA. 1977; 237: 1692
        • Salzman E.W.
        • Deykin D.
        • Shapiro R.M.
        • et al.
        Hemorrhagic complications of heparin therapy.
        N Engl J Med. 1975; 292: 1046
        • Sane D.C.
        • Califf R.M.
        • Topol E.J.
        • et al.
        Bleeding during thrombolytic therapy for acute myocardial infarction: Mechanisms and management.
        Ann Intern Med. 1989; 111: 1010
        • Saour J.N.
        • Sieck J.O.
        • Layla A.R.M.
        • et al.
        Trial of different intensities of anticoagulation in patients with prosthetic heart valves.
        N Engl J Med. 1990; 322: 428
        • Schreiber T.L.
        • Miller D.H.
        • Silvasi D.
        • et al.
        Superiority of warfarin over aspirin long term after thrombolytic therapy for acute myocardial infarction.
        Am Heart J. 1990; 119: 1238
        • Scott W.W.
        • Fishman E.K.
        • Siegelman S.S.
        Anticoagulants and abdominal pain.
        JAMA. 1984; 252: 2053
        • Sheridan D.
        • Carter C.
        • Kelton J.C.
        A diagnostic test for heparin-induced thrombocytopenia.
        Blood. 1986; 67: 27
        • Silverstein A.
        Neurological complications of anticoagulation therapy.
        Arch Intern Med. 1979; 139: 217
        • Simon H.B.
        • Daggett W.M.
        • DeSanctis R.W.
        Hemothorax as a complication of anticoagulant therapy in the presence of pulmonary infarction.
        JAMA. 1969; 208: 1830
        • Simon T.
        • Bell W.
        • Black E.B.
        • et al.
        Urokinase-streptokinase embolism trial.
        JAMA. 1974; 229: 1606
        • Simoons M.L.
        Thrombolytic therapy in acute myocardial infarction.
        Ann Rev Med. 1989; 40: 181
        • Smith P.
        • Arnesen H.
        • Holme I.
        The effect of warfarin on mortality and reinfarction after myocardial infarction.
        N Engl J Med. 1990; 323: 147
        • Sonnenblick M.
        • Jacobsohn W.
        Hyper-transaminasemia with heparin therapy.
        Br J Med. 1975; 3: 77
        • Stanton P.E.
        • Wilson J.P.
        • Lamis P.A.
        • et al.
        Acute abdominal conditions induced by anticoagulant therapy.
        Am Surg. 1974; 40: 1
        • Sukthomya C.
        • Levin B.
        Pseudotumors of kidney secondary to anticoagulant therapy.
        Radiology. 1967; 88: 701
        • Taberner D.A.
        • Thomson J.M.
        • Poller L.
        Comparison of prothrombin complex concentrate and vitamin K in oral anticoagulant reversal.
        Br Med J. 1976; 2: 83
        • Tabibian N.
        Acute gastrointestinal bleeding in anticoagulated patients: A prospective evaluation.
        Am J Gastroenterol. 1989; 84: 10
        • Talstad I.
        Heparin therapy adjusted for body weight.
        Am J Clin Pathol. 1985; 83: 378
        • Theroux P.
        • Ouimet H.
        • McCans J.
        • et al.
        Aspirin, heparin, or both to treat acute unstable angina.
        N Engl J Med. 1988; 319: 1105
        • Tiefenbrunn A.J.
        • Ludbrook P.A.
        Coronary thrombolysis—it’s worth the risk.
        JAMA. 1989; 261: 2107
        • Towne J.B.
        • Bernhard V.M.
        • Hussey C.
        • et al.
        White clot syndrome: Peripheral vascular complications of heparin therapy.
        Arch Surg. 1979; 114: 372
        • van Breda A.
        • Eatzen B.T.
        • Deutsch A.S.
        Urokinase versus streptokinase in local thrombolysis.
        Radiology. 1987; 165: 109
        • Verstrsece M.
        Use of •fhrombclytic drugs in non-coronary disorders.
        Drugs. 1989; 38: 801
        • Verstrsece M.
        • Bory M.
        • Collen D.
        • ec a.l.
        Randomised trial of intravenous recombinant tissue-type plasminogen activator versus intravenous streptokinase in acute myocardial infarction.
        Lancet. 1985; 1: 842
        • Walker A.M.
        • Jick H.
        Predictors of bleeding during heparin therapy.
        JAMA. 1980; 244: 1209
        • Wall T.C.
        • Phillips H.R.
        • Stack R.S.
        • et al.
        Results of high dose intravenous urokinase for acute myocardial infarction.
        Am J Cardiol. 1990; 65: 124
        • Warkentin T.E.
        • Kelton J.G.
        Heparin-induced thrombocytopenia.
        Ann Rev Med. 1989; 40: 31
        • Wei J.Y.
        • Markis J.E.
        • Malagold M.
        • et al.
        Cardiovascular reflexes stimulated by reperfusion of ischemic myocardium in acute myocardial infarction.
        Circulation. 1983; 67: 796
        • Wheeler A.P.
        • Jaquiss R.D.
        • Newman J.H.
        Physician practices in the treatment of pulmonary embolism and deep venous thrombosis.
        Arch Intern Med. 1988; 148: 1321
      4. Hematology. 1990; : 1576
        • Wilson I.D.
        • Goetz F.C.
        Selective hypoaldosteronism after prolonged heparin administration.
        Am J Med. 1964; 36: 635
        • Wintzen A.R.
        • de Jong H.
        • Loeliger E.A.
        • et al.
        The risk of intracerebral hemorrhage during oral anticoagulant treatment: A population study.
        Ann Neurol. 1984; 16: 553
        • Wintzen A.R.
        • Tijssen J.G.P.
        Subdural hematoma and oral anticoagulant therapy.
        Arch Neurol. 1982; 39: 69
        • Zeller F.P.
        • Spinier S.A.
        Alteplase: A tissue plasminogen activator for acute myocardial infarction.
        Drug Intelligence and Clinical Pharmacy. 1988; 22: 6
        • Zimran A.
        • Shilo S.
        • Fisher D.
        • et al.
        Histomorphometric evaluation of reversible heparin-induced osteoporosis in pregnancy.
        Arch Intern Med. 1986; 146: 386
        • Zuccarello M.
        • Scanarini M.
        • D’Avella D.
        • et al.
        Spontaneous spinal extradural hematoma during anticoagulant therapy.
        Surg Neurol. 1980; 14: 411
        • Zweifler A.J.
        Relation of prothrombin concentration to bleeding during oral anticoagulant therapy.
        N Engl J Med. 1962; 267: 283