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Incidence and predictors of major hemorrhagic complications from thrombolytic therapy in patients with massive pulmonary embolism

      Abstract

      PURPOSE: The risk factors for bleeding in patients receiving recombinant tissue-type plasminogen activator for massive pulmonary embolism are not known.
      PATIENTS AND METHODS: The hospital records of 132 consecutive patients who received recombinant tissue-type plasminogen activator for massive pulmonary embolism were retrospectively reviewed. Bleeding was estimated by using the bleeding severity index, a method previously validated in patients receiving anticoagulants. Multivariate stepwise logistic regression was used to identify independent risk factors for bleeding. Four other definitions of bleeding in large pulmonary embolism thrombolytic trials were also used, and the agreement among these criteria was assessed.
      RESULTS: According to the bleeding severity index, 33 patients (25%) had one or more major bleeding complications. Hemorrhage at the venous puncture site for angiography was the most frequent complication (15 patients, 11%). Major bleeding at the catheterization site was more common at the femoral site (14 of 63 patients = 22%) than at the brachial site (1 of 63 patients = 2%; P = 0.0004). The use of the five different bleeding definitions resulted in a variation in the major bleeding rate from 3% to 43%. The kappa coefficient varied from 0.07 to 0.84, indicating poor agreement between most of the classifications.
      CONCLUSION: The use of the femoral vein for pulmonary angiography was the only variable significantly associated with major bleeding. Most of the differences observed in the pulmonary embolism thrombolytic trials are likely related to the differences in the definition of bleeding rather than to the thrombolytic regimen.
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      References

        • Goldhaber S.Z
        • Haire W.D
        • Feldstein M.L
        • et al.
        Alteplase versus heparin in acute pulmonary embolism.
        Lancet. 1993; 341: 507-511
        • McIntyre K.M
        • Sasahara A.A
        Hemodynamic and ventricular responses to pulmonary embolism.
        Prog Cardiovasc Dis. 1974; 17: 175-190
        • Dalla-Volta S
        • Palla A
        • Santolicandro A.M
        • et al.
        PAIMS 2.
        J Am Coll Cardiol. 1992; 20: 520-526
        • Meyer G
        • Sors H
        • Charbonnier B
        • et al.
        Effects of intravenous urokinase versus alteplase on total pulmonary resistance in acute massive pulmonary embolism.
        J Am Coll Cardiol. 1992; 19: 239-245
        • Sors H
        • Pacouret G
        • Azarian R
        • et al.
        Hemodynamic effects of bolus vs 2h infusion of alteplase in acute massive pulmonary embolism.
        Chest. 1994; 106: 712-717
        • Levine M.N
        • Goldhaber S.Z
        • Gore J.M
        • et al.
        Hemorrhagic complications of thrombolytic therapy in the treatment of myocardial infarction and venous thromboembolism.
        Chest. 1995; 108: 291S-301S
        • Landefeld C.S
        • McGuire III, E
        • Rosenblatt M.W
        A bleeding risk index for estimating the probability of major bleeding in hospitalized patients starting anticoagulant therapy.
        Am J Med. 1990; 89: 569-578
        • De Jaegere P
        • Arnold A.A
        • Balk A.H
        • Simoons M.L
        Intracranial hemorrhage in association with thrombolytic therapy.
        J Am Coll Cardiol. 1992; 19: 289-294
        • Gore J.M
        • Granger C.B
        • Simoons M.L
        • et al.
        Stroke after thrombolysis.
        Circulation. 1995; 92: 2811-2818
        • Simoons M.L
        • Maggioni A.P
        • Knatterud G
        • et al.
        Individual risk assessment for intracranial haemorrhage during thrombolytic therapy.
        Lancet. 1993; 342: 1523-1528
        • Kanter D.S
        • Mikkola K.M
        • Patel S.R
        • et al.
        Thrombolytic therapy for pulmonary embolism. Frequency of intracranial hemorrhage and associated risk factors.
        Chest. 1997; 111: 1241-1245
        • Stein P.D
        • Hull R.D
        • Raskob G
        Risks for major bleeding from thrombolytic therapy in patients with acute pulmonary embolism.
        Ann Intern Med. 1994; 121: 313-317
        • Mikkola K.M
        • Patel S.R
        • Parker J.A
        • et al.
        Increasing age is a major risk factor for hemorrhagic complications after pulmonary embolism thrombolysis.
        Am Heart J. 1997; 134: 69-72
        • Meyer G
        • Charbonnier B
        • Stern M
        • et al.
        Thrombolysis in acute pulmonary embolism.
        in: Julian D.G Kubler W Norris R.M Swan H.J Collen D Verstraete M Thrombolysis in Cardiovascular Disease. Marcel Dekker, New York1989: 337-360
        • Miller G.A.H
        • Sutton G.C
        • Kerr I.H
        • et al.
        Comparison of streptokinase and heparin in treatment of isolated acute massive pulmonary embolism.
        Br Med J. 1971; 2: 681-684
        • Meyer G
        • Collignon M.A
        • Guinet F
        • et al.
        Comparison of perfusion lung scanning and angiography in the estimation of vascular obstruction in acute pulmonary embolism.
        Eur J Nucl Med. 1990; 17: 315-319
        • Landefeld C.S
        • Anderson P.A
        • Goodnough L.T
        • et al.
        The bleeding severity index.
        J Clin Epidemiol. 1989; 42: 711-718
      1. The Urokinase Pulmonary Embolism Trial. A National Cooperative Study. Circulation 1973;47:1–108S.

        • Levine M
        • Hirsh J
        • Weitz J
        • et al.
        A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism.
        Chest. 1990; 98: 1473-1479
        • Goldhaber S.Z
        • Agnelli G
        • Levine M.N
        Reduced dose bolus alteplase vs. conventional alteplase infusion for pulmonary embolism thrombolysis. An international multicentre randomized study.
        Chest. 1994; 106: 718-724
        • Norusis M.J
        Logistic regression analysis.
        in: SPSS-X Advanced Statistics Student Guide. SPSS, Chicago1990: 119-146
        • Cohen J
        A coefficient of agreement for nominal scales.
        Educ Psych Meas. 1960; 20: 37-46
        • The GUSTO investigators
        An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction.
        NEJM. 1993; 329: 673-682
      2. Gruppo Italiano per lo studio della Sofravvivenza nell’Infarto Miocardico GISSI-2. A factorial randomized trial of anistreplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Lancet 1990;336:65–81.

      3. ISIS 3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41 299 cases of suspected acute myocardial infarction. Lancet 1992;339:753–770.

        • Collins R
        • Peto R
        • Baigent C
        • Sleight P
        Aspirin, heparin, and fibrinolytic therapy in suspected acute myocardial infarction.
        NEJM. 1997; 336: 847-860
        • Goldhaber S.Z
        • Kessler C.M
        • Heit J
        • et al.
        Randomised controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism.
        Lancet. 1988; ii: 293-298
        • Goldhaber S.Z
        • Kessler C.M
        • Heit J.A
        • et al.
        Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism.
        J Am Coll Cardiol. 1992; 20: 24-30
        • Perrier A
        • Bounameaux H
        • Morabia A
        • et al.
        Diagnosis of pulmonary embolism by a decision analysis-based strategy including clinical probability, D-Dimer levels, and ultrasonography.
        Arch Intern Med. 1996; 156: 531-536
        • The UKEP study research group
        The UKEP study.
        Eur Heart J. 1987; 8: 2-10
        • Verstraete M
        • Miller G.A.H
        • Bounameaux H
        • et al.
        Intravenous and intrapulmonary recombinant tissue-type plasminogen activator in the treatment of acute massive pulmonary embolism.
        Circulation. 1988; 77: 353-360