Randomized controlled trial of tissue plasminogen activator in proximal deep venous thrombosis

doi:10.1016/0002-9343(90)90148-7

The American Journal of Medicine

Volume 88, Issue 3, March 1990, Pages 235-240

https://doi.org/10.1016/0002-9343(90)90148-7 Get rights and content

Abstract

purpose: To compare the efficacy and safety of recombinant human tissue-type plasminogen activator (rt-PA, supplied as Activase®) with heparin alone or rt-PA plus heparin in the treatment of venographiacally documented proximal deep venous thrombosis (DVT) of the leg.

patients and methods: Sixty-four patients underwent 65 randomizations to rt-PA alone (n = 36), rt-PA plus heparin (n = 17), or heparin alone (n = 12) in a prospective, multicenter, randomized, open-label trial, with efficacy assessed by a radiology panel unaware of treatment assignment. Patients randomly assigned to rt-PA received 0.05 mg/kg/hour for 24 hours via a peripheral vein, with a maximum dose of 150 mg. All patients then received heparin and warfarin for the remainder of the hospitalization. Follow-up venography was performed 24 to 36 hours after initiation of therapy.

results: Complete or more than 50 % lysis occurred in 10 (28%) patients treated with rt-PA, five (29%) patients with rt-PA plus heparin, and no patient treated with heparin. No lysis occurred in 16 (44%) patients treated with rt-PA plus heparin, and 10 (83%) patients who received heparin alone (p = 0.04). There was one major complication, a nonfatal intracranial hemorrhage in a patient who received rt-PA alone. At 7 to 10 days after initiation of treatment, the level of serum glutamic oxaloacetic transaminase nearly doubled among all patients, including those assigned to received heparin alone.

conclusion: (1) rt-PA and rt-PA plus heparin cause more clot lysis than heparin alone; (2) the addition of heparin to rt-PA does not improve the lysis rate; (3) DVT treated with heparin is commonly associated with a rise in the transaminase level; (4) heparin does not increase the risk of bleeding from rt-PA therapy; and (5) alternative dosing regimens and modes of administration of rt-PA should be investigated to improve further its efficacy and safety in the treatment of acute DVT.

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Citation Excerpt :
The use of thrombolysis should be rare for patients with DVT limited to veins below the common femoral vein. We identified 11 systematic reviews119-129 and 19 randomized trials (n = 1944).130-148 Trials included individuals with objectively confirmed symptomatic proximal DVT.
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Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support patients, clinicians, and others in decisions about treatment of VTE.
Methods: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and adult patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment.
Results: The panel agreed on 28 recommendations for the initial management of VTE, primary treatment, secondary prevention, and treatment of recurrent VTE events.
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Clinical studiesRandomized controlled trial of tissue plasminogen activator in proximal deep venous thrombosis

Abstract

Lancet

Am J Med

Lancet

Lancet

Thromb Res

Blood

Lancet

Chest

Thrombolysis with human extrinsic (tissue-type) plasminogen activator in dogs with femoral vein thrombosis

J Clin Invest

Thrombolysis with human extrinsic (tissue-type) plasminogen activator in rabbits with experimental jugular vein thrombosis

J Clin Invest

A comparison of the thrombolytic and hemorrhagic effects of tissue-type plasminogen activator and streptokinase in rabbits

Circulation

The Thrombolysis in Myocardial Infarction (TIMI) Trial

N Engl J Med

Roentgen diagnosis of venous thrombosis in the leg

Arch Surg

Monitoring of hemostasis parameters during coronary thrombolysis with recombinant tissue-type plasminogen activator

Thromb Haemost

Gerinnungsphysiologische schnelimethode zur bestimmung des fibrinogens

Acta Haematol

A rapid, simple, sensitive method for measuring fibrinolytic split products in human serum

Clinical studies
Randomized controlled trial of tissue plasminogen activator in proximal deep venous thrombosis