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

Goldhaber, Samuel Z.; Meyerovitz, Michael F.; Braunwald, Eugene; Green, David; Vogelzang, Robert L.; Citrin, Paul; Heit, John A.; Sobel, Michael; Wheeler, H. Brownell; Plante, Dennis A.; Kim, Hugh; Hopkins, Alan R.; Tufte, Margaret; Stump, David C.

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

Cited by 147 publications

(66 citation statements)

References 27 publications

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“…Moreover, the spectrum of indications for thrombolytic drugs such as streptokinase or recombinant tissue plasminogen activator (rtPA) comprises lung embolism, ischemic stroke, deep-vein thrombosis and acute arterial occlusions of the lower limbs [17, 18, 19, 20]. In contrast, the use of thrombolytic agents in retinal vessel occlusion is in its infancy, although several studies have indicated that fibrinolysis may be associated with a better visual prognosis in CRVO [21, 22, 23, 24, 25].…”

Section: Introductionmentioning

confidence: 99%

Visual Outcome after Treatment with Low-Dose Recombinant Tissue Plasminogen Activator or Hemodilution in Ischemic Central Retinal Vein Occlusion

et al. 1999

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The ischemic type of central retinal vein occlusion (CRVO) is associated with a poor visual and ocular prognosis. Although several reports have indicated that hemodilution or thrombolytic therapy may be of benefit, there is still no consensus among ophthalmologists about the management of this disorder. In our study, we retrospectively evaluated the visual outcome after medical treatment in 58 patients with ischemic CRVO and severe visual loss (≤20/50). We separately investigated three different groups, depending on the following criteria: onset of symptoms within 11 days prior to admission and thrombolytic treatment with 50 mg of recombinant tissue plasminogen activator (rtPA) and intravenous heparinization (n = 23) or hemodilution therapy (n = 22) or onset of symptoms >11 days before the initial visit and hemodilution (n = 13). An advancement of 2 or more lines on the logarithmic visual acuity chart was noted in 10 cases (44%) in the rtPA group and in 3 subjects (14%) in the early-phase hemodilution group, whereas only 1 patient in the late-phase hemodilution group showed a comparable improvement. Our findings suggest that treatment with low-dose rtPA or hemodilution aimed at early restoration of blood flow has the potential to improve the visual prognosis in ischemic CRVO. The finding that thrombolysis had a favorable outcome supports the hypothesis that specific subgroups of patients may benefit from this therapeutic approach. Further investigation will be required to definitively prove the effectiveness of fibrinolytic agents.

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Section: Introductionmentioning

confidence: 99%

Visual Outcome after Treatment with Low-Dose Recombinant Tissue Plasminogen Activator or Hemodilution in Ischemic Central Retinal Vein Occlusion

et al. 1999

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“…In deep venous thrombosis treated with tissue plasminogen activator (TPA), nearly two thirds of patients have minimal or no significant lysis evident on repeat venography at 24 hours. 4,5 In patients with pulmonary embolism, TPA restores blood flow within 24 hours to only about a third of occluded lung segments, as judged by serial perfusion scanning. 6,7 In grim contrast to the therapeutic successes seen in patients treated for acute myocardial infarction with TPA, those treated for pulmonary embolism with TPA show no proven reduction in mortality.…”

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confidence: 99%

“…10 Although heparin accelerates inhibition of thrombin and factor Xa by antithrombin, it does not accelerate endogenous fibrinolysis, in vitro or in patients. [5][6][7] Plasminogen activators are the only agents currently available for accelerating the degradation of thrombi (ie, causing clots to undergo lysis faster than they would dissolve by endogenous fibrinolysis). Plasminogen activators convert plasminogen to plasmin, the fibrinolytic enzyme that degrades the thrombus.…”

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confidence: 99%

The Contribution of Activated Factor XIII to Fibrinolytic Resistance in Experimental Pulmonary Embolism

Reed

Houng

1999

Circulation

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Background —The resistance of thrombi to fibrinolysis induced by plasminogen activators remains a major impediment to the successful treatment of thrombotic diseases. This study examines the contribution of activated factor XIII (factor XIIIa) to fibrinolytic resistance in experimental pulmonary embolism. Methods and Results —The fibrinolytic effects of specific inhibitors of factor XIIIa–mediated fibrin-fibrin cross-linking and α2-antiplasmin–fibrin cross-linking were measured in anesthetized ferrets with pulmonary emboli. Five experimental groups were treated with heparin (100 U/kg) and/or tissue plasminogen activator (TPA, 1 mg/kg) and the percent (mean±SD) lysis of emboli was determined: (1) control, normal factor XIIIa activity (14.1±4.8% lysis); (2) inhibited factor XIIIa activity (42.7±7.4%); (3) normal factor XIIIa activity+TPA (32.3±7.7%); (4) inhibited factor XIIIa activity+TPA (76.0±11.9%); and (5) inhibited α2-antiplasmin–fibrin cross-linking+TPA (54.7±3.9%). Inhibition of factor XIIIa activity increased endogenous lysis markedly (group 1 versus 2; P <0.0001), to a level comparable to that achieved with TPA (group 2 versus 3; P <0.05). Among groups receiving TPA, selective inhibition of factor XIII-mediated α2-antiplasmin–fibrin cross-linking enhanced lysis (group 3 versus 5; P <0.0005). Complete inhibition of factor XIIIa also amplified lysis (group 3 versus 4; P <0.0001) and had greater effects than inhibition of α2-antiplasmin cross-linking alone (group 4 versus 5; P <0.0005). No significant fibrinogen degradation occurred in any group. Conclusions —Factor XIIIa–mediated fibrin-fibrin and α2-antiplasmin–fibrin cross-linking both caused experimental pulmonary emboli to resist endogenous and TPA-induced fibrinolysis. This suggests that factor XIIIa may play a critical role in regulating fibrinolysis in human thrombosis.

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“…As discussed above, recurrent VTE is associated with the development of PTS. Finally, small randomized trials have observed the use of contemporary surgical venous thrombectomy and systemic thrombolysis to be associated with reduced PTS rates compared with anticoagulation alone, but at the price of greater invasiveness and more complications, including major bleeding (36)(37)(38)(39)(40)(41)(42).…”

Section: Noninterventional Methods To Prevent Ptsmentioning

confidence: 99%

Endovascular Interventions for Acute and Chronic Lower Extremity Deep Venous Disease: State of the Art

Sista

Vedantham

Kaufman³

et al. 2015

Radiology

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

Cited by 147 publications

References 27 publications

Visual Outcome after Treatment with Low-Dose Recombinant Tissue Plasminogen Activator or Hemodilution in Ischemic Central Retinal Vein Occlusion

Visual Outcome after Treatment with Low-Dose Recombinant Tissue Plasminogen Activator or Hemodilution in Ischemic Central Retinal Vein Occlusion

The Contribution of Activated Factor XIII to Fibrinolytic Resistance in Experimental Pulmonary Embolism

Endovascular Interventions for Acute and Chronic Lower Extremity Deep Venous Disease: State of the Art

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