Acute Pulmonary Embolism Treated With Tissue Plasminogen Activator

Blood samples from 24 patients who received recombinant human tissue-type plasminogen activator (rt-PA) for angiographically documented acute pulmonary embolism were examined to identify and quantify fibrinolysis. Before and after the intravenous administration of 50 mg rt-PA over a 2 hr period, levels of total fibrinogen, fibrin(ogen) degradation products (FDP), and cross-linked fibrin degradation products (XDP) were measured in each patient. Elevated levels of XDP were found in all patients before treatment (mean 2.0 ,ug/ml, normal < 0.2 ,ug/ml), and these increased 12-fold with treatment. Fibrinogen levels fell 30% and FDP levels increased 24-fold for the entire group of patients. Over this 2 hr period, 10 of 24 patients (responders) demonstrated 25% or greater improvement in the extent of pulmonary artery thrombus as quantified by Urokinase Pulmonary Embolism Trial score, and these patients were found to have a significantly lower XDP/FDP ratio after rt-PA (p < .04) than those patients who failed to respond. These data suggest that (1) the intravenous administration of pharmacologic doses of rt-PA in patients with pulmonary embolism produces both fibrinolysis and fibrinogenolysis, (2) successful thrombolysis in these patients is associated with a preponderance of fibrinogenolysis over fibrinolysis, (3) the XDP/FDP ratio is a useful indicator of fibrinolytic specificity, and (4) in patients with acute pulmonary embolism the endogenous fibrinolytic pathways are activated, albeit ineffectively, as indicated by the increased circulating XDP levels seen in all 24 patients before the administration of rt-PA.

Section: Methodsmentioning

confidence: 99%

Recombinant tissue plasminogen activator in patients with pulmonary embolism: correlation of fibrinolytic specificity and efficacy.

Vaughan¹,

Goldhaber²,

Kim³

et al. 1987

“…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. 6,7 Indeed, some experts suggest that the mortality of pulmonary embolism, despite more modern therapies, has remained unchanged for the past 30 years.…”

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confidence: 99%

“…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. 6,7 Indeed, some experts suggest that the mortality of pulmonary embolism, despite more modern therapies, has remained unchanged for the past 30 years. 8,9 Because improved thrombolysis could translate to reduced mortality and morbidity, there is a pressing need for a better understanding of the causes of fibrinolytic resistance.…”

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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%

See 1 more Smart Citation

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

Reed

Houng

1999

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.

“…These devices remove, fragment, macerate, or aspirate the embolic mass, resulting in smaller particles that eventually migrate to the periphery of the pulmonary circulation and thereby improve central hemodynamics. 96 The goal is rapid relief of central obstruction, based on the premise that the cross-sectional area of the distal arterioles is several times that of the proximal pulmonary vessels. 97,98 Under certain circumstances, thrombectomy devices can be used in conjunction with catheter-directed lysis.…”

Section: Percutaneous Embolectomymentioning

confidence: 99%

Invasive Approaches to Treatment of Venous Thromboembolism

Augustinos

Ouriel

2004

Abstract-Deep vein thrombosis (DVT) occurs in one-quarter of a million individuals annually in the United States and results in significant disability from pulmonary embolism and chronic venous insufficiency, especially when the proximal iliofemoral is involved. Treatment has centered on early institution of adequate anticoagulation to prevent thrombus propagation and embolism, but anticoagulation alone does not always restore venous patency and many patients are left with venous outflow obstruction and valvular incompetence-the anatomic underpinnings of the postthrombotic syndrome. Various strategies have been used to restore patency of thrombosed veins, including open surgical thrombectomy, pharmacological thrombolysis, and percutaneous mechanical thrombectomy. Each modality has benefits and shortcomings. Surgical thrombectomy had previously been abandoned secondary to poor long-term results.More recently, with improved techniques and better patient selection, surgical thrombectomy has regained a therapeutic role in treating acute DVT in young patients with short segment occlusions. The advent of percutaneous techniques has allowed thrombolysis, percutaneous mechanical thrombectomy, and stenting to be used in conjunction with each other-allowing for better resolution of venous clot burden than when an individual modality is used alone. Practitioners who treat patients with DVT should be familiar with all the options available to restore venous patency, preserve valvular function, and thereby minimize the risk of late postthrombotic complications.