Increasing age is a major risk factor for hemorrhagic complications after pulmonary embolism thrombolysis

doi:10.1016/S0002-8703(97)70108-X

American Heart Journal

Volume 134, Issue 1, July 1997, Pages 69-72

https://doi.org/10.1016/S0002-8703(97)70108-X Get rights and content

Abstract

We reviewed our database of 312 patients with pulmonary embolism who received thrombolysis in five clinical trials. At baseline, none had a history of stroke, internal bleeding within 6 months, surgery within 10 days, or occult blood in stool. Sixty-six major bleeding episodes occurred within 72 hours of administering thrombolysis in 61 (20%) patients: bleeding at the catheterization site (34 cases), gross hematuria (9), intracranial hemorrhage (5), and 18 other bleeding episodes that led to at least a 10% hematocrit decrease. Patients with a major bleeding complication were on average older than patients with no hemorrhagic complication (mean age 62.9 ± 1.9 years vs 56.2 ± 1.1 years; p = 0.005). In an adjusted analysis, there was a fourfold increased risk of bleeding among patients older than 70 years compared with patients younger than 50 years (relative risk [RR] 3.9; 95% confidence interval [CI] 1.7 to 8.9). By using age as a continuous variable, we found a 4% (RR 1.04; 95% CI 1.02 to 1.06) increase in risk of bleeding for each incremental year of age. In addition, patients with higher body mass index had an increased risk of bleeding. Patients who had undergone catheterization had a five times greater risk of bleeding (RR 5.2; 95% CI 1.5 to 17.8). In summary, increasing age, larger body mass index, and catheterization predisposed to bleeding complications after pulmonary embolism thrombolysis. (Am Heart J 1997;134:69-72.)

Section snippets

Methods

Goldhaber et al. 1, 2, 3, 4, 5, 6, 7 have undertaken five multicenter trials of thrombolytic therapy for pulmonary embolism between 1985 and 1994. Data on all patients were combined to create the database for this overview. Of the 373 patients, 55 from the fourth trial were excluded from this analysis because they were randomized to receive heparin alone. ⁶ An additional six patients were excluded because they did not actually receive a thrombolytic agent in spite of randomization assignment.

Discussion

We found that increased age (>70 years) is an important risk factor for a hemorrhagic complication after pulmonary embolism thrombolysis in a population that has already been screened for standard bleeding risk factors. An increased risk of bleeding also was associated with increasing BMI and catheterization. It appears that a high concentration of TPA or urokinase given over a short period results in fewer bleeding complications than does a moderate concentration of a thrombolytic agent

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The mortality associated with high-risk pulmonary embolism (PE) is remarkably high, and reperfusion to unload right ventricle should be a priority. However, several registries report reperfusion underuse. In Portugal, epidemiological data about the incidence, rate of reperfusion and mortality of high-risk PE are not known.
Nationwide population-based temporal trend study in the incidence and outcome of high-risk PE, who were admitted to hospitals of the National Health Service in Portugal between 2010 and 2018. High-risk PE was defined as patients with PE who developed cardiogenic shock or cardiac arrest. International Classification of Diseases (ICD), 9th and 10th revision, Clinical Modification codes, were used for data from the period between 2010 and 2016 (ICD-9-CM) and 2017–2018 (ICD-10-CM), respectively. The assessment focused on trends in the use of reperfusion treatment, which was defined by application of thrombolysis or pulmonary embolectomy. A comparison was made between the use or non-use of reperfusion therapy in order to examine trends in in-hospital mortality among high-risk PE cases.
From 2010 and 2018, there were 40.311 hospitalization episodes for PE in adult patients at hospitals of the National Health Service in mainland Portugal. There was a significant increase in the annual incidence of PE (41/100.000 inhabitants in 2010 to 46/100.000 in 2018; R²=0.582, p = 0.010). The average annual incidence was 45/100.000 inhabitants/year, with 2,7% of the PE episodes (1104) categorized as high-risk. The mortality rate associated with high-risk PE was high, although it has decreased over the years (74.2% in 2010 to 63.6% in 2018; R²=0.484; p = 0.022). Thrombolytic therapy was underused in high-risk PE, and its usage has not increased in recent years (17.3% in 2010 to 21.1% in 2018, R²=-0.127; p = 0.763). Surgical pulmonary embolectomy was used in 0.27% of cases, and there was no registry of catheter-directed thrombolysis. Patients with high-risk PE undergoing reperfusion therapy had lower in-hospital mortality compared to non-reperfused patients (OR=0.52; IC95% 0.38–0.70).
In Portugal, between 2010 and 2018, very few patients with PE developed high-risk forms of the disease, but the mortality rate among those patients was high. The low reperfusion rate could be associated with high in-hospital mortality and highlights the need to implement advanced therapies, as an alternative to systemic thrombolysis.
Major in-hospital bleeding in patients with pulmonary embolism treated with systemic thrombolysis
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2020, Revista Clinica Espanola
La correcta estratificación del riesgo de la embolia pulmonar (EP) es esencial para la toma de decisiones, en cuanto al tratamiento y para definir el lugar de ingreso del paciente. En la EP de riesgo alto se requiere un restablecimiento urgente de la circulación pulmonar e ingreso en una unidad de críticos. El tratamiento de reperfusión de elección es la trombólisis sistémica, aunque en determinadas situaciones, sobre todo cuando existe contraindicación para esta, valoraremos realizar una embolectomía quirúrgica o alguna de las terapias guiadas por catéter. En el resto de EP, el tratamiento de elección será la anticoagulación. En la actualidad, los anticoagulantes orales de acción directa han pasado a ser el tratamiento de elección para el tratamiento de la EP, por su mejor perfil de seguridad, aunque las heparinas de bajo peso molecular seguidas de los antivitaminas K siguen siendo el tratamiento más utilizado, por el hecho de estar financiados por el sistema público. En los casos de EP con parada cardiorrespiratoria o shock cardiogénico, siempre que esté disponible en nuestro centro, deberemos considerar la indicación de la extracorporeal membrane oxygenation (ECMO). La reciente creación de los equipos de respuesta multidisciplinar (PERT team) han supuesto una mejoría en la atención de los pacientes con EP de riesgo intermedio-alto y alto. Durante el seguimiento de los pacientes con EP, es imprescindible realizar un correcto cribado de la hipertensión pulmonar tromboembólica crónica, para poder realizar un correcto abordaje diagnóstico y, en el caso que lo precisase, terapéutico.
The correct stratification of pulmonary embolism risk (PE) is essential for decision-making, regarding treatment and defining the patient's place of admission. In high-risk PE, urgent re-establishment of pulmonary circulation and admission to a critical unit is required. The reperfusion treatment of choice is systemic thrombolysis, although in certain situations, especially when there is a contraindication for it, we will evaluate a surgical embolectomy or one of the catheter-guided therapies. In the rest of PE, the treatment of choice will be anticoagulation. Currently, direct oral anticoagulants have become the treatment of choice for the treatment of PE, due to their better safety profile. However, low molecular weight heparins and subsequently antivitamins K, remain the most used treatment, because they are funded by the public system. In cases of PE with cardiorespiratory arrest and / or cardiogenic shock, whenever available at our center, we must consider the indication of extracorporeal membrane oxygenation. The recent creation of PE response teams (PERT team), have meant an improvement in the care of patients with intermediate-high and high risk PE. During the follow-up of patients with PE, it is essential to perform a correct screening of chronic thromboembolic pulmonary hypertension, in order to perform a correct diagnostic and therapeutic approach.
Thrombolysis in Pulmonary Embolism: An Evidence-Based Approach to Treating Life-Threatening Pulmonary Emboli
2020, Critical Care Clinics
Technical success and short-term outcomes after treatment of lower extremity deep vein thrombosis with the ClotTriever system: A preliminary experience
2020, Journal of Vascular Surgery: Venous and Lymphatic Disorders
Citation Excerpt :
In patients with contraindications to thrombolysis or those in need of immediate clot removal, the device may have a comparative advantage when compared with preexisting strategies. Intravenous thrombolysis has been shown to have a significantly increased risk of hemorrhagic complications for patients with acute pulmonary embolus or stroke who are more than 80 years old and it is relatively contraindicated in this cohort.24,25 Pregnant women require unique attention in the management of acute thrombotic conditions owing to their hypercoagulable state, increased risk of postpartum hemorrhage, and potential effect of thrombolysis on the fetus.26
Deep vein thrombosis (DVT) may be associated with significant pain, swelling and the development of post-thrombotic syndrome. Early clot removal is facilitated by the use of percutaneous mechanical thrombectomy devices. Current techniques, however, vary in rates of technical success and in some cases are limited by the concomitant need for thrombolytics. An alternative percutaneous venous thrombectomy system (ClotTriever, Inari Medical, Irvine, Calif) may be helpful in the management of lower extremity DVT without the concomitant use of thrombolytics.
A retrospective review of patients treated for DVT using the device was conducted. Demographics, initial presentation, and perioperative course were recorded. Outcomes after treatment were extracted from clinical records. Technical success was defined as complete clot evacuation after intervention.
Twelve patients were included in the study. The cohort was 50% female (6 patients) with a mean age of 55.6 years (range, 32-86 years). Two patients (16.7%) presented with chronic asymptomatic DVT who developed symptoms from an acute, recurrent iliofemoral DVT over the days before presentation. One patient (8.4%) presented with phlegmasia cerulea dolens, with the remaining patients presenting with disabling pain and swelling. Access was obtained via the popliteal vein (11 patients) and small saphenous vein (1 patient). Lytic therapy was not used in any case. Complete clot evacuation was obtained in all patients in a single session without repeat interventions. Symptom resolution before discharge was achieved in 100% of cases. There was no incidence of postoperative anemia (mean hemoglobin, 10.7 g/dL preoperatively vs 10.4 g/dL postoperatively) or acute kidney failure (mean creatinine, 0.86 mg/dL preoperatively vs 0.81 mg/dL postoperatively). The average length of stay was 2 days (range, 1-4 days) without the need for intensive care admission. At early follow-up, 11 patients (91.7%) continued to report significant symptom resolution. Two of 10 patients (20%) developed recurrent occlusive DVTs on follow-up duplex ultrasound examination.
This novel percutaneous venous thrombectomy system is safe and effective for removing large volumes of lower extremity acute thrombus in a single session, without the need for lytic therapy, intensive care unit admission, or repeat intervention. Further studies are warranted to determine mid-term and long-term outcomes.
Pulmonary Embolism in 2017: How We Got Here and Where Are We Going?
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In the 1970s, both the Urokinase Pulmonary Embolism and Urokinase-Streptokinase Pulmonary Embolism trials began the quest to develop thrombolytic therapy for the treatment of acute massive and submassive pulmonary embolism (PE). The goals of these studies were the immediate reduction in clot burden, restoration of hemodynamic stability, and improved survival. Major bleeding became the major barrier for clinicians to employ these therapies. From 1980s to the present time, a number of studies using recombinant tissue-type plasminogen activator for achieving these same above outcomes were completed but major bleeding continued to remain an adoption barrier. Finally, the concept of bringing the thrombolytic agent into the clot has entered the quest for the Holy Grail in the treatment of PE. This article will review all the major trials using peripheral thrombolysis and provide insight into the need for a team approach to pulmonary care (Pulmonary Embolism Response Team), standardization of pulmonary classification, and the need for trials designed for both short- and long-term outcomes using thrombolysis for selected PE populations.

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^☆: From School of Medicine, Lund University, Hospital of University of Pennsylvania, Harvard Medical School, Beth Israel Hospital, and Brigham and Women’s Hospital.

^☆☆: Reprint requests: Samuel Z. Goldhaber, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115.

^★: 0002-8703/97/$5.00 + 0 4/1/82318

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Increasing age is a major risk factor for hemorrhagic complications after pulmonary embolism thrombolysis☆,☆☆,★

Abstract

Section snippets

Methods

Discussion

Lancet

J Am Coll Cardiol

Lancet

J Am Coll Cardiol

Lancet

Chest

J Am Coll Cardiol