Thrombolytic therapy in acute venous thromboembolism

Abstract Although anticoagulation remains the mainstay of treatment of acute venous thromboembolism (VTE), the use of thrombolytic agents or thrombectomy is required to immediately restore blood flow to thrombosed vessels. Nevertheless, systemic thrombolysis has not clearly been shown to improve outcomes in patients with large clot burdens in the lung or legs as compared with anticoagulation alone; this is in part due to the occurrence of intracranial hemorrhage in a small percentage of patients to whom therapeutic doses of a thrombolytic drug are administered. Algorithms have been developed to identify patients at high risk for poor outcomes resulting from large clot burdens and at low risk for major bleeding in an effort to improve outcomes in those receiving thrombolytic therapy. In acute pulmonary embolism (PE), hemodynamic instability is the key determinant of short-term survival and should prompt consideration of immediate thrombolysis. In hemodynamically stable PE, systemic thrombolysis is not recommended and should be used as rescue therapy if clinical deterioration occurs. Evidence is accumulating regarding the efficacy of administering reduced doses of thrombolytic agents systemically or via catheters directly into thrombi in an effort to lower bleed rates. In acute deep venous thrombosis, catheter-directed thrombolysis with thrombectomy can be used in severe or limb-threatening thrombosis but has not been shown to prevent postthrombotic syndrome. Because the management of acute VTE can be complex, having a rapid-response team (ie, PE response team) composed of physicians from different specialties may aid in the management of severely affected patients.

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Clinical Outcomes of May–Thurner Syndrome in Pediatric Patients: A Single Institutional Experience

TH Open ◽

10.1055/s-0040-1714694 ◽

2020 ◽

Vol 04 (03) ◽

pp. e189-e196

Author(s):

Deepti M. Warad ◽

Amulya Nageswara Rao ◽

Haraldur Bjarnason ◽

Vilmarie Rodriguez

Keyword(s):

Pediatric Patients ◽

Retrospective Chart Review ◽

Signs And Symptoms ◽

Adjunctive Treatment ◽

Bleeding Complications ◽

Postthrombotic Syndrome ◽

Common Iliac Vein ◽

Endovascular Stents ◽

Systemic Thrombolysis ◽

Catheter Directed Thrombolysis

Abstract Introduction May–Thurner syndrome (MTS) is a vascular anatomic variant resulting in compression of the left common iliac vein by the right common iliac artery, affecting approximately 22% of the population. In adults, following acute deep vein thrombosis (DVT) of the iliofemoral veins, the incidence of postthrombotic syndrome (PTS) and recurrent DVT are high if treated with anticoagulation alone, warranting adjunctive treatment with thrombolysis and stent placement. However, there is paucity of literature documenting the course of treatment and associated outcomes in pediatric patients with MTS. Methods A retrospective chart review of pediatric patients (≤ 18 years of age) with radiologic confirmation of MTS with or without DVT evaluated and/or treated at our institution from January 1, 2005 through December 31, 2015 was conducted. Results Seventeen patients (4 male; 13 female) were identified. Median age was 15.4 years (range 8.8–17.1 years) with a median follow-up of 1.2 years (range 0.4–7.5 years). Thirteen (76.5%) patients presented with left lower extremity DVT. Management included catheter-directed thrombolysis (n = 5), systemic thrombolysis (n = 1), and mechanical thrombectomy (n = 1). Fifteen patients were treated with anticoagulation including two patients with endovascular stents without DVT. Median duration of anticoagulation was 6.3 months (range 3.2–18.7 months). Ten patients (59%) underwent stent placements.Complete and partial thrombus resolution was noted in six patients each and no resolution in one patient. Four patients had recurrence/progression of thrombus (n = 3 with stents) at a median time of 29 days (range 12–495 days). No bleeding complications were observed. Clinically documented or self-reported PTS was noted in 8 patients (62%). Conclusion There are no clear guidelines for MTS management in children and adolescents. In our cohort, thrombolysis, anticoagulation, or stent placements were not associated with bleeding risks, with recurrence/progression of DVT and signs and symptoms of PTS noted in 30 and 62%, respectively. Further studies are needed to determine a standardized treatment approach of the pediatric patient with MTS with or without thrombosis.

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Urban-Rural Variation in Use of Thrombolytic Therapy for Pulmonary Embolism

Blood ◽

10.1182/blood-2019-125493 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3409-3409

Author(s):

Jeremy Y Feng ◽

Charles B Ross ◽

Rachel P Rosovsky

Keyword(s):

Pulmonary Embolism ◽

Thrombolytic Therapy ◽

Research Funding ◽

Diagnosis Related Groups ◽

Severity Of Illness ◽

Primary Diagnosis ◽

Systemic Thrombolysis ◽

Catheter Directed Thrombolysis ◽

Urban Rural ◽

Block Test

Background: Thrombolytic therapy is widely accepted for persistent hypotension or shock due to acute pulmonary embolism (PE), with randomized and observational studies demonstrating earlier hemodynamic improvement and possible mortality benefit. The extent to which thrombolytic therapy is used in urban versus non-urban settings is unclear. Methods: We conducted a retrospective cohort study of 92,706 (unweighted) and 180,189 (weighted) admissions with primary diagnosis of PE, for patient aged 18 years and above, that occurred in 2016, at all general acute-care hospitals within the 27 states included in the Nationwide Readmissions Database (NRD). Admissions for primary PE diagnosis and their respective severity levels (minor, moderate, major, extreme) were identified using the All Patient Refined Diagnosis Related Groups. We identified systemic and catheter-directed thrombolytic use using ICD-10-PCS codes. Hospital locations were classified as metropolitan (population ≥50K), micropolitan (10K-50K), and noncore (<10K). National estimates were calculated using post-stratification weights designed to compensate for any over- or under-represented hospital types in the NRD relative target universe of all hospitals in the U.S. PROC SURVEYFREQ and SURVEYLOGISTICS (SAS 9.4) were used to account for complex sampling design in variance calculations. Results: Of all primary PE admissions, 89.5% (95% CI, 88.7-90.2%) occurred at hospitals in metropolitan, 8.0% (95% CI, 7.3-8.7%) in micropolitan, and 2.6% (95% CI, 2.3-2.8%) in noncore areas. Rates of systemic thrombolytic use differed by location: 2.5% (95% CI, 2.3-2.6%) of admissions in metropolitan, 1.1% (95% CI, 0.7-1.4%) in micropolitan, and 0.1% (95% CI, 0-0.3%) in noncore areas (P<.001 for block test; Figure 1). Rates of catheter-directed thrombolytic use also differed: 2.4% (95% CI, 2.1-2.8%) of admissions in metropolitan, 1.5% (95% CI, 0.5-2.5%) in micropolitan, and 0.1% (95% CI, 0-0.2%) in noncore areas (P<.001 for block test). Differences persisted after adjusting for severity of illness for both approaches of thrombolysis (P<.001 in each block test of hospital location). Of patients with highest severity (major and extreme), systemic thrombolysis occurred in 4.0% (95% CI, 3.7-4.3%) of admissions in metropolitan, 1.9% (95% CI, 1.2-2.6%) in micropolitan, and 0.5% (95% CI, 0-1.1%) in noncore hospitals. In this same population, catheter-directed thrombolysis occurred in 2.4% (95% CI, 2.1-2.8%) of admissions in metropolitan, 1.5% (95% CI 0.5-2.5%) in micropolitan, and 0.1% (95% CI, 0-0.2%) in noncore hospitals. Conclusion: There was significant variation in use of systemic and catheter-directed thrombolysis for pulmonary embolism by hospital location. Thrombolytic therapy was rarely reported among noncore hospitals and occurred at a substantially lower rate at micropolitan than at metropolitan hospitals even when adjusted for illness severity. Implications: Efforts should be directed to understand drivers of urban-rural differences in use of thrombolytic therapies (e.g., knowledge, experience, support, resources) to identify potential levers to increase appropriate use of thrombolytic therapy particularly at hospitals in smaller, non-metropolitan communities. Disclosures Rosovsky: Janssen Pharmaceuticals: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Dova Pharmaceuticals: Consultancy.

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Pulmonary embolism: update on management and controversies

BMJ ◽

10.1136/bmj.m2177 ◽

2020 ◽

pp. m2177 ◽

Cited By ~ 2

Author(s):

Lisa Duffett ◽

Lana A Castellucci ◽

Melissa A Forgie

Keyword(s):

Pulmonary Embolism ◽

Risk Factor ◽

Venous Thromboembolism ◽

Recurrent Events ◽

Vitamin K Antagonists ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Therapeutic Options ◽

Systemic Thrombolysis ◽

Catheter Directed Thrombolysis ◽

Increased Risk

ABSTRACTPulmonary embolism is a common and potentially fatal cardiovascular disorder that must be promptly diagnosed and treated. The diagnosis, risk assessment, and management of pulmonary embolism have evolved with a better understanding of efficient use of diagnostic and therapeutic options. The use of either clinical probability adjusted or age adjusted D-dimer interpretation has led to a reduction in diagnostic imaging to exclude pulmonary embolism. Direct oral anticoagulation therapies are safe, effective, and convenient treatments for most patients with acute venous thromboembolism, with a lower risk of bleeding than vitamin K antagonists. These oral therapeutic options have opened up opportunities for safe outpatient management of pulmonary embolism in selected patients. Recent clinical trials exploring the use of systemic thrombolysis in intermediate to high risk pulmonary embolism suggest that this therapy should be reserved for patients with evidence of hemodynamic compromise. The role of low dose systemic or catheter directed thrombolysis in other patient subgroups is uncertain. After a diagnosis of pulmonary embolism, all patients should be assessed for risk of recurrent venous thromboembolism to guide duration of anticoagulation. Patients with a venous thromboembolism associated with a strong, transient, provoking risk factor can safely discontinue anticoagulation after three months of treatment. Patients with an ongoing strong risk factor, such as cancer, or unprovoked events are at increased risk of recurrent events and should be considered for extended treatment. The use of a risk prediction score can help to identify patients with unprovoked venous thromboembolism who can benefit from extended duration therapy. Despite major advances in the management of pulmonary embolism, up to half of patients report chronic functional limitations. Such patients should be screened for chronic thromboembolic pulmonary hypertension, but only a small proportion will have this as the explanation of their symptoms. In the remaining patients, future studies are needed to understand the pathophysiology and explore interventions to improve quality of life.

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Pulmonary Embolism and Postoperative Care

Cardiothoracic Critical Care ◽

10.1093/med/9780190082482.003.0006 ◽

2020 ◽

pp. 59-72

Author(s):

Daniel Haines ◽

Joel Grigsby

Keyword(s):

Pulmonary Embolism ◽

Thrombolytic Therapy ◽

Right Ventricular ◽

Treatment Options ◽

Right Ventricular Dysfunction ◽

Myocardial Necrosis ◽

Systemic Thrombolysis ◽

Catheter Directed Thrombolysis ◽

The Stability ◽

Acute Pe

This chapter assesses pulmonary embolism (PE), which is an obstruction of the pulmonary circulation by an occlusive material. The material may be thrombus, air, tumor, or fat. PE are classified as acute, subacute, or chronic; but they can be further classified into massive and submassive. Submassive PE is defined as an acute PE without systemic hypotension but with either right ventricular dysfunction or myocardial necrosis, while massive PE is defined as an acute PE with sustained shock. There are several strategies for treating PE depending on the stability of the patient and the location of the clot. Systemic thrombolysis, catheter-directed thrombolysis, and catheter-directed clot removal are all treatment options, if there are no contraindications. Bleeding risk is the largest contraindication for thrombolytic therapy. Meanwhile, surgical embolectomy is warranted for hemodynamically unstable patients as well as patients with contraindications to or who failed thrombolytic therapy and catheter-based approaches. Right ventricular failure is a serious complication following pulmonary embolectomy and is managed by a compilation of volume removal, inotropic support, pulmonary vasodilation, and mechanical support, if needed.

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Pragmatic Use of Catheter-Directed Thrombolysis in Venous Thromboembolism and a Comparative Evaluation With Traditional Therapies in Submassive Pulmonary Embolism

Journal of Pharmacy Practice ◽

10.1177/08971900211004833 ◽

2021 ◽

pp. 089719002110048

Author(s):

Mary Bradley ◽

Todd Bull ◽

Peter Hountras ◽

Robert MacLaren

Keyword(s):

Pulmonary Embolism ◽

Venous Thromboembolism ◽

Hospital Mortality ◽

Group Versus ◽

Chart Audit ◽

Systemic Thrombolysis ◽

Ivc Filters ◽

Catheter Directed Thrombolysis ◽

Submassive Pulmonary Embolism ◽

Traditional Therapies

Background: Catheter-directed thrombolysis (CDT) is a novel treatment for venous thromboembolism (VTE). Limited data describe pragmatic use of CDT and compare CDT to other VTE therapies. Objective: Assess the use of CDT and comparatively evaluate CDT, anticoagulation, and systemic thrombolysis in submassive pulmonary embolism (PE). Methods: Retrospective, single-center, chart audit. Part 1 described all patients who received CDT for VTE. Part 2 matched patients with submassive PE who received CDT, heparin, or systemic thrombolysis and assessed length of stay (LOS), bleeding, all cause in-hospital mortality, and escalation of care. Results: For part 1, 70 CDT patients were identified; 42 with DVT and 28 with PE. ICU LOS was longer (2.5 ± 2.9 vs. 4.9 ± 8.4 days, p = 0.07), escalation of care more frequent (0% vs. 35.7%, p < 0.0001), and hospital mortality greater (2.4% vs. 21.4%, p = 0.014) in the PE group. For part 2, 21 CDT patients were matched to 21 heparin and 21 systemic thrombolysis patients. All CDT and tPA patients were admitted to the ICU versus only 6 (28.6%, p < 0.001) heparin patients. ICU LOS was significantly longer in the CDT group versus systemic tPA and systemic anticoagulation (80.7 ± 64.1 vs. 48.2 ± 27.7 vs. 24.9 ± 59.1 hours; p = 0.0048). More IVC filters and thrombectomies were performed in the CDT group. Conclusions: CDT is frequently used for both DVT and PE and requires ICU admission. Escalation of care is common when CDT is used for PE. For submassive PE, CDT is associated with prolonged ICU LOS compared to heparin or systemic thrombolysis. Resource utilization with CDT requires further evaluation.

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Local and systemic thrombolytic therapy for acute venous thromboembolism

Clinics in Chest Medicine ◽

10.1016/s0272-5231(02)00051-5 ◽

2003 ◽

Vol 24 (1) ◽

pp. 73-91 ◽

Cited By ~ 25

Author(s):

Selim M Arcasoy ◽

Anil Vachani

Keyword(s):

Venous Thromboembolism ◽

Thrombolytic Therapy ◽

Systemic Thrombolytic Therapy ◽

Acute Venous Thromboembolism

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Thrombolysis for Venous Thromboembolism During Pregnancy: A Literature Review

Vascular and Endovascular Surgery ◽

10.1177/1538574418777822 ◽

2018 ◽

Vol 52 (7) ◽

pp. 527-534 ◽

Cited By ~ 5

Author(s):

Vy T. Ho ◽

Anahita Dua ◽

Kedar Lavingia ◽

Kara Rothenberg ◽

Christina Rao ◽

...

Keyword(s):

Venous Thromboembolism ◽

Literature Review ◽

Complication Rate ◽

Mechanical Thrombectomy ◽

Maternal Complication ◽

Systemic Thrombolysis ◽

Catheter Directed Thrombolysis ◽

Pubmed Database ◽

Fetal Complications ◽

In Pregnancy

Background: Pregnancy is a hypercoagulable state, conferring an increased risk of venous thromboembolism (VTE). However, treatment algorithms for deep venous thrombosis and pulmonary embolism are based on studies of nonpregnant patients. Methods: A literature review of cases in which thrombolysis was used for the treatment of VTE during pregnancy was conducted using the PubMed (National Institutes of Health) database. Results: A PubMed database search of English language articles for reports of thrombolysis for the treatment of VTE in pregnancy identified 215 cases, including 183 cases of systemic thrombolysis, 19 cases of catheter-directed thrombolysis, and 13 cases of mechanical thrombectomy. For systemic thrombolysis, the maternal complication rate was 4.40% and the fetal complication rate was 1.65%. For catheter-directed thrombolysis, the maternal complication rate was 14.75% and the fetal complication rate was 5.2%. In cases of mechanical thrombectomy, there were no reported maternal or fetal complications. Conclusions: Although conservative strategies are preferred in pregnancy, thrombolysis is an adjunct for limb or life-threatening VTE. Review of past reports suggests low rates of maternal and fetal complications following systemic thrombolysis and mechanical thrombectomy but higher rates of complications after catheter-directed thrombolysis in the treatment of VTE during pregnancy.

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Risk Factors for Bleeding during Treatment of Acute Venous Thromboembolism

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650643 ◽

1996 ◽

Vol 76 (05) ◽

pp. 682-688 ◽

Cited By ~ 33

Author(s):

Jos P J Wester ◽

Harold W de Valk ◽

Karel H Nieuwenhuis ◽

Catherine B Brouwer ◽

Yolanda van der Graaf ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Surface Area ◽

Body Surface Area ◽

Body Surface ◽

Small Body ◽

Bleeding Risk ◽

Risk Scores ◽

Risk Of Bleeding ◽

Acute Venous Thromboembolism

Summary Objective: Identification of risk factors for bleeding and prospective evaluation of two bleeding risk scores in the treatment of acute venous thromboembolism. Design: Secondary analysis of a prospective, randomized, assessor-blind, multicenter clinical trial. Setting: One university and 2 regional teaching hospitals. Patients: 188 patients treated with heparin or danaparoid for acute venous thromboembolism. Measurements: The presenting clinical features, the doses of the drugs, and the anticoagulant responses were analyzed using univariate and multivariate logistic regression analysis in order to evaluate prognostic factors for bleeding. In addition, the recently developed Utrecht bleeding risk score and Landefeld bleeding risk index were evaluated prospectively. Results: Major bleeding occurred in 4 patients (2.1%) and minor bleeding in 101 patients (53.7%). For all (major and minor combined) bleeding, body surface area ≤2 m2 (odds ratio 2.3, 95% Cl 1.2-4.4; p = 0.01), and malignancy (odds ratio 2.4, 95% Cl 1.1-4.9; p = 0.02) were confirmed to be independent risk factors. An increased treatment-related risk of bleeding was observed in patients treated with high doses of heparin, independent of the concomitant activated partial thromboplastin time ratios. Both bleeding risk scores had low diagnostic value for bleeding in this sample of mainly minor bleeders. Conclusions: A small body surface area and malignancy were associated with a higher frequency of bleeding. The bleeding risk scores merely offer the clinician a general estimation of the risk of bleeding. In patients with a small body surface area or in patients with malignancy, it may be of interest to study whether limited dose reduction of the anticoagulant drug may cause less bleeding without affecting efficacy.

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