scholarly journals Submassive Pulmonary Embolism: Current Perspectives and Future Directions

2021 ◽  
Vol 10 (15) ◽  
pp. 3383
Author(s):  
Phillip C. Nguyen ◽  
Hannah Stevens ◽  
Karlheinz Peter ◽  
James D. McFadyen
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Thrombolytic Therapy ◽  
Current Evidence ◽  
Conflicting Evidence ◽  
Submassive Pulmonary Embolism ◽  
High Risk Disease ◽  
Systemic Thrombolytic Therapy ◽  
Meta Analyses

Submassive pulmonary embolism (PE) lies on a spectrum of disease severity between standard and high-risk disease. By definition, patients with submassive PE have a worse outcome than the majority of those with standard-risk PE, who are hemodynamically stable and lack imaging or laboratory features of cardiac dysfunction. Systemic thrombolytic therapy has been proven to reduce mortality in patients with high-risk disease; however, its use in submassive PE has not demonstrated a clear benefit, with haemodynamic improvements being offset by excess bleeding. Furthermore, meta-analyses have been confusing, with conflicting results on overall survival and net gain. As such, significant interest remains in optimising thrombolysis, with recent efforts in catheter-based delivery as well as upcoming studies on reduced systemic dosing. Recently, long-term cardiorespiratory limitations following submassive PE have been described, termed post-PE syndrome. Studies on the ability of thrombolytic therapy to prevent this condition also present conflicting evidence. In this review, we aim to clarify the current evidence with respect to submassive PE management, and also to highlight shortcomings in current definitions and prognostic factors. Additionally, we discuss novel therapies currently in preclinical and early clinical trials that may improve outcomes in patients with submassive PE.

scholarly journals Systemic Thrombolytic Therapy for Massive and Submassive Pulmonary Embolism

2018 ◽  
Vol 33 (1) ◽  
pp. 74-89 ◽  
Author(s):  
Lauren A. Igneri ◽  
John M. Hammer
Keyword(s):  
Pulmonary Embolism ◽  
Thrombolytic Therapy ◽  
English Language ◽  
Right Ventricular Dysfunction ◽  
Hemodynamic Instability ◽  
Minor Bleeding ◽  
Increased Risk ◽  
Submassive Pulmonary Embolism ◽  
Systemic Thrombolytic Therapy

Objective: To critically evaluate the published literature assessing the safety and efficacy of thrombolytic therapy for massive and submassive pulmonary embolism (PE). Methods: A search of human trials in the English-language (September 2017) was conducted through the MEDLINE database using the following terms: PE, tissue plasminogen activator, tenecteplase, and alteplase. 67 unique articles were identified, of which 24 clinical trials discussing clinical outcomes related to administration of either intravenous tenecteplase or alteplase were included. Results: Thrombolytic therapy with anticoagulation significantly reduced mortality compared to anticoagulation alone in massive PE. In submassive PE, thrombolytics reduced the rate of right ventricular dysfunction and hemodynamic collapse; however, there is an increased risk of major and minor bleeding with no benefit on long-term functional outcomes. Conclusions: Patients with massive PE should receive thrombolytics when no major contraindications to therapy exist. Patients with submassive PE at highest risk for progression to hemodynamic instability should receive anticoagulation and be monitored for clinical deterioration. If an imminent risk of hemodynamic instability or cardiac arrest occurs, thrombolytics should be administered if no contraindications exist. Net mortality benefit and risk of bleeding must be considered when deciding to administer thrombolytic therapy in massive or submassive PE.

scholarly journals Coagulation properties of the blood coagulation system in acute pulmonary embolism and their dynamics against the background of systemic thrombolytic therapy for patients with different risk of hospital mortality

2020 ◽  
Vol 27 (1) ◽  
pp. 27-38
Author(s):  
O. A. Koval ◽  
O. M. Klygunenko ◽  
O. Yu. Muryzina
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Thrombolytic Therapy ◽  
Mortality Risk ◽  
Fibrinolytic Activity ◽  
Acute Pulmonary Embolism ◽  
Activated Partial Thromboplastin Time ◽  
Systemic Thrombolytic Therapy ◽  
Group 2 ◽  
Group 1

The aim – to evaluate the dynamics of blood coagulation changes in patients with acute pulmonary embolism before and after systemic thrombolytic therapy (TLT), by comparing high and intermediate-high risk groups. Materials and methods. 45 patients, 29 male (62 %) and 17 female (38 %), 55.6±13.6 years old admitted into an intensive care unit with the first episode of acute PE and received systemic thrombolysis, were included into prospective nonrandomized investigation. Accoding to the ESC Guideline on pulmonary embolism (2014) these patients were split into two groups: unstable high-risk pulmonary embolism patients having or hypotension or episodes of syncope (group 1, n=28, 62 %), and patients with intermediate-high mortality risk with stable hemodynamic indexes (group 2, n=17, 38 %) but with massive bilateral embolism (U1-2=2.2, p=0.33), verified by multispiral computed tomography pulmonary angiography (angio-regimen), hemodynamically overload, with signs of right and ventricular dysfunction and positive troponin tests. The 30-day mortality risk for PESI corresponds to Grade V (IV): 152 ± 19 points in group 1, 138.0±9.7 in group 2 (p1-2<0.01). Results and discussion. In both groups, a similar (p1-2>0.25) initial procoagulant status was revealed by changes in thrombin formation indexes: prothrombin time (PT) increased to 19.8 [16, 23] sec, and prothrombin index increased to 96.1 % [86, 106], reduction of activated partial thromboplastin time to 23.5 [21, 24] sec. The content of the main coagulation substrate fibrinogen increased up to 4.3 [4.1, 4.5] g/l (p1-2=0.25), and markers of thrombinemia increased as follows: soluble fibrin up to 17.0 [16, 18] mg, D-dimer up to 5214 [3605, 5643] ng/ml. The systemic fibrinolytic activity was initially suppressed: the values of spontaneous fibrinolysis were reduced to 9.5 [6.0, 12.2] %, self-retraction – to 31.9 [26.1, 36.1] %. On the 5th day after the TLT on the background of basic therapy, the following dynamics was observed: increase of (Z=5.62, p<0.00001) activated partial thromboplastin time values – up to 46.1 ± 6.0 s (p1-2=0.36) and PT – up to 22.9 (18–26) s, while fibrinogen decreased – down to 3.5 g/l. Despite favorable changes, markers of thrombinemia remained increased: although fibrin values decreased (Z=3.03, p<0.001) to 13.7 mg, but still exceeded the upper limit of the reference range in both groups (p1-2=0.21). The values of spontaneous fibrinolysis increased to 11.9 % [9.9, 12.4], and self-retraction (Z=0.64, p<0.01) to 32.0 % [27.9, 33.0], remaining significantly lower than the reference level and indicating high risk of relapse of thromboembolic events. Conclusions. For patients with acute pulmonary embolism, regardless of the presence of high or intermediate-high risk, according to the main coagulation indexes, the procoagulant state of hemostasis, inhibition of fibrinolytic activity, decrease in clot density in vitro are identical in strength and direction. On the 5th day after TLT on the basic anticoagulation therapy and despite a certain level of therapeutic anticoagulation, a rather high level of markers of thrombinemia, inhibition of fibrinolysis and retraction persists. The presence of the same coagulation changes in strength and orientation, the depletion of fibrinolytic mechanisms of hemostasis, the positive clinical impact of TLT in the intermediate-high risk group supports indications for TLT in this group of patients.

scholarly journals The Analysis of Long-Term Results and Quality of Life in Patients with Massive Pulmonary Embolism in the Course of Treatment with Thrombolytic and Anticoagulant Drugs

2019 ◽  
Vol 8 (3) ◽  
pp. 274-278
Author(s):  
A. G. Pronin
Keyword(s):  
Quality Of Life ◽  
Pulmonary Embolism ◽  
Pulmonary Hypertension ◽  
High Risk ◽  
Thrombolytic Therapy ◽  
Early Death ◽  
Massive Pulmonary Embolism ◽  
Long Term Results

Relevance Chronic post-embolic pulmonary hypertension (CPEPH) is a complication of pulmonary thromboembolism found almost in every 10th patient. A special risk group consists of patients with a moderately high risk of pulmonary embolism associated death according to stratification of the probability of early death of the European Society of Cardiology. The development of this condition is potentially preventable with timely and adequate therapy in these patients. We have improved the approach to the treatment of pulmonary embolism patients, which allows indications for thrombolytic therapy to be clarified and expanded. The aim of the study is to evaluate its effectiveness in the long-term period, as well as analyze the qualities of life of patients with massive pulmonary embolism, who underwent thrombolytic and anticoagulant therapy.Material and methods The treatment, as well as the analysis of long-term results and quality of life of 71 patients aged 29 to 88 years with diagnosed pulmonary embolism with a moderately high risk of early death were performed. All patients underwent general clinical and biochemical blood tests, D-dimer, ECG, echocardiography, ultrasound of the lower extremities veins, CT angiopulmonography. We registered the dynamics of echocardiographic symptoms of the right heart overload over 6 months (right ventricle size, pulmonary hypertension, the degree of tricuspid regurgitation), and assessed the quality of life based on a survey with the establishment of the appearance of shortness of breath, tachycardia, hospitalizations for heart failure during the study period. Depending on the type of therapy, the patients were divided into two groups: 38 patients with thrombolytic therapy and 33 patients with anticoagulant therapy. Subsequently, their comparative analysis was carried out.Results and conclusion In patients with pulmonary embolism of moderately high risk of early death, who underwent thrombolytic therapy, chronic postembolic pulmonary hypertension developed 2.9 times less and a higher quality of life retained in these patients than in patients treated with anticoagulant drugs.

scholarly journals Low-dose urokinase thrombolytic therapy for patients with acute intermediate-high-risk pulmonary embolism: A retrospective cohort study

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248603
Author(s):  
Cuilian Weng ◽  
Xincai Wang ◽  
Long Huang ◽  
Xingsheng Lin ◽  
Qinghua Liu
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Thrombolytic Therapy ◽  
Anticoagulant Therapy ◽  
Low Dose ◽  
Therapy Group ◽  
Minor Bleeding ◽  
Short Term

Introduction Patients at intermediate-high risk of developing a pulmonary embolism (PE) are very likely to experience adverse outcomes, such as cardiovascular instability and death. The role of thrombolytic therapy in intermediate-high-risk PE remains controversial. Objectives This study aimed to determine the efficacy and safety of low-dose urokinase (UK) thrombolytic therapy for intermediate-high-risk PE. Patients and methods This retrospective study included 81 consecutive patients with intermediate-high-risk PE from two centers. Patients received low-dose UK or low-molecular-weight heparin (anticoagulant therapy group). The efficacy outcomes were mortality, computed tomography pulmonary angiography (CTPA)-confirmed absorption, and dyspnea. Safety was assessed as the incidence of bleedings. Results The in-hospital mortality, 9-month mortality, and long-term mortality at the last follow-up were comparable for the low-dose UK group and the anticoagulant therapy group (6.45% vs. 0%, p = 0.144, 9.68% vs. 8.16%, p = 0.815, and 12.90% vs. 12.24%, p = 0.931, respectively). CTPA-confirmed absorption at one month after admission was higher in the low-dose UK group than in the anticoagulant therapy group (p = 0.016). The incidences of short-term dyspnea at discharge and long-term dyspnea at the last follow-up were lower in the low-dose UK group than in the anticoagulant therapy group (27.59% vs. 52%, p = 0.035, 33.33% vs. 58.14%, p = 0.043, respectively). No major bleeding occurred. The incidence of minor bleeding was not significantly different between the two groups (3.23% vs. 6%, p = 0.974). Conclusion In intermediate-high-risk PE, a low-dose UK might increase CTPA-confirmed absorption and improve short-term and long-term dyspnea without affecting mortality or increasing the bleeding risk.

scholarly journals Letter to the Editor

2021 ◽  
Vol 20 (3) ◽  
pp. 234-234
Author(s):  
N Smallwood ◽  
Keyword(s):  
Pulmonary Embolism ◽  
Thrombolytic Therapy ◽  
Recent Article ◽  
Ventricular Dysfunction ◽  
Right Ventricular Dysfunction ◽  
Haemodynamic Stability ◽  
Submassive Pulmonary Embolism ◽  
Systemic Thrombolytic Therapy ◽  
Nice Guidance ◽  
Potential Benefits

I read the recent article by Apsey et al with interest, which recommended "the potential benefits of thrombolytic therapy in massive and submassive pulmonary embolism". This would appear to go against current NICE guidance which states "Do not offer pharmacological systemic thrombolytic therapy to people with PE and haemodynamic stability with or without right ventricular dysfunction". Both recent NICE and European pulmonary embolism (PE) guidance are clear that only high-risk PE (previously called 'massive') should routinely be thrombolysed.

Treatment: thrombolysis

ESC CardioMed ◽  
2018 ◽  
pp. 2778-2781
Author(s):  
Guy Meyer
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Thrombolytic Therapy ◽  
Standard Of Care ◽  
Level Of Evidence ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Meta Analyses ◽  
Large Randomized Trial

According to recent guidelines, thrombolysis is considered as the standard of care in patients with high-risk pulmonary embolism. Although this recommendation is based on a limited level of evidence, these patients have a high risk of mortality justifying the increased risk of bleeding associated with thrombolytic therapy. Conversely, the role of thrombolytic therapy in intermediate-risk pulmonary embolism has been debated for many years but has been recently clarified by a large randomized trial and subsequent meta-analyses. In these patients, thrombolytic therapy is associated with a reduction in the combined endpoint of mortality and haemodynamic decompensation, but this is not paralleled by a decrease in overall mortality. In addition, the use of thrombolytic therapy in these patients is associated with a significant increase in major extracranial and intracranial bleeding. Thrombolytic therapy should thus be reserved for the few patients who experience haemodynamic worsening while receiving anticoagulant treatment. Although promising, the effectiveness of reduced dosages is not yet established and should be evaluated in further studies.

Treatment: thrombolysis

ESC CardioMed ◽  
2018 ◽  
pp. 2778-2781
Author(s):  
Guy Meyer
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Thrombolytic Therapy ◽  
Standard Of Care ◽  
Level Of Evidence ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Meta Analyses ◽  
Large Randomized Trial

According to recent guidelines, thrombolysis is considered as the standard of care in patients with high-risk pulmonary embolism. Although this recommendation is based on a limited level of evidence, these patients have a high risk of mortality justifying the increased risk of bleeding associated with thrombolytic therapy. Conversely, the role of thrombolytic therapy in intermediate-risk pulmonary embolism has been debated for many years but has been recently clarified by a large randomized trial and subsequent meta-analyses. In these patients, thrombolytic therapy is associated with a reduction in the combined endpoint of mortality and haemodynamic decompensation, but this is not paralleled by a decrease in overall mortality. In addition, the use of thrombolytic therapy in these patients is associated with a significant increase in major extracranial and intracranial bleeding. Thrombolytic therapy should thus be reserved for the few patients who experience haemodynamic worsening while receiving anticoagulant treatment. Although promising, the effectiveness of reduced dosages is not yet established and should be evaluated in further studies.

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