Thrombolytic Therapy For Pulmonary Embolism Research Articles

Left atrial intramural haematoma mimicking a thrombus traversing the interatrial septum following thrombolytic therapy for pulmonary embolism.

Left atrial intramural haematoma mimicking a thrombus traversing the interatrial septum following thrombolytic therapy for pulmonary embolism.

Life-threatening thrombotic complications in a pediatric in the intensive care unit

Introduction. This article highlights the problem of thrombus formation in pediatric patients staying in ICU, namely, the problem of prevention and management of pulmonary embolism in children. Currently, there is a tendency to increasing pulmonary embolism occurrence in children, though there are no clear guidelines on the medicine dosage for the systemic thrombolytic therapy of pulmonary embolism in children and for the acute coronary syndrome in children with Kawasaki disease.Clinical observations. The authors present two clinical cases from their practice when a successful management was obtained in children with life threatening thrombotic complications due to the applied systemic thrombolytic therapy.Conclusion. The obtained success in the described clinical cases have resulted from a thorough analysis of ratios “risk-benefit” and “efficiency-safety”. But the authors conclude that further research work in this direction is still needed.

Thrombolytic therapy for pulmonary embolism.

Thrombolytic therapy is usually reserved for people with clinically serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic agents may dissolve blood clots more rapidly than heparin and may reduce the death rate associated with PE. However, there are still concerns about the possible risk of adverse effects of thrombolytic therapy, such as major or minor haemorrhage. This is the fourth update of the Cochrane review first published in 2006. To assess the effects of thrombolytic therapy for acute pulmonary embolism. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 17 August 2020. We undertook reference checking to identify additional studies. We included randomised controlled trials (RCTs) that compared thrombolytic therapy followed by heparin versus heparin alone, heparin plus placebo, or surgical intervention for people with acute PE (massive/submassive). We did not include trials comparing two different thrombolytic agents or different doses of the same thrombolytic drug. Two review authors (ZZ, QH) assessed the eligibility and risk of bias of trials and extracted data. We calculated effect estimates using the odds ratio (OR) with a 95% confidence interval (CI) or the mean difference (MD) with a 95% CI. The primary outcomes of interest were death, recurrence of PE and haemorrhagic events. We assessed the certainty of the evidence using GRADE criteria. We identified three new studies for inclusion in this update. We included 21 trials in the review, with a total of 2401 participants. No studies compared thrombolytics versus surgical intervention. We were not able to include one study in the meta-analysis because it provided no extractable data. Most studies carried a high or unclear risk of bias related to randomisation and blinding. Meta-analysis showed that, compared to control (heparin alone or heparin plus placebo), thrombolytics plus heparin probably reduce both the odds of death (OR 0.58, 95% CI 0.38 to 0.88; 19 studies, 2319 participants; low-certainty evidence), and recurrence of PE (OR 0.54, 95% CI 0.32 to 0.91; 12 studies, 2050 participants; low-certainty evidence). Effects on mortality weakened when six studies at high risk of bias were excluded from analysis (OR 0.71, 95% CI 0.45 to 1.13; 13 studies, 2046 participants) and in the analysis of submassive PE participants (OR 0.61, 95% CI 0.37 to 1.02; 1993 participants). Effects on recurrence of PE also weakened after removing one study at high risk of bias for sensitivity analysis (OR 0.60, 95% CI 0.35 to 1.04; 11 studies, 1949 participants). We downgraded the certainty of evidence to low because of 'Risk of bias' concerns. Major haemorrhagic events were probably more common in the thrombolytics group than in the control group (OR 2.84, 95% CI 1.92 to 4.20; 15 studies, 2101 participants; moderate-certainty evidence), as were minor haemorrhagic events (OR 2.97, 95% CI 1.66 to 5.30; 13 studies,1757 participants; low-certainty evidence). We downgraded the certainty of the evidence to moderate or low because of 'Risk of bias' concerns and inconsistency. Haemorrhagic stroke may occur more often in the thrombolytics group than in the control group (OR 7.59, 95% CI 1.38 to 41.72; 2 studies, 1091 participants). Limited data indicated that thrombolytics may benefit haemodynamic outcomes, perfusion lung scanning, pulmonary angiogram assessment, echocardiograms, pulmonary hypertension, coagulation parameters, composite clinical outcomes, need for escalation and survival time to a greater extent than heparin alone. However, the heterogeneity of the studies and the small number of participants involved warrant caution when interpreting results. The length of hospital stay was shorter in the thrombolytics group than in the control group (mean difference (MD) -1.40 days, 95% CI -2.69 to -0.11; 5 studies, 368 participants). Haemodynamic decompensation may occur less in the thrombolytics group than in the control group (OR 0.36, 95% CI 0.20 to 0.66; 3 studies, 1157 participants). Quality of life was similar between the two treatment groups. None of the included studies provided data on post-thrombotic syndrome or on cost comparison. Low-certainty evidence suggests that thrombolytics may reduce death following acute pulmonary embolism compared with heparin (the effectiveness was mainly driven by one trial with massive PE). Thrombolytic therapy may be helpful in reducing the recurrence of pulmonary emboli but may cause more major and minor haemorrhagic events, including haemorrhagic stroke. More studies of high methodological quality are needed to assess safety and cost effectiveness of thrombolytic therapy for people with pulmonary embolism.

Pulmonary embolism: old problem, new approaches to treatment

There is no indication when to perform thrombolytic or anticoagulant therapy in patients with moderate-high risk of early death in accordance with the stratification of the European society of cardiology. The purpose of the study: to establish clinical, laboratory, and instrumental criteria for the choice of therapy volume optimization in patients with moderate-high risk of early death. Material and methods. The study included 154 patients with pulmonary embolism (PE) of high, moderate-high, moderate-low risk of death. An analysis was performed to determine the most significant indications for thrombolytic therapy in PE. Results. The presence of established «undoubted» criteria indicates the need for thrombolytic therapy. These include an increase in the size of the right ventricle compared to the left, paradoxical movement of the interventricular septum, hypokinesia of the right ventricle on еchocardiography. «Questionable» criteria were also identified: more than 50 mm Hg increased pulmonary artery pressure, more than 20 mm dilation of the inferior Vena cava, more than 3 cm dilatation of the right ventricle on еchocardiography, deep SIQIII on ECG, syncopal states in the anamnesis, increased NT-proBNP values, less than 90% arterial blood saturation. Thrombolytic therapy is indicated for patients with a combination of 2 or more of these criteria, in other cases anticoagulant therapy is prescribed. Conclusion. The use of established criteria makes it possible to differentiate treatment of patients with moderate-high risk of early death and reduce the likelihood of developing chronic post-thromboembolic pulmonary hypertension by 2.9 times.

Potential risk during catheter-directed thrombolytic therapy for pulmonary embolism and how to avoid it

Pulmonary embolism (PE) remains one of the highest causes of cardiovascular mortality worldwide. Systemic thrombolysis for acute PE reduces cardiovascular collapse but has the potential to cause major complications, including intracranial hemorrhage, systemic hemorrhage, immunologic complications, hypotension, and myocardial rupture. Catheter-directed thrombolysis accompanied with high-frequency ultrasound reduces systemic dose, allows increased local dose, and expedites clot lysis at the site of embolism. Although rare, some patients may have a patent foramen ovale or other atrial septal defect (ASD) which cannot be visualized during fluoroscopy which may complicate this procedure. A 41-year-old diabetic smoker presented to the emergency department with hypoxia, tachycardia, and light headedness. Computed tomography angiography (CTA) of the chest revealed bilateral PE with right ventricular enlargement and right heart strain pattern. Transthoracic echocardiogram revealed right ventricular enlargement. He was diagnosed with submassive PE. He underwent right heart catheterization with two angled pigtail catheters manipulated through the right heart to reach the right and left pulmonary arteries, however on frontal fluoroscopy, the catheters appeared slightly more caudal than would be expected. Lateral fluoroscopy was performed which did not show the catheter going through the expected anterior curvilinear course of the right ventricle and pulmonary trunk. Contrast was injected into each pigtail catheter and this demonstrated retrograde flow of contrast back into the left atrium, confirming that the catheters were positioned in the pulmonary veins, having passed through an ASD. On review of CTA chest, there was a visible patent foramen ovale. Congenital heart defects are rare but can complicate certain procedures and interventionalists need to be aware of this possibility. Catheter position more caudal than the pulmonary artery silhouettes should alert the operator to the incorrect placement in the pulmonary veins through an ASD. In these circumstances, lateral fluoroscopy will show absence of the catheters along the expected anterior curvilinear route of the right ventricle, pulmonary infundibulum, and pulmonary trunk. Contrast injection will show centripetal flow back to the left atrium rather than the centrifugal flow away from the heart. Other potential confirmatory methods include pressure monitoring and blood gas sampling. In addition, careful scrutiny of the CT angiogram for an ASD before the procedure may alert the operator to this potential pitfall. The interventionalist must remain vigilant to unexpected anatomical variants to avoid potential harm.

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

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.

P5715Trends in indications and outcome in thrombolytic therapy: a retrospective single center study

Abstract Background Thrombolytic therapy is used as a lifesaving treatment for a broad range of acute thrombotic events. The role of thrombolysis for its various indications has rapidly evolved. Purpose To provide a contemporary overview of current indications and outcome of thrombolytic therapy in clinical practice. Methods This retrospective single-center study analyzed indications, complications and short-term mortality of systemic thrombolytic therapy between 2010 and 2016 in a university hospital, totaling 763 cases. Major bleedings were defined using criteria published by the International Society on Thrombosis and Haemostasis (ISTH). Results Thrombolytic drugs were mostly used for ischemic strokes (66.6%) and peripheral arterial disease (16.9%). Acute coronary syndrome only represented a minority of cases (in this PCI-center). Overall seven- and thirty-day-mortality were 7.3% and 12.0%, respectively. Major bleeding occurred in 8.3% of patients and was fatal in 0.9% of all patients. Both major bleeding and mortality differed by the indication for thrombolysis. Thrombolytic therapy for pulmonary embolism and peripheral arterial disease were associated with the highest rates of major bleeding, 28.6% and 23.3% respectively. Short-term mortality was highest in patients receiving thrombolysis for pulmonary embolism. Predictors for major bleeding included use of antiplatelet and anticoagulation drugs prior to thrombolysis. Major bleedings, age and concomitant anticoagulation were associated with lower survival rates. Indications in absolute numbers – 2010 – – 2011 – – 2012 – – 2013 – – 2014 – – 2015 – – 2016 – Ischemic Stroke 56 63 66 57 96 88 82 Peripheral Arterial Disease 21 23 21 28 14 16 6 Pulmonary Embolism 4 9 10 10 5 8 8 Deep Vein Thrombosis 2 1 2 0 2 3 3 Acute Coronary Syndrome 0 1 0 1 0 0 0 Mechanical Heart Valve Thrombosis 1 3 3 1 2 7 1 Other 5 8 3 10 2 5 6 TOTAL 89 108 105 107 121 127 106 Mortality and major bleeding in % Conclusion The use of thrombolytic therapy has evolved, with stroke now being the most frequent indication. Mortality and bleeding rates are significant and vary considerably per indication. Major bleedings, age and maintenance anticoagulant therapy were risk factors associated with lower survival rates, but the underlying disease and patient population seem to play a major role in survival as well.

Systemic Thrombolytic Therapy for Pulmonary Embolism in Early Postoperative Period Following Laparoscopic Vaginal Hysterectomy

A 51-year-old female underwent a laparoscopic-assisted vaginal hysterectomy for fibroid uterus. After an uneventful procedure, the patient developed symptoms of Pulmonary Thromboembolism (PTE). The PTE was managed with, systemic thrombolysis using tissue plasminogen activator (Tenecteplase), appropriate support of inotropes and anticoagulants. While there is less incidence of PTE in laparoscopic procedures, in particular, in gynecology, there is a definite risk even in a patient with low-risk factors, which has been highlighted. Prompt diagnosis, aggressive therapy and adequate haemodynamic support go a long way to reduce mortality and morbidity from this life-threatening complication.

Thrombolytic therapy for pulmonary embolism.

Thrombolytic therapy is usually reserved for patients with clinically serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic agents may dissolve blood clots more rapidly than heparin and may reduce the death rate associated with PE. However, there are still concerns about the possible risk of adverse effects of thrombolytic therapy, such as major or minor haemorrhage. This is the third update of the Cochrane review first published in 2006. To assess the effects of thrombolytic therapy for acute pulmonary embolism. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 16 April 2018. We undertook reference checking to identify additional studies. We included randomised controlled trials (RCTs) that compared thrombolytic therapy followed by heparin versus heparin alone, heparin plus placebo, or surgical intervention for patients with acute PE. We did not include trials comparing two different thrombolytic agents or different doses of the same thrombolytic drug. Two review authors (JY, QH) assessed the eligibility and quality of trials and extracted data. We calculated effect estimates using the odds ratio (OR) with 95% confidence interval (CI) or the mean difference (MD) with 95% CI. We assessed the quality of the evidence using GRADE criteria. We identified no new studies for inclusion in this 2018 update. We included in the review 18 trials with a total of 2197 participants. We were not able to include one study in the meta-analysis because it provided no data that we could extract. Most of the studies carried a high risk of bias because of high or unclear risk related to randomisation and blinding. Meta-analysis showed that, compared with heparin alone, or heparin plus placebo, thrombolytics plus heparin can reduce the odds of death (OR 0.57, 95% CI 0.37 to 0.87, 2167 participants, P = 0.01, low-quality evidence) and recurrence of PE (OR 0.51, 95% CI 0.29 to 0.89, 1898 participants, P = 0.02, low-quality evidence). Effects on mortality weakened when we excluded from analysis four studies at high risk of bias (OR 0.66, 95% CI 0.42 to 1.06, 2054 participants, P = 0.08). The incidence of major and minor haemorrhagic events was higher in the thrombolytics group than in the control group (OR 2.90, 95% CI 1.95 to 4.31, 1897 participants, P < 0.001, low-quality evidence; OR 3.09, 95% CI 1.58 to 6.06, 1553 participants, P = 0.001, very low-quality evidence, respectively). We downgraded the quality of the evidence to low or very low because of design limitations, potential influence of pharmaceutical companies, and small sample sizes. Length of hospital stay (mean difference (MD) -0.89, 95% CI -3.13 to 1.34) and quality of life were similar between the two treatment groups. Limited information from a small number of trials indicated that thrombolytics may improve haemodynamic outcomes, perfusion lung scanning, pulmonary angiogram assessment, echocardiograms, pulmonary hypertension, coagulation parameters, clinical outcomes, and survival time to a greater extent than heparin alone. However, the heterogeneity of the studies and the small number of participants involved warrant caution when results are interpreted. Similarily, fewer participants from the thrombolytics group required escalation of treatment. None of the included studies reported on post-thrombotic syndrome or compared the costs of different treatments. Low-quality evidence suggests that thrombolytics reduce death following acute pulmonary embolism compared with heparin. The included studies used a variety of thrombolytic drugs. Thrombolytic therapy may be helpful in reducing the recurrence of pulmonary emboli but may cause major and minor haemorrhagic events and stroke. More high-quality, blinded randomised controlled trials assessing safety and cost-effectiveness of therapies for pulmonary embolism are required.

Low-dose, short course alteplase treatment of submassive pulmonary embolism: a case series from the National Institutes of Health Clinical Center.

: Guidelines-recommend thrombolytic therapy for pulmonary embolism in patients with severe hemodynamic compromise and low risk of bleeding. Thrombolytics in submassive pulmonary embolism have an unfavorable risk/benefit ratio and remain controversial. Based on our experience with extensive, lower extremity thrombi, nine patients with symptomatic, submassive pulmonary embolisms (five medical, four surgical) were treated with low-dose alteplase (<10 mg/day, infused over 6 h per treatment). Alteplase was delivered by pulse spray and/or directed or undirected central venous catheters depending on clot size and location. All patients improved symptomatically and as determined objectively by pulmonary artery pressures and/or imaging, though acute benefits ranged from substantial to modest. One surgical patient required re-exploration for bleeding at the site of a recent retroperitoneal lymph node dissection. This experience may help guide the design of a randomized controlled trial to determine the safety and efficacy of low-dose alteplase for submassive pulmonary embolism.

Deciding on thrombolytic therapy in pulmonary embolism - is there room for lactate?

Introduction. Diagnostic and therapeutic algorithms for pulmonary embolism (PE) have been frequently modified; however, determining clinical probability, which dictates further procedures, has remained the first step. The objective was to illustrate therapeutic dilemma in a patient with intermediate high risk for 30-day mortality. Case outline. The patient was a 56-years-old woman who was referred to our institution for suspected PE. According to the Wells score, the patient was deemed as low-probability for venous thromboembolism, and after further stratification she was placed in a group with intermediate high risk for 30-day mortality. PE was confirmed by computerised tomography pulmonary angiography and she initially received heparin. During the further clinical course, she developed hemodynamic instability, and she received thrombolytic therapy, with a positive outcome. The patient also had increased lactate at admission ? marker of tissue hypoperfusion which is not a part of the routine laboratory work-up in PE patients. Conclusion. Current guidelines state that patients with intermediate high risk for 30-day mortality should be treated with heparin, and then continuously monitored in order to timely recognize potential hemodynamic instability and consequently apply thrombolytics. In the outlined case, thrombolytic therapy was applied only after the patient developed hemodynamic instability, although previously she had early signs of tissue hypoperfusion.

Multiple overlapping systematic reviews facilitate the origin of disputes: the case of thrombolytic therapy for pulmonary embolism

ObjectiveTo explore disagreements in multiple systematic reviews (SRs) assessing the benefit-to-harm ratio of thrombolytic therapy in patients with intermediate-risk pulmonary embolism (PE). Study Design and SettingMEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Database of Abstracts and Reviews of Effectiveness were searched up to April 14, 2016. We included SRs and guidelines that evaluated thrombolytic therapy, compared with anticoagulation alone, in intermediate-risk PE. We calculated pooled risk ratio (RR) and absolute risk difference (RD), with interquartile range (IQR), for all-cause mortality, recurrent PE, and major bleeding. ResultsWe marked the Pulmonary Embolism Thrombolysis trial, the largest trial, as a research milestone. Since its release in 2014, 12 SRs (2–15 included trials) and two major guidelines were published. Studies were concordant in reporting that thrombolysis reduced all-cause mortality (median RD −1.55%, IQR −1.60% to −1.40%; median RR 0.55, IQR 0.48–0.61). Discordant results were found for major bleeding (median RD 4.70%, IQR 0.90%–5.70%), with SRs reporting results in opposite directions. Relevant magnitude of effects and precision for benefits and harms were never prespecified. ConclusionFourteen evidence syntheses were published within 25 months. Conclusions suggested mortality reduction associated with thrombolytics. Therapy harm was more dispersed and alternatively considered. Interpretation of the benefit-to-harm ratio was elusive, and modest incremental advantages might or not be important, facilitating the origin of disputes.

Long-Term Antiarrhythmic Effects of Thrombolytic Therapy in Pulmonary Embolism

The role of thrombolytic therapy in acute pulmonary embolism patients is still controversial considering the occurrence of arrhythmias. Short-term effects of thrombolytics are well-known whereas long-term effects on cardiac electrophysiology have not been reported before. The objective of our study was to assess the arrhythmic differences in pulmonary embolism patients who received thrombolytics followed by anticoagulation or anticoagulation alone. Sixty patients who received thrombolytic therapy followed by anticoagulation (group 1) and 60 patients who received anticoagulation alone (group 2) were included in this retrospective, single-centre observational study. Twenty-four-hour ambulatory electrocardiography was performed 31 ± 9 months after pulmonary embolism hospitalisation in order to compare arrhythmias originating from both ventricles and atria. The age and gender distribution of the patients were statistically similar. Ventricular arrhythmias were found to be the same between t-PA and non t-PA groups. All types of atrial arrhythmias were found to be increased in non t-PA group even though left and right atrial volume indexes were statistically identical between the two groups. In long-term pulmonary embolism, follow-up thrombolytic therapy was demonstrated to have atrial antiarrhythmic effects.

Volumetric capnography: lessons from the past and current clinical applications.

Dead space is an important component of ventilation–perfusion abnormalities. Measurement of dead space has diagnostic, prognostic and therapeutic applications. In the intensive care unit (ICU) dead space measurement can be used to guide therapy for patients with acute respiratory distress syndrome (ARDS); in the emergency department it can guide thrombolytic therapy for pulmonary embolism; in peri-operative patients it can indicate the success of recruitment maneuvers. A newly available technique called volumetric capnography (Vcap) allows measurement of physiological and alveolar dead space on a regular basis at the bedside. We discuss the components of dead space, explain important differences between the Bohr and Enghoff approaches, discuss the clinical significance of arterial to end-tidal CO2 gradient and finally summarize potential clinical indications for Vcap measurements in the emergency room, operating room and ICU.

Thrombolytic therapy for pulmonary embolism.

Thrombolytic therapy (powerful anticoagulation drugs) is usually reserved for patients with clinically serious or massive pulmonary embolism (PE). Evidence suggests that thrombolytic agents may dissolve blood clots more rapidly than heparin and reduce the death rate associated with PE. However, there are still concerns about the possible risk of adverse effects of thrombolytic therapy, such as major or minor haemorrhages. This is the second update of the Cochrane review first published in 2006. To assess the effects of thrombolytic therapy in patients with acute pulmonary embolism. For this update the Cochrane Vascular Group searched their Specialised Register (last searched September 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library (last searched Issue 8, 2014). We also searched individual trial collections and private databases, along with bibliographies of relevant articles. We handsearched relevant medical journals. Randomised controlled trials (RCTs) that compared thrombolytic therapy followed by heparin versus heparin alone, heparin plus placebo or surgical intervention in patients with acute PE. We did not include trials comparing two different thrombolytic agents or different doses of the same thrombolytic drug. Two authors (BD and QH) assessed the eligibility and quality of trials and extracted data. We identified 18 trials with a total of 2197 participants for inclusion in the review. We were not able to include one study in the meta-analysis because it had no data to extract. Most of the studies carried a high risk of bias because of high or unclear risk relating to randomisation and blinding. Meta-analysis showed that, compared with heparin alone, or heparin plus placebo, thrombolytics plus heparin can reduce the odds of death (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.37 to 0.87, P = 0.02, low quality evidence) and recurrence of PE (OR 0.51; 95% CI 0.29 to 0.89, P = 0.02, low quality evidence). The effects of death weakened when we excluded four studies at high risk of bias from analysis: OR 0.66, 95% CI 0.42 to 1.06, P = 0.08. The incidence of major and minor haemorrhagic events was higher in the thrombolytics group than in the control group, and this difference was statistically significant (OR 2.90, 95% CI 1.95 to 4.31, P < 0.001, low quality evidence; OR 3.09, 95% CI 1.58 to 6.06, P = 0.001, very low quality evidence, respectively). Length of hospital stay (mean difference (MD) -1.35, 95% CI -4.27 to 1.58) and quality of life were similar between the two treatment groups. Stroke was reported in one study and occurred more often in the thrombolytics group than in the control group, although the confidence interval was wide (OR 12.10, 95% CI 1.57 to 93.39). Limited information from a small number of trials indicated that thrombolytics may improve haemodynamic outcomes, perfusion lung scanning, pulmonary angiogram assessment, echocardiograms, pulmonary hypertension, coagulation parameters, clinical outcomes and survival time to a greater extent than heparin alone. However, the heterogeneity of the studies and small number of participants involved warrant caution when interpreting results. Similarily, fewer patients from the thrombolytics group required escalation of treatment. None of the included studies reported on post-thrombotic syndrome or compared the cost of the different treatments. There is low quality evidence that thrombolytics reduce death following acute pulmonary embolism compared with heparin. Furthermore, thrombolytic therapies included in the review were heterogeneous. Thrombolytic therapy may be helpful in reducing the recurrence of pulmonary emboli but may cause more major and minor haemorrhagic events and stroke. More high quality double blind RCTs assessing safety and cost-effectiveness are required.

Bleeding risk with systemic thrombolytic therapy for pulmonary embolism: scope of the problem.

Acute pulmonary embolism represents a major complication of venous thromboembolism that is associated with high morbidity and mortality. Guidelines recommend the rapid initiation of anticoagulation and consideration of thrombolytic therapy in select patients, including those with hypotension or at high risk of developing hypotension. Evaluation for thrombolytic therapy should only be considered after assessment of contraindications and risk for major bleeding. The objective of this perspective article is to evaluate the bleeding risk associated with systemic thrombolytic therapy in the management of acute pulmonary embolism and discuss strategies to minimize this risk. Risk stratification of acute pulmonary embolism will be discussed to identify patient populations that warrant specific consideration of risk for major bleeding with thrombolytic therapy. In addition, the incidence, patient-specific risk factors, and pharmacologic characteristics, including concurrent anticoagulation and thrombolytic therapy, will be evaluated in the context of risk for major hemorrhage. Finally, supporting evidence for strategies to minimize risk of hemorrhage, including evaluation of contraindications, weight adjusted dosing, infusion strategy and catheter-directed thrombolytic administration will be evaluated. Despite published guidelines and review articles, select aspects to thrombolytic therapy for the management of pulmonary embolism remain controversial and under recognized, including risk of major hemorrhage. When making decisions about the role of thrombolytic therapy in pulmonary embolism, clinicians must be knowledgeable about the associated risks of thrombolytic therapy and individually evaluate patient risk factors prior to determining appropriate candidacy for thrombolytic therapy. For patients considered to be at high risk of major bleeding, strategies to minimize risk should be considered, including weight-adjusted doses and catheter directed therapy. Additional research is needed specific to the acute pulmonary embolism setting to validate risk factors and strategies to minimize major hemorrhage.

An overview of thrombolytic therapy for pulmonary embolism: a single centre experience

Pulmonary embolism (PE) is considered to be a major cause of mortality, morbidity and hospitalization in Europe. Haemody-namic benefits of thrombolysis in patients with shock and hypotension are undeni-able, but the role of thrombolytic therapy on the outcome of haemodynamically sta-ble patients still remains controversial. This is a retrospective analysis of patients with acute PE treated with thrombolytic therapy in medical intensive care unit (ICU), University Hospital Sveti Duh, be-tween March 2014 and April 2015 . Twenty two of 75 (29%) patients with PE received thrombolytic therapy. The mean age of patients was 63 years, 45% were male and 55% female. The major symp-toms were: dyspnea (73%), chest pain (18%) and syncope (9%). 27% of patients receiving thrombolytic therapy were haemodynamically unstable and 73% were stable. All patients had an extensive clot burden on computed tomographic pul-monary angiography (CTPA). All haemo-dynamically stable patients had echocar-diographic signs of right ventricular (RV) dysfunction. Troponin I was positive in all haemodynamically unstable patients and in 50% of haemodynamically stable pa-tients. Only one (5%) haemodynamically unstable patient died but not because of PE or therapy complication. All other patients survived and recovered completely. Two patients (9%) had major non-intracranial bleeding complications, which were suc-cessfully treated with supportive therapy.

Spontaneous hemothorax following thrombolytic and anticoagulant therapy for massive pulmonary embolism

Massive spontaneous hemothorax following combined thrombolytic and anticoagulant therapy for pulmonary embolism(PE) is a rare event that is little documented in the literature. Here, we describe a rare case of spontaneous hemothorax in a 23-year-old woman with underlying systemic lupus erythematosus following combined administration of tissue plasminogen activator and low-molecular-weight heparin for massive PE. This report of our successful treatment of this case by video-assisted thoracoscopic thoracotomy demonstrates that although the occurrence is rare, massive hemothorax following anticoagulant and/or thrombolytic therapy for PE should be suspected if patients experience chest pain, dyspnea, or signs of anemia, and follow-up physical examination and hemogram should be performed to facilitate diagnosis of this life-threatening complication.

P144 Case Series: Choosing Thrombolysis in Acute Pulmonary Embolism (PE) – Massiveness or Instability?

Background PE has significant mortality risk particularly in “PE with haemodynamic instability” or “massive PE” where blood pressure, attributable to PE, is sustained below 90mmHg. [1,2] Thrombolysis in this patient group is associated with reduced mortality and faster restoration of lung perfusion with approval by NICE [1,2] Another important group of patients with apparent haemodynamic stability but documented right ventricular (RV) compromise or myocardial injury (e.g. echocardiogram evidence of RV strain or raised Troponin) is recognised (“sub-massive” PE) where considerable debate remains as to reliable prognostication and appropriateness of thrombolysis. Aims Recognising a tendency in our district general hospital to treat PE aggressively, we sought to assess our own practise with regards to thrombolytic therapy in PE to better understand our interpretation of NICE guidance and the wider literature. Objective Assess routine quantification of haemodynamic instability of the acutely unwell patient in the clinical environment and the extent with which knowledge of right ventricular compromise and cardiac biomarkers influenced decision to thrombolyse. Methods Retrospective review of case records. Data was extracted from the medical records by one of the authors followed by joint scrutiny by all authors. Results From June 2010 over 24 months, 17 patients (6 males, 11 females) have been thrombolysed. Median age 62 (range 24–90). Of these one patient died 4 days later of sepsis and multi organ failure, and one developed a haematoma in her arm which resolved with conservative management. Of these patients only two Massive i.e. haemodynamically unstable with one thrombolysed on the ITU. In the submassive PEs, supporting evidence for thrombolysis was CT in 5 cases, and echo 5, both in 2, and lab (troponin rise) in 9 cases. Conclusion Thrombolysis in PE especially in submassive PEs remains an area of controversy and clinically a dilemma at times. Our case series shows that patient selection supported by relevant investigations, appropriate patients can benefit without any untoward events. References NICE CG144 Venous thromboembolic diseases: full guideline. Jaff MR et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011.

How to Evaluate the Effectiveness of Catheter-Directed Thrombolytic Therapy in Pulmonary Embolism

How to Evaluate the Effectiveness of Catheter-Directed Thrombolytic Therapy in Pulmonary Embolism