Streptokinase and Urokinase in the Treatment of Pulmonary Thromboemboli

1976 ◽  
Vol 35 (01) ◽  
pp. 057-069 ◽  
Author(s):  
William R Bell
Keyword(s):  
Pulmonary Embolism ◽  
Thrombolytic Therapy ◽  
Phase I ◽  
Phase Ii ◽  
Clinical History ◽  
Pulmonary Angiography ◽  
Lung Perfusion ◽  
Bleeding Complications ◽  
Significant Difference ◽  
Cardiopulmonary Hemodynamics

SummaryIn Phase I of this study of 160 patients with pulmonary embolism, it was demonstrated that 12 hours of urokinase accelerated the resolution of pulmonary thromboemboli compared to heparin alone. Phase II compared 12 hours of urokinase, 24 hours of urokinase and 24 hours of streptokinase in 167 patients. All patients had a clinical history and angiographic diagnosis of pulmonary embolism. Patients were randomly allocated to treatment. All physicians making patient observations were unaware of drug assignment.Resolution of the thromboembolism 24–30 hours after therapy had been instituted was determined by pulmonary angiography, lung perfusion scans and cardiopulmonary hemodynamics. Twenty-four hours of urokinase did not demonstrate greater clot resolution than 12 hours of urokinase. Twenty-four hours of urokinase resulted in greater improvement than streptokinase in lung perfusion scans, but not in angiograms. In patients with massive embolism, this difference was statistically significant. Hemodynamic differences varied.Bleeding complications and morbidity due to allergic reactions with streptokinase and urokinase were minimal. There was no statistically significant difference in mortality in the three treatment groups.From the Phase I and Phase II data it is reasonable to conclude that all three regimens of thrombolytic therapy are more effective than heparin alone in accelerating resolution of pulmonary emboli. Thrombolytic therapy offers the clinician an alternative to pulmonary embolectomy.

The Phase II Urokinase-Streptokinase Pulmonary Embolism Trial

1975 ◽  
Vol 33 (03) ◽  
pp. 464-476 ◽  
Author(s):  
Arthur A Sasahara ◽  
William R Bell ◽  
Toby L Simon ◽  
James M Stengle ◽  
Sol Sherry
Keyword(s):  
Pulmonary Embolism ◽  
Phase I ◽  
Phase Ii ◽  
Randomized Study ◽  
The United States ◽  
Pulmonary Angiography ◽  
Group 12 ◽  
Two Phases ◽  
Comparative Results ◽  
Lung Scanning

SummaryThe controlled clinical trials of thrombolytic agents in the United States have been carried out in two phases, under the auspices of the National Heart and Lung Institute. Phase I was devoted to the comparison of 12-hour Urokinase (12h–UK) followed by heparin (H) with heparin alone in patients with acute pulmonary embolism (Walsh et al. 1969). The results showed that patients treated with UK had more rapid and greater resolution of pulmonary thromboemboli in the first twenty-four hours of therapy than patients treated with H alone, as assessed by serial pulmonary angiography, hemodynamics and lung scanning (The Urokinase Pulmonary Embolism Trial, 1970, 1973 ; Hyers et al. 1970). Because of the relatively small size of the Trial and the low mortality of treated pulmonary embolism, mortality differences were not sought - nor was one found. Although there was early difference in amount of clot resolution, patients treated with H alone showed similar improvement by two weeks.The Phase II Urokinase-Streptokinase Pulmonary Embolism Trial (USPET) was begun to assess the comparative results of UK and Streptokinase (SK) therapy. Because of favorable results obtained with SK in other countries, it was deemed necessary to make this comparison (Browse and James, 1964 ; Hirsh et al. 1968 ; Miller et al. 1969, 1971 ; Chesterman et al. 1969). A third group, 12-hour UK, was added to relate this study (24-hour UK and SK) with the Phase I results which employed only a 12-hour infusion of UK. This Phase II Trial represents the first controlled, randomized study of UK and SK in thromboembolic disorders.

scholarly journals Gender-related differences in clinical presentation, electrocardiography signs, laboratory markers and outcome in patients with acute pulmonary embolism

2016 ◽  
Vol 73 (9) ◽  
pp. 844-849 ◽  
Author(s):  
Slobodan Obradovic ◽  
Boris Dzudovic ◽  
Sinisa Rusovic ◽  
Vesna Subota ◽  
Dragana Obradovic
Keyword(s):  
Pulmonary Embolism ◽  
Acute Pulmonary Embolism ◽  
Clinical Presentation ◽  
Univariate Analysis ◽  
Pulmonary Angiography ◽  
Laboratory Findings ◽  
Laboratory Markers ◽  
Significant Difference ◽  
Echocardiographic Examination ◽  
Gender Specific Differences

Background/Aim. Acute pulmonary embolism (PE) is a potentially life threating event, but there are scarce data about genderrelated differences in this condition. The aim of this study was to identify gender-specific differences in clinical presentation, the diagnosis and outcome between male and female patients with PE. Methods. We analysed the data of 144 consecutive patients with PE (50% women) and compared female and male patients regarding clinical presentation, electrocardiography (ECG) signs, basic laboratory markers and six-month outcome. All the patients confirmed PE by visualized thrombus on the multidetector computed tomography with pulmonary angiography (MDCTPA), ECG and echocardiographic examination at admission. Results. Compared to the men, the women were older and a larger proportion of them was in the third tertile of age (66.0% vs 34.0%, p = 0.008). In univariate analysis the men more often had hemoptysis [OR (95% CI) 3.75 (1.16-12.11)], chest pain [OR (95% CI) 3.31 (1.57-7.00)] febrile state [OR (95% CI) 2.41 (1.12-5.22)] and pneumonia at PE presentation [OR (95% CI) 3.40 (1.25-9.22)] and less likely had heart decompensation early in the course of the disease [OR (95%CI) 0.48 (0.24-0.97)]. In the multivariate analysis a significant difference in the rate of pneumonia and acute heart failure between genders disappeared due to strong influence of age. There was no significant difference in the occurrence of typical ECG signs for PE between the genders. Women had higher level of admission glycaemia [7.7 mmol/L (5.5-8.2 mmol/L) vs 6.9 mmol/L (6.3-9.6 mmol/L), p = 0.006] and total number of leukocytes [10.5 x 109/L (8.8-12.7 x 109/L vs 8.7 x 109/L (7.0-11.6 x 109/L)), p = 0.007]. There was a trend toward higher plasma level of brain natriuretic peptide in women compared to men 127.1 pg/mL (55.0-484.0 pg/mL), p = 0.092] vs [90.3 pg/mL (39.2-308.5 pg/mL). The main 6-month outcomes, death and major bleeding, had similar frequencies in both sexes. Conclusion. There are several important differences between men and women in the clinical presentation of PE and basic laboratory findings which can influence the diagnosis and treatment of PE.

scholarly journals Analysis of the Cochrane Review: Thrombolysis for Acute Deep Vein Thrombosis. Cochrane Database Syst Rev. 2014,1: CD002783.

2015 ◽  
Vol 28 (1) ◽  
pp. 12 ◽  
Author(s):  
Liliana Sousa Nanji ◽  
André Torres Cardoso ◽  
João Costa ◽  
António Vaz-Carneiro
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Thrombolytic Therapy ◽  
Bleeding Complications ◽  
Controlled Trials ◽  
Vein Thrombosis ◽  
Post Thrombotic Syndrome ◽  
Recurrent Deep Vein Thrombosis ◽  
Acute Deep Vein Thrombosis ◽  
Deep Vein

<p>The standard treatment for acute deep vein thrombosis (DVT) targets to reduce immediate complications, however thrombolysis could reduce the long-term complications of post-thrombotic syndrome in the affected limb. This systematic review aimed to assess the effects of thrombolytic therapy and anticoagulation <em>versus </em>anticoagulation in people with deep vein thrombosis of the lower limb through the effects on pulmonary embolism, recurrent deep vein thrombosis, major bleeding, post-thrombotic complications, venous patency and venous function. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last search in April 2013) and CENTRAL (2013, Issue 4). A total of 17 randomised controlled trials (RCTs) and 1103 participants were included. In the experimental group receiving thrombolysis, complete clot lysis occurred more frequently and there was greater improvement in venous patency. The incidence of post-thrombotic syndrome decreased by a 1/3 and venous ulcers were less frequent. There were more bleeding complications and 3 strokes occurred in less recent studies, yet there seemed to be no significant effect on mortality. Data on the occurrence of pulmonary embolism and recurrent deep vein thrombosis were inconclusive. There are advantages to thrombolysis, yet the application of rigorous criteria is warranted to reduce bleeding complications. Catheter-directed thrombolysis is the current preferred method, as opposed to systemic thrombolysis in the past, and other studies comparing these procedures show that results are similar.</p><p><strong>Keywords:</strong> Randomized Controlled Trials as Topic; Thrombolytic Therapy; Venous Thrombosis.</p>

scholarly journals Ipsi- and Contralateral Moxibustion Generate Similar Analgesic Effect on Inflammatory Pain

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Chuan-Yi Zuo ◽  
Peng Lv ◽  
Cheng-Shun Zhang ◽  
Ru-Xue Lei ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Pain Relief ◽  
Phase I ◽  
Phase Ii ◽  
Inflammatory Pain ◽  
Analgesic Effect ◽  
Withdrawal Latency ◽  
Significant Difference ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant ◽  
Biting Time

The aim of this study was to investigate whether contralateral moxibustion would generate a similar analgesic effect with ipsilateral moxibustion. Contra- and ipsilateral moxibustion were separately applied to Zusanli (ST36) acupoints of inflammatory pain mice. The analgesic effect was evaluated, respectively, by licking/biting time (LBT) of formalin-induced inflammatory pain and thermal withdrawal latency (TWL) of complete Freund’s adjuvant- (CFA-) induced inflammatory pain. For formalin-induced pain, compared with formalin group, the total LBT of ipsi- and contralateral moxibustion reduced in both phase I and phase II, but there was no significant difference between ipsi- and contralateral moxibustion. For CFA-induced inflammatory pain, compared with CFA group, TWL of ipsi- and contra-Moxi groups increased immediately after moxibustion intervention; however there was no obvious difference between ipsi- and contralateral moxibustion at any timepoint. It indicated that contralateral moxibustion had a similar analgesic effect with ipsilateral moxibustion in both formalin- and CFA-induced pain. These results suggest that both ipsi- and contralateral moxibustion could be applied for pain relief.

Characteristics and Outcomes of Pulmonary Embolism IN CANCER PATIENTS and IN PATIENTS without CANCER.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5065-5065
Author(s):  
Asha Karippot ◽  
Michael Maroules ◽  
Vincent A DeBari
Keyword(s):  
Pulmonary Embolism ◽  
Cancer Patients ◽  
Conflicts Of Interest ◽  
Pulmonary Arteries ◽  
Therapeutic Interventions ◽  
Bleeding Complications ◽  
Cancer Group ◽  
Ct Angiogram ◽  
Significant Difference ◽  
Baseline Characteristics

Abstract Abstract 5065 Background Venous thromboembolism (VTE), a frequent complication in cancer and, occasionally, a harbinger of occult cancer, is one of the leading causes of death in cancer patients. VTE recurs with a three-fold greater frequency in cancer patients than in patients who do not have cancer, and requires long-term anticoagulation. There is a two-fold greater risk of bleeding complications in these patients compared to patients who do not have cancer. Because pulmonary embolism (PE) is a life-threatening sequel of VTE, we sought to evaluate the hypothesis that cancer patients suffer from extensive pulmonary embolism (involving central pulmonary artery or bilateral pulmonary arteries) and to determine if we could detect differences in two clinical outcomes, length of stay (LOS) and mortality. Patients and Methods This retrospective cohort of subjects with pulmonary embolism (PE) was developed using data beginning in January 2003 to December 2007 at a 680 bed, urban teaching hospital. The cohort of 118 patients with PE diagnosed with CT angiogram yielded 41 patients in cancer group (20 males and 21 females) and 47 (23 males and 24 females) patients in non cancer group. Other baseline characteristics gathered for the two groups included age, gender, race, co-morbidities, ambulatory status and therapeutic interventions. Criteria for being assigned to the “central PE” were a filling defect in the pulmonary arteries or the main stem. Patients who showed filling defects in both central and peripheral vessels were also assigned to the “central PE”. All other patients with filling defects in one or more peripheral vessels were assigned to the “peripheral PE” group. Results The baseline characteristics did not show significant differences between the groups. Our data demonstrated that central PE was strongly associated with the cancer group (26/41; 63.4%) compared with 15 of 47 (31.9%) in the non-cancer group (OR = 3.70; 95% CI: 1.53 to 8.95; p = 0.0051). The common cancers associated with VTE were genito–urinary (13) followed by gastro-intestinal (10), then lung and breast (6 in each group). LOS was significantly greater in the cancer group (median: 9d; IQR: 7-19d) compared to non-cancer group (median: 7d; IQR: 5-11d; p = 0.032. We detected no significant difference in overall mortality between the two groups (p = 0.11). Kaplan-Meier analysis of survival, similarly, demonstrated no significant difference (95% CI of HR: 0.62 to 3.18; p = 0.42) Conclusion Cancer patients appear to be at a higher risk for central PE and have longer stay in the hospital after diagnosis than patients without cancer. However, in this study we did not detect increased mortality over a twelve-month observation period. Disclosures No relevant conflicts of interest to declare.

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

2018 ◽  
Vol 146 (7-8) ◽  
pp. 436-439
Author(s):  
Dusanka Obradovic ◽  
Biljana Joves ◽  
Svetislava Milic ◽  
Jovan Matijasevic ◽  
Stanislava Sovilj-Gmizic
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Thrombolytic Therapy ◽  
Hemodynamic Instability ◽  
Positive Outcome ◽  
Pulmonary Angiography ◽  
Clinical Probability ◽  
Tissue Hypoperfusion ◽  
Therapeutic Algorithms ◽  
Wells Score

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.

Pulmonary embolism rule out: positivity and factors affecting the yield of CT angiography

2020 ◽  
Vol 96 (1140) ◽  
pp. 594-599 ◽  
Author(s):  
Tanya Aggarwal ◽  
Ali Eskandari ◽  
Sarv Priya ◽  
Aidan Mullan ◽  
Ishan Garg ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Patient Characteristics ◽  
Pulmonary Angiography ◽  
Test Results ◽  
Factors Affecting ◽  
Significant Difference ◽  
The Usa ◽  
Male Sex ◽  
The Difference ◽  
Rule Out

ObjectiveCT pulmonary angiography (CTPA) is one of the most commonly ordered CT imaging tests. It is often believed to be overutilised with few recent studies showing a yield of less than 2%. This study aimed to determine the overall positivity rate of CTPA examinations and understand the factors that affect the yield of the CTPA examination.MethodsWe retrospectively analysed 2713 patients who received the CTPA exam between 2016 and 2018. Type of study ordered (CTPA chest or CTPA chest with abdomen and pelvis CT), patient location (emergency department (ED), outpatient, inpatient, intensive care unit (ICU)) and patient characteristics—age, sex and body mass index (BMI) were recorded. A logistic regression analysis was performed to determine what factors affect the positivity rate of CT scans for pulmonary embolism (PE).ResultsWith 296 positive test results, the overall CTPA positivity was 10.9%. Male sex was associated with higher CTPA positivity, gender difference was maximum in 18-year to 35-year age group. Overweight and obese patients had significantly higher positivity as compared with BMI<25 (p<0.05). Higher positivity rate was seen in the BMI 25–40 group (11.9%) as compared with BMI>40 (10.1%) (p<0.05). Significant difference (p<0.001) was also found in CTPA examination yield from ICU (15.3%) versus inpatients (other than ICU) (12.4%) versus ED (9.6%), and outpatients (8.5%). The difference in CTPA yield based on the type of CT order (CTPA chest vs CTPA chest with CT abdomen and pelvis), patient’s age and sex was not significant.ConclusionCTPA yield of 10.9% in this study is comparable to acceptable positivity rate for the USA and is higher than recent studies showing positivity of <2%. Patient characteristics like obesity and ICU or inpatient location are associated with higher rate of CT positivity.

Massive pulmonary embolism in a young boy with T-cell leukaemia

2014 ◽  
Vol 34 (03) ◽  
pp. 233-236
Author(s):  
C. Martin ◽  
F. Alt ◽  
A. Wingerter ◽  
G. Staatz ◽  
H. Schinzel ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Thrombolytic Therapy ◽  
Acute Pulmonary Embolism ◽  
Recombinant Tissue Plasminogen Activator ◽  
Massive Pulmonary Embolism ◽  
Bleeding Complications ◽  
Cell Leukaemia ◽  
Malignant Diseases ◽  
Systemic Thrombolytic Therapy ◽  
Tissue Plasminogen

SummaryAcute pulmonary embolism (PE) is a serious complication in association with malignant diseases. We describe the successful treatment of PE applying a systemic thrombolytic therapy in a 4-year-old boy with acute lymphoblastic leukaemia.The thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) 0.1 mg/ kg bodyweight per hour for six hours was continued for six days without important side effects. In particular no bleeding complications were observed. Computed tomography with contrast revealed a remarkable regression of the central PE. Without further delays the chemotherapy was resumed.

Resminostat and sorafenib combination therapy for advanced hepatocellular carcinoma in patients previously untreated with systemic chemotherapy.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 252-252 ◽  
Author(s):  
Masatoshi Kudo ◽  
Baek-Yeol Ryoo ◽  
Ho Yeong Lim ◽  
Do Young Kim ◽  
Takuji Okusaka ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Phase I ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Histone Deacetylases ◽  
Specific Effect ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
Significant Difference

252 Background: Resminostat is an oral hydroxamate-type inhibitor of class I, IIB, and IV histone deacetylases. A European Phase II study of second-line combination therapy with resminostat and sorafenib for hepatocellular carcinoma (HCC) in patients (pts) revealed a promising improvement in overall survival (OS). Here we report the findings on safety and efficacy of an Asian Phase I/II study on first-line combination therapy with sorafenib and resminostat in HCC pts. Methods: Pts with advanced or metastatic HCC considered Child-Pugh A and ECOG 0/1 were enrolled in Japan and Korea. Sorafenib was administered at 400 mg (bid) in both Phase I and II. Resminostat was administered on days 1 to 5 every 14 days. In Phase I, the dose of resminostat was escalated from 400 mg/day (DL1) to 600 mg/day (DL2). In Phase II, pts were randomly assigned to sorafenib monotherapy or sorafenib/resminostat combination therapy at a ratio of 1:1. The primary endpoint was time to progression (TTP). Tumor response was assessed according to RECIST version 1.1 every 6 weeks. Results: A total of 9 pts were enrolled in Phase I (DL1, 3 pts; DL2, 6 pts). Higher incidences of G3-4 toxicities, including one DLT (G4 thrombocytopenia), were observed at DL2. Therefore, DL1 was determined as the recommended dose for Phase II. A total of 170 pts were enrolled in Phase II. The median TTP was 2.8 months in the combination and control arm, respectively (HR: 0.984). No significant difference was observed in the median OS. Retrospective analysis revealed favorable results for the combination option in certain subgroups: for example, HBV+ (TTP: HR, 0.630; OS: HR, 0.846); no prior therapy (TTP: HR, 0.629; OS: HR, 0.590); and platelet count > = 151.000 (TTP: HR, 0.646; OS: HR, 0.509). Conclusions: Although the primary endpoint was not reached in this Phase II all-comer HCC study, the results of the subgroup analysis suggest a population-specific effect for the combination therapy, especially in one which is HBV+. This warrants the further development of this combination as first-line therapy in a well-defined subset of pts with advanced HCC. Clinical trial information: NCT02400788.

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