ArticleLiterature Review

Management of acute pulmonary thromboembolism

Authors:
  • Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado de Baja California
  • UMAE Cardiología Centro Médico Nacional Siglo XXI
Article

Management of acute pulmonary thromboembolism

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Abstract

Acute pulmonary embolism (APE) is considered a cardiovascular emergency and is one of the most important causes of morbidity and mortality in hospitalized patients. Pulmonary embolism diagnosis has to be made early in the course of the disease and its management installed immediately. Pulmonary embolism management includes hemodynamic support, anticoagulation, thrombolysis and embolectomy. We present an overview of the treatment of APE.

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... Certain patients are unable to benefit from this treatment due to contraindications to thrombolysis. Surgical thrombectomy of the pulmonary artery is also associated with high mortality and disability risks (13). However, advances in interventional therapies and instruments mean that the interventional treatment of acute MPE has achieved satisfactory effects and has received increasing attention (14). ...
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Pulmonary embolism may escape prompt diagnosis since clinical symptoms and signs are nonspecific. The occurrence of syncope as the sole initial symptom in a previously healthy patient with no predisposing factors to embolism and no hemodynamic instability is extremely rare, which may have been a factor in the delayed diagnosis. We describe a case of agnogenic massive pulmonary embolism with syncope as the initial symptom. A 41-year-old previously healthy female was admitted to the Department of Neurology, Taizhou People's Hospital in March 2012, for two transitory episodes of syncope during a 5-h period. Following admission, chest computed tomography demonstrated embolism in the right main pulmonary and left inferior pulmonary arteries. Color ultrasonography revealed a dilated right ventricle and right heart overload, severe tricuspid regurgitation and severe pulmonary hypertension. Following the final diagnosis, the patient was successfully treated with interventional mechanical thrombectomy combined with thrombolytic therapy with local and systemic low-dose urokinase. We consider that raised awareness and early diagnosis and treatment were key factors in ensuring a satisfactory prognosis.
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To test the efficacy of thrombolytic therapy in massive pulmonary embolism, we conducted a prospective randomized controlled trial. Eight patients were randomized to receive either 1,500,000 IU of streptokinase in 1 hour through a peripheral vein followed by heparin or heparin alone. All patients had major risk factors for deep vein thrombosis (DVT) and were considered to have high clinical suspicion for pulmonary embolism (PE). At baseline all patients had a similar degree of systemic arterial hypotension, pulmonary arterial hypertension, and right ventricular dysfunction. The time of onset of cardiogenic shock in both groups was comparable (2.25 0.5 hours in the streptokinase group and 1.75 0.96 hours in the heparin group). The four patients who were randomized to streptokinase improved in the first hour after treatment, survived, and in 2 years of follow-up are without pulmonary arterial hypertension. All four patients treated with heparin alone died from 1 to 3 hours after arrival at the emergency room (p=0.02). Post-thrombolytic therapy the diagnosis of PE was sustained in the streptokinase group by high probability V/Q lung scans and proven DVT. A necropsy study performed in three patients in the heparin group showed massive pulmonary embolism and right ventricular myocardial infarction, without significant coronary arterial obstruction. The results indicate that thrombolytic therapy reduces the mortality rate of massive acute pulmonary embolism.
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This is a retrospective study documenting the use of tenecteplase in 41 cases of suspected or confirmed pulmonary embolism receiving in-hospital tenecteplase as per weight-adjusted dosing in addition to standard heparin and oral anticoagulant therapy. The presenting symptoms of dyspnoea, chest pain, hemoptysis and syncope were found in 40 (97.56%), 19 (46.34%), 6 (14.63%) and 9 (21.95%) patients, respectively. There was one case of mortality who was a 26 yrs old female of postpartum pulmonary thrombo-embolism with severe hypotension, cyanosis, bilateral crepitations in lungs and pulmonary hypertension. In the 40 survived patients, there was alleviation of dyspnoea and hemoptysis in all patients. Significant reduction in tachycardia (P < 0.0001) and increase in the oxygen saturation (SaO₂) (P < 0.0001) were seen at discharge as compared to at the time of presentation. Eighteen patients had hypotension which recovered in all patients till the time of discharge (P < 0.0001). There was a significant reduction in right ventricular systolic pressure in all 18 patients who underwent 2-D echocardiography both before and after the tenecteplase therapy. Resolution of pulmonary embolism on CT pulmonary angiography was documented in only two patients. No bleeding events or any other adverse events were reported during this study. The present study suggests favourable efficacy of tenecteplase in patients with suspected or confirmed acute pulmonary embolism. Although no major adverse events were noted, a large prospective study on the use of tenecteplase in pulmonary embolism is suggested.
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Objetivo: Evaluar la eficacia y seguridad del tratamiento de la tromboembolia pulmonar submasiva (TEP) con enoxaparina en comparación con heparina no fraccionada. Pacientes y métodos: Se incluyó en el estudio, de forma prospectiva, a 56 pacientes con TEP que no precisaron tratamiento fibrinolítico. Se asignaron de forma aleatoria a dos grupos de tratamiento: el grupo A, que recibió enoxaprina (1 mg/kg cada 12 h) y el grupo B, al que se le administraron dosis ajustadas de heparina no fraccionada. La anticoagulación oral se inició una vez que el diagnóstico se comprobó y se mantuvo durante 6 meses. Se evaluó la incidencia de recurrencia tromboembólica y de hemorragia mayor al cabo de ese tiempo. Resultados: Seis pacientes fueron excluidos del estudio. De los 50 finalmente incluidos, 29 fueron asignados al grupo A (enoxaparina) y 21 al grupo B (heparina no fraccionada). Tres pacientes del grupo A (10,7%) fueron diagnosticados de recurrencia tromboembólica, mientras que dicha complicación se constató en dos pacientes del grupo B (9,5%). No se encontraron diferencias significativas. Dos pacientes fallecieron, siendo una de las muertes achacada a hemorragia secundaria a la anticoagulación oral (grupo A) y la otra a un proceso independiente a la enfermedad tromboembólica. Conclusiones: El empleo de enoxaparina en el tratamiento inicial del TEP parece ser tan efectivo y seguro como el uso de heparina no fraccionada
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Propagation of venous thrombi or rethrombosis after coronary thrombolytic therapy can occur despite heparin administration. To explore potential mechanisms, we set out to determine whether clot-bound thrombin is relatively protected from inhibition by heparin-antithrombin III but susceptible to inactivation by antithrombin III-independent inhibitors. Using plasma fibrinopeptide A (FPA) levels as an index of thrombin activity, we compared the ability of thrombin inhibitors to block FPA release mediated by fluid-phase thrombin with their activity against the clot-bound enzyme. Incubation of thrombin with citrated plasma results in concentration-dependent FPA generation, which reaches a plateau within minutes. In contrast, there is progressive FPA generation when fibrin clots are incubated with citrated plasma. Heparin, hirudin, hirudin dodecapeptide (hirugen), and D-phenylalanyl-L-prolyl-L-arginyl chloromethyl ketone (PPACK) produce concentration-dependent inhibition of FPA release mediated by fluid-phase thrombin. However, heparin is much less effective at inhibiting thrombin bound to fibrin because a 20-fold higher concentration is necessary to block 70% of the activity of the clot-bound enzyme than is required for equivalent inhibition of fluid-phase thrombin (2.0 and 0.1 U/ml, respectively). In contrast, hirugen and PPACK are equally effective inhibitors of fluid- and solid-phase thrombin, while hirudin is only 50% as effective against the clot-bound enzyme. None of the inhibitors displace bound 125I-labeled thrombin from the clot. These studies indicate that (a) clot-bound thrombin is relatively protected from inhibition by heparin, possibly because the heparin binding site on thrombin is inaccessible when the enzyme is bound to fibrin, and (b) clot-bound thrombin is susceptible to inactivation by antithrombin III-independent inhibitors because the sites of their interaction are not masked by thrombin binding to fibrin. For these reasons, antithrombin III-independent inhibitors may be more effective than heparin in certain clinical settings.
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The management of heparin therapy in patients who have a subtherapeutic activated partial thromboplastin time (APTT) despite high doses of heparin is problematic because the risk of heparin-associated bleeding increases with dose. Results of experimental studies in animals indicate that when the APTT response to heparin is blunted by infusion of procoagulants, dose escalation can be avoided without compromising efficacy, by monitoring treatment with a heparin assay. A randomized, controlled trial was conducted in which patients with acute deep vein thrombosis, pulmonary embolism, or axillary vein thrombosis who required 35,000 U or more of intravenous heparin by continuous infusion during the previous 24 hours were allocated to have their heparin therapy monitored either by anti-factor Xa levels (targeted range, 0.35 to 0.67 U/mL) or by the APTT (targeted range, 60 to 85 seconds). Both ranges were equivalent to a heparin level of 0.2 to 0.4 U/mL by protamine titration. Three (4.6%) of 65 patients in the anti-factor Xa group experienced recurrent venous thromboembolism compared with four (6.1%) of 66 patients in the APTT group (difference, 1.5%; confidence interval, -6.7% to 8.4%) (P = .7). There were four bleeding events (6.1%) in the APTT group compared with one (1.5%) in the anti-factor Xa group (difference, 4.6%; confidence interval, -3.3% to 7.5%) (P = .4). During the period of heparin therapy before warfarin treatment was begun, the patients in the APTT group required a statistically significantly greater amount of heparin compared with the patients in the anti-factor Xa group. The daily mean APTT was subtherapeutic in patients in the anti-factor Xa group, and it was within the therapeutic range in the APTT group. The daily mean anti-factor Xa levels for both groups were within the therapeutic range. The heparin assay is a safe and effective method for monitoring heparin treatment in patients with acute venous thromboembolism whose APTT remains subtherapeutic despite large daily doses of heparin. In such patients, dosage escalation can be avoided if the heparin level is therapeutic.
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The standard initial treatment of hemodynamically stable patients with pulmonary embolism is intravenous unfractionated heparin, requiring laboratory monitoring and hospitalization. We conducted a randomized, open-label trial involving 2213 patients with acute symptomatic pulmonary embolism to compare the efficacy and safety of the synthetic antithrombotic agent fondaparinux with those of unfractionated heparin and to document noninferiority in terms of efficacy. Patients received either fondaparinux (5.0, 7.5, or 10.0 mg in patients weighing less than 50, 50 to 100, or more than 100 kg, respectively) subcutaneously once daily or a continuous intravenous infusion of unfractionated heparin (ratio of the activated partial-thromboplastin time to a control value, 1.5 to 2.5), both given for at least five days and until the use of vitamin K antagonists resulted in an international normalized ratio above 2.0. The primary efficacy outcome was the three-month incidence of the composite end point of symptomatic, recurrent pulmonary embolism (nonfatal or fatal) and new or recurrent deep-vein thrombosis. Forty-two of the 1103 patients randomly assigned to receive fondaparinux (3.8 percent) had recurrent thromboembolic events, as compared with 56 of the 1110 patients randomly assigned to receive unfractionated heparin (5.0 percent), for an absolute difference of -1.2 percent in favor of fondaparinux (95 percent confidence interval, -3.0 to 0.5). Major bleeding occurred in 1.3 percent of the patients treated with fondaparinux and 1.1 percent of those treated with unfractionated heparin. Mortality rates at three months were similar in the two groups. Of the patients in the fondaparinux group, 14.5 percent received the drug in part on an outpatient basis. Once-daily, subcutaneous administration of fondaparinux without monitoring is at least as effective and is as safe as adjusted-dose, intravenous administration of unfractionated heparin in the initial treatment of hemodynamically stable patients with pulmonary embolism.
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Low-molecular-weight heparin has greatly simplified the management of deep venous thrombosis. However, for patients who present with pulmonary embolism, the role of low-molecular-weight heparin is uncertain and unfractionated heparin remains widely used. To compare the efficacy and safety of fixed-dose subcutaneous low-molecular-weight heparin with that of dose-adjusted intravenous unfractionated heparin to treat acute pulmonary embolism. The MEDLINE, EMBASE, and Cochrane Library databases were searched up to 1 August 2003. Additional data sources were manual searches of abstract proceedings and personal contact with investigators and pharmaceutical companies. Randomized trials comparing fixed-dose subcutaneous low-molecular-weight heparin with dose-adjusted intravenous unfractionated heparin for the treatment of nonmassive symptomatic pulmonary embolism or asymptomatic pulmonary embolism in the context of symptomatic deep venous thrombosis. Two reviewers independently selected studies and extracted data on study design; quality; and clinical outcomes, including symptomatic venous thromboembolism, death, and major and minor bleeding. Odds ratios for individual outcomes were calculated for each trial and were pooled by using the Mantel-Haenszel method. Fourteen trials involving 2110 patients with pulmonary embolism met the inclusion criteria. Separate outcome data for patients with pulmonary embolism were not available from 2 trials (159 patients), leaving 12 trials for meta-analysis. Compared with unfractionated heparin, low-molecular-weight heparin was associated with a non-statistically significant decrease in recurrent symptomatic venous thromboembolism at the end of treatment (1.4% vs. 2.4%; odds ratio, 0.63 [95% CI, 0.33 to 1.18]) and at 3 months (3.0% vs. 4.4%; odds ratio, 0.68 [CI, 0.42 to 1.09]). Similar estimates were obtained for patients who presented with symptomatic pulmonary embolism (1.7% vs. 2.3%; odds ratio, 0.72 [CI, 0.35 to 1.48]) or asymptomatic pulmonary embolism (1.2% vs. 3.2%; odds ratio, 0.53 [CI, 0.15 to 1.88]). For major bleeding complications, the odds ratio favoring low-molecular-weight heparin (1.3% vs. 2.1%; odds ratio, 0.67 [CI, 0.36 to 1.27]) was also not statistically significant. Fixed-dose low-molecular-weight heparin treatment appears to be as effective and safe as dose-adjusted intravenous unfractionated heparin for the initial treatment of nonmassive pulmonary embolism.
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To establish the prevalence of pulmonary embolism (PE) in autopsy material at a tertiary cardiac referral center and its importance as a cause of death in patients with heart disease (HD). Case series. National Heart Institute, Mexico City. One thousand thirty-two patients who died at our institution from 1985 to 1994 in whom an autopsy study was performed. Of the 1,032 autopsies reviewed, 231 cases (24.4%) of PE were found; 100 of these patients had a diagnosis of massive PE. Massive PE (obstruction of either of the main pulmonary arteries or more than two lobar arteries) was found to be the third cause of death in this HD population. By age-group distribution, the global prevalence of massive events was higher in patients < 10 years old. Clinical suspicion (premortem) was raised in only 18% of the cases. PE was a frequent cause of morbidity and mortality in patients with HD who underwent autopsies. The incidence of massive PE was high in children.
Article
Experiments in animals have demonstrated that recombinant tissue plasminogen activator (rt-PA) produces continuing thrombolysis after it is cleared from the circulation and that thrombolysis is both increased and accelerated, and bleeding is reduced when rt-PA is administered over a short period. In previous studies in patients with thrombotic disease, rt-PA has been shown to be an effective thrombolytic agent when administered by continuous infusion over a period between 90 minutes and 8 hours. To determine whether a short course regimen of rt-PA can achieve thrombolysis, a double-blind randomized trial has been conducted in which patients with objectively established acute symptomatic pulmonary embolism who were receiving heparin were allocated to either a 2-minute infusion of rt-PA at a dose of 0.6 mg/kg (33 patients) or saline placebo (25 patients). Perfusion lung scanning was used to assess the change in pulmonary perfusion at 24 hours and seven days post-study drug administration. Thirty-four percent of the rt-PA patients had a greater than 50 percent resolution in the perfusion defect at 24 hours compared to 12 percent of placebo patients (p = 0.026). At 24 hours, the mean relative improvement in the perfusion defect was 37.0 percent in rt-PA treated patients compared to 18.8 percent in the placebo group (p = 0.017). By day 7, no difference in lung scan resolution was detected between the groups. There were no major bleeds in either group nor were there any differences in transfusion requirements between groups. Minor bleeding occurred in 15 of the rt-PA patients mainly at angiogram-catheter insertion and venipuncture sites. These results suggest that a bolus regimen of rt-PA produces accelerated thrombolysis and provides an alternative and convenient approach to thrombolytic therapy in patients with pulmonary embolism.
Article
Background: Low-molecular-weight heparin has greatly simplified the management of deep venous thrombosis. However, for patients who present with pulmonary embolism, the role of low-molecular-weight heparin is uncertain and unfractionated heparin remains widely used. Purpose: To compare the efficacy and safety of fixed-dose subcutaneous low-molecular-weight heparin with that of dose-adjusted intravenous unfractionated heparin to treat acute pulmonary embolism. Data Sources: The MEDLINE, EMBASE, and Cochrane Library databases were searched up to 1 August 2003. Additional data sources were manual searches of abstract proceedings and personal contact with investigators and pharmaceutical companies. Study Selection: Randomized trials comparing fixed-dose subcutaneous low-molecular-weight heparin with dose-adjusted intravenous unfractionated heparin for the treatment of nonmassive symptomatic pulmonary embolism or asymptomatic pulmonary embolism in the context of symptomatic deep venous thrombosis. Data Extraction: Two reviewers independently selected studies and extracted data on study design; quality; and clinical outcomes, including symptomatic venous thromboembolism, death, and major and minor bleeding. Odds ratios for individual outcomes were calculated for each trial and were pooled by using the Mantel-Haenszel method. Data Synthesis: Fourteen trials involving 2110 patients with pulmonary embolism met the inclusion criteria. Separate outcome data for patients with pulmonary embolism were not available from 2 trials (159 patients), leaving 12 trials for meta-analysis. Compared with unfractionated heparin, low-molecular-weight heparin was associated with a non-statistically significant decrease in recurrent symptomatic venous thromboembolism at the end of treatment (1.4% vs. 2.4%; odds ratio, 0.63 [95% Cl, 0.33 to 1.18]) and at 3 months (3.0% vs. 4.4%; odds ratio, 0.68 [Cl, 0.42 to 1.09]). Similar estimates were obtained for patients who presented with symptomatic pulmonary embolism (1.7% vs. 2.3%; odds ratio, 0.72 [Cl, 0.35 to 1.48]) or asymptomatic pulmonary embolism (1.2% vs. 3.2%; odds ratio, 0.53 [Cl, 0.15 to 1.88]). For major bleeding complications, the odds ratio favoring low-molecular-weight heparin (1.3% vs. 2.1%; odds ratio, 0.67 [Cl, 0.36 to 1.27]) was also not statistically significant Conclusions: Fixed-dose low-molecular-weight heparin treatment appears to be as effective and safe as dose-adjusted intravenous unfractionated heparin for the initial treatment of nonmassive pulmonary embolism.
Article
Objectives: The present study investigated current management strategies as well as the clinical course of acute major pulmonary embolism. Background: The clinical outcome of patients with acute pulmonary embolism who present with overt or impending right heart failure has not yet been adequately elucidated. Methods: The 204 participating centers enrolled a total of 1,001 consecutive patients. The inclusion criteria were based on the clinical findings at presentation and the results of electrocardiographic, echocardiographic, nuclear imaging and cardiac catheterization studies. Results: Echocardiography was the most frequently performed diagnostic procedure (74%). Lung scan or pulmonary angiography were performed in 79% of clinically stable patients but much less frequently in those with circulatory collapse at presentation (32%, p < 0.001). Thrombolytic agents were given to 478 patients (48%), often despite the presence of contraindications (193 [40%] of 478). The frequency of initial thrombolysis was significantly higher in clinically unstable than in normotensive patients (57% vs. 22%, p < 0.001). Overall in-hospital mortality rate ranged from 8.1% in the group of stable patients to 25% in those presenting with cardiogenic shock and to 65% in patients necessitating cardiopulmonary resuscitation. Major bleeding was reported in 92 patients (9.2%), but cerebral bleeding was uncommon (0.5%). Finally, recurrent pulmonary embolism occurred in 172 patients (17%). Conclusions: Current management strategies of acute major pulmonary embolism are largely dependent on the degree of hemodynamic instability at presentation. In the presence of severe hemodynamic compromise, physicians often rely on the findings of bedside echocardiography and proceed to thrombolytic treatment without seeking further diagnostic certainty in nuclear imaging or angiographic studies.
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The scope and spectrum of pulmonary embolism (PE) that are likely to challenge the intensivist are dominantly confined to 2 scenarios; first, a patient presenting with undifferentiated shock or respiratory failure and, second, an established intensive care unit (ICU) or hospital patient who develops hemodynamically unstable PE after admission. In either scenario, the diagnostic approach and therapeutic options are challenging. Differentiating PE from other life-threatening cardiopulmonary disorders can be exceedingly difficult. This article will review a structured pathophysiologic approach to the diagnostic, resuscitative and management strategies related to PE in the ICU.
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This article concerning the pharmacokinetics and pharmacodynamics of vitamin K antagonists (VKAs) is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). It describes the antithrombotic effect of the VKAs, the monitoring of anticoagulation intensity, and the clinical applications of VKA therapy and provides specific management recommendations. Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh the risks, burdens, and costs. Grade 2 recommendations suggest that the individual patient's values may lead to different choices. (For a full understanding of the grading, see the "Grades of Recommendation" chapter by Guyatt et al, CHEST 2008; 133:123S-131S.) Among the key recommendations in this article are the following: for dosing of VKAs, we recommend the initiation of oral anticoagulation therapy, with doses between 5 mg and 10 mg for the first 1 or 2 days for most individuals, with subsequent dosing based on the international normalized ratio (INR) response (Grade 1B); we suggest against pharmacogenetic-based dosing until randomized data indicate that it is beneficial (Grade 2C); and in elderly and other patient subgroups who are debilitated or malnourished, we recommend a starting dose of < or = 5 mg (Grade 1C). The article also includes several specific recommendations for the management of patients with nontherapeutic INRs, with INRs above the therapeutic range, and with bleeding whether the INR is therapeutic or elevated. For the use of vitamin K to reverse a mildly elevated INR, we recommend oral rather than subcutaneous administration (Grade 1A). For patients with life-threatening bleeding or intracranial hemorrhage, we recommend the use of prothrombin complex concentrates or recombinant factor VIIa to immediately reverse the INR (Grade 1C). For most patients who have a lupus inhibitor, we recommend a therapeutic target INR of 2.5 (range, 2.0 to 3.0) [Grade 1A]. We recommend that physicians who manage oral anticoagulation therapy do so in a systematic and coordinated fashion, incorporating patient education, systematic INR testing, tracking, follow-up, and good patient communication of results and dose adjustments [Grade 1B]. In patients who are suitably selected and trained, patient self-testing or patient self-management of dosing are effective alternative treatment models that result in improved quality of anticoagulation management, with greater time in the therapeutic range and fewer adverse events. Patient self-monitoring or self-management, however, is a choice made by patients and physicians that depends on many factors. We suggest that such therapeutic management be implemented where suitable (Grade 2B).
Article
Since publication of the seventh American College of Chest Physicians (ACCP) supplement on antithrombotic and thrombolytic therapy, the results of clinical trials have provided important new information on the management of thromboembolic disorders, and the science of developing recommendations has advanced. In the accompanying supplement, we provide the new and updated recommendations and review several important changes that we have made in our guideline development process. We again made a conscious effort to increase the participation of female authors and contributors from outside North America, the latter reflecting the widespread use and dissemination of these guidelines internationally. The grading system for the recommendations was adopted in 2006 by the ACCP for all its guidelines, is similar to the increasingly widely used Grades of Recommendation, Assessment, Development, and Evaluation approach, and is described in detail in one of the introductory chapters. While most of the evidence on which recommendations are made remains low quality in fields of pediatric thrombosis, thrombosis in pregnancy, and thrombosis in valvular heart disease, rigorous studies in other fields have resulted in new and strong evidence-based recommendations for many indications.
Article
Intravenous tissue-type plasminogen activator (IV tPA) frequently fails to recanalize proximal middle cerebral artery (MCA-M1) obstructions, preventing favorable outcomes. Only neurointerventional procedures prevail in these cases, but well-equipped centers remain scarce. A new therapeutic strategy consisting of a second IV thrombolysis with low-dose tenecteplase was applied. Consecutive patients with an MCA-M1 occlusion that did not reopen at the end of IV tPA perfusion received IV tenecteplase (0.1 mg/kg). Partial or complete thrombolysis in myocardial infarction recanalization (Thrombolysis In Myocardial Infarction grade 2/3) and intracerebral hemorrhage were assessed by magnetic resonance aging approximately 24 hours later. Clinical outcomes at 3 months were evaluated with the modified Rankin score. Among 40 patients with MCA-M1 occlusions who received IV tPA, 13 were treated according to the protocol of sequential combined IV thrombolytics. Baseline National Institutes of Health Stroke Scale score was 15. At a mean of 16.8 hours after IV thrombolysis, the recanalization rate was 100% (2 with Thrombolysis In Myocardial Infarction grade 2, 11 with Thrombolysis In Myocardial Infarction grade 3). Intracerebral hemorrhage occurred in 4 of 13 (31%) patients, with no symptomatic hemorrhage. Good clinical outcomes (modified Rankin score = 0/1) were achieved in 9 of 13 (69%) patients. Functional outcomes were very similar to those of 13 patients with early IV-tPA recanalization. Among 4 patients treated as protocol violations, 1 presented with a lack of recanalization and a parenchymal hematoma type 2. For patients with MCA-M1 occlusions treated with IV tPA but without early recanalization, a second bolus of IV tenecteplase (0.1 mg/kg) may be a relatively safe, effective, and easy option in carefully selected cases, but additional studies are needed to confirm these findings.
Article
The purpose of this study was to evaluate and compare our recent clinical experience with temporary inferior vena cava (IVC) filters (TF) and retrievable IVC filters (RF). Patients who received TF or RF implantation between October 2002 and May 2009 were studied. The early clinical outcomes between the 2 groups were compared. Nonpermanent IVC filters were placed in 119 patients (34 in TF and 85 in RF). Retrieval of RF and removal of TF were successful in 98.7% and 100%, respectively. The incidence of filter-related complications for TF was significantly higher than for RF (26.5% vs 3.5%; P = .0004). However, no symptomatic pulmonary embolism (PE) was observed during filter placement. TF and RF provided similar protection from PE. We prefer RF because they can be left in permanently if it is impossible to remove or retrieve the filter for some reason.
Article
Treatment with streptokinase or heparin was allocated randomly to 20 patients with major pulmonary embolism verified by angiography. In addition, 4 patients treated with streptokinase and 1 patient treated with heparin were included in the trial prior to the start of treatment. Streptokinase of heparin was given for 72 hours and pulmonary angiography was repeated. The angiographic evidence of thrombolysis was significantly greater (p less than 0.01) in the 14 patients treated with streptokinase than in the 11 treated with heparin. In the heparin group, 1 patient died from massive embolism 15 hours after the start of treatment. In another patient who died 4 weeks later from cerebral glibolastoma, persistent massive embolism contributed to the fatal outcome. In the streptokinase group, 1 patient with a metastatic pulmonary carcinoma died 3 weeks after the start of treatment from gangrene of both legs following thrombotic occlusion of the inferior vena cava. Bleeding was more common after treatment with streptokinase than with heparin, but was not a serious problem in any patient. It is concluded that patients with life-threatening pulmonary embolism should be offered the benefits of streptokinase.
Article
We compared the efficacy and safety of different dosages of a low-molecular-weight heparin, CY 216 D (Fraxiparine), in the treatment of submassive pulmonary embolism with unfractionated heparin in a prospective, randomized, dose-finding study. The primary outcome was the evolution of pulmonary vascular obstruction. We enrolled 101 patients. Four patient groups were formed: standard heparin by continuous intravenous infusion (group 1) and Fraxiparine subcutaneously 400, 600, and 900 anti-Xa Institute Choay units/kg, respectively (groups 2, 3, and 4). Inclusions were stopped prematurely in groups 3 and 4 because of the incidence of major bleedings. At day 8, the improvement of the pulmonary vascular obstruction and the major bleedings were similar in groups 1 and 2. The Fraxiparine dosage of 400 anti-Xa Institute Choay units/kg is as effective and safe as unfractionated heparin in the treatment of submassive pulmonary embolism.
Article
The effect of alteplase versus heparin in pulmonary embolism has not been studied extensively with serial pulmonary angiograms. The aim of this randomized, open trial was to evaluate the efficacy and safety of alteplase followed by heparin, versus heparin alone, in 36 patients with angiographically documented pulmonary embolism. Twenty patients were allocated randomly to a 2-h infusion of alteplase (10 mg bolus, then 90 mg over 2 h) followed by heparin; the other 16 patients were given intravenous heparin at a continuous infusion rate of 1,750 IU/h. The vascular obstruction, assessed by the Miller index at pulmonary angiography, decreased significantly in alteplase-treated patients (p less than 0.01) from a baseline of 28.3 +/- 2.9 to a value of 24.8 +/- 5.2 2 h after the start of infusion; in the heparin group there was no change (from 25.3 +/- 5.3 to 25.2 +/- 5.4). Mean pulmonary artery pressure decreased significantly from a baseline of 30.2 +/- 7.8 mm Hg to 21.4 +/- 6.7 in the alteplase group and increased in the heparin group (from 22.3 +/- 10.5 to 24.8 +/- 11.2 mm Hg). For a subset of patients, lung scans were performed at baseline and on days 7 and 30. There were no differences between the two groups in the follow-up lung scans, but there were significant decreases from the baseline values. Bleeding occurred in 14 of 20 alteplase-treated patients and in 6 of 16 in the heparin group (p = NS). There were three major bleeding episodes in the alteplase group and two in the heparin group. Two patients died after fibrinolysis (one of acute renal failure after cardiac tamponade and one of cardiac arrest after cerebral hemorrhage) and one patient in the heparin group died of recurrent pulmonary embolism. Alteplase resulted in a greater and faster improvement of the angiographic and hemodynamic variables compared with heparin. However, the high frequency of bleeding observed with alteplase in this trial suggests that patients should be carefully selected before thrombolytic therapy is given.
Article
Low-molecular-weight heparin has a high bioavailability and a prolonged half-life in comparison with conventional unfractionated heparin. Limited data are available for low-molecular-weight heparin as compared with unfractionated heparin for the treatment of deep-vein thrombosis. In a multicenter, double-blind clinical trial, we compared fixed-dose subcutaneous low-molecular-weight heparin given once daily with adjusted-dose intravenous heparin given by continuous infusion for the initial treatment of patients with proximal-vein thrombosis, using objective documentation of clinical outcomes. Six of 213 patients who received low-molecular-weight heparin (2.8 percent) and 15 of 219 patients who received intravenous heparin (6.9 percent) had new episodes of venous thromboembolism (P = 0.07; 95 percent confidence interval for the difference, 0.02 percent to 8.1 percent). Major bleeding associated with initial therapy occurred in 1 patient receiving low-molecular-weight heparin (0.5 percent) and in 11 patients receiving intravenous heparin (5.0 percent), a reduction in risk of 91 percent (P = 0.006). This apparent protection against major bleeding was lost during long-term therapy. Minor hemorrhagic complications were infrequent. Ten patients receiving low-molecular-weight heparin (4.7 percent) died, as compared with 21 patients receiving intravenous heparin (9.6 percent), a risk reduction of 51 percent (P = 0.049). Low-molecular-weight heparin is at least as effective and as safe as classic intravenous heparin therapy under the conditions of this study and more convenient to administer. The simplified therapy provided by low-molecular-weight heparin may allow patients with uncomplicated proximal deep-vein thrombosis to be cared for in an outpatient setting.
We investigated interactions between cardiac output, VA/Q distribution pattern, pulmonary gas exchange, O2 transport, and tissue oxygenation in 16 patients during the acute phase of pulmonary embolism (PE). The effects of breathing room air, O2 therapy (FIO2 = 0.40) (11 patients), and dobutamine (four patients) were studied after right catheterization using the multiple inert gas elimination technique. The pattern of VA/Q ratio distributions was found to depend essentially on cardiac output level. The individual blood flow perfusing ventilated areas was found to be inversely related to the mean VA/Q ratio of blood flow distribution. PVO2 was directly related to cardiac index (p less than 0.02), and negatively related to the mean VA/Q of blood flow distribution. In view of the influence of low VA/Q ratios and PVO2 on arterial hypoxemia, our results showed that the heart's response to PE conditioned the strategy of pulmonary gas exchange and O2 transport. Oxygen breathing led to a slight but consistent fall in cardiac output (-0.6 +/- 0.5 L/min, p less than 0.01). However, although PaO2 remained normal and PVO2 was slightly improved, we found no evidence for a role of hypoxic pulmonary vasoconstriction in the pulmonary hypertension observed during the acute phase of PE. Administration of dobutamine improved O2 transport and tissue oxygenation, although PaO2 remained constant or even fell in some cases because of increased VA/Q mismatch.
Article
Experiments in animals have demonstrated that recombinant tissue plasminogen activator (rt-PA) produces continuing thrombolysis after it is cleared from the circulation and that thrombolysis is both increased and accelerated, and bleeding is reduced when rt-PA is administered over a short period. In previous studies in patients with thrombotic disease, rt-PA has been shown to be an effective thrombolytic agent when administered by continuous infusion over a period between 90 minutes and 8 hours. To determine whether a short course regimen of rt-PA can achieve thrombolysis, a double-blind randomized trial has been conducted in which patients with objectively established acute symptomatic pulmonary embolism who were receiving heparin were allocated to either a 2-minute infusion of rt-PA at a dose of 0.6 mg/kg (33 patients) or saline placebo (25 patients). Perfusion lung scanning was used to assess the change in pulmonary perfusion at 24 hours and seven days post-study drug administration. Thirty-four percent of the rt-PA patients had a greater than 50 percent resolution in the perfusion defect at 24 hours compared to 12 percent of placebo patients (p = 0.026). At 24 hours, the mean relative improvement in the perfusion defect was 37.0 percent in rt-PA treated patients compared to 18.8 percent in the placebo group (p = 0.017). By day 7, no difference in lung scan resolution was detected between the groups. There were no major bleeds in either group nor were there any differences in transfusion requirements between groups. Minor bleeding occurred in 15 of the rt-PA patients mainly at angiogram-catheter insertion and venipuncture sites. These results suggest that a bolus regimen of rt-PA produces accelerated thrombolysis and provides an alternative and convenient approach to thrombolytic therapy in patients with pulmonary embolism.
Article
Management of patients with the adult respiratory distress syndrome should be directed toward maintaining adequate cardiac output and tissue oxygenation without exacerbating pulmonary edema. The aim of therapy should be to maintain low left ventricular filling pressure, which will tend to decrease the rate of edema formation. If cardiac output is low or decreases as a function of therapy, flow may be increased with inotropic agents. When a marked decline in cardiac output complicates pulmonary embolism, norepinephrine may be an excellent drug for at least short-term maintenance of hemodynamic stability. When a moderate decrease in cardiac output complicates an increase in right ventricular afterload, isoproterenol or dobutamine may be used to increase flow. Rapid administration of recombinant tissue plasminogen activator may be the treatment of choice of pulmonary thromboembolism associated with a low output state.
Article
Dissolution of pulmonary emboli with heparin and urokinase is ascribed, respectively, to anticoagulation and fibrinolysis. Since truly independent assessment of these effects in man is lacking, we administered each drug alone. Fibrinogen and plasminogen plasma levels and the resolution of pulmonary emboli were measured in three randomized groups of 10 patients each: groups A and C infused with small repeated doses of urokinase and a large single dose of urokinase, respectively, and group B who received heparin. After 6 h of treatment, fibrinogen fell in all the groups, while, after 12 h, remained equally reduced in groups A and B and declined further in group C. Plasminogen behaved similarly. Up to 60 h, statistical analysis showed that these effects were related to timing and amounts of urokinase and heparin infusion. These observations suggest that heparin may induce a lytic state. As to signs of pulmonary emboli resolution, no differences between groups were found in lung perfusion and gas exchange recovery at any time (from 1 day to 1 year) and in pulmonary artery pressure reduction at 1 week. The greater angiographic and scintigraphic recovery observed with urokinase, versus heparin alone, after 1 day of treatment in the Urokinase Pulmonary Embolism Trial may be ascribed to a synergistic effect with urokinase of heparin administered during the diagnostic work-out. The indications of heparin and urokinase should be evaluated in the light of these results.
Article
Intravenous dobutamine was used in ten patients requiring aggressive therapy for massive pulmonary embolism with circulatory failure. Except in one patient who rapidly died, a 30-min dobutamine infusion (8.3 +/- 2.7 micrograms/kg . min) increased both cardiac index (from 1.7 +/- 0.4 to 2.3 +/- 0.6 L/min . m2, p less than .001) and stroke index (from 16.6 +/- 6.7 to 21 +/- 5 ml/m2, p less than .01), and also reduced pulmonary vascular resistance. Additional hemodynamic improvement was observed until weaning from dobutamine, which was successfully completed 3.3 +/- 0.9 days after the start of infusion.
Article
A vacuum-cup device attached to a standard balloon-tipped catheter has been used successfully to extract large pulmonary emboli in dogs by a transvenous technique. Removal of pulmonary emboli in critically ill patients should be possible without the added burden of general anesthesia and thoracotomy.
Article
The authors investigated the effects of treatment on ventricular performance when cardiac output (CO) was reduced significantly because of an acute increase in pulmonary vascular resistance (PVR). In eight anesthetized, ventilated dogs, the effects of volume expansion (100 ml 6% dextran) on ventricular performance were determined before and after PVR was elevated. Resistance was increased by microembolization of the pulmonary vascular bed with glass beads (80-100 microns). When PVR was normal, volume expansion increased (P less than 0.05) stroke volume (SV) and mean blood pressure (BP). Alternatively, when RV afterload was increased, volume resulted in RV failure, i.e., decrease in SV (P less than 0.01) from 9.1 to 6.3 ml and a decrease (P less than 0.05) in mean BP from 97 to 65 mmHg, despite increased right ventricular end diastolic pressure (RVEDP) (P less than 0.05). Right ventricular dysfunction occurred with volume expansion, despite constant PVR and a decrease (P less than 0.01) in mean pulmonary artery pressure (PAP). In contrast to volume, norepinephrine infusion decreased biventricular filling pressures (P less than 0.01) and increased (P less than 0.01) SV from 6.2 to 11.3 ml. Accordingly, when RV afterload is increased significantly, even a relatively small increase in blood volume may result in RV dysfunction. Alternatively, inotropic agents with pressor effects may be the treatment of choice to increase CO when RV afterload is increased.
Article
Data from a non-randomised study have hinted that in patients with acute pulmonary embolism (PE), thrombolysis followed by heparin more rapidly reverses right-ventricular dysfunction and restores pulmonary tissue perfusion than does heparin alone. We have pursued this idea in a randomised protocol. 46 haemodynamically stable patients were randomised to recombinant tissue plasminogen activator (alteplase, rt-PA) 100 mg over 2 h followed by intravenous heparin and 55 to heparin alone. Right-ventricular wall motion was assessed qualitatively, and right-ventricular end diastolic area was estimated by planimetry from echocardiograms at baseline and at 3 and 24 hours. Pulmonary perfusion scans were obtained at baseline and 24 hours. In 39% of rt-PA patients but in only 17% of heparin alone patients right-ventricular wall motion at 24 hours had improved from baseline and in 2% and 17%, respectively, it worsened (p = 0.005). rt-PA patients also had a significant decrease in right-ventricular end-diastolic area during the 24 hours after randomisation and a significant absolute improvement in pulmonary perfusion (14.6% vs 1.5%). No clinical episodes of recurrent PE were noted among rt-PA patients, but there were 2 fatal and 3 non-fatal clinically suspected recurrent PEs within 14 days in patients randomised to heparin alone. rt-PA rapidly improves right-ventricular function and pulmonary perfusion among patients with PE and may lead to a lower rate of adverse clinical outcomes.
Article
Massive pulmonary embolism (PE), defined by systemic hypotension and need for inotropic support, has a high mortality rate. Transvenous catheter pulmonary embolectomy performed with the patient receiving local anesthetic provides an expeditious alternative to lytic therapy or open embolectomy on cardiopulmonary bypass. The indication for embolectomy in this series of 46 patients was hypotension despite inotropic support in all but four patients (91%); the latter sustained major embolism and were respirator dependent. In the first 10 patients treated from 1970 to 1974, a metal cup attached to a straight catheter was used. Hemodynamic improvement occurred in nine of 10 initial patients, but recurrent PE and a mortality rate of 50% prompted addition of a vena caval filter and directional control to the catheter. Subsequently 36 patients were treated with this combination from 1975 to 1992. Emboli were extracted in 76% (35 of 46) of the total series with a 30-day survival rate of 70% (32 of 46). Hemodynamic data showed an average reduction in mean pulmonary artery pressure of 8 mm Hg and a significant increase in mean cardiac output from 2.59 L/min to 4.47 L/min (p = 0.003) after embolectomy. Complications included wound hematoma (15%), pulmonary infarct (11%), recurrent deep venous thrombosis (6%), pleural effusion (4%), and myocardial infarction (4%). Successful embolectomy was most likely for categories of major PE (4 of 4, 100%) and massive PE (27 of 33, 82%) and least likely for chronic PE (5 of 9, 56%) (p < 0.03). Successful embolectomy also predicted long-term survival (p < 0.01), which was 89 months for the series (range 1 to 237 months). Catheter pulmonary embolectomy by surgeon and radiologist is of maximal benefit for major or massive PE but less likely to benefit patients with chronic recurrent PE.
Article
To assess the hemodynamic effects of fluid loading in patients with acute circulatory failure caused by acute massive pulmonary embolism (AMPE). Prospective study. Respiratory critical care unit of a university hospital. Thirteen patients free of previous cardiopulmonary disease with angiographically proven AMPE (Miller index = 24 +/- 1), with acute circulatory failure defined by a cardiac index (CI) lower than 2.5 L/min/m2. Infusion of 500 mL of dextran 40 over 20 mins. Fluid loading induced a substantial increase in right atrial pressure from 9 +/- 1 mm Hg to 17 +/- 1 mm Hg and in right ventricular end-diastolic volume index from 123 +/- 14 mL/m2 to 150 +/- 11 mL/m2 (p < .05 for both comparisons). The increase in right ventricular preload was associated with an increase in Cl from 1.6 +/- 0.1 to 2.0 +/- 0.1 L/min/m2 (p < .05), whereas right ventricular ejection fraction (15 +/- 3% at baseline vs. 16 +/- 3% after fluid loading) and total pulmonary vascular resistance index (1689 +/- 187 dyne x sec/cm5 x m2 at baseline vs. 1492 +/- 166 dyne x sec/ cm5 x m2 after fluid loading) remained unchanged. The increase in Cl induced by fluid loading was inversely correlated to baseline right ventricular end-diastolic volume index (r = -.89 ; p< .05). These results suggest that fluid loading can improve hemodynamic status in patients with acute circulatory failure caused by AMPE.
Article
Pulmonary embolism (PE) remains poorly understood. Rates of clinical outcomes such as death and recurrence vary widely among trials. We therefore established the International Cooperative Pulmonary Embolism Registry (ICOPER), with the aim of identifying factors associated with death. 2454 consecutive eligible patients with acute PE were registered from 52 hospitals in seven countries in Europe and North America. The primary outcome measure was all-cause mortality at 3 months. The prognostic effect of baseline factors on survival was assessed with multivariate analyses. 2110 (86.0%) patients had PE proven by necropsy, high-probability lung scan, pulmonary angiography, or venous ultrasonography plus high clinical suspicion; ICOPER accepted without independent review diagnoses and interpretation of imaging provided by participating centres; 3-month follow-up was completed in 98.0% of patients. The overall crude mortality rate at 3 months was 17.4% (426 of 2454 deaths, including 52 patients lost to follow-up): 179 of 397 (45.1%) deaths were ascribed to PE and 70 of 397 (17.6%) to cancer, and no information on the cause of death was available for 29 patients. After exclusion of 61 patients in whom PE was first discovered at necropsy, the mortality rate at 3 months was 15.3% (365 of 2393 deaths). On multiple-regression modelling, age over 70 years (hazard ratio 1.6 [95% CI 1.1-2.3]), cancer (2.3 [1.5-3.5]), congestive heart failure (2.4 [1.5-3.7]), chronic obstructive pulmonary disease (1.8 [1.2-2.7]), systolic arterial hypotension (2.9 [1.7-5.0]), tachypnoea (2.0 [1.2-3.2]), and right-ventricular hypokinesis on echocardiography (2.0 [1.3-2.9]) were identified as significant prognostic factors. PE remains an important clinical problem with a high mortality rate. Data from ICOPER provide rates and highlight adverse prognostic categories that will help in planning of future trials of high-risk PE patients.
Article
A 63-year-old woman was transferred to Brigham and Women’s Hospital with massive saddle pulmonary embolism (PE) diagnosed by chest CT scan. She was being treated at a suburban hospital for ulcerative colitis manifested by 10 episodes of bloody diarrhea daily. The diagnosis of PE was suspected when she suffered sudden onset of syncope and hypotension, followed by arterial oxygen desaturation and tachycardia. Echocardiography showed an extremely dilated right ventricle with septal flattening. At Brigham and Women’s Hospital, she underwent urgent cardiac catheterization. The mixed venous oxygen saturation percentage was in the 50s. Manual injection of contrast agent into the main pulmonary artery confirmed massive bilateral PE. A Gunther Tulip (Cook, Inc) vena caval filter was placed just below the renal veins, and she was taken to the operating room, where she underwent successful emergency pulmonary embolectomy (Figure 1). Figure 1. This pulmonary embolectomy specimen measures 11×6×1.5 cm in aggregate. Massive PE is life-threatening. Some patients may present with abrupt onset of critical illness, and others may suffer stuttering but progressive clinical deterioration despite therapeutic levels of anticoagulation. In the International Cooperative Pulmonary Embolism Registry (ICOPER) of 2454 consecutive patients from 7 countries,1 4.2% had massive PE. In the United States, ≈150 000 patients per year are diagnosed with acute PE,2 resulting in thousands of recognized deaths annually from massive PE. Many additional deaths occur each year in the United States as a result of undiagnosed massive PE that is mistaken for acute myocardial infarction or ventricular arrhythmia. The principal criteria for categorizing PE as massive are arterial hypotension and cardiogenic shock. Arterial hypotension is defined as a systolic arterial pressure <90 mm Hg or a drop in systolic arterial pressure of at least 40 mm Hg for at least 15 minutes.3 Shock is manifested by tissue hypoperfusion …
Article
To evaluate a percutaneous pulmonary embolism (PE) thrombectomy catheter that aspirates, macerates, and removes thrombus. Nine in vitro tests were performed by using porcine thrombi at a PE test station that provides continuous fluid output of 2 L/min at a pressure of 50 mmHg. Macroembolization was defined as embolized particles larger than 1.5 mm in dimension; microembolization was defined as particles that range in size from 0.1 to 1.5 mm. In static in vitro tests, researchers measured plasma-free hemoglobin levels in a 36-year-old man to assess mechanical hemolysis. Investigational review board approval and informed consent were obtained. The Department of Agriculture, Veterinary Bureau, Bern, Switzerland approved in vivo tests. Researchers investigated device effectiveness in 10 pigs that developed cardiogenic shock but survived massive PE after injection of two or three porcine thrombi into the external jugular vein via a surgically implanted 24-F sheath. Pulmonary angiography and hemodynamic measurements, including mean aortic and mean pulmonary artery pressure, heart rate, and mixed venous oxygen saturation, were obtained at baseline, after embolization, and after thrombectomy. Repeated-measures analysis of variance was performed to compare hemodynamic measurements at baseline, after embolization, and after thrombectomy. Cardiovascular structures were examined at necropsy for rupture, perforation, dissection, or hemorrhage. During a mean aspiration time of 69 seconds +/- 19, thrombi were completely extracted from 14-mm test tubes, with an aspirated fluid volume of 201 mL +/- 64. Although no macroembolization was observed, microembolization was quantified at 1.9 g +/- 1.3. Catheter aspiration was not associated with an increase in plasma-free hemoglobin. In 10 animals, aortic pressure increased from 52 mmHg +/- 24 before thrombectomy to 90 mmHg +/- 32 after thrombectomy, mixed venous oxygen saturation increased from 48% +/- 19% to 61% +/- 12%, pulmonary artery pressure decreased from 33 mmHg +/- 9 to 22 mmHg +/- 4, and heart rate decreased from 162 beats per minute +/- 24 to 114 beats per minute +/- 14. We did not observe macro- or microscopic damage to treated or untreated cardiovascular structures. The PE thrombectomy device was highly effective, facilitating rapid reversal of cardiogenic shock without device-related complications.
Article
Fondaparinux sodium (Arixtra; GlaxoSmithKline) is the first of a new class of antithrombotic agents. It is a chemically synthesised pentasaccharide mimicking the site of heparin that binds to antithrombin. It is purely a factor Xa inhibitor and an inhibitor of thrombin generation that requires binding to antithrombin. Fondaparinux sodium differs from heparin, low-molecular-weight heparin and heparinoids, and cannot be used interchangeably. It has been approved in the US and Europe for the prophylaxis of venous thrombosis after orthopaedic surgery by a fixed dose of 2.5 mg/day without monitoring. Using this pentasaccharide as a backbone, other structures have been synthesised. Idraparinux sodium (Sanofi-Aventis) differs structurally from fondaparinux sodium as it has additional methyl groups, a long half-life, and once-weekly administration. Both drugs are being developed as antithrombotics for venous and arterial thrombosis, acute coronary syndrome, stroke and as adjuncts to thrombolytic therapy.
Article
The antithrombotic management of venous thromboembolism (VTE) has gone through major developments. Indirect inhibitors such as low molecular weight heparin and the pentasaccharide fondaparinux represent improvements over traditional drugs such as unfractionated heparin for acute treatment of VTE with more targeted approaches, predictable pharmacokinetic profiles and lack of need for monitoring. Vitamin K antagonists, with inherent limitations of multiple food and drug interactions and frequent need for monitoring, remain the only oral anticoagulants approved for long-term secondary thromboprophylaxis in VTE with the removal of the oral direct thrombin inhibitor ximelagatran from the world market due to safety concerns. Newer anticoagulant drugs such as parenteral pentasaccharides (idraparinux and SSR-126517-E), oral direct thrombin inhibitors (dabigatran), oral direct Factor Xa inhibitors (rivaroxaban, apixaban, YM-150 and DU-176b) and tissue factor-Factor VIIa complex inhibitors (NAPc2) are tailor-made to target specific procoagulant complexes and have the potential to greatly expand our antithrombotic armamentarium for both acute and long-term treatment of VTE, especially as non-monitored parenteral and oral anticoagulants with a wide therapeutic window and a predictable anticoagulant response.
Article
Massive angiographic pulmonary embolism (PE) with right ventricular dysfunction (RVD) is associated with a high early mortality rate. The therapeutic alternatives for this condition include thrombolysis, surgical embolectomy, or percutaneous mechanical thrombectomy (PMT). We describe our experience using PMT in patients with massive PE and RVD with unsuccessful thrombolysis, increased bleeding risk, or major contraindications for thrombolytic therapy. Clinical, hemodynamic, and angiographic parameters prior to and following PMT were evaluated. Our primary objective was to describe the incidence of in-hospital cardiovascular death, and of major and minor complications. Mid-term outcomes included analysis of occurrence of cardiovascular death, recurrent pulmonary embolism, change of New York Heart Association functional class, and hospital readmission. From July 2004 to May 2007, 69 patients were referred to the cardiac catheterization laboratory with a diagnosis of acute PE, 18 of whom met the criteria for massive PE and are the subject of this study. All patients underwent thrombus fragmentation using a pigtail catheter that was complemented in 13 patients with thrombus aspiration. A percutaneous thrombectomy device (Aspirex; Straub Medical; Wangs, Switzerland) was used in 11 patients. Hemodynamic, angiographic, and blood oxygenation parameters improved after the procedure. A significant increase was observed for systolic systemic BP (74.3+/-7.5 mm Hg vs 89.4+/-11.3 mm Hg, p=0.001) [mean+/-SD], as was a decrease in mean pulmonary artery pressure (37.1+/-8.5 mm Hg vs 32.3+/-10.5 mm Hg , p=0.0001). The in-hospital major complications rate was 11.1%; one patient died from refractory shock, and one patient had intracerebral hemorrhage with minor neurologic sequelae. No cardiovascular deaths or recurrent pulmonary thromboembolism were documented during clinical follow-up (12.3+/-9.4 months). In patients with massive PE, RVD and major contraindications to thrombolytic therapy, increased bleeding risk, failed thrombolysis, or unavailable surgical thrombectomy, PMT appears to be a useful therapeutic alternative.
Article
Anticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). Such treatment is divided into 2 stages: Rapid initial anticoagulation is given to minimize the risk of thrombus extension and fatal pulmonary embolism, whereas extended anticoagulation is aimed at preventing recurrent VTE, thereby reducing the risk of postphlebitic syndrome. With currently available drugs, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists, such as warfarin. Emerging anticoagulants have the potential to streamline VTE treatment. These agents include idraparinux, a long-acting synthetic pentasaccharide that is given subcutaneously on a once-weekly basis, and new oral anticoagulants that target thrombin or factor Xa. This article (1) reviews the pharmacology of these agents, (2) outlines their potential strengths and weaknesses, (3) describes the results of clinical trials with these new drugs, and (4) identifies the evolving role of new anticoagulants in the management of VTE.
Natural history of pulmonary embolism
  • JE Dalen
  • JS Alpert
Un enfoque diferente del estado actual de la trombólisis en la tromboembolia pulmonar
  • C Jerjes-Sánchez
  • A Ramírez-Rivera
  • P Gutiérrez-Fajardo
Long-term experience with transvenous catheter pulmonary embolectomy
  • LJ Greenfeld
  • MC Proctor
  • DM Williams