Trombosis venosa y embolia pulmonar / DVT and PE

Febrero 9, 2016. No. 2231

Coagulación y la pared vascular en el embolismo pulmonar Coagulation and the vessel wall in pulmonary embolism. Alias S, Lang IM. Pulm Circ. 2013 Dec;3(4):728-38. doi: 10.1086/674768. Abstract Venous thromboembolism comprises deep-vein thrombosis, thrombus in transit, acute pulmonary embolism, and chronic thromboembolic pulmonaryhypertension (CTEPH). Pulmonary thromboemboli commonly resolve, with restoration of normal pulmonary hemodynamics. When they fail to resorb, permanent occlusion of the deep veins and/or CTEPH are the consequences. Apart from endogenous fibrinolysis, venous thrombi resolve by a process of mechanical fragmentation, through organization of the thromboembolus by invasion of endothelial cells, leukocytes, and fibroblasts leading to recanalization. Recent data utilizing various models have contributed to a better understanding of venous thrombosis and the resolution process that is directed at maintaining vascular patency. This review summarizes the plasmatic and cellular components of venous thrombus formation and resolution. KEYWORDS: CTEPH; pulmonary embolism; thrombosis; thrombus resolution  PDF El impacto de trombosis venosa profunda en los pacientes graves: meta-análisis y resultados clínicos importantes The impact of deep vein thrombosis in critically ill patients: a meta-analysis of major clinical outcomes. Malato A, Dentali F, Siragusa S, Fabbiano F, Kagoma Y, Boddi M, Gensini GF, Peris A, Crowther M, Napolitano M. Blood Transfus. 2015 Oct;13(4):559-68. doi: 10.2450/2015.0277-14. Abstract BACKGROUND: Critically ill patients appear to be at high risk of developing deep vein thrombosis (DVT) and pulmonary embolism during their stay in the intensive care unit (ICU). However, little is known about the clinical course of venous thromboembolism in the ICU setting. We therefore evaluated, through a systematic review of the literature, the available data on the impact of a diagnosis of DVT on hospital and ICU stay, duration of mechanical ventilation and mortality in critically ill patients. We also tried to determine whether currently adopted prophylactic measures need to be revised and improved in the ICU setting. MATERIALS AND METHODS: MEDLINE and EMBASE databases were searched up to week 4 of June 2012. Two reviewers selected studies and extracted data. Pooled results are reported as relative risks and weighted mean differences and are presented with 95% confidence intervals (CI). RESULTS: Seven studies for a total of 1,783 patients were included. A diagnosis of DVT was frequent in these patients with a mean rate of 12.7% (95% CI: 8.7-17.5%). DVT patients had longer ICU and hospital stays compared to those without DVT (7.28 days; 95% CI: 1.4-13.15; and 11.2 days; 95% CI: 3.82-18.63 days, respectively). The duration of mechanical ventilation was significantly increased in DVT patients (weighted mean difference: 4.85 days; 95% CI: 2.07-7.63). DVT patients had a marginally significant increase in the risk of hospital mortality (relative risk 1.31; 95% CI: 0.99-1.74; p=0.06), and a not statistically significant increase in the risk of ICU mortality (RR 1.64; 95% CI: 0.91-2.93; p=0.10). CONCLUSIONS: A diagnosis of DVT upon ICU admission appears to affect clinically important outcomes including duration of ICU and hospital stay and hospital mortality. Larger, prospective studies are warranted. PDF  Modelos de predicción de diagnóstico para la sospecha de embolia pulmonar: revisión sistemática y validación externa independiente en la atención primaria. Diagnostic prediction models for suspected pulmonary embolism: systematic review and independent external validation in primary care. Hendriksen JM, Geersing GJ, Lucassen WA, Erkens PM, Stoffers HE, van Weert HC, Büller HR, Hoes AW, Moons KG. BMJ. 2015 Sep 8;351:h4438. doi: 10.1136/bmj.h4438. Abstract OBJECTIVE: To validate all diagnostic prediction models for ruling out pulmonary embolism that are easily applicable in primary care. DESIGN: Systematic review followed by independent external validation study to assess transportability of retrieved models to primary care medicine. SETTING: 300 general practices in the Netherlands. PARTICIPANTS: Individual patient dataset of 598 patients with suspected acute pulmonary embolism in primary care. MAIN OUTCOME MEASURES: Discriminative ability of all models retrieved by systematic literature search, assessed by calculation and comparison of C statistics. After stratification into groups with high and low probability of pulmonary embolism according to pre-specified model cut-offs combined with qualitative D-dimer test, sensitivity, specificity, efficiency (overall proportion of patients with low probability of pulmonary embolism), and failure rate (proportion of pulmonary embolism cases in group of patients with low probability) were calculated for all models. RESULTS: Ten published prediction models for the diagnosis of pulmonary embolism were found. Five of these models could be validated in the primary care dataset: the original Wells, modified Wells, simplified Wells, revised Geneva, and simplified revised Geneva models. Discriminative ability was comparable for all models (range of C statistic 0.75-0.80). Sensitivity ranged from 88% (simplified revised Geneva) to 96% (simplified Wells) and specificity from 48% (revised Geneva) to 53% (simplified revised Geneva). Efficiency of all models was between 43% and 48%. Differences were observed between failure rates, especially between the simplified Wells and the simplified revised Geneva models (failure rates 1.2% (95% confidence interval 0.2% to 3.3%) and 3.1% (1.4% to 5.9%), respectively; absolute difference -1.98% (-3.33% to -0.74%)). Irrespective of the diagnostic prediction model used, three patients were incorrectly classified as having low probability of pulmonary embolism; pulmonary embolism was diagnosed only after referral to secondary care. CONCLUSIONS: Five diagnostic pulmonary embolism prediction models that are easily applicable in primary care were validated in this setting. Whereas efficiency was comparable for all rules, the Wells rules gave the best performance in terms of lower failure rates. PDF

Anestesiología y Medicina del Dolor 52 664 6848905 vwhizar@anestesia-dolor.org anestesia-dolor.org Copyright © 2015

Tratamiento de TVP y TEP / DVT and PE management

Febrero 10, 2016. No. 2232

Tratamiento anticoagulante de la TVP y TEP: Elestado actualdel manejo. Anticoagulant Treatment of Deep Vein Thrombosis and Pulmonary Embolism: The Present State of the Art. Thaler J, Pabinger I, Ay C. Front Cardiovasc Med. 2015 Jul 14;2:30. doi: 10.3389/fcvm.2015.00030. eCollection 2015. Abstract Venous thromboembolism (VTE), a disease entity comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent and potentially life-threatening event. To date different agents are available for the effective treatment of acute VTE and the prevention of recurrence. For several years, the standard of care was the subcutaneous application of a low molecular weight heparin (LMWH) or fondaparinux, followed by a vitamin K antagonist (VKA). The so-called direct oral anticoagulants (DOAC) were introduced rather recently in clinical practice for the treatment of VTE. DOAC seem to have a favorable risk-benefit profile compared to VKA. Moreover, DOAC significantly simplify VTE treatment because they are administered in fixed doses and no routine monitoring is needed. Patients with objectively diagnosed DVT or PE should receive therapeutic anticoagulation for a minimum of 3 months. Whether a patient ought to receive extended treatment needs to be evaluated on an individual basis, depending mainly on risk factors determined by characteristics of the thrombotic event and patient related factors. In specific patient groups (e.g., pregnant women, cancer patients, and elderly patients), treatment of VTE is more challenging than that in the general population and additional issues need to be considered in those patients. The aim of this review is to give an overview of the currently available treatment modalities of acute VTE and secondary prophylaxis. In particular, specific aspects regarding the initiation of VTE treatment, duration of anticoagulation, and specific patient groups will be discussed. KEYWORDS: anticoagulation; deep vein thrombosis; pulmonary embolism; secondary prevention; venous thromboembolism PDF  Anticoagulantes orales directos en el tratamiento del tromboembolismo venoso, con un enfoque en los pacientes con embolia pulmonar: una revisión basada en la evidencia. Direct oral anticoagulants in the treatment of venous thromboembolism, with a focus on patients with pulmonary embolism: an evidence-based review. Gómez-Outes A, Suárez-Gea ML, Lecumberri R, Terleira-Fernández AI, Vargas-Castrillón E. Vasc Health Risk Manag. 2014 Nov 7;10:627-39. doi: 10.2147/VHRM.S50543. eCollection 2014. Abstract Pulmonary embolism (PE) is a relatively common cardiovascular emergency. PE and deep vein thrombosis (DVT) are considered expressions of the same disease, termed as venous thromboembolism (VTE). In the present review, we describe and meta-analyze the efficacy and safety data available with the direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) in clinical trials testing these new compounds in the acute/long-term and extended therapy of VTE, providing subgroup analyses in patients with index PE. We analyzed ten studies in 35,019 randomized patients. A total of 14,364 patients (41%) had index PE. In the acute/long-term treatment of VTE, the DOAC showed comparable efficacy in preventing recurrent VTE to standard treatment in patients with index PE (risk ratio [RR]: 0.88; 95% confidence interval [CI]: 0.70-1.11) and index DVT (RR: 0.93; 95% CI: 0.75-1.16) (P for subgroup differences =0.76). VTE recurrence depending on PE anatomical extension and presence/absence of right ventricular dysfunction was only reported in two trials, with results being consistent with those obtained in the overall study populations. In the single trial comparing extended therapy of VTE with DOAC versus warfarin, the point estimate for recurrent VTE tended to disfavor the DOAC in patients with index PE (RR: 2.05; 95% CI: 0.83-5.03) and in patients with index DVT (RR: 1.11; 95% CI: 0.49-2.50) (P for subgroup differences =0.32). In trials that compared DOAC versus placebo for extended therapy, the reduction in recurrent VTE was consistent in patients with PE (RR: 0.15; 95% CI: 0.01-1.82) and in patients with DVT (RR: 0.25; 95% CI: 0.10-0.61) (P for subgroup differences =0.71). The DOAC were associated with a consistently lower risk of clinically relevant bleeding (CRB) than standard treatment of acute VTE and higher risk of CRB than placebo for extended therapy of VTE regardless of index event. In summary, the DOAC were as effective as, and safer than, standard treatment of (hemodynamically stable) PE. Their efficacy in preventing recurrent VTE seemed consistent regardless of anatomical extension of PE (extensive, intermediate, or limit) or presence/absence of right ventricular dysfunction although the data are limited. For extended therapy, the DOAC were more effective than placebo in preventing recurrent VTE but were associated with an increase in CRB regardless of index event. KEYWORDS: anticoagulant; apixaban; dabigatran; edoxaban; pulmonary embolism; rivaroxaban PDF  Los avances en el manejo y tratamiento de la embolia pulmonar. Developments in the management and treatment of pulmonary embolism. Limbrey R, Howard L. Eur Respir Rev. 2015 Sep;24(137):484-97. doi: 10.1183/16000617.00006614. Abstract Pulmonary embolism (PE) is a serious and costly disease for patients and healthcare systems. Guidelines emphasise the importance of differentiating between patients who are at high risk of mortality (those with shock and/or hypotension), who may be candidates for thrombolytic therapy or surgery, and those with less severe presentations. Recent clinical studies and guidelines have focused particularly on risk stratification of intermediate-risk patients. Although the use of thrombolysis has been investigated in these patients, anticoagulation remains the standard treatment approach. Individual risk stratification directs initial treatment. Rates of recurrence differ between subgroups of patients with PE; therefore, a reviewof provoking factors, along with the risks of morbidity and bleeding, guides the duration of ongoing anticoagulation. The direct oral anticoagulants have shown similar efficacy and, in some cases, reduced major bleeding compared with standard approaches for acute treatment. They also offer the potential to reduce the burden on patients and outpatient services in the post-hospital phase. Rivaroxaban, dabigatran and apixaban have been shown to reduce the risk of recurrent venous thromboembolism versus placebo, when given for >12 months. Patients receiving direct oral anticoagulants do not require regular coagulation monitoring, but follow-up, ideally in a specialist PE clinic in consultation with primary care providers, is recommended. PDF

Anestesiología y Medicina del Dolor 52 664 6848905 vwhizar@anestesia-dolor.org anestesia-dolor.org Copyright © 2015

Manejo extendido de TEP / Extended treatment of PE

Febrero 11, 2016. No. 2233

Tratamiento anticoagulante extendido y aspirina para la prevención secundaria de la enfermedad tromboembólica: una revisión sistemática y meta-análisis. Extended Anticoagulant and Aspirin Treatment for the Secondary Prevention of Thromboembolic Disease: A Systematic Review and Meta-Analysis. Marik PE, Cavallazzi R. PLoS One. 2015 Nov 20;10(11):e0143252. doi: 10.1371/journal.pone.0143252. eCollection 2015. Abstract BACKGROUND: Patients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended "life-long" anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a "weak provoking factor" there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event. OBJECTIVE: A systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued. DATA SOURCES: MEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles. STUDY SELECTION: Randomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy. DATA EXTRACTION: Independent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent. DATA SYNTHESIS: Seven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11-0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69-3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40-1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm. CONCLUSIONS: VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients' risk for recurrent PE as well as the patients' values and preferences. PDF

Anestesiología y Medicina del Dolor 52 664 6848905 vwhizar@anestesia-dolor.org anestesia-dolor.org Copyright © 2015