Carmen Fernández-Capitán

The influence of extreme body weight on clinical outcome of patients with venous thromboembolism: findings from a prospective registry (RIETE).

Summary.  Background: Data evaluating the safety of using weight‐based dosing of low‐molecular‐weight heparin (LMWH) in either underweight or obese patients with venous thromboembolism (VTE) are limited. Thus, recommendations based on evidence from clinical trials might not be suitable for patients with extreme body weight. Patients and Methods: Patients with objectively confirmed, symptomatic acute VTE are consecutively enrolled into the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. For this analysis, data from patients in the following ranges of body weight were examined: <50, 50–100, and >100 kg. Patient characteristics, underlying conditions, treatment schedules and clinical outcomes during the first 15 days of treatment were compared. Results: As of August 2004, 8845 patients with acute VTE were enrolled from 94 participating centers. Of these, 169 (1.9%) weighed <50 kg, 8382 (95%) weighed 50–100 kg and 294 (3.3%) weighed >100 kg. Patients weighing <50 kg were more commonly females, were taking non‐steriodal antiinflammatory drugs (NSAIDs), and had severe underlying diseases more often than patients weighing 50–100 kg. Their incidence of overall bleeding complications was significantly higher than in patients weighing 50–100 kg (odds ratio 2.2; 95% CI: 1.2–4.0). Patients weighing >100 kg were younger, most commonly males, and had cancer less often than those weighing 50–100 kg. Incidences of recurrent VTE, fatal pulmonary embolism or major bleeding complications were similar in both groups. Conclusions: Patients with VTE weighing <50 kg have a significantly higher rate of bleeding complications. The clinical outcome of patients weighing over 100 kg was not significantly different from that in patients weighing 50–100 kg.

Validation of a score for predicting fatal bleeding in patients receiving anticoagulation for venous thromboembolism

BACKGROUND The only available score to assess the risk for fatal bleeding in patients with venous thromboembolism (VTE) has not been validated yet. METHODS We used the RIETE database to validate the risk-score for fatal bleeding within the first 3 months of anticoagulation in a new cohort of patients recruited after the end of the former study. Accuracy was measured using the ROC curve analysis. RESULTS As of December 2011, 39,284 patients were recruited in RIETE. Of these, 15,206 had not been included in the former study, and were considered to validate the score. Within the first 3 months of anticoagulation, 52 patients (0.34%; 95% CI: 0.27-0.45) died of bleeding. Patients with a risk score of <1.5 points (64.1% of the cohort) had a 0.10% rate of fatal bleeding, those with a score of 1.5-4.0 (33.6%) a rate of 0.72%, and those with a score of >4 points had a rate of 1.44%. The c-statistic for fatal bleeding was 0.775 (95% CI 0.720-0.830). The score performed better for predicting gastrointestinal (c-statistic, 0.869; 95% CI: 0.810-0.928) than intracranial (c-statistic, 0.687; 95% CI: 0.568-0.806) fatal bleeding. The score value with highest combined sensitivity and specificity was 1.75. The risk for fatal bleeding was significantly increased (odds ratio: 7.6; 95% CI 3.7-16.2) above this cut-off value. CONCLUSIONS The accuracy of the score in this validation cohort was similar to the accuracy found in the index study. Interestingly, it performed better for predicting gastrointestinal than intracranial fatal bleeding.

Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: a prospective cohort study

IntroductionCell-free plasma mitochondrial DNA (mt-DNA) and nuclear DNA (n-DNA) are biomarkers with prognostic utility in conditions associated with a high rate of cell death. This exploratory study aimed to determine the plasma levels of both nucleic acids in patients with massive and submassive pulmonary embolism (PE) and to compare them with other biomarkers, such as heart-type fatty acid-binding protein (H-FABP) and troponin I (Tn-I)MethodsThis was a prospective observational study of 37 consecutive patients with massive PE, 37 patients with submassive PE, and 37 healthy subjects. Quantifications of plasma mt-DNA and n-DNA with real-time quantitative polymerase chain reaction (PCR), and plasma H-FABP and Tn-I by commercial assays, were done on blood samples drawn within 4 hours after presentation at the emergency department.ResultsPlasma mt-DNA and n-DNA concentrations were much higher in patients with massive PE (median, 2,970 GE/ml; interquartile range (IQR), 1,050 to 5,485; and 3,325 GE/ml, IQR: 1,080 to 5,790, respectively) than in patients with submassive PE (870 GE/ml and 1,245 GE/ml, respectively; P < 0.01) or controls (185 GE/ml and 520 GE/ml, respectively). Eighteen patients with massive PE died of a PE-related cause by day 15 of observation. Plasma mt-DNA and n-DNA values were 2.3-fold and 1.9-fold higher in the subgroup of nonsurviving patients than in survivors. H-FABP and Tn-I values were also higher in patients with massive PE who died (7.3 ng/ml and 0.023 ng/ml, respectively) than in those who survived (6.4 ng/ml, and 0.016 ng/ml, respectively). By receiver operating curve (ROC) analysis, the best cutoff values for predicting 15-day mortality were 3,380 GE/ml for mt-DNA, 6.8 ng/ml for H-FABP, 3,625 GE/ml for n-DNA, and 0.020 ng/ml for Tn-I, based on the calculated areas under the curve (AUCs) of 0.89 (95% confidence interval (CI), 0.78 to 0.99), 0.76 (95% CI, 0.69 to 093), 0.73 (95% CI, 0.58 to 0.91), and 0.59 (95% CI, 0.41 to 0.79), respectively. By stepwise logistic regression, a plasma mt-DNA concentration greater than 3,380 GE/ml (adjusted odds ratio (OR), 8.22; 95% CI, 1.72 to 39.18; P < 0.001) and a plasma value of H-FBAP >6.8 ng/ml (OR, 5.36; 95% CI, 1.06 to 27.08; P < 0.01) were the only independent predictors of mortality.Conclusionsmt-DNA and H-FBAP might be promising markers for predicting 15-day mortality in massive PE, with mt-DNA having better prognostic accuracy.

Clinical Prognosis of Nonmassive Central and Noncentral Pulmonary Embolism: A Registry-Based Cohort Study

Background Whether the localization of nonmassive pulmonary embolism (PE) is associated with the short‐term and long‐term prognosis of patients remains unknown. Our aim was to characterize associations of nonmassive PE localization with risks of recurrent VTE, major bleeding, and mortality during and after anticoagulation. Methods Among participants of the Registro Informatizado de la Enfermedad ThromboEmbòlica (RIETE) registry with incident symptomatic nonmassive PE diagnosed by CT scan, we compared risks of recurrent VTE, major bleeding, and mortality during and after anticoagulation between central PE (main pulmonary artery) and noncentral PE (more peripheral arteries) using Cox proportional hazard‐adjusted models. Results Of the 6,674 participants, patients with central PE (40.5%) had age (mean 66 years), sex (46.9% male sex), and proportion of idiopathic (45.0%) and cancer‐related (22.3%) PE that were similar to those of patients with noncentral PE. During anticoagulation (5,256.1 patient‐years), the risk of recurrent VTE was similar between the two groups (2.5 vs 2.1 per 100 patient‐years; adjusted hazard ratio [aHR], 1.32; 95% CI, 0.91‐1.90), as were risks of major bleeding and mortality. After anticoagulation was discontinued (2,175.4 patient‐years), participants with central PE had a borderline greater risk of recurrent VTE than did participants with noncentral PE (11.0 vs 8.0 per 100 patient‐years; aHR, 1.34; 95% CI, 1.01‐1.78) but not when restricted to participants after unprovoked PE (13.8 vs 11.9 per 100 patient‐years; aHR, 1.15; 95% CI, 0.79‐1.68; P = .48). Risks of major bleeding and mortality were similar. Conclusions In nonmassive PE, central localization of PE is associated with greater risk of recurrent VTE after anticoagulation cessation. However, the low magnitude of this association and the absence of association after unprovoked PE suggest that the clinical relevance of this finding is limited and that the duration of anticoagulation should not be tailored to PE localization after nonmassive unprovoked PE.

Influence of recent immobilization or surgery on mortality in cancer patients with venous thromboembolism

BACKGROUND The influence of recent immobilization or surgery on mortality in cancer patients with venous thromboembolism (VTE) has not been thoroughly studied. METHODS We used the RIETE Registry data to compare the 3-month mortality rate in cancer patients with VTE, with patients categorized according to the presence of recent immobilization, surgery or neither. The major outcomes were fatal pulmonary embolism (PE) and fatal bleeding within the first 3 months. RESULTS Of 6,746 patients with active cancer and acute VTE, 1,224 (18%) had recent immobilization, 1,055 (16%) recent surgery, and 4,467 (66%) had neither. The all-cause mortality was 23.4% (95% CI: 22.4-24.5), and the PE-related mortality: 2.5% (95% CI: 2.1-2.9). Four in every ten patients dying of PE had recent immobilization (37%) or surgery (5.4%). Only 28% of patients with immobilization had received prophylaxis, as compared with 67% of the surgical. Fatal PE was more common in patients with recent immobilization (5.0%; 95% CI: 3.9-6.3) than in those with surgery (0.8%; 95% CI: 0.4-1.6) or neither (2.2%; 95% CI: 1.8-2.6). On multivariate analysis, patients with immobilization were at an increased risk for fatal PE (odds ratio: 1.8; 95% CI: 1.2-2.5). CONCLUSIONS One in every three cancer patients dying of PE had recent immobilization for ≥ 4 days. Many of these deaths could have been prevented with adequate thromboprophylaxis.

Uterine bleeding during anticoagulation in women with venous thromboembolism

BACKGROUND Women presenting with uterine bleeding during the course of anticoagulant therapy for venous thromboembolism (VTE) present a difficult therapeutic dilemma due to the absence of evidence-based recommendations. METHODS We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the clinical characteristics of women presenting with uterine bleeding during anticoagulation for VTE, its frequency, time course, management and 30-day outcomes. RESULTS As of October 2016, 31,951 women with VTE were recruited in RIETE. During the course of anticoagulant therapy, 53 (0.17%) developed major uterine bleeding, 118 (0.37%) non-major uterine bleeding and 948 (2.97%) had major bleeding in other sites. Median time elapsed from VTE to bleeding was: 32, 71 and 22 days, respectively. Mean age was: 56±17, 52±20 and 75±14 years, respectively. Women with major uterine bleeding more likely had cancer (51%), anemia (72%), raised platelet count (19%) or recent major bleeding (11%) at VTE presentation than those in the other subgroups. During the first 30 days after bleeding, 17%, 1.7% and 31% of women died, respectively. Of 11 women with uterine bleeding who died, 9 (82%) had cancer, two (18%) died of bleeding and one (9.1%) died of pulmonary embolism after discontinuing anticoagulation. CONCLUSIONS Uterine bleeding during the course of anticoagulation for VTE is not uncommon and mostly affects young women. Those with cancer, anaemia, raised platelet count or recent bleeding at baseline are at an increased risk for uterine bleeding during anticoagulation.

Gammagrafía pulmonar y tomografía computarizada helicoidal en el diagnóstico de embolia pulmonar en España. Datos del Sistema Nacional de Salud y el Registro RIETE

Fundamento y objetivo Analizar las tendencias de utilizacion de gammagrafia de ventilacion-perfusion (gammaV/Q), tomografia computarizada helicoidal (TCH) y arteriografia pulmonar para el diagnostico de embolia pulmonar (EP) en Espana, considerando los datos del Sistema Nacional de Salud (SNS) y el Registro RIETE y examinar las analogias diagnosticas de la gammaV/Q y la TCH en RIETE, con especial referencia a la gammaV/Q de probabilidad intermedia/indeterminada (GV/QPI). Material y metodo Se examinaron las tendencias anuales en pruebas de imagen para diagnosticar EP en 5.678 pacientes espanoles incluidos en el Registro RIETE (2001 a 2005) y se compararon con los pertenecientes al SNS (periodo 1999-2003). En el RIETE se compararon los resultados analogos entre los casos con gammaV/Q y TCH concomitantes y arteriografia y gammaV/Q o TCH. Resultados Hubo una tendencia creciente en la utilizacion de TCH, que supero en 2002 (RIETE) y en 2003 (SNS) a la gammaV/Q. En 732 casos con ambas pruebas, se obtuvieron resultados analogos en el 53%. En 116 casos con gammaV/QPI, la TCH disponible fue positiva a EP en un 87%. Cuando ademas habia signos clinicos de EP, la TCH fue positiva en un 95%. En 29 casos con angiografia pulmonar (AP) y TCH, los resultados fueron analogos en un 83% y en 31 casos con arteriografia y gammaV/Q, en un 77%. Conclusiones Actualmente, en Espana, la TCH es el metodo mas utilizado para el diagnostico de EP, aunque siguen realizandose numerosos estudios con gammaV/Q. En los resultados de gammaV/QPI es aconsejable estudiar la posible trombosis venosa profunda y, si la hay, los resultados del RIETE permiten asegurar la coexistencia de EP en un 87-95% de casos.

Venous thromboembolism in patients immobilised at home

The natural history of venous thromboembolism (VTE), its impact on outcome and the rationale for prophylaxis are well established for hospitalised, acutely ill medical patients [1–10], but are less clear for nonhospitalised immobilised patients. Current guidelines for antithrombotic therapy recommend the use of prophylaxis in hospitalised, acutely ill medical patients, and suggest against its use in chronically immobilised persons at home and in patients with isolated lower-leg injuries requiring leg immobilisation [11]. However, there are no suggestions on the use of VTE prophylaxis in acutely ill medical patients immobilised at home. Fatal PE after immobility at home was more frequent than after immobility in hospital http://ow.ly/J0UIr

Historia natural de la enfermedad tromboembólica venosa en el área mediterránea. Una revisión sistemática

BACKGROUND Patients with cardiovascular diseases living in the Mediterranean area have a better outcome than those in other parts of the world, but it is not known whether these differences also occur with venous thromboembolism (VTE). METHODS We searched the Medline and EMBASE databases to identify clinical trials and cohort studies of patients with VTE who had been treated with anticoagulant therapy for 3 months. Two reviewers independently extracted the data in a standardized manner. A total of 24 studies that included 7,225 patients (2,414 from the Mediterranean region and 4,811 from other regions) were analyzed. RESULTS The patients from the Mediterranean area were predominately women and older, and the idiopathic VTE was less frequent than in other regions. Compared with patients from other regions, patients from the Mediterranean region had an increased rate of recurrent deep vein thrombosis (4.35% vs. 2.68%; odds ratio [OR], 1.65; 95% confidence interval [95% CI] 1.27-2.15), fatal recurrent VTE (0.75% vs. 0.35%; OR, 2.11; 95% CI 1.09-4.12) and fatal bleeding (0.25% vs. 0.06%; odds ratio: 3.99; 95% CI 1.00-16.0). The case-fatality rate (CFR) for recurrent VTE was 12.8% (95% CI 7.99-19.1) in the Mediterranean region and 8.41% (5.15-12.9) in other areas. The CFR for major bleeding was 11.3% (95% CI 4.72-22.1) and 3.22% (95% CI 0.83-8.53), respectively. CONCLUSIONS Compared to other regions, patients with VTE from the Mediterranean region have greater mortality during the first 3 months of treatment due to a greater incidence of recurrent VTE and severe hemorrhaging.