Background: Fatal bleeding is a serious consequence of anticoagulant therapy, but factors associated with fatal bleeding during the first 3 months of treatment of venous thromboembolism (VTE) are ...uncertain. Methods: Using data from RIETE, an ongoing registry of consecutive patients with acute VTE, we assessed risk factors for fatal bleeding among all patients. We then used this information to derive a clinical model that would stratify a patient’s risk of fatal bleeding during the first 3 months of treatment. Results: Of 24 395 patients, 546 (2.24%) had a major bleed and 135 (0.55%) had a fatal bleed. The gastrointestinal tract was the most common site (40% of fatal bleeds), followed by intracranial bleeding (25%). Fatal bleeding was independently associated with the following factors at the time of VTE diagnosis: age >75 years (OR, 2.16), metastatic cancer (OR, 3.80), immobility ≥ 4 days (OR, 1.99), a major bleed within the past 30 days (OR, 2.64), an abnormal prothrombin time (OR, 2.09), a platelet count < 100 × 109 L−1 (OR, 2.23), creatinine clearance < 30 mL min−1 (OR, 2.27), anemia (OR, 1.54), and distal deep vein thrombosis (OR, 0.39). INR at the time of bleeding is not known. A clinical prediction rule for risk of fatal bleeding that included nine baseline factors was derived. Fatal bleeding occurred in 0.16% (95% CI, 0.11–0.23) of the low‐risk, 1.06% (95% CI, 0.85–1.30) of the moderate‐risk, and 4.24% (95% CI, 2.76–6.27) of the high‐risk category. Conclusions: Patient characteristics and laboratory variables can identify patients at high risk for fatal bleeding during treatment of VTE.
To determine the sensitivity and negative predictive value of D-dimer levels measured by fast enzyme-linked immunoabsorbent assay (ELISA) in pulmonary embolism.
Prospective study of consecutive ...patients with suspicion of pulmonary embolism attended in the Emergency Room of the Hospital de la Princesa in Madrid, Spain. Thromboembolism was diagnosed with an algorithm established in the hospital, and D-dimer levels were determined by fast ELISA (VIDAS D-dimer Assay) in each patient suspected of pulmonary embolism. Patients with negative findings from a test not considered a reference method for thromboembolism were followed for 3 months.
Of 132 patients with clinical suspicion, 28 (21.2%) were positive and 104 (78.7%) were negative for embolism. D-dimer levels were below 0.5 μg/mL in 31 patients, 30 of whom did not have pulmonary thromboembolism whereas 1 did. D-dimer levels were abowe 0.5 μg/mL in 101 patients; thromboembolism did not occur in 74 of these but was reported in the remaining 27. For a value of 1 μg/mL, 66 patients had values below the cut off, 3 of whom presented pulmonary embolism. The remaining 66 patients had D-dimer levels above or equal to 1 μg/mL; 25 of them had a positive diagnosis for embolism and 41 had a negative diagnosis. Sensitivity and negative predictive values were 96.4% (95% confidence interval CI, 79.8%-99.9%) and 96.8% (95% CI, 81.5%-98.8%), respectively, at a cut off of 0.5 μg/mL; and 89.2% (95% CI, 70.6%-97.2%) and 95.45% (95% CI, 86.4%-98.8 %), respectively, at a cut off of 1 μg/mL.
In an emergency room, thromboembolism can be excluded if plasma levels of D-dimer measured by fast ELISA are below 0.5 μg/mL because of the high negative predictive value at this cut off.
Determinar la sensibilidad y el valor predictivo negativo del dímero-D, por enzimoinmunoanálisis (ELISA) rápido, en la embolia pulmonar.
Estudio prospectivo de pacientes atendidos consecutivamente por sospecha clínica de embolia en el Servicio de Urgencias del Hospital de la Princesa de Madrid. El diagnóstico de tromboembolia se basó en el algoritmo establecido en el hospital, y se determinó el dímero-D por ELISA (VIDAS) en cada paciente con sospecha de embolia pulmonar. A los pacientes con resultado negativo para tromboembolia, establecido por una prueba no considerada de referencia, se les realizó seguimiento clínico a los 3 meses.
De 132 pacientes con sospecha clínica, 28 (21,2%) fueron positivos y 104 (78,7%) negativos para embolia. El dímero-D fue < a 0,5 μg/ml en 31 pacientes, de los que 30 no tuvieron tromboembolia pulmonar y 1 sí la tuvo. De los 101 pacientes con dímero-D > 0,5 μg/ml, en 74 no se produjo tromboembolia y en 27 sí.
Si se considera como punto de corte 1 μg/ml, hubo 66 pacientes con valores inferiores, de los que 3 presentaron embolia pulmonar. Otros 66 pacientes mostraron un dímero-D ≤ 1 μg/ml; de ellos, 25 tuvieron un diagnóstico positivo para embolia y 41 negativo. La sensibilidad y el valor predictivo negativo para 0,5 μg/ml fue de 96,4 (intervalo de confianza IC del 95%, 79,8-99,9) y 96,8 (IC del 95%, 81,5-98,8), respectivamente; para 1 μg/ml fue de 89,2 (IC del 95%, 70,6-97,2) y 95,45 (IC del 95%, 86,4-98,8), respectivamente.
Los valores de dímero-D plasmático, determinados por la técnica de ELISA rápido (VIDAS), < 0,5 μg/ml permiten excluir con alto valor predictivo negativo una tromboembolia pulmonar en un servicio de urgencias.
Deep vein thrombosis (DVT) is a difficult to diagnostic disease. The aim of this study was to determine the utility and accuracy of a risk stratification questionnaire and a diagnostic strategy, ...which were applied to patients with suspected DVT on lower extremities in an emergency department.
A prospective cohort study was performed in 569 outpatients with clinical suspected DVT during 14 months. The applied questionnaire stratified patients into three pre-test probability categories. Items included signs, symptoms, risk factors and potential alternative diagnosis, which were based on a modified Wells clinical model. DVT was diagnosed by the combined use of clinical model, compression ultrasonography (CUS) and follow-up CUS one week later in those moderate-high risk patients with an initial normal test. These patients were followed over three months for the development of venous thromboembolic complications.
Two hundred three (35.7%) patients were classified as having a low, 186 (32.7%) moderate and 180 (31.6%) high clinical probability. Overall, DVT was diagnosed in 153 patients (26%; CI95%, 23.2-30.7%): 144 (96%) at the initial CUS, 6 (3.5%) at the second testing and 3 over the 3-month follow-up period. 22 patients had a low pretest probability (11%; CI95%, 7-16%), 43 (23%; CI95%, 17-30%) moderate, and 88 (49%; CI95%, 41-56%) high pretest probability. The difference in the prevalence of DVP among risk categories was significant (p < 0.00001). When the high and moderate groups were joined, the model had a 86% sensitivity, a 90% negative predictive value and a 43% specificity for diagnosis of DVT.
The clinical model used in this study is accurate and feasible, though it is not enough to take clinical decisions. The diagnostic strategic used is effective but not efficient.
The relationship between platelet count and outcome in patients with acute venous thromboembolism (VTE) has not been consistently explored. RIETE is an ongoing registry of consecutive patients with ...acute VTE. We categorised patients as having very low- ( 450,000/µl) platelet count at baseline, and compared their three-month outcome. As of October 2012, 43,078 patients had been enrolled in RIETE: 21,319 presenting with pulmonary embolism and 21,759 with deep-vein thrombosis. In all, 502 patients (1.2%) had very low-; 5,472 (13%) low-; 28,386 (66%) normal-; 7,157 (17%) high-; and 1,561 (3.6%) very high platelet count. During the three-month study period, the recurrence rate was: 2.8%, 2.2%, 1.8%, 2.1% and 2.2%, respectively; the rate of major bleeding: 5.8%, 2.6%, 1.7%, 2.3% and 4.6%, respectively; the rate of fatal bleeding: 2.0%, 0.9%, 0.3%, 0.5% and 1.2%, respectively; and the mortality rate: 29%, 11%, 6.5%, 8.8% and 14%, respectively. On multivariate analysis, patients with very low-, low-, high- or very high platelet count had an increased risk for major bleeding (odds ratio OR: 2.70, 95% confidence interval CI: 1.85–3.95; 1.43 1.18–1.72; 1.23 1.03–1.47; and 2.13 1.65–2.75) and fatal bleeding (OR: 3.70 1.92–7.16, 2.10 1.48–2.97, 1.29 0.88–1.90 and 2.49 1.49–4.15) compared with those with normal count. In conclusion, we found a U-shaped relationship between platelet count and the three-month rate of major bleeding and fatal bleeding in patients with VTE.
Background: Patients with major bleeding who subsequently develop clinically apparent venous thromboembolism (VTE) present a particularly difficult therapeutic dilemma. Methods: RIETE is a ...prospective registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. We retrospectively studied those who had experienced recent major bleeding (< 30 days prior to VTE) to assess the influence of the site of bleeding and the time elapsed to VTE on their 3 month outcome. Results: Of 12 294 patients enrolled up to July 2005, 306 (2.5%) had recent major bleeding: gastrointestinal (GI) tract, 116 (38%); intracranial, 94 (31%); other, 96 (31%). During the study period, 19 patients 6.2%; 95% confidence interval (CI) 3.5–8.9 with recent bleeding rebled (eight died): 13 of them (68%) during the first 2 weeks. Multivariate analysis confirmed that patients with recent GI bleeding had an increased risk for both major rebleeding (hazard ratio 2.8; 95% CI 1.4–5.3) and death (hazard ratio 1.9; 95% CI 1.2–3.1) compared to those with no recent bleeding. Those who bled in other sites had an increased risk only for death (hazard ratio 2.0; 95% CI 1.2–3.3). An elapsed time of < 2 weeks from bleeding to the index VTE event was also associated with an increased risk for major rebleeding (hazard ratio 2.4; 95% CI 1.2–5.0) and death (hazard ratio 2.8; 95% CI 1.8–4.5). Conclusion: The incidence of new bleeding or death depends on the site of prior bleeding and the time elapsed until VTE. This information may help to identify the best therapeutic approach for these high‐risk patients.
Summary
A score that can accurately determine the risk of major bleeding during anticoagulant therapy may help to make decisions on anticoagulant use. RIETE is an ongoing registry of consecutive ...patients with acute venous thromboembolism (VTE). We composed a score to predict the risk for major bleeding within three months of anticoagulant therapy. Of 19,274 patients enrolled, 13,057 (67%) were randomly assigned to the derivation sample, 6,572 to the validation sample. In the derivation sample 314 (2.4%) patients bled (fatal bleeding, 105). On multivariate analysis, age >75 years, recent bleeding, cancer, creatinine levels >1.2 mg/dl, anemia, or pulmonary embolism at baseline were independently associated with an increased risk for major bleeding. A score was composed assigning 2 points to recent bleeding, 1.5 to abnormal creatinine levels or anemia, 1 point to the remaining variables. In the derivation sample 2,654 (20%) patients scored 0 points (low risk); 9,645 (74%) 1–4 points (intermediate); 758 (5.8%) >4 points (high risk). The incidences of major bleeding were: 0.3% (95% confidence interval CI: 0.1–0.6), 2.6% (95% CI: 2.3–2.9), and 7.3% (95% CI: 5.6–9.3), respectively. The likelihood ratio test was:0.14 (95% CI:0.07–0.27) for patients at low risk;2.96 (95% CI:2.18–4.02) for those at high risk. In the validation sample the incidence of major bleeding was:0.1%,2.8%,and 6.2%,respectively. In conclusion, a risk score based on six variables documented at entry can identify VTE patients at low, intermediate, or high risk for major bleeding during the first three months of therapy.
An optimal approach to the diagnosis of deep vein thrombosis (DVT) in lower limbs in the emergency department is still unknown. In this prospective cohort study, we aimed to evaluate the accuracy of ...the widely available plasma D-dimer test (VIDAS) and establish the usefulness of combining D-dimer testing with a clinical model to reduce the need for serial ultra-sonographies and improve the diagnostic strategy of DVT. We performed a cohort study in 383 consecutive outpatients referred to the emergency department of Hospital La Princesa, with clinical suspicion of DVT. The patients were stratified into three pre-test probability categories using an explicit clinical model (Wells score), and underwent a quantitative automated ELISA D-dimer assay (VIDAS D-Dimer bioMérieux). Patients were managed according to the diagnostic strategy based on clinical probability and compression ultrasonography (CU). Patients for whom DVT was considered a high pre-test probability with negative ultrasonographic findings in the initial CU, returned the following week for repeat ultrasonography. All patients with DVT excluded did not receive anticoagulant therapy, and were followed up for three months to monitor the development of venous thromboembolic complications. DVT was confirmed in 102 patients (26.6%): 95 in the initial test, four in the second test, and three who developed venous thromboembolic complications in the three-month follow-up period. The calculated D-dimer cut-off level was 1 micro g/ml. One hundred patients (98%) with DVT had positive D-dimer. D-dimer had a sensitivity of 98% and a negative predictive value of 98.6%. Among the high-probability patients with positive D-dimer tests and initial negative CU, 9.75% had DVT on repeat CU at one week. The study results suggest that the addition of VIDAS D-dimer to this diagnostic algorithm could improve the management of patients with suspected DVT in daily practice. A diagnostic approach of DVT based on D-dimer (cut-off > or =1 microg/ml) as the first diagnostic tool for the exclusion of DVT, and the clinical probability model as the tool that identifies those patients requiring a second ultrasonography is useful and suitable for daily medical practice.
Deep vein thrombosis (DVT) of the limbs is a common disease and causes significant morbidity and mortality. It is frequently the prelude to pulmonary embolism (PE), it can recur in 30% of patients ...and in 25–40% of cases they can develop post-thrombotic syndrome (PTS), with a significant impact in functional status and quality of life. This document contains the recommendations on the diagnosis and treatment of acute DVT from the Thromboembolic Disease group of the Spanish Society of Internal Medicine (SEMI).
PE and thrombosis of unusual venous territories (cerebral, renal, mesenteric, superficial, etc.) are outside its scope, as well as thrombosis associated with catheter and thrombosis associated with cancer, which due to their peculiarities will be the subject of other positioning documents of the Thromboembolic Disease group of the Spanish Society of Internal Medicine (SEMI).
La trombosis venosa profunda (TVP) de miembros es una enfermedad frecuente y conlleva una morbimortalidad importante. Es, con frecuencia, la antesala de la embolia de pulmón (EP), puede recurrir en el 30% de los pacientes y en el 25–40% de los casos pueden desarrollar el síndrome postrombótico (SPT), con un importante impacto funcional y en la calidad de vida. En este documento se recogen las recomendaciones sobre el diagnóstico y tratamiento de la TVP aguda del grupo de Enfermedad Tromboembólica de la Sociedad Española de Medicina Interna (SEMI). Quedan fuera del alcance del mismo la EP y las trombosis de territorios venosos inusuales (cerebral, renal, mesentérica, superficiales, etc.), así como la trombosis asociada a catéter y la asociada a cáncer, que por sus peculiaridades serán objeto de otros documentos de posicionamiento del grupo de Enfermedad Tromboembólica de la Sociedad Española de Medicina Interna (SEMI).
PDF
