Bleeding complications associated with anticoagulant therapy in patients with cancer

Background: Cancer patients with venous thromboembolism (VTE) have an increased incidence of bleeding complications while on anticoagulant therapy. Methods: RIETE is an ongoing registry of consecutive patients with acute VTE. We tried to identify which cancer patients are at a higher risk for major bleeding. Results: Up to May 2009, 4,709 patients with active cancer had been enrolled in RIETE registry. During the first 3 months of anticoagulant therapy, 200 (4.2%) patients developed major bleeding. Then, 38 (0.8%) further patients bled beyond the first 90 days of therapy, 3 bled after withholding anticoagulant therapy. The most common sites of bleeding were the gastrointestinal tract (118 patients, 49%), genitourinary system (43 patients, 18%) and the brain (27 patients, 11%). In all, 160 patients (66%) died within 30 days after bleeding: 88 (55%) died of bleeding, 3 (1.9%) died of recurrent pulmonary embolism. Conclusions: Major bleeding is a frequent and severe complication in cancer patients with VTE, even beyond the third month. One third of the patients who bled died due the bleeding event

Venous thromboembolism during pregnancy, postpartum or during contraceptive use: Findings from the RIETE Registry

Venous thromboembolism (VTE) is a leading cause of maternal death during pregnancy or postpartum, and in women using hormonal contraceptives. However, important issues concerning its natural history and therapy remain unsolved, and most of the protocols for treatment of VTE in this patient population are based on data extrapolated from other populations. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute VTE. We examined the clinical characteristics and three-month outcome of all enrolled women with pregnancy, postpartum or using hormonal contraceptives. As of December 2008, 173 pregnant women, 135 postpartum, and 798 contraceptive users were enrolled. Of these, 438 (40%) presented with pulmonary embolism (PE) and 668 with deep-vein thrombosis (DVT). Most women with acute PE had dyspnea (72%) or chest pain (75%), but only 2.0% had hypoxaemia. During the three-month study period, five women (0.45%; 95% CI: 0.17-1.00) died (3 had fatal PE), 13 (1.18%; 95% CI: 0.66-1.95) had VTE recurrences, and seven (0.63%; 95% CI: 0.28-1.25) major bleeding. Two of the three women with fatal PE died during the first few hours after arriving at the emergency ward, with no time to start any therapy. The outcome of pregnant or postpartum women with VTE is similar to that in contraceptive users, even though the treatment is different. The non-specific nature of PE signs may have caused some delay in PE diagnosis. \ua9 Schattauer 2010

Outcomes in Neurosurgical Patients Who Develop Venous Thromboembolism

International audienceOBJECTIVES: Registro Informatizado de Enfermedad TromboEmbólica (RIETE) database was used to investigate whether neurosurgical patients with venous thromboembolism (VTE) were more likely to die of bleeding or VTE and the influence of anticoagulation on these outcomes.METHODS:Clinical characteristics, treatment details, and 3-month outcomes were assessed in those who developed VTE after neurosurgery.RESULTS: Of 40 663 patients enrolled, 392 (0.96%) had VTE in less than 60 days after neurosurgery. Most patients in the cohort (89%) received initial therapy with low-molecular-weight heparin, (33% received subtherapeutic doses). In the first week, 10 (2.6%) patients died (8 with pulmonary embolism [PE], no bleeding deaths; P = .005). After the first week, 20 (5.1%) patients died (2 with fatal bleeding, none from PE). Overall, this cohort was more likely to develop a fatal PE than a fatal bleed (8 vs 2 deaths, P = .058).CONCLUSIONS: Neurosurgical patients developing VTE were more likely to die from PE than from bleeding in the first week, despite anticoagulation

Fatal events in cancer patients receiving anticoagulant therapy for venous thromboembolism

none144siIn cancer patients treated for venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), analyzing mortality associated with recurrent VTE or major bleeding is needed to determine the optimal duration of anticoagulation. This was a cohort study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry database to compare rates of fatal recurrent PE and fatal bleeding in cancer patients receiving anticoagulation for VTE. As of January 2013, 44,794 patients were enrolled in RIETE, of whom 7911(18%) had active cancer. During the course of anticoagulant therapy (mean, 181 ±210 days), 178 cancer patients (4.3%) developed recurrent PE (5.5 per 100 patient-years; 95% CI: 4.8-6.4), 194 (4.7%) had recurrent DVT (6.2 per 100 patient-years; 95% confidence interval [CI]: 5.3-7.1), and 367 (8.9%) bled (11.3 per 100 patient-years; 95% CI: 10.2-12.5). Of 4125 patients initially presenting with PE, 43 (1.0%) died of recurrent PE and 45 (1.1%) of bleeding; of 3786 patients with DVT, 19 (0.5%) died of PE, and 55 (1.3%) of bleeding. During the first 3 months of anticoagulation, there were 59 (1.4%) fatal PE recurrences and 77 (1.9%) fatal bleeds. Beyond the third month, there were 3 fatal PE recurrences and 23 fatal bleeds. In RIETE cancer patients, the rate of fatal recurrent PE or fatal bleeding was much higher within the first 3 months of anticoagulation therapy.openFarge D.; Trujillo-Santos J.; Debourdeau P.; Bura-Riviere A.; Rodriguez-Beltran E.M.; Nieto J.A.; Peris M.L.; Zeltser D.; Mazzolai L.; Hij A.; Monreal M.; Durante A.; Alcalde M.; Arcelus J.I.; Ballaz A.; Barba R.; Barron M.; Barron-Andres B.; Bascunana J.; Bedate P.; Blanco-Molina A.; Bueso T.; Casado I.; Conget F.; Del Molino F.; Del Toro J.; Falga C.; Fernandez-Capitan C.; Fuentes M.I.; Gallego P.; Garcia J.; Garcia-Bragado F.; Gavin O.; Gomez V.; Gonzalez J.; Gonzalez-Bachs E.; Grau E.; Guil M.; Guijarro R.; Gutierrez J.; Hernandez L.; Jara-Palomares L.; Jaras M.J.; Jimenez D.; Jimenez S.; Lobo J.L.; Lopez-Jimenez L.; Lopez-Saez J.B.; Lorente M.A.; Lorenzo A.; Luque J.M.; Madridano O.; Macia M.; Maestre A.; Marchena P.J.; Martin M.; Monreal M.; Mora J.M.; Munoz F.J.; Nauffal M.D.; Nieto J.A.; Nunez M.J.; Ogea J.L.; Otero R.; Pedrajas J.M.; Peris M.L.; Riera-Mestre A.; Rivas A.; Rodriguez-Davila M.A.; Roman P.; Rosa V.; Ruiz J.; Ruiz-Ribo M.D.; Ruiz-Gamietea A.; Ruiz-Gimenez N.; Sahuquillo J.C.; Samperiz A.; Sanchez Munoz-Torrero J.F.; Soler S.; Tiberio G.; Tilvan R.M.; Tolosa C.; Trujillo J.; Uresandi F.; Valdes M.; Valero B.; Valle R.; Vela J.; Vidal G.; Villalobos A.; Villalta J.; Gadelha T.; Maly R.; Hirmerova J.; Tomko T.; Bertoletti L.; Bura-Riviere A.; Farge-Bancel D.; Grange C.; Hij A.; Mahe I.; Merah A.; Quere I.; Schellong S.; Babalis D.; Papadakis M.; Tzinieris I.; Faul J.; Braester A.; Brenner B.; Tzoran I.; Zeltser D.; Barillari G.; Ciammaichella M.; Dalla Valle F.; Di Micco P.; Duce R.; Maida R.; Pasca S.; Piovella C.; Poggio R.; Prandoni P.; Quintavalla R.; Rocci A.; Rota L.; Schenone A.; Tiraferri E.; Tonello D.; Tufano A.; Visona A.; Zalunardo B.; Brinquinho M.; Gomes D.; Goncalves F.; Santos M.; Saraiva M.; Bosevski M.; Kovacevic D.; Alatri A.; Aujeski D.; Bounameaux H.; Calanca L.; Mazzolai L.; Caprini J.Farge, D.; Trujillo-Santos, J.; Debourdeau, P.; Bura-Riviere, A.; Rodriguez-Beltran, E. M.; Nieto, J. A.; Peris, M. L.; Zeltser, D.; Mazzolai, L.; Hij, A.; Monreal, M.; Durante, A.; Alcalde, M.; Arcelus, J. I.; Ballaz, A.; Barba, R.; Barron, M.; Barron-Andres, B.; Bascunana, J.; Bedate, P.; Blanco-Molina, A.; Bueso, T.; Casado, I.; Conget, F.; Del Molino, F.; Del Toro, J.; Falga, C.; Fernandez-Capitan, C.; Fuentes, M. I.; Gallego, P.; Garcia, J.; Garcia-Bragado, F.; Gavin, O.; Gomez, V.; Gonzalez, J.; Gonzalez-Bachs, E.; Grau, E.; Guil, M.; Guijarro, R.; Gutierrez, J.; Hernandez, L.; Jara-Palomares, L.; Jaras, M. J.; Jimenez, D.; Jimenez, S.; Lobo, J. L.; Lopez-Jimenez, L.; Lopez-Saez, J. B.; Lorente, M. A.; Lorenzo, A.; Luque, J. M.; Madridano, O.; Macia, M.; Maestre, A.; Marchena, P. J.; Martin, M.; Monreal, M.; Mora, J. M.; Munoz, F. J.; Nauffal, M. D.; Nieto, J. A.; Nunez, M. J.; Ogea, J. L.; Otero, R.; Pedrajas, J. M.; Peris, M. L.; Riera-Mestre, A.; Rivas, A.; Rodriguez-Davila, M. A.; Roman, P.; Rosa, V.; Ruiz, J.; Ruiz-Ribo, M. D.; Ruiz-Gamietea, A.; Ruiz-Gimenez, N.; Sahuquillo, J. C.; Samperiz, A.; Sanchez Munoz-Torrero, J. F.; Soler, S.; Tiberio, G.; Tilvan, R. M.; Tolosa, C.; Trujillo, J.; Uresandi, F.; Valdes, M.; Valero, B.; Valle, R.; Vela, J.; Vidal, G.; Villalobos, A.; Villalta, J.; Gadelha, T.; Maly, R.; Hirmerova, J.; Tomko, T.; Bertoletti, L.; Bura-Riviere, A.; Farge-Bancel, D.; Grange, C.; Hij, A.; Mahe, I.; Merah, A.; Quere, I.; Schellong, S.; Babalis, D.; Papadakis, M.; Tzinieris, I.; Faul, J.; Braester, A.; Brenner, B.; Tzoran, I.; Zeltser, D.; Barillari, G.; Ciammaichella, M.; Dalla Valle, F.; Di Micco, P.; Duce, R.; Maida, R.; Pasca, S.; Piovella, C.; Poggio, R.; Prandoni, P.; Quintavalla, R.; Rocci, A.; Rota, L.; Schenone, A.; Tiraferri, E.; Tonello, D.; Tufano, A.; Visona, A.; Zalunardo, B.; Brinquinho, M.; Gomes, D.; Goncalves, F.; Santos, M.; Saraiva, M.; Bosevski, M.; Kovacevic, D.; Alatri, A.; Aujeski, D.; Bounameaux, H.; Calanca, L.; Mazzolai, L.; Caprini, J

Silent pulmonary embolism in patients with proximal deep vein thrombosis in the lower limbs

BACKGROUND: One in every three patients with deep vein thrombosis (DVT) in the lower limbs may have silent pulmonary embolism (PE), but its clinical relevance has not been thoroughly studied. METHODS: We used the RIETE Registry data to study patients with proximal DVT and no PE symptoms, but with a systematic search for PE. We compared the outcome of DVT patients with silent PE and those with no PE. RESULTS: Of 2375 patients with DVT, 842 (35%) had silent PE and 1533 had no PE. During the first 15 days of anticoagulation, patients presenting with silent PE had a higher incidence of symptomatic PE events than those with no PE (0.95% vs. 0.13%; P = 0.015), with a similar incidence of major bleeding (0.95% vs. 1.63%; P = 0.09). In patients with silent PE, the incidence of PE events during the first 15 days was equal to the incidence of major bleeding (eight events each), but in those with no PE the incidence of PE events was eight times lower (3 vs. 25 bleeding events). Multivariate analysis confirmed that DVT patients with silent PE had a higher incidence of symptomatic PE events during the first 15 days than those with no PE (odds ratio, 4.80; 95% CI, 1.27-18.1), with no differences in bleeding. CONCLUSIONS: DVT patients with silent PE at baseline had an increased incidence of symptomatic PE events during the first 15 days of anticoagulant therapy. This effect disappeared after 3 months of anticoagulation

Outcomes in Neurosurgical Patients Who Develop Venous Thromboembolism: A Review of the RIETE Registry

OBJECTIVES: Registro Informatizado de Enfermedad TromboEmb\uf3lica (RIETE) database was used to investigate whether neurosurgical patients with venous thromboembolism (VTE) were more likely to die of bleeding or VTE and the influence of anticoagulation on these outcomes. METHODS: Clinical characteristics, treatment details, and 3-month outcomes were assessed in those who developed VTE after neurosurgery. RESULTS: Of 40 663 patients enrolled, 392 (0.96%) had VTE in less than 60 days after neurosurgery. Most patients in the cohort (89%) received initial therapy with low-molecular-weight heparin, (33% received subtherapeutic doses). In the first week, 10 (2.6%) patients died (8 with pulmonary embolism [PE], no bleeding deaths; P = .005). After the first week, 20 (5.1%) patients died (2 with fatal bleeding, none from PE). Overall, this cohort was more likely to develop a fatal PE than a fatal bleed (8 vs 2 deaths, P = .058). CONCLUSIONS: Neurosurgical patients developing VTE were more likely to die from PE than from bleeding in the first week, despite anticoagulation

D-dimer levels and 90-day outcome in patients with acute pulmonary embolism with or without cancer

BACKGROUND: The prognostic value of D-dimer testing in patients with acute pulmonary embolism (PE) has not been thoroughly studied. METHODS: We used the RIETE Registry data to assess the 90-day prognostic value of increased IL Test D-dimer levels at baseline in patients with PE, according to the presence or absence of cancer. RESULTS: As of May 2013, 3,283 patients with acute PE underwent D-dimer testing using IL Test D-dimer. Among 2,588 patients without cancer, those with D-dimer levels in the highest quartile had a higher rate of fatal PE (2.6% vs. 0.9%; p=0.002), fatal bleeding (1.1% vs. 0.3%; p=0.017) and all-cause death (9.1% vs. 4.4%; p<0.001) at 90 days compared with those with levels in the lowest quartiles. Among 695 patients with cancer, those with levels in the highest quartile had a similar rate of fatal PE or fatal bleeding but higher mortality (35% vs. 24%; p<0.01). On multivariate analysis, non-cancer patients with D-dimer levels in the highest quartile had an increased risk for fatal PE (odds ratio [OR]: 3.3; 95% CI: 1.6-6.6), fatal bleeding (OR: 4.3; 95% CI: 1.4-13.7) and all-cause death (OR: 2.1; 95% CI: 1.4-3.1) compared with patients with levels in the lowest quartiles. CONCLUSIONS: Non-cancer patients with acute PE and IL Test D-dimer levels in the highest quartile had an independently higher risk for fatal PE, fatal bleeding and all-cause death at 90 days than those with levels in the lowest quartiles. In patients with cancer, D-dimer levels failed to predict fatal PE or fatal bleeding

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 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

Low-molecular-weight or Unfractionated Heparin in Venous Thromboembolism: The Influence of Renal Function

BACKGROUND: In patients with acute venous thromboembolism and renal insufficiency, initial therapy with unfractionated heparin may have some advantages over low-molecular-weight heparin. METHODS: We used the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) Registry data to evaluate the 15-day outcome in 38,531 recruited patients. We used propensity score matching to compare patients treated with unfractionated heparin with those treated with low-molecular-weight heparin in 3 groups stratified by creatinine clearance levels at baseline: >60 mL/min, 30 to 60 mL/min, or <30 mL/min. RESULTS: Patients initially receiving unfractionated heparin therapy (n = 2167) more likely had underlying diseases than those receiving low-molecular-weight heparin (n = 34,665). Propensity score-matched groups of patients with creatinine clearance levels >60 mL/min (n = 1598 matched pairs), 30 to 60 mL/min (n = 277 matched pairs), and <30 mL/min (n = 210 matched pairs) showed an increased 15-day mortality for unfractionated heparin compared with low-molecular-weight heparin (4.5% vs 2.4% [P = .001], 5.4% vs 5.8% [P = not significant], and 15% vs 8.1% [P = .02], respectively), an increased rate of fatal pulmonary embolism (2.8% vs 1.2% [P = .001], 3.2% vs 2.5% [P = not significant], and 5.7% vs 2.4% [P = .02], respectively), and a similar rate of fatal bleeding (0.3% vs 0.3%, 0.7% vs 0.7%, and 0.5% vs 0.0%, respectively). Multivariate analysis confirmed that patients treated with unfractionated heparin were at increased risk for all-cause death (odds ratio, 1.8; 95% confidence interval, 1.3-2.4) and fatal pulmonary embolism (odds ratio, 2.3; 95% confidence interval, 1.5-3.6). CONCLUSIONS: In comparison with low-molecular-weight heparin, initial therapy with unfractionated heparin was associated with a higher mortality and higher rate of fatal pulmonary embolism in patients with creatinine clearance levels >60 mL/min or <30 mL/min, but not in those with levels between 30 and 60 mL/min

Factors Associated with elevated Pulmonary Arterial Pressure Levels on the Echocardiographic Assessment in Patients with Prior Pulmonary Embolism

BACKGROUND: Factors associated with the detection of raised systolic pulmonary artery pressure (sPAP) levels in patients with a prior episode of pulmonary embolism (PE) are not well known. METHODS: We used the RIETE Registry database to identify factors associated with the finding of sPAP levels 6550 mm Hg on trans-thoracic echocardiography, in 557 patients with a prior episode of acute, symptomatic PE. RESULTS: Sixty-two patients (11.1%; 95% CI: 8.72-14.1) had sPAP levels 6550 mm Hg. These patients were more likely women, older, and more likely had chronic lung disease, heart failure, renal insufficiency or leg varicosities than those with PAP levels <50mm Hg. During the index PE event, they more likely had recent immobility, and more likely presented with hypoxemia, increased sPAP levels, atrial fibrillation, or right bundle branch block. On multivariate analysis, women aged 6570 years (hazard ratio [HR]: 2.0; 95% CI: 1.0-3.7), chronic heart or chronic lung disease (HR: 2.4; 95% CI: 1.3-4.4), atrial fibrillation at PE presentation (HR: 2.8; 95% CI: 1.3-6.1) or varicose veins (HR: 1.8; 95% CI: 1.0-3.3) were all associated with an increased risk to have raised sPAP levels. Chronic heart disease, varicose veins, and atrial fibrillation were independent predictors in women, while chronic heart disease, atrial fibrillation, a right bundle branch block or an S1Q3T3 pattern on the electrocardiogram were independent predictors in men. CONCLUSIONS: Women aged 6570 years more likely had raised sPAP levels than men after a PE episode. Additional variables influencing this risk seem to differ according to gender