Identifying patients with prostate cancer at increased risk for haematuria during anticoagulation for venous thromboembolism.

BACKGROUND: Haematuria is a common complication in prostate cancer patients receiving anticoagulation for venous thromboembolism (VTE). Early identification of at-risk patients might help to reduce its incidence and severity. METHODS: We used data from the RIETE registry to develop a prognostic score for haematuria during the first year of anticoagulation for VTE. The prognostic score was built using regression coefficients. RESULTS: From March 2001 through March 2021, 1934 patients with prostate cancer and acute VTE were enrolled. Of these, 1034 (53 %) initially presented as pulmonary embolism and 900 (47 %) as isolated deep vein thrombosis (DVT). During anticoagulation (median 181 days; inter-quartile range: 97-354), 99 patients (5.1 %) developed haematuria (fatal 1, major 27, non-major 72). The incidence rate was: 8 events per 100 patient-years (95%CI 6.5-9.7). Median time to haematuria was 53 days (IQR 4-134). On multivariable analysis, recent haematuria, initial presentation as DVT, comorbidity, metastases, haemoglobin levels <11 g/dL, creatinine >1.2 mg/dL, and radiotherapy independently predicted the risk for haematuria. C-statistics was 0.71 (95%CI: 0.65-0.77). A cut-off of ≥1.5 points classified 312 patients (20 %) at high-risk and had the highest sensitivity (51 %; 95%CI: 39-62) and specificity (82 %; 95%CI: 79-83). Our score improved the performance and non-event net reclassification index (NRI) of the RIETE score (c-statistics: 0.61; 95%CI: 0.54-0.68; NRI: 0.09) or VTE-BLEED score (c-statistics: 0.64; 95%CI: 0.58-0.71; NRI: 0.76). CONCLUSIONS: A prognostic score for haematuria during anticoagulation for VTE performed well in patients with prostate cancer, and improved identification compared to other validated scores.

Major gastrointestinal bleeding in patients receiving anticoagulant therapy for venous thromboembolism.

INTRODUCTION: The gastrointestinal (GI) tract is a frequent site of bleeding in patients receiving anticoagulant therapy for venous thromboembolism (VTE). At-risk patients have not been consistently identified yet. METHODS: We used the RIETE registry to assess the clinical characteristics of patients developing major GI bleeding during the course of anticoagulation. Then, we built a predictive score based on multivariable analysis, aiming to identify patients at increased risk for major GI bleeding. RESULTS: We included 87,431 patients with acute VTE. During the course of anticoagulation, 778 (0.89%) suffered major GI bleeding, 815 (0.93%) non-major GI bleeding and 1462 (1.67%) had major bleeding outside the GI tract. During the first 30 days after major GI bleeding, 7.6% of patients re-bled, 3.9% had VTE recurrences and 33% died. On multivariable analysis, male sex, age ≥70 years, initial VTE presentation as pulmonary embolism, active cancer, prior VTE, recent major bleeding in the GI tract, esophageal varicosities, anemia, abnormal prothrombin time, renal insufficiency and use of corticosteroids were associated to an increased risk for major GI bleeding. Using the predictive score, 39,591 patients (45%) were at low risk; 36,602 (42%) at intermediate-risk; 9315 (11%) at high-risk; and 1923 (2.2%) at very high risk. Their rates of major GI bleeding were: 0.21%, 0.96%, 2.41% and 6.08%, respectively. The c-statistics was 0.771 (95%CI. 0.755-0.786). CONCLUSIONS: We have developed a score which has the potential to identify patients at increased risk for GI bleeding, but needs to be externally validated."

Psychotropic Drugs and Outcome in Patients Receiving Anticoagulant Therapy for Venous Thromboembolism.

BACKGROUND: The influence (if any) of the use of psychotropic drugs on outcome in patients receiving anticoagulant therapy for venous thromboembolism (VTE) has not been consistently evaluated. METHODS: We used data from the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the risk for VTE recurrences, major bleeding, or death during the course of anticoagulant therapy, according to the use of psychotropics at baseline. RESULTS: Among 49,007 patients with VTE enrolled from February 2009 to September 2019, total 5,230 (11%) were using psychotropics at baseline: antidepressants 3,273 (6.7%), antipsychotics 1,588 (3.2%), and anticholinesterases 369 (0.7%). During the course of anticoagulation, 1,259 patients developed VTE recurrences, 1,231 bled, and 3,988 died (fatal pulmonary embolism 269 and fatal bleeding 187). On multivariable analysis, patients using psychotropics at baseline had a similar risk for VTE recurrences (adjusted hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.58-1.12), a nonsignificantly higher risk for major bleeding (adjusted HR: 1.15; 95% CI: 0.97-1.35), and a higher risk for intracranial bleeding (adjusted HR: 1.83; 95% CI: 1.32-2.53) or death (adjusted HR: 1.44; 95% CI: 1.32-1.57) compared with those not using psychotropics. When separately analyzed, the highest risk for intracranial bleeding was found in patients using antidepressants (adjusted HR: 1.60; 95% CI: 1.08-2.37) or antipsychotics (adjusted HR: 2.02; 95% CI: 1.17-3.49) but not in those on anticholinesterases (adjusted HR: 1.69; 95% CI: 0.62-4.60). CONCLUSION: During the course anticoagulation for VTE, patients using psychotropics at baseline were at increased risk for intracranial bleeding.

Thirty-day outcomes in patients with proximal deep vein thrombosis who discontinued anticoagulant therapy prematurely.

INTRODUCTION: In patients receiving anticoagulation for deep vein thrombosis (DVT), a variety of reasons (including active bleeding or high-risk for bleeding) may lead into premature discontinuation of therapy (prior to completing 90 days). The relative frequency and clinical consequences of premature discontinuation in contemporary patients remain unknown. METHODS: We used the data from RIETE, an international registry of patients with venous thromboembolism (VTE), to identify patients with proximal (above knee) lower limb DVT who prematurely discontinued anticoagulation. We assessed the incidence of the composite outcome: pulmonary embolism (PE)-related death, sudden death, or recurrent VTE within the subsequent 30 days after discontinuation and compared the risk of these events vs. the risk in patients without premature discontinuation, once adjusted for demographics and clinical factors. RESULTS: Of 26,335 patients with proximal DVT recruited from 2001 to 2018, 1322 (5.02%) prematurely discontinued anticoagulation. Thirty days after discontinuation, 12 (0.91%) patients suffered fatal PE (n = 8) or sudden death (n = 4) and 33 (2.50%) had non-fatal recurrent VTE (PE = 15; recurrent DVT = 18). In patients with premature discontinuation, the 30-day incidence of the composite outcome was 1.62 per 1000 patient-days (95%CI: 0.00-3.80). During the first week after discontinuation, the incidence rate was 4.09 per 1000 patient-days (95%CI: 0.65-7.52). The adjusted odds of the composite outcome was 7.88 times (95%CI: 6.39-9.72) higher in patients who discontinued prematurely than in those without premature discontinuation. CONCLUSION: Premature discontinuation of anticoagulation occurred in 5% of patients with proximal DVT, and was associated an 8-fold increased odds for the composite outcome.

Frequency and prognostic impact of acute kidney injury in patients with acute pulmonary embolism. Data from the RIETE registry.

RATIONALE: Acute kidney injury (AKI) is associated with a poor outcome. Although pulmonary embolism (PE) may promote AKI through renal congestion and/or hemodynamic instability, its frequency and influence on outcome in patients with acute PE have been poorly studied. METHODS: The frequency of AKI (defined according to the "Kidney Disease: Improving Global Outcomes" definition) at baseline and its influence on the 30-day mortality was evaluated in patients with acute PE from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. We used multivariate analysis to assess whether the presence of AKI influenced the risk for 30-day death. RESULTS: The study included 21,131 patients, of whom 6222 (29.5%) had AKI at baseline: 4385 patients (21%) in stage 1, 1385 (6.5%) in stage 2 and 452 (2%) in stage 3. The proportion of patients with high-risk PE in those with no AKI, AKI stage 1, AKI stage 2 or AKI stage 3 was: 2.8%, 5.3%, 8.8% and 12%, respectively (p < 0.001). After 30 days, 1236 patients (5.9%) died. Overall mortality was 4% in patients with no AKI, 8.4% in AKI stage 1, 14% in AKI stage 2 and 17% in AKI stage 3 (all p < 0.001). AKI was independently associated with an increased risk of all-cause death at 30 days (odds ratio = 1.25; 95%CI: 1.02-1.54). CONCLUSIONS: One in every 3-4 patients with acute PE had AKI at baseline. The presence of AKI independently predicted 30-day mortality. This study suggests that AKI may deserve to be evaluated as a prognostic factor in patients with acute PE.

Impact of Thrombus Sidedness on Presentation and Outcomes of Patients with Proximal Lower Extremity Deep Vein Thrombosis.

Small studies have suggested differences in demographics and outcomes between left- and right-sided deep vein thrombosis (DVT), and also unilateral versus bilateral DVT. We investigated the clinical presentation and outcomes of patients with DVT based on thrombus sidedness. The authors used the data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE) database (2001-2016) to identify patients with symptomatic proximal lower-extremity DVT. Main outcomes included cumulative 90-day symptomatic pulmonary embolism (PE) and 1-year mortality. Overall, 30,445 patients were included. The majority of DVTs occurred in the left leg (16,421 left-sided, 12,643 right-sided, and 1,390 bilateral; p < 0.001 for chi-squared test comparing all three groups). Comorbidities were relatively similar in those with left-sided and right-sided DVT. Compared with those with left-sided DVT, patients with right-sided DVT had higher relative frequency of PE (26% versus 23%, p < 0.001) and 1-year mortality (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.00-1.18). This difference in mortality did not persist after multivariable adjustment (OR: 1.01; 95% CI: 0.93-1.1). Patients with bilateral DVT had a greater burden of comorbidities such as heart failure, and recent surgery compared with those with unilateral DVT (p < 0.001), and higher relative frequency of PE (48%), and 1-year mortality (24.1%). Worse outcomes in patients with bilateral DVT were attenuated but persisted after multivariable adjustment for demographics and risk factors (OR: 1.64; 95% CI: 1.43-1.87). Patients with bilateral DVT had worse outcomes during and after discontinuation of anticoagulation. There is a left-sided preponderance for proximal lower-extremity DVT. Compared with those with left-sided DVT, patients with right-sided DVT have slightly higher rates of PE. Bilateral DVT is associated with markedly worse short-term and 1-year outcomes.

Low discriminating power of the modified Ottawa VTE risk score in a cohort of patients with cancer from the RIETE registry.

Treatment of patients with cancer-associated venous thromboembolism (VTE) remains a major challenge. The modified Ottawa score is a clinical prediction rule evaluating the risk of VTE recurrences during the first six months of anticoagulant treatment in patients with cancer-related VTE. We aimed to validate the Ottawa score using data from the RIETE registry. A total of 11,123 cancer patients with VTE were included in the analysis. According to modified Ottawa score, 2,343 (21 %) were categorised at low risk for VTE recurrences, 4,525 (41 %) at intermediate risk, and 4,255 (38 %) at high risk. Overall, 477 episodes of VTE recurrences were recorded during the course of anticoagulant therapy, with an incidence rate for low, intermediate, and high risk groups of 6.88 % (95 % CI 5.31-8.77), 11.8 % (95 % CI 10.1-13.6), and 21.3 % (95 % CI 18.8-24.1) patient-years, respectively. Overall mortality had an incidence rate of 21.1 % (95 % CI 18.2-24.3), 79.4 % (95 % CI: 74.9-84.1), and 134.7 % (95 % CI: 128.3-141.4) patient-years, respectively. The accuracy and discriminating power of the modified Ottawa score for VTE recurrence was modest, with low sensitivity, specificity and positive predictive value, and a C-statistics of 0.58 (95 % CI: 0.56-0.61). In our analysis, the modified Ottawa score did not accurately predict VTE recurrence among patients with cancer-associated thrombosis, thus hindering its use in clinical practice. It is time to define a new score including other clinical predictors.

Gender-related differences in the outcome of patients with venous thromboembolism and thrombophilia.

BACKGROUND: In patients with venous thromboembolism (VTE) and factor V Leiden (FVL) or prothrombin 20210G-A mutation (PTM), the influence of gender on outcome has not been consistently studied. METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbolica) database to assess the existence of gender differences in the rate of VTE recurrences (deep vein thrombosis [DVT] or pulmonary embolism [PE]) or major bleeding during the course of anticoagulation and after its discontinuation in FVL and PTM carriers. RESULTS: From March 2001 to September 2016, 11,224 VTE patients underwent thrombophilia testing. Of these, 1,563 were FVL carriers (863 men and 700 women) and 1,231 were PTM carriers (659 men and 572 women). During the course of anticoagulant therapy, men with FVL had a 6-fold higher rate of VTE recurrences than major bleeds (31 vs. 5 events). In women with FVL, the rate of VTE recurrences was 2-fold higher (16 vs. 8), as was in men (17 vs. 8) or women (17 vs. 9) with PTM. After discontinuing anticoagulation, men with FVL had a 3-fold higher rate of DVT recurrences than women (hazard ratio [HR]: 3.13; 95% CI: 1.79-5.67), with no differences in PE recurrences. Among patients with PTM, there were no gender differences in the rate of DVT (HR: 1.89; 95% CI: 1.00-3.65) or PE recurrences (HR: 1.82; 95% CI: 0.83-4.12). CONCLUSIONS: During the anticoagulation course, men with FVL are at a much higher risk for VTE recurrences than bleeding. After discontinuing anticoagulation, men with FVL are at an increased risk for DVT recurrences.

A RIETE registry analysis of recurrent thromboembolism and hemorrhage in patients with catheter-related thrombosis.

BACKGROUND: Few studies have investigated the treatment and the outcomes of patients with catheter-related thrombosis (CRT). METHODS: The RIETE registry (Registro Informatizado de Enfermedad TromboEmbólica [Computerized Registry of Patients with Venous Thromboembolism]) is a prospective international registry of consecutive patients with objectively confirmed venous thromboembolism (VTE). We analyzed the characteristics, treatment, and outcomes of patients with CRT. RESULTS: Of 558 patients with CRT, 45 (8%) presented with a pulmonary embolism (PE) concomitantly. More patients had central line-associated thrombosis compared with port systems, but catheter type did not influence the risk of presenting with a PE. Patients with only CRT were more often prescribed low-molecular-weight heparin for the duration of their anticoagulant treatment compared with patients presenting with concomitant PE. VTE recurrences and major bleeding events occurred frequently during treatment with anticoagulation (7 per 100 patient-years and 8.9 per 100 patient years, respectively). The rates of fatal PE recurrences (1.85 per 100 patient-years) and fatal bleeding (2.32 per 100 patient-years) were similar. Patients with an additional transient risk factor for VTE had the lowest risk for VTE recurrences (odds ratio [OR], 0.07; 90% confidence interval [CI], 0.01-0.45) compared with patients with CRT and no additional transient risk factors. PE at presentation increased the risk of recurrent thrombosis by 2.4 times. Renal insufficiency was also an independent predictor of recurrent thrombosis (OR, 3.93; 90% CI, 2.0-7.7). The odds of recurrent thrombosis was decreased by 77% in patients who received anticoagulation therapy for >90 days compared with patients with a shorter treatment (OR, 0.23; 90% CI, 0.1-0.56). CONCLUSIONS: Concomitant PE occurs less frequently in CRT than lower extremity deep venous thrombosis, but it is associated with a worse outcome. CRT occurs in high-risk patients, and duration of anticoagulation must be predicated on balancing these risks.

Comparison of four scores to predict major bleeding in patients receiving anticoagulation for venous thromboembolism: findings from the RIETE registry.

Stratification of the individual bleeding risk prior to initiation of anticoagulation in patients with acute venous thromboembolism (VTE) has the potential to assist clinicians in making decisions about the proper intensity and duration of antithrombotic therapy. It is unclear which of the validated and internationally accepted scores recommended for the achievement of this important task has the best predictive value. We compared the predictive value of four validated scores (by Landefeld, Beyth, Kuijer and Ruiz-Gimenez, respectively) for the development of major bleeding complications occurring in the first 3 months in patients with acute VTE treated with conventional anticoagulation. Based on the population of RIETE Registry (international registry of patients with acute VTE), we identified those patients presenting all the required prognostic variables, and then calculated the ability of each score for predicting the bleeding risk. Of 40,265 eligible patients, we identified 8,717 meeting the recruitment criteria. Overall, 0.9 % of patients experienced at least one episode of major bleeding within 90 days of the index event. The proportion of patients classified as having a low risk varied between 1.2 and 3.7 %, that of patients having an intermediate risk between 76 and 93 %, and that of patients classified as having a high risk between 6.1 and 18 %. The area under the receiver operating characteristic ranged between 0.55 and 0.60, the positive predictive value between 1.5 and 3.2, and the likelihood ratio between 0.72 and 1.59. In conclusion, all four scores show a very low ability to predict the bleeding risk in patients with acute VTE undergoing conventional anticoagulation.

Prognostic significance of multidetector CT in normotensive patients with pulmonary embolism: results of the protect study.

BACKGROUND: In patients with acute pulmonary embolism (PE), rapid and accurate risk assessment is paramount in selecting the appropriate treatment strategy. The prognostic value of right ventricular dysfunction (RVD) assessed by multidetector CT (MDCT) in normotensive patients with PE has lacked adequate validation. METHODS: The study defined MDCT-assessed RVD as a ratio of the RV to the left ventricle short axis diameter greater than 0.9. Outcomes assessed through 30 days after the diagnosis of PE included all-cause mortality and 'complicated course', which consisted of death from any cause, haemodynamic collapse or recurrent PE. RESULTS: MDCT detected RVD in 533 (63%) of the 848 enrolled patients. Those with RVD on MDCT more frequently had echocardiographic RVD (31%) than those without RVD on MDCT (9.2%) (p<0.001). Patients with RVD on MDCT had significantly higher brain natriuretic peptide (269±447 vs 180±457 pg/ml, p<0.001) and troponin (0.10±0.43 vs 0.03±0.24 ng/ml, p=0.001) levels in comparison with those without RVD on MDCT. During follow-up, death occurred in 25 patients with and in 13 patients without RVD on MDCT (4.7% vs 4.3%; p=0.93). Those with and those without RVD on MDCT had a similar frequency of complicated course (3.9% vs 2.3%; p=0.30). CONCLUSIONS: The PROgnosTic valuE of CT study showed a relationship between RVD assessed by MDCT and other markers of cardiac dysfunction around the time of PE diagnosis, but did not demonstrate an association between MDCT-RVD and prognosis.

Platelet count and outcome in patients with acute venous thromboembolism.

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- (<80,000/µl), low- (80,000/µl to 150,000/µl), normal- (150,000/µl to 300,000/µl), high- (300,000/µl to 450,000/µl), or very high (>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.

Clinical outcome of patients with upper-extremity deep vein thrombosis: results from the RIETE Registry.

BACKGROUND: There is little information on the clinical outcome of patients with upper-extremity deep vein thrombosis (DVT). METHODS: RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute DVT or pulmonary embolism (PE). In this analysis, we analyzed the demographic characteristics, treatment, and 3-month outcome of all patients with DVT in the arm. RESULTS: Of the 11,564 DVT patients enrolled, 512 patients (4.4%) had arm DVT. They presented less often with clinically overt PE (9.0% vs 29%; odds ratio, 0.24; 95% confidence interval [CI], 0.18 to 0.33) than those with lower-limb DVT, but their 3-month outcome was similar. Of the 512 patients with arm DVT, 196 patients (38%) had cancer and 228 patients (45%) had catheter-related DVT. During follow-up, those with cancer DVT had an increased incidence of major bleeding (4.1% vs 0.9%; odds ratio, 4.4; 95% CI, 1.2 to 21), recurrent venous thromboembolism (6.1% vs 2.8%; odds ratio, 2.2; 95% CI, 0.91 to 5.6; p = 0.04), and death (22% vs 3.5%; odds ratio, 7.8; 95% CI, 4.0 to 16). Thirty patients had the composite event of recurrent DVT, symptomatic PE, or major bleeding. They were significantly older, more often had cancer, and presented more frequently with symptomatic PE on hospital admission. On multivariate analysis, only cancer patients with arm DVT had an increased risk for the composite event (odds ratio, 3.0; 95% CI, 1.4 to 6.4). CONCLUSIONS: At presentation, patients with arm DVT have less often clinically overt PE than those with lower-limb DVT, but their 3-month outcome is similar. Among patients with arm DVT, those with cancer have the worse outcome.

Venous thromboembolism in patients with renal insufficiency: findings from the RIETE Registry.

BACKGROUND: Current guidelines make no specific recommendations for venous thromboembolism (VTE) treatment in patients with renal insufficiency, but some experts recommend some reduction in heparin dose. METHODS: Registro Informatizado de Enfermedad TromboEmbólica (RIETE) is an ongoing, prospective registry of consecutively enrolled patients with objectively confirmed, symptomatic, acute VTE. In this analysis we retrospectively analyzed the effect of renal insufficiency on the incidence of fatal pulmonary embolism (PE) and fatal bleeding within 15 days of diagnosis. RESULTS: Up to March 2005, 10,526 patients with acute VTE were enrolled in RIETE, of whom 9234 (88%) had a creatinine clearance (CrCl) greater than 60 mL/min, 704 (6.7%) had a CrCl 30 to 60 mL/min, and 588 (5.6%) had a CrCl less than 30 mL/min. The incidence of fatal PE during the study period was 1.0%, 2.6%, and 6.6%, respectively. Fatal bleeding occurred in 0.2%, 0.3%, and 1.2% of the patients, respectively. On multivariate analysis, patients with a CrCl less than 30 mL/min were independently associated with an increased risk for fatal PE and fatal bleeding. In addition, initial diagnosis of PE, immobility for 4 days or more, cancer, and initial therapy with unfractionated heparin were independent predictors of fatal PE; whereas immobility for 4 days or more and cancer were independent predictors of fatal bleeding. CONCLUSIONS: Patients with VTE who have renal insufficiency had an increased incidence of both fatal PE and fatal bleeding, but the risk of fatal PE far exceeded that of fatal bleeding. Our data support the use of full-dose anticoagulant therapy, even in patients with a CrCl less than 30 mL/min.

Management of patients with acute venous thromboembolism: findings from the RIETE registry.

Guidelines for the treatment of venous thromboembolism (VTE) are mainly based on randomized controlled trials, but a number of patients with VTE are excluded from trials due to co-morbidities (i.e., recent bleeding, renal insufficiency, thrombocytopenia, abnormal prothrombin time or pregnancy). Thus, treatment regimens derived from clinical studies may not be suitable for all patient groups. RIETE (Registro Informatizado de la EnfermedadTromboEmbólica) is a Spanish registry of consecutively enrolled patients with objectively confirmed, symptomatic acute VTE. We compared the clinical outcome during the first 3 months of therapy of VTE patients with at least one of the mentioned co-morbidities with that in patients without them. Of 6855 patients enrolled up to February 2004, 1635 (24%) had at least one reason to be excluded from clinical trials: recent bleeding (2.6%); renal insufficiency (13.6%); thrombocytopenia (2.5%); abnormal prothrombin time (9.1%) and pregnancy (0.7%). During the 3-month follow-up period the rates of fatal pulmonary embolism (odds ratio: 3.3; 95% CI: 2.5-5.2); minor bleeding (odds ratio: 1.8; 95% CI: 1.3-2.2); major bleeding (odds ratio: 3.1; 95% CI: 2.3-4.1) and fatal bleeding (odds ratio: 4.1; 95% CI: 2.1-8.0) were significantly higher in patients with at least one of these co-morbidities than in the remaining 5220 patients. The clinical outcome was significantly worse inpatients with either recent bleeding, renal insufficiency, thrombocytopenia, abnormal prothrombin time, or pregnancy. The expanding RIETE database of "real-world"outcomes may lead to improved treatment of VTE, especially for those patients not usually included in randomized clinical trials.