Predicting the risk for major bleeding in elderly patients with venous thromboembolism using the Charlson index. Findings from the RIETE.

Old patients receiving anticoagulant therapy for venous thromboembolism (VTE) are at an increased risk for bleeding. We used data from the RIETE registry to assess the prognostic ability of the Comorbidity Charlson Index (CCI) to predict the risk for major bleeding in patients aged > 75 years receiving anticoagulation for VTE beyond the third month. We calculated the area under the receiver-operating characteristic curve (AUC), the category-based net reclassification index (NRI) and the net benefit (NB). We included 4303 patients with a median follow-up of 706 days (interquartile range [IQR] 462-1101). Of these, 147 (3%) developed major bleeding (27 died of bleeding). The AUC was 0.569 (95% CI 0.524-0.614). Patients with CCI ≤ 4 points were at a lower risk for adverse outcomes than those with CCI > 10 (major bleeding 0.81 (95% CI 0.53-1.19) vs. 2.21 (95% CI 1.18-3.79) per 100 patient-years; p < 0.05; all-cause death 1.9 (95% CI 1.45-2.44) vs. 15.67 (95% CI 12.63-19.22) per 100 patient-years; p < 0.05). A cut-off point of 4 points (CCI4) had a sensitivity of 82% (95% CI 75-89) and a specificity of 30% (95% CI 29-31) to predict major bleeding beyond the third month. CCI4 reclassification improved the NB of the RIETE bleeding score to predict bleeding beyond the third month (CCI4 NB 1.78% vs. RIETE NB 0.44%). Although the AUC of the CCI to predict major bleeding was modest, it could become an additional help to select patients aged > 75 years that obtain more benefit of extended anticoagulation, due to a lower risk for bleeding and better survival.

Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis.

Introduction: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity. Materials and methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed. Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (HMOX1; T/T genotype OR 9.9 p < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p = 0.04 and T/T genotype OR 12.9, p < 0.0001), and rs713400 (eQTL for TMPRSS2; C/T + T/T genotype OR 1.86, p = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (CD69; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p = 0.01), rs2660 (OAS1; A/G genotype OR 0.6, p = 0.08), rs896 (VIPR1; T/T genotype OR 0.4, p = 0.02) and rs33980500 (TRAF3IP2; C/T + T/T genotype OR 0.3, p = 0.01) were associated with lower risk of viremia. Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.

Clinical characteristics, time course, and outcomes of major bleeding according to bleeding site in patients with venous thromboembolism.

BACKGROUND: Bleeding is the most dreaded complication of anticoagulant therapy for acute venous thromboembolism (VTE). Limited data exist about patient characteristics, time course and outcomes of major bleeding, according to the bleeding site. METHODS: We used the data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry (03/2001-07/2018) and identified patients who suffered from major bleeding during anticoagulation. We assessed patient characteristics, time course, and 30-day outcomes including mortality, re-bleeding, and VTE recurrences, according to bleeding site. RESULTS: Among 78,136 patients with VTE receiving anticoagulation, 2244 (2.9%) suffered from major bleeding (gastrointestinal in 800, intracranial in 417, hematoma in 410, genitourinary in 222, retroperitoneal in 145; other sites in 250). There were variations in baseline characteristics, including older age (P < 0.001) and predominance of women (70.2% [95% confidence interval [CI]]: 65.6-74.6% versus 50.5%, 95% CI: 48.2-52.9, P < 0.001) in patients with hematoma, compared with other patients. Overall, 82.7% of hematomas and 81.4% of retroperitoneal bleeds occurred in the first 90 days after the diagnosis of the VTE event, compared with only 50.6% of intracranial bleeds. Across the bleeding subgroups, 30-day all-cause mortality rates were highest in patients who suffered from intracranial bleeding (41.0%; 99% confidence interval [CI]: 34.8-47.4%), and lowest in patients who suffered from hematoma (17.8%; 99% CI: 13.2-23.2%). Patients who suffered from a major bleeding event in the first 30 days after VTE had significantly higher odds at 90-day follow-up to develop mortality (including from bleeding), recurrent VTE, and recurrent major bleeding (all Ps < 0.001). Variations were observed in the results according to the bleeding site. CONCLUSIONS: Major bleeding is a serious complication in VTE patients. Patient characteristics, time course and outcomes varied substantially according to the bleeding site. Additional studies are needed to tease out the impact of patient risk factors, treatment regimens, and a potential distinct effect from the site of bleeding. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02832245 (RIETE registry).

Prediction of Major Bleeding in Anticoagulated Patients for Venous Thromboembolism: Comparison of the RIETE and the VTE-BLEED Scores.

The performance of validated bleeding risk scores in patients with venous thromboembolism (VTE) could be different depending on the time after index event or the site of bleeding. In this study we compared the "classic" Registro Informatizado de Enfermedad TromboEmbólica (RIETE) score and the more recently developed VTE-BLEED score for the prediction of major bleeding in patients under anticoagulant therapy in different time intervals after VTE diagnosis. Out of 82,239 patients with acute VTE, the proportion of high-risk patients according to the RIETE and VTE-BLEED scores was 7.1 and 62.3%, respectively. The performance of both scores across the different study periods (first 30 days after VTE diagnosis, days 31-90, days 91-180, and days 181-360) was similar, with areas under the receiving operating characteristics (ROC) curve (AUC) ranging between 0.69 and 0.72. However, the positive predictive values were low, ranging between 0.6 and 3.9 (better for early major bleeding than for later periods). A sensitivity analysis limited to patients with unprovoked VTE showed comparable results. Both scores showed a trend toward a better prediction of extracranial than intracranial major bleeding, the RIETE score resulting more useful for early extracranial bleeding and the VTE-BLEED for late intracranial hemorrhages. Our study reveals that the usefulness of available bleeding scores may vary depending on the characteristics of the patient population and the time frame evaluated. Dynamic scores could be more useful for this purpose.

Refinement of a modified simplified Pulmonary Embolism Severity Index for elderly patients with acute pulmonary embolism.

OBJECTIVE: To evaluate the utility of a modified (i.e., without the variable "Age >80 years") simplified Pulmonary Embolism Severity Index (sPESI) in elderly patients with acute symptomatic pulmonary embolism (PE), and to derive and validate a refined version of the sPESI for identification of elderly patients at low risk of adverse events. METHODS: The study included normotensive patients aged >80 years with acute PE enrolled in the RIETE registry. We used multivariable logistic regression analysis to create a new risk score to predict 30-day all-cause mortality. We externally validated the new risk score in elderly patients from the COMMAND VTE registry. RESULTS: Multivariable logistic regression identified four predictors for mortality: high-risk sPESI, immobilization, coexisting deep vein thrombosis (DVT), and plasma creatinine >2 mg/dL. In the RIETE derivation cohort, the new model classified fewer patients as low risk (4.0% [401/10,106]) compared to the modified sPESI (35% [3522/10,106]). Low-risk patients based on the new model had a lower 30-day mortality than those based on the modified sPESI (1.2% [95% CI, 0.4-2.9%] versus 4.7% [95% CI, 4.0-5.4%]). In the COMMAND VTE validation cohort, 1.5% (3/206) of patients were classified as having low risk of death according to the new model, and the overall 30-day mortality of this group was 0% (95% CI, 0-71%), compared to 5.9% (95% CI, 3.1-10.1%) in the high-risk group. CONCLUSIONS: For predicting short-term mortality among elderly patients with acute PE, this study suggests that the new model has a substantially higher sensitivity than the modified sPESI. A minority of these patients might benefit from safe outpatient therapy of their disease.

Acenocoumarol Pharmacogenetic Dosing Algorithm versus Usual Care in Patients with Venous Thromboembolism: A Randomised Clinical Trial.

Patients with venous thromboembolism (VTE) require immediate treatment with anticoagulants such as acenocoumarol. This multicentre randomised clinical trial evaluated the effectiveness of a dosing pharmacogenetic algorithm versus a standard-of-care dose adjustment at the beginning of acenocoumarol treatment. We included 144 patients with VTE. On the day of recruitment, a blood sample was obtained for genotyping (CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2, APOE). Dose adjustment was performed on day 3 or 4 after the start of treatment according to the assigned group and the follow-up was at 12 weeks. The principal variable was the percentage of patients with an international normalised ratio (INR) within the therapeutic range on day 7. Thirty-four (47.2%) patients had an INR within the therapeutic range at day 7 after the start of treatment in the genotype-guided group compared with 14 (21.9%) in the control group (p = 0.0023). There were no significant differences in the time to achieve a stable INR, the number of INRs within the range in the first 6 weeks and at the end of study. Our results suggest the use of a pharmacogenetic algorithm for patients with VTE could be useful in achieving target INR control in the first days of treatment.

Clinical outcome of patients with major bleeding after venous thromboembolism. Findings from the RIETE Registry.

The natural history of patients with venous thromboembolism (VTE) who develop a major bleeding complication while on anticoagulant therapy is not well known. RIETE is a prospective registry of consecutive patients with symptomatic, objectively confirmed, acute VTE. The clinical characteristics, treatment decisions and outcome of all VTE patients who had major bleeding during the first three months of anticoagulant therapy were retrospectively studied. As of January 2007, 17, 368 patients were included in RIETE. Of these, 407 (2.3%) had major bleeding during the study period: 144 gastrointestinal, 119 haematoma, 51 intracranial, 43 genitourinary, 50 other. In 286 (69%) patients anticoagulant therapy was discontinued, in 74 (18%) not modified, in 38 (9.1%) a vena cava filter was inserted. During the first 30 days after bleeding, 24 (5.9%) patients re-bled, 20 (4.9%) had recurrent VTE, 133 (33%) died. Of these, 75 died of bleeding, 12 of recurrent pulmonary embolism. Most deaths occurred shortly after the bleeding episode (median: 1 day). On multivariate analysis, insertion of a vena cava filter was the only variable independently associated with a lower incidence of fatal bleeding (odds ratio [OR]: 0.10; 95% confidence interval [CI]: 0.01-0.79) and all-cause mortality (OR: 0.21; 95% CI: 0.07-0.63). In conclusion, the occurrence of major bleeding in patients with VTE is outstanding in terms of overall mortality (33% within 30 days), fatal bleeding (18%) or re-bleeding (5.9%). However, these patients also have an increased incidence of recurrent VTE (4.9%) and fatal pulmonary embolism (1.2%).

Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry.

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.

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.

Rapid D-dimer test combined a clinical model for deep vein thrombosis. Validation with ultrasonography and clinical follow-up in 383 patients.

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 venous thrombosis of lower extremities in an Emergency Department. Utility of a clinical diagnosis model]. / Trombosis venosa profunda en miembros inferiores en un servicio de urgencias. Utilidad de un modelo clínico de estratificación de riesgo.

BACKGROUND: 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. PATIENTS AND METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

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.

Efficiency and effectiveness of the use of an acenocoumarol pharmacogenetic dosing algorithm versus usual care in patients with venous thromboembolic disease initiating oral anticoagulation: study protocol for a randomized controlled trial.

BACKGROUND: Hemorrhagic events are frequent in patients on treatment with antivitamin-K oral anticoagulants due to their narrow therapeutic margin. Studies performed with acenocoumarol have shown the relationship between demographic, clinical and genotypic variants and the response to these drugs. Once the influence of these genetic and clinical factors on the dose of acenocoumarol needed to maintain a stable international normalized ratio (INR) has been demonstrated, new strategies need to be developed to predict the appropriate doses of this drug. Several pharmacogenetic algorithms have been developed for warfarin, but only three have been developed for acenocoumarol. After the development of a pharmacogenetic algorithm, the obvious next step is to demonstrate its effectiveness and utility by means of a randomized controlled trial. The aim of this study is to evaluate the effectiveness and efficiency of an acenocoumarol dosing algorithm developed by our group which includes demographic, clinical and pharmacogenetic variables (VKORC1, CYP2C9, CYP4F2 and ApoE) in patients with venous thromboembolism (VTE). METHODS AND DESIGN: This is a multicenter, single blind, randomized controlled clinical trial. The protocol has been approved by La Paz University Hospital Research Ethics Committee and by the Spanish Drug Agency. Two hundred and forty patients with VTE in which oral anticoagulant therapy is indicated will be included. Randomization (case/control 1:1) will be stratified by center. Acenocoumarol dose in the control group will be scheduled and adjusted following common clinical practice; in the experimental arm dosing will be following an individualized algorithm developed and validated by our group. Patients will be followed for three months. The main endpoints are: 1) Percentage of patients with INR within the therapeutic range on day seven after initiation of oral anticoagulant therapy; 2) Time from the start of oral anticoagulant treatment to achievement of a stable INR within the therapeutic range; 3) Number of INR determinations within the therapeutic range in the first six weeks of treatment. DISCUSSION: To date, there are no clinical trials comparing pharmacogenetic acenocoumarol dosing algorithm versus routine clinical practice in VTE. Implementation of this pharmacogenetic algorithm in the clinical practice routine could reduce side effects and improve patient safety. TRIAL REGISTRATION: Eudra CT. Identifier: 2009-016643-18.

Clinical validity of negative helical computed tomography for clinical suspicion of pulmonary embolism.

BACKGROUND: Helical computed tomography has been introduced for the diagnosis of pulmonary embolism. OBJECTIVE: To determine the clinical safety of withholding anticoagulant treatment in patients with suspicion of pulmonary embolism and negative helical computed tomography study. METHODS: During a 9-month period, we performed a prospective study including 209 consecutive patients who underwent helical computed tomography for clinical suspicion of pulmonary embolism. In 53 patients (25.5%), helical computed tomography was diagnostic for pulmonary embolism, and in 24 patients (11.5%) it was indeterminate. In 132 patients (63%), the examination was negative for pulmonary embolism and no anticoagulation treatment was given. A clinical 3-month follow-up was carried out. During this period, 29 patients (22%) were excluded because anticoagulation therapy was initiated for other reasons, or because other diagnostic techniques were performed for pulmonary embolism. Four patients were lost in the 3-month period. In the end, 99 patients (75%) were included in the clinical follow-up. RESULTS: Out of the 99 patients, 9 (9%) died during the 9-month follow-up, the cause of death in each case was not due to thromboembolic venous disease. No venous thromboembolic events were detected in the other 90 patients. Negative predictive value of helical computed tomography for pulmonary embolism was 99.09% (95% CI, 95.03-99.97%). CONCLUSIONS: In patients with clinical suspicion of pulmonary embolism and initial negative helical computed tomography from whom anticoagulants are withheld, no thromboembolic disease was detected in a 3-month follow-up. We consider helical computed tomography an effective method for ruling out pulmonary embolism as well as a front-line tool for diagnosis.