Incidence and impact of anticoagulation-associated abnormal menstrual bleeding in women after venous thromboembolism.

Preliminary data and clinical experience have suggested an increased risk of abnormal uterine bleeding (AUB) in women of reproductive age treated with anticoagulants, but solid data are lacking. The TEAM-VTE study was an international multicenter prospective cohort study in women aged 18 to 50 years diagnosed with acute venous thromboembolism (VTE). Menstrual blood loss was measured by pictorial blood loss assessment charts at baseline for the last menstrual cycle before VTE diagnosis and prospectively for each cycle during 3 to 6 months of follow-up. AUB was defined as an increased score on the pictorial blood loss assessment chart (>100 or >150) or self-reported AUB. AUB-related quality of life (QoL) was assessed at baseline and the end of follow-up using the Menstrual Bleeding Questionnaire. The study was terminated early because of slow recruitment attributable to the COVID-19 pandemic. Of the 98 women, 65 (66%) met at least one of the 3 definitions of AUB during follow-up (95% confidence interval [CI], 57%-75%). AUB occurred in 60% of women (36 of 60) without AUB before VTE diagnosis (new-onset AUB; 95% CI, 47%-71%). Overall, QoL decreased over time, with a mean Menstrual Bleeding Questionnaire score increase of 5.1 points (95% CI, 2.2-7.9), but this decrease in QoL was observed only among women with new-onset AUB. To conclude, 2 of every 3 women who start anticoagulation for acute VTE experience AUB, with a considerable negative impact on QoL. These findings should be a call to action to increase awareness and provide evidence-based strategies to prevent and treat AUB in this setting. This was an academic study registered at www.clinicaltrials.gov as #NCT04748393; no funding was received.

[Clinical usefulness of three quantitative D-dimers tests in outpatients with suspected deep vein thrombosis]. / Análisis de 3 métodos para determinar el dímero D en pacientes con sospecha de trombosis venosa profunda.

BACKGROUND AND OBJECTIVE: The diagnostic approach in outpatients with suspected deep vein thrombosis (DVT) of the lower limbs includes D-dimer measurement (DD). Elevated DD is not a diagnostic value for DVT. However, a normal value contributes to ruling out DVT. We do not know the best method to determine DD. Therefore, we have analyzed the clinical utility of three quantitative assays to determine DD in outpatients with suspected DVT. PATIENTS AND METHODS: Consecutive outpatients with suspected DVT of the lower limbs who were referred to the DVT medical consultation were enrolled in the study. We used a diagnostic algorithm that included determining the pretest clinical probability (PCP) (Wells scale), DD level using three different quantitative methods (ELISA mini-VIDAS(®), Acure-care DDMR and DD-Plus). The DVT diagnosis was confirmed by seriated compression ultrasonography of the lower limbs. We analyzed the concordance between the three analytic methods to quantify DD and the characteristics. RESULTS: A total of 306 patients (mean age 60 years, 62% women) with suspected DVT of the lower limbs were included. The compression ultrasonography confirmed the diagnosis of DVT in 23.8% of the patients. Anticoagulation treatment was not performed in patients in whom DVT was ruled out, and no thromboembolic event occurred during the 3 months of follow-up. The best concordance test results were between ELISA mini-VIDAS(®) and Acure-care DDMR assays. Both assays demonstrated elevated sensibility and a negative predictive value. ELISA mini-VIDAS(®) was the best analytic method for the subgroup of patients with low clinical probability. CONCLUSIONS: The ELISA mini-VIDAS(®) method to determine DD rules out DVT in patients with low clinical probability.

Differential biomarker profiles between unprovoked venous thromboembolism and cancer.

BACKGROUND: The relationship between cancer and venous thromboembolic disease (VTD) are complex because the activated coagulation factors are not only involved in thrombosis but also in malignant processes, such as angiogenesis and metastasis. OBJECTIVE: To compare phenotypes of extracellular vesicles (EVs), and levels of D-dimer, soluble P-selectin (sP-selectin) and antigenic tissue factor (TF) between unprovoked VTD patients, who did not develop cancer during one-year follow-up, and those with advanced stage of cancer but not associated with VTD. METHODS: A prospective study in which we included 138 unprovoked VTD patients and 67 advanced cancer patients, who did not develop thrombosis. Levels of EVs of different cellular origin (platelet, endothelium and leukocyte), EVs positive for tissue factor (TF) and P-selectin glycoprotein ligand 1 were quantified by flow cytometry. D-dimer, soluble P-selectin (sP-selectin) and antigenic TF were determined by ELISA. RESULTS: TF-positive EVs, D-dimer, and sP-selectin were markedly elevated in unprovoked VTD patients compared to cancer patients without association with thrombosis. CONCLUSIONS: Levels of TF-positive EVs, D-dimer and sP-selectin are able to discriminate between unprovoked VTD patients not related to cancer and cancer patients not associated with VTD. These results could lead to the application of EVs as biomarkers of both diseases. Key messages: Circulating EVs, specifically TF-positive EVs, in combination with plasmatic markers of hypercoagulable states, such as D-dimer, sP-selectin and antigen TF, are able to discriminate between cancer patients without thrombosis and patients with unprovoked VTD. Research fields could be opened. Future studies will assess if these biomarkers together serve as predicting thrombotic events in cancer populations.

Relationship between type of unprovoked venous thromboembolism and cancer location: An individual patient data meta-analysis.

BACKGROUND: Unprovoked venous thromboembolism (VTE) may be the first manifestation of an underlying cancer. We aimed to assess the period prevalence of occult cancer detection stratified by VTE location (deep vein thrombosis [DVT], pulmonary embolism [PE] or both) and the anatomical relationship between occult cancer and VTE. METHODS: Post-hoc analysis of a systematic review and individual patient data meta-analysis of adults with unprovoked VTE with at least 12 months of follow-up. Cancer types were grouped according to thoracic, abdomino-pelvic, or other locations. RESULTS: A total of 2300 patients were eligible including 1218 with DVT only (53%), 719 with PE only (31%), and 363 with both PE and DVT (16%). The pooled 12-month period prevalence of cancer in DVT only, PE only, and DVT + PE was 5.6% (95% CI, 4.4 to 7.2), 4.3% (95% CI, 2.7 to 6.9), and 5.6% (95% CI, 1.7 to 15.5), respectively. Most occult cancers were located in the abdomen (68.4%). The proportion of patients with an abdomino-pelvic cancer was not different in patients with DVT + PE (81%; 95% CI, 54 to 96) than in those with DVT (68%; 95% CI, 57 to 78) or PE alone (65%; 95% CI, 48 to 79). CONCLUSION: The 12-month prevalence of occult cancer was similar in patients with DVT only, PE only, or both. Most cancers were located in the abdomen, and there was no relationship between VTE type and cancer location.

Predicting the risk of cancer after unprovoked venous thromboembolism: external validation of the RIETE score.

Essentials Patients at high-risk of occult cancer may benefit from extensive screening. We validated the RIETE cancer score in the MVTEP study. One in three patients were classified as high-risk, 10% of whom had cancer diagnosed. The RIETE score identifies a subgroup at high risk for cancer. SUMMARY: Background Most recent trials evaluating extensive screening strategies for occult cancer in patients with unprovoked venous thromboembolism have failed, because, among other reasons, of an overall low rate of occult cancer. The RIETE investigators recently proposed a score aimed at identifying a subgroup at higher risk. Methods We retrospectively computed the RIETE score for all patients included in the MVTEP study, which evaluated the accuracy of [¹8F]fluorodeoxyglucose-positron emission tomography in the screening of occult cancer in patients with unprovoked venous thromboembolism. Performance of the RIETE score was assessed according to the proportion of patients classified in each risk group, and the corresponding rates of cancer diagnosis. Results Among the 386 patients included in the analysis, 136 patients (35.3%) were classified as high risk by the RIETE score. Cancer was diagnosed in 16 (11.8%) of them, whereas it was diagnosed in nine (3.6%) of the 250 patients with a low RIETE cancer score: odds ratio of 3.6 (95% confidence interval [CI] 1.53-8.32). The area under the receiver operating characteristic curve was 0.63 (95% CI 0.51-0.74). Conclusion The RIETE score seems to be able to identify a subgroup at high risk for cancer (10%) in our specific dataset of patients with unprovoked venous thromboembolism.

Lung cancer mortality in Spain: estimating the future burden to the year 2028.

OBJECTIVE: To use lung cancer mortality rates from 1979 to 2008 in Andalusia, southern Spain (population >8,000,000), to provide an estimate of the future number of deaths for the period 2009-2028. DESIGN: The numbers of lung cancer deaths from 1979 to 2008 were obtained from the Andalusian Institute for Statistics (AIS). Data were arranged in 5-year age groups using an age-period-cohort model. Age-standardised rates (ASR) per 100, 000 were calculated for males and females. Population projections for Andalusia 2009-2028 were downloaded from the AIS database. RESULTS: In males, the ASR varied from 46.1 in 2004-2008 to 34.6 in 2024-2028, with a projected 33% decrease. In females, the ASR varied from 4.9 in 2004-2008 to 8.9 per 100,000 in 2024-2028, with a projected 45% increase. This reflects an annual change of -1.3% for males and of +2.7% for females for the period 2009-2028. The sex ratio is projected to drop from a male:female ratio of 11 (1979-1983) to 3.8 (2024-2028). CONCLUSIONS: Our projections emphasise the significance of a continuously increasing trend in female lung cancer mortality, with a drop in the projected sex ratio.

Dyslipidemia as a long-term marker for survival in pulmonary embolism.

OBJECTIVES: To analyse survival rate after 24 months in consecutive patients with a diagnosis of PE as well as associated factors. METHODS: Prospective cohort study during a follow-up period of two years in a series of consecutive patients with PE. RESULTS: During the follow-up period, 34 out of 148 patients died (23%). Factors independently associated with reduced survival rate were: creatinine levels > 2 (OR, 8.8; 95% CI, 1.1 - 70.87), previous neoplasm (OR, 8.8; 95% CI, 3.69 - 20.98), dementia (OR, 6.85; 95% CI, 2.1 - 22.33) and dyslipidemia (OR, 5.07; 95% CI, 1.92 - 13.44). Forty four percent of the patients with dyslipidemia died vs. 20.8% of patients without this condition. CONCLUSIONS: In our study dyslipidemia shows as a long-term negative prognostic marker for survival in patients with EP.

Utility of high-resolution computed tomography and BAL in cryptogenic organizing pneumonia.

BACKGROUND: Cryptogenic organizing pneumonia (COP) is a rare disease, and its diagnosis requires histological confirmation. The objective of our study was to describe the findings of the thoracic high-resolution computed tomography (HR-CT) and bronchoalveolar lavage (BAL) in patients with confirmed COP and evaluate the complementary diagnostic use of BAL and thoracic HR-CT. METHODS: Patients recorded in the registry of interstitial pulmonary diseases between 1991 and 2008 were located and the COP patients selected. RESULTS: We identified 21 patients with histological confirmation of COP. The median age was 58.0 ± 15.9 years, and 61.9% of patients were female. The most frequent thoracic HR-CT profile was patchy infiltrate (71.4%), followed by parenchymatous consolidation (42.9%). The most frequent BAL profile was mixed alveolitis (62%) with lymphocyte predominance, a CD4/CD8 index of 0.4 and foamy macrophages. The effectiveness of transbronchial biopsy was 66.6%. The diagnostic utility of Poletti's BAL criteria gives us a specificity of 88.8%, although the sensitivity obtained was low. The specificity of certain HR-CT profiles is 99%. In addition, we observed a complementary use of the HR-CT and the BAL. CONCLUSIONS: The imaging findings and BAL could be useful for patients with appropriate clinical presentation and for those whose transbronchial biopsy is negative or for whom a confirmatory biopsy cannot be performed.