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.

Sex-Related Differences in Patient Characteristics, Risk Factors, and Symptomatology in Older Adults with Pulmonary Embolism: Findings from the SERIOUS-PE Study.

Sex-specific factors are implicated in pulmonary embolism (PE) presentation in young patients, as indicated by increased risk in pregnancy. Whether sex differences exist in PE presentation, comorbidities, and symptomatology in older adults, the age group in which most PEs occur, remains unknown. We identified older adults (aged ≥65 years) with PE in a large international PE registry replete with information about relevant clinical characteristics (RIETE registry, 2001-2021). To provide national data from the United States, we assessed sex differences in clinical characteristics and risk factors of Medicare beneficiaries with PE (2001-2019). The majority of older adults with PE in RIETE (19,294/33,462, 57.7%) and in the Medicare database (551,492/948,823, 58.7%) were women. Compared with men, women with PE less frequently had atherosclerotic diseases, lung disease, cancer, or unprovoked PE, but more frequently had varicose veins, depression, prolonged immobility, or history of hormonal therapy (p < 0.001 for all). Women less often presented with chest pain (37.3 vs. 40.6%) or hemoptysis (2.4 vs. 5.6%) but more often with dyspnea (84.6 vs. 80.9%) (p < 0.001 for all). Measures of clot burden, PE risk stratification, and use of imaging modalities were comparable between women and men. PE is more common in elderly women than in men. Cancer and cardiovascular disease are more common in men, whereas transient provoking factors including trauma, immobility, or hormone therapy are more common in elderly women with PE. Whether such differences correlate with disparities in treatment or differences in short- or long-term clinical outcomes warrants further investigation.

Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism: Rationale and design of the SERIOUS-PE study.

BACKGROUND: Sex is an important factor associated with pulmonary embolism (PE) disease presentation and outcomes, which may be related to pathobiological, social, and treatment-based differences. We are seeking to illuminate sex differences in pulmonary embolism presentation, care, and outcomes using an international registry and a national US database of people 65 years and older, the age group in which the majority of these events occur. METHODS: The Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism (SERIOUS-PE) study has been designed to address knowledge gaps in this area. This study will use data from the Registro Informatizado Enfermedad TromboEmbolica (RIETE) registry and the US Medicare Fee-For-Service beneficiaries. RIETE is a large international registry of patients with venous thromboembolism with data collected on PE presentation, risk factors, co-morbidities, drug and interventional therapies, as well as 30-day and 1-year outcomes (including recurrent VTE, major bleeding, and mortality). Data from US Medicare Fee-For-Service beneficiaries will be used to understand the sex differences in PE hospitalizations, advanced therapies, and outcomes at 30-day and 1-year follow-up. Assessment of outcomes in both databases will be performed in unadjusted models, as well as those adjusted for demographics, co-morbidities, and treatments, to understand whether the potential sex differences in outcomes are related to differences in risk factors and co-morbidities, potential disparities in treatment, or a plausible biological difference in women versus men. Linear trends will be assessed over time. RESULTS: RIETE data from March 2001 through March 2021 include 33,462 elderly patients with PE, of whom 19,294 (57.7%) were women and 14,168 (42.3%) were men. In the Medicare Fee-For-Service database, between January 2001 and December 31, 2019, 1,030,247 patients were hospitalized with a principal discharge diagnosis of PE, of whom 599,816 (58.2%) were women and 430,431 (41.8%) were men. CONCLUSIONS: Findings from the SERIOUS-PE study will help address important knowledge gaps related to sex differences in presentation and risk factors, treatment patterns, and outcomes of older adults with PE. The results may guide changes in prognostic prediction rules based on sex-specific findings, identify sex-based disparities in care delivery that should be addressed by quality improvement, or uncover potential differences in response to available therapies that warrant testing in dedicated randomized trials.

Imaging modalities for confirming pulmonary embolism during pregnancy: results from a multicenter international study.

OBJECTIVES: We explored the variations in use of imaging modalities for confirming pulmonary embolism (PE) according to the trimester of pregnancy. METHODS: We included all pregnant patients with confirmed acute PE from RIETE, a prospective registry of patients with PE (03/2001-02/2020). Imaging modalities included computed tomography pulmonary angiography (CTPA), ventilation-perfusion (V/Q) scan, or presence of signs of acute PE along with imaging-confirmed proximal deep vein thrombosis (pDVT) without pulmonary vascular imaging. We compared the imaging modalities to postpartum patients with PE, and other non-pregnant women with PE. RESULTS: There were 157 pregnant patients (age: 32.7 ± 0.5), 228 postpartum patients (age: 33.9 ± 0.5), and 23,937 non-pregnant non-postpartum women (age: 69.5 ± 0.1). CTPA was the most common modality for confirming PE, from 55.7% in first trimester to 58.3% in second trimester, and 70.0% in third trimester. From first trimester to third trimester, V/Q scanning was used in 21.3%, 16.7%, and 18.3% of cases, respectively. Confirmed pDVT along with the presence of signs/symptoms of PE was the confirmatory modality for PE in 21.3% of patients in first trimester, 19.4% in second trimester, and 6.7% in third trimester. The proportion of postpartum patients confirmed with CTPA (85.5%) was comparable to that of non-pregnant non-postpartum women (83.2%). From the first trimester of pregnancy to postpartum period, there was a linear increase in the proportion of patients with PE diagnosed with CTPA (p = 0.039). CONCLUSION: CTPA was the primary modality for confirming PE in all trimesters of pregnancy, although its proportional use was higher in later stages of pregnancy. KEY POINTS: • Computed tomography pulmonary angiography (CTPA) was the primary modality of diagnosis in all trimesters of pregnancy among patients with confirmed pulmonary embolism, even in the first trimester. • From the first trimester of pregnancy to postpartum period, there was a linear increase in the proportion of patients with pulmonary embolism who were diagnosed based on CTPA. • In the postpartum period, use of CTPA as the modality to confirm pulmonary embolism was comparable to non-pregnant patients.

PICO Questions and DELPHI Methodology for the Management of Venous Thromboembolism Associated with COVID-19.

Patients with coronavirus disease 2019 (COVID-19) have a higher risk of venous thromboembolic disease (VTE) than patients with other infectious or inflammatory diseases, both as macrothrombosis (pulmonar embolism and deep vein thrombosis) or microthrombosis. However, the use of anticoagulation in this scenario remains controversial. This is a project that used DELPHI methodology to answer PICO questions related to anticoagulation in patients with COVID-19. The objective was to reach a consensus among multidisciplinary VTE experts providing answers to those PICO questions. Seven PICO questions regarding patients with COVID-19 responded with a broad consensus: 1. It is recommended to avoid pharmacological thromboprophylaxis in most COVID-19 patients not requiring hospital admission; 2. In most hospitalized patients for COVID-19 who are receiving oral anticoagulants before admission, it is recommended to replace them by low molecular weight heparin (LMWH) at therapeutic doses; 3. Thromboprophylaxis with LMWH at standard doses is suggested for COVID-19 patients admitted to a conventional hospital ward; 4. Standard-doses thromboprophylaxis with LMWH is recommended for COVID-19 patients requiring admission to Intensive Care Unit; 5. It is recommended not to determine D-Dimer levels routinely in COVID-19 hospitalized patients to select those in whom VTE should be suspected, or as a part of the diagnostic algorithm to rule out or confirm a VTE event; 6. It is recommended to discontinue pharmacological thromboprophylaxis at discharge in most patients hospitalized for COVID-19; 7. It is recommended to withdraw anticoagulant treatment after 3 months in most patients with a VTE event associated with COVID-19. The combination of PICO questions and DELPHI methodology provides a consensus on different recommendations for anticoagulation management in patients with COVID-19.

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.

Clinical Characteristics and Outcomes of Women Presenting with Venous Thromboembolism during Pregnancy and Postpartum Period: Findings from the RIETE Registry.

Although venous thromboembolism (VTE) is a leading cause of maternal mortality, there is a paucity of real-world clinical data on clinical presentation and management of VTE during pregnancy and postpartum period. Using data from the international RIETE (Registro Informatizado Enfermedad Trombo Embólica) registry, pregnant and postpartum women with VTE were identified. Baseline characteristics, risk factors, therapies, and outcomes were compared. From March 2001 to July 2019, 596 pregnant and 523 postpartum women had symptomatic, objectively confirmed VTE. Pregnant or postpartum women were less likely to have another risk factor for VTE (i.e., immobility, cancer, recent travel) than nonpregnant women aged < 50 years. The prevalence of thrombophilia was higher among pregnant and postpartum women compared with nonpregnant women (53.2% vs. 46%). Pulmonary embolism (PE) was less commonly diagnosed in pregnant versus postpartum women (27% vs. 42%). Pregnant women with PE were commonly treated with low molecular weight heparin (73% vs. 29%), and received more inferior vena cava filters (6.0% vs. 4.2%) compared with postpartum women. By 90 days, one pregnant and one postpartum woman died after PE, and one died after a deep venous thrombosis. The incidence of recurrent VTE was low. In this largest cohort of pregnant and postpartum women with confirmed VTE, we found that pregnant and postpartum women with VTE were unlikely to present with other risk factors for VTE. Adverse outcomes in our study were uncommon.

Patient-Level, Institutional, and Temporal Variations in Use of Imaging Modalities to Confirm Pulmonary Embolism.

BACKGROUND: The choice of the imaging modality for diagnosis of pulmonary embolism (PE) could be influenced by provider, patient or hospital characteristics, or over time. However, little is known about the choice of the diagnostic modalities in practice. The aim of this study was to evaluate the variations in the use of imaging modalities for patients with acute PE. METHODS: Using the data from Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective international registry of patients with venous thromboembolism (March 2001-January 2019), we explored the imaging modalities used in patients with acute PE. The imaging modalities included computed tomography pulmonary angiography, ventilation/perfusion scanning, pulmonary angiography, a combination of these tests, or PE signs and symptoms plus imaging-confirmed proximal deep vein thrombosis but no chest imaging. RESULTS: Among 38 025 patients with confirmed PE (53.1% female, age: 67.3±17 years), computed tomography pulmonary angiography was the dominant modality of diagnosis in all RIETE enrollees (78.2% [99% CI, 77.6-78.7]); including pregnant patients (58.9% [99% CI, 47.7%-69.4%]) and patients with severe renal insufficiency (62.5% [99% CI, 59.9-65.0]). A greater proportion of patients underwent ventilation/perfusion scanning in larger hospitals compared with smaller hospitals (13.1% versus 7.3%, P<0.001). The use of computed tomography pulmonary angiography varied between 13.3% and 98.3% across the countries, and its use increased over time (46.5% in 2002 to 91.7% in 2018, P<0.001). CONCLUSIONS: In a large multinational PE registry, variations were observed in the use of imaging modalities according to patient or institutional factors and over time. However, computed tomography pulmonary angiography was the dominant modality of diagnosis, even in pregnancy and severe renal insufficiency. The safety, costs, and downstream effects of these tests on PE-related and non-PE-related outcomes warrant further investigation.

Venous Thromboembolism in Women Undergoing Assisted Reproductive Technologies: Data from the RIETE Registry.

Venous thromboembolism (VTE) during or after assisted reproductive technologies (ART) is predicted to rise due to the increased number of women undergoing this technique. We present data collected in the RIETE registry up to October 2016. Overall, 41 (0.6%) out of 6,718 women of childbearing age with VTE had an ART-related event. Most of them underwent autologous ART cycles; 23 had isolated deep vein thrombosis (DVT) (56.1%), 12 isolated pulmonary embolism (PE) (29.3%) and 6 simultaneous occurrence of both the events (14.6%). VTE occurred in 20 successful and 21 unsuccessful (i.e. not resulting in a clinical pregnancy) ART cycles. No recurrence was observed at 90 days. Logistic regression showed that isolated PE was significantly more frequent than DVT alone or combined with PE in unsuccessful in vitro fertilization (IVF) (odds ratio [OR]: 4.13, 95% confidence interval [CI]: 1.4-12.4), as well as in contraceptive users (OR: 2.96, 95% CI: 1.95-4.5) and in puerperium (OR: 1.96, 95% CI: 1.16-3.3). After grouping isolated PE and DVT + PE, we found that PE was significantly more frequent in women with unsuccessful IVF and higher body mass index (OR: 5.0, 95% CI: 1.2-20.7 and OR: 1.0, 95%CI: 1.0-1.1, respectively). These data document a higher risk of PE in unsuccessful cycles than in successful ones. The risk is higher than that observed during pregnancy, puerperium and contraception.

Management and outcome of major bleeding in patients receiving vitamin K antagonists for venous thromboembolism.

BACKGROUND: The optimal management of major bleeding in patients receiving vitamin K antagonists (VKA) for venous thromboembolism (VTE) is unclear. METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to assess the management and 30-day outcomes after major bleeding in patients receiving VKA for VTE. RESULTS: From January 2013 to December 2017, 267 of 18,416 patients (1.4%) receiving long-term VKA for VTE had a major bleeding (in the gastrointestinal tract 78, intracranial 72, hematoma 50, genitourinary 20, other 47). Overall, 151 patients (57%) received blood transfusion; 110 (41%) vitamin K; 37 (14%) fresh frozen plasma; 29 (11%) pro-haemostatic agents and 20 (7.5%) a vena cava filter. During the first 30 days, 59 patients (22%) died (41 died of bleeding) and 13 (4.9%) had a thrombosis. On multivariable analysis, patients with intracranial bleeding (hazard ratio [HR]: 4.58; 95%CI: 2.40-8.72) and those with renal insufficiency at baseline (HR: 2.73; 95%CI: 1.45-5.15) had an increased mortality risk, whereas those receiving vitamin K had a lower risk (HR: 0.47; 0.24-0.92). On the other hand, patients receiving fresh frozen plasma were at increased risk for thrombotic events (HR: 4.22; 95%CI: 1.25-14.3). CONCLUSIONS: Major bleeding in VTE patients receiving VKA carries a high mortality rate. Intracranial bleeding and renal insufficiency increased the risk. Fresh frozen plasma seems to increase this risk for recurrent VTE.

Arterial Ischemic Events Are a Major Complication in Cancer Patients with Venous Thromboembolism.

BACKGROUND: Venous thromboembolism is common in patients with malignancies, affecting up to 10% of this patient population. The association between arterial ischemic events and venous thromboembolism also has been established. However, the influence of arterial ischemic events on outcomes in cancer patients with venous thromboembolism has not been fully determined. METHODS: The current study analyzed clinical characteristics, time course, risk factors, incidence and severity of venous thromboembolism recurrences, arterial ischemic events and major bleeding in 5717 patients with active cancer and venous thromboembolism recruited into RIETE (multi-center prospective registry of patients with objectively confirmed venous thromboembolism). RESULTS: During the anticoagulation course (median 7.3 months), 499 (8.7%) patients developed venous thromboembolism recurrences, 63 (1.1%) developed arterial events, and 346 (6.1%) suffered from major bleeding. Overall, major bleeding and arterial events appeared earlier (median 35 and 36 days, respectively) than venous thromboembolism recurrences (median 97 days). Thirty-day mortality rates after each event were: 20% after recurrent pulmonary embolism, 13% after recurrent deep vein thrombosis, 41% after major bleeding, 40% after myocardial infarction, 64% after ischemic stroke, and 83% after lower limb amputation. Bleeding was the leading cause of death (67 fatal bleeds), whereas cumulative mortality due to arterial ischemic events (n = 27) was similar to that related to pulmonary embolism recurrences (n = 26). CONCLUSIONS: In this study, arterial ischemic events and major bleeding appeared early after venous thromboembolism in patients with active cancer and were among frequent causes of their deaths. The risk and severity of arterial events need to be considered in this clinical setting.

Evaluación cuantitativa de los cambios microvasculares capilaroscópicos en pacientes con cardiopatía isquémica establecida / Quantitative evaluation of capillaroscopic microvascular changes in patients with established coronary heart disease

Introducción y objetivos: Las alteraciones microvasculares se han asociado a la mayoría de los factores de riesgo cardiovascular, así como a múltiples enfermedades inflamatorias. Sin embargo, se desconoce si estas anomalías son más frecuentes en pacientes con enfermedades coronarias. Nuestro objetivo fue evaluar si existe una relación entre la presencia de cardiopatía isquémica y la existencia de alteraciones capilares funcionales y estructurales en la microcirculación cutánea evaluada mediante videocapilaroscopia. Material y métodos: Comparamos 2 muestras emparejadas de 30 participantes con o sin cardiopatía isquémica pero con un perfil antropométrico y clínico similar. Realizamos una videocapilaroscopia en el dorso del tercer dedo de la mano no dominante cuantificando la densidad capilar basal, así como la densidad capilar tras la oclusión arterial y venosa para evaluar su funcionalidad y la densidad capilar máxima. También calculamos el reclutamiento capilar. Resultados: La densidad microvascular fue significativamente menor en los pacientes con cardiopatía isquémica que en los controles tanto a nivel basal como tras el estudio dinámico (oclusión arterial y venosa). No encontramos diferencias en el reclutamiento capilar. Conclusiones: En nuestro estudio, los pacientes con cardiopatía isquémica presentaban cambios microvasculares tanto funcionales como estructurales. Dado que estos resultados han sido obtenidos de una pequeña muestra, se precisarán estudios que valoren la microcirculación en pacientes coronarios y si esta está relacionada con la respuesta terapéutica y/o el pronóstico de la enfermedad (AU)

Introduction and objectives: Microcirculation disturbances have been associated to most of the cardiovascular risk factors as well as to multiple inflammatory diseases. However, whether these abnormalities are specifically augmented in patients with coronary heart disease is still unknown. We aimed to evaluate if there is a relationship between the presence of coronary heart disease and the existence of functional and structural capillary abnormalities evaluated in the cutaneous microcirculation by videocapillaroscopy. Material and methods: Two matched samples of 30 participants with and without coronary heart disease but with similar clinical and anthropometric characteristics were evaluated by videocapillaroscopy at the dorsal skin of the third finger of the non-dominant hand. We calculated basal capillary density as well as capillary density after a period of arterial and venous occlusion in order to evaluate functionality and maximum capillary density. We also measured capillary recruitment. Results: capillary density at rest was significantly lower in patients suffering from coronary heart disease than in controls. This fact was also found after dynamic tests (arterial and venous occlusion), suggesting functional impairments. Capillary recruitment of the samples was not different in our sample. Conclusions: In our study, patients with coronary heart disease exhibit functional and structural microvascular disturbances. Although this is a very preliminary study, these findings open the door for further studying the microvascular functionality in coronary patients and how it relates to the response to treatment and/or the prognosis of the disease (AU)

Quantitative evaluation of capillaroscopic microvascular changes in patients with established coronary heart disease. / Evaluación cuantitativa de los cambios microvasculares capilaroscópicos en pacientes con cardiopatía isquémica establecida.

INTRODUCTION AND OBJECTIVES: Microcirculation disturbances have been associated to most of the cardiovascular risk factors as well as to multiple inflammatory diseases. However, whether these abnormalities are specifically augmented in patients with coronary heart disease is still unknown. We aimed to evaluate if there is a relationship between the presence of coronary heart disease and the existence of functional and structural capillary abnormalities evaluated in the cutaneous microcirculation by videocapillaroscopy. MATERIAL AND METHODS: Two matched samples of 30 participants with and without coronary heart disease but with similar clinical and anthropometric characteristics were evaluated by videocapillaroscopy at the dorsal skin of the third finger of the non-dominant hand. We calculated basal capillary density as well as capillary density after a period of arterial and venous occlusion in order to evaluate functionality and maximum capillary density. We also measured capillary recruitment. RESULTS: Microvascular capillary density at rest was significantly lower in patients suffering from coronary heart disease than in controls. This fact was also found after dynamic tests (arterial and venous occlusion), suggesting functional impairments. Capillary recruitment of the samples was not different in our sample. CONCLUSIONS: In our study, patients with coronary heart disease exhibit functional and structural microvascular disturbances. Although this is a very preliminary study, these findings open the door for further studying the microvascular functionality in coronary patients and how it relates to the response to treatment and/or the prognosis of the disease.

Outcome after discontinuing anticoagulant therapy in women with venous thromboembolism during hormonal use.

INTRODUCTION: Whether women developing venous thromboembolism (VTE) while using hormonal therapy should be classified as having "unprovoked" or "provoked" VTE is controversial. METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of symptomatic VTE recurrences after discontinuing anticoagulation in 3 subgroups of women aged ≤50years without cancer, pregnancy or puerperium: (1) those with hormonal therapy and no additional risk factors (hormonal users only); (2) those with unprovoked VTE; and (3) those with additional risk factors, with or without hormonal therapy. RESULTS: As of March 2016, 1513 women had been followed-up for at least one month after discontinuing anticoagulation. Of these, 654 (43%) were hormonal users only, 390 (26%) had unprovoked VTE and 469 (31%) had transient risk factors with or without hormonal therapy. After discontinuing anticoagulation, the rate of VTE recurrences in women with hormonal use only (2.44 per 100 patient-years; 95% CI: 1.53-3.69) was significantly lower than in those with unprovoked VTE (6.03; 95% CI: 3.97-8.77) and similar to those with transient risk factors (2.58; 95% CI: 1.50-4.13). Interestingly, the rate of VTE recurrences presenting as pulmonary embolism in women with hormonal use only (0.55 per 100 patient-years; 95% CI: 0.18-1.29) was similar to those with transient risk factors (0.46; 95% CI: 0.09-1.33) and 4-fold lower than in women with unprovoked VTE (2.23; 95% CI: 1.07-4.10). CONCLUSIONS: After discontinuing anticoagulation, the rate of VTE recurrences in hormonal users only was significantly lower than in women with unprovoked VTE and similar to the rate in women with additional risk factors.

Sex differences in patients receiving anticoagulant therapy for venous thromboembolism.

In patients with venous thromboembolism (VTE), the outcome during the course of anticoagulant therapy may differ according to the patient's sex. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of VTE recurrences, major bleeding, and mortality due to these events according to sex.As of August 2013, 47,499 patients were enrolled in RIETE, of whom 24,280 (51%) were women. Women were older, more likely presented with pulmonary embolism (PE), and were more likely to have recent immobilization but less likely to have cancer than men. During the course of anticoagulation (mean duration: 253 d), 659 patients developed recurrent deep vein thrombosis (DVT), 576 recurrent PE, 1368 bled, and 4506 died. Compared with men, women had a lower rate of DVT recurrences (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.67-0.91), a similar rate of PE recurrences (HR: 0.98; 95% CI: 0.83-1.15), a higher rate of major bleeding (HR: 1.21; 95% CI: 1.09-1.35), and higher mortality due to PE (HR: 1.24; 95% CI: 1.04-1.47). On multivariable analysis, any influence of sex on the risk for recurrent DVT (HR: 0.88; 95% CI: 0.75-1.03), major bleeding (HR: 1.10; 95% CI: 0.98-1.24), or fatal PE (HR: 1.01; 95% CI: 0.84-1.22) was no longer statistically significant.In conclusion, women had fewer DVT recurrences and more bleeds than men during the course of anticoagulation. These differences were not due to sex, but very likely to other patient characteristics more common in female patients and differences in treatment choice.

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 ≥50 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 ≥50 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 ≥70 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 ≥70 years more likely had raised sPAP levels than men after a PE episode. Additional variables influencing this risk seem to differ according to gender.

Oral contraception in women with mild thrombophilia: what have we learned recently?

Mild thrombophilias include heterozygous forms of Factor V Leiden and prothrombin G20210A mutation and high levels of factor VIII. These defects are responsible for only a moderate increase of venous thromboembolism (VTE) risk compared with strong thrombophilias (antithrombin III, protein C and protein S deficiencies and homozygous forms of factor V Leiden and G20210A prothrombin mutation). Combined oral contraceptives increase the VTE risk in women in a fertile age, and in a far more important way in thrombophilia carrier women. Universal screening of thrombophilia test before the use of combined oral contraceptives is not recommended. However, selective VTE-history based screening is associated with a better cost-effectiveness, especially in asymptomatic relatives of carriers of strong thrombophilia. Currently, combined oral contraceptives are discouraged in women with any thrombophilic defects. The VTE risk is higher during pregnancy and postpartum period compared to hormonal contraceptive use period in women with mil thrombophilia. For this reason, a careful election of an alternative birth control method is necessary in these women.

Fever and deep venous thrombosis. Findings from the RIETE registry.

Fever is a presenting sign in some patients with acute deep venous thrombosis (DVT), but its influence on outcome has not been thoroughly investigated. RIETE is an ongoing, international, observational registry of consecutive patients with symptomatic, objectively confirmed, acute venous thromboembolism. The aim of the present study was to assess the prevalence of fever in patients with acute DVT, and to compare their outcome during the first month of therapy, according to the presence or absence of fever. As of September 2009, 14,480 patients with symptomatic DVT have been enrolled in RIETE. Of these, 707 (4.9%) had fever at presentation. During the 30-day study period, 448 patients (3.1%) died, 171 (1.2%) developed DVT recurrences, 376 (2.6%) had pulmonary embolism, and 384 (2.6%) had a major bleeding. Patients initially presenting with fever had a higher mortality (5.8% vs. 2.9%; odds ratio: 2.6; 95% CI 1.9-3.5) than those without fever. Among the causes of death, pulmonary embolism (0.7% vs. 0.1%) and infection (1.1% vs. 0.3%) were significantly more common in patients presenting with fever. Multivariate analysis confirmed that DVT patients with fever had an increased mortality (hazard ratio: 2.00; 95% CI 1.44-2.77) irrespectively of the patient's age, body weight, and risk factors for VTE. Fever is not uncommon in patients with DVT, and carries a worse outcome.