Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding.

OBJECTIVES: To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding. RESULTS: In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation. CONCLUSIONS: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.

Epidemiological, clinical, therapeutic and evolutionary specificities of the association between venous thromboembolic event and cancer in sub-Saharan Africa: Case of Togo.

BACKGROUND: Our study aimed to describe the clinical, paraclinical, therapeutic and outcomes of patients with venous thromboembolic event (VTE) associated with cancer in the context of limited resources. MATERIALS AND METHODS: This was a descriptive cross-sectional study over a period of six years from March 1, 2016 to March 31, 2022, in the cardiology department and the oncology unit of the Sylvanus Olympio Teaching Hospital of Lome. Our study examined medical records of patients who were at least 18 years old and had venous thromboembolic disease and cancer that was histologically confirmed. This study did not include records that were incomplete or records from patients with coronavirus disease. RESULTS: Our study included 87 patients with average age of 56.36±15.26 years. The discovery of VTE occurred incidentally in 28.74%. Venous thrombosis was isolated in 68.96% and proximal in 95%. Pulmonary embolism was bilateral in 77.77%. Gynaecological and urological cancers were found in 33.33% and 32.19% respectively. Adenocarcinoma was the histological type of cancer found in 47.13%. Cancers were at a very advanced stage in 74.71%. Treatment with antivitamin K was prescribed in 12.65%. In our study, there were 58 patients who passed away with a mortality rate of 66.66%. The cause of death was a complication of VTE in 22.42% and related to the course of cancer in 63.79% of cases. CONCLUSION: VTE during cancer is particular with a fatal evolution due to the severity of VTE and the very advanced stage of cancer.

Safety and efficacy of extended thrombophilia screening directed venous thromboembolic events (VTE) prophylaxis in live liver donors: do we really need extended thrombophilia screening routinely?

Background and aims: The study aimed to determine the prevalence of hereditary thrombophilia, and stratify its severity among live liver donors in Pakistan. Also, the authors evaluated the safety and efficacy of thrombophilia profile testing directed venous thromboembolic events (VTE) prophylaxis while balancing bleeding risk and the need for routine thrombophilia testing before live liver donation among living donor candidates. Materials and methods: Protein S (PS), protein C (PC), anti-thrombin (AT) III, and anti-phospholipid antibody panel (APLA) levels were measured in 567 potential donor candidates. Donors were divided into normal, borderline and high-risk groups based on Caprini score. The safety endpoints were VTE occurrence, bleeding complications or mortality. Results: Among 567 donors, 21 (3.7%) were deficient in protein C, and 14 (2.5%) were deficient in anti-thrombin-III. IgM and IgG. Anti-phospholipids antibodies were positive in 2/567 (0.4%) and 2/567 (0.4%), respectively. IgM and IgG lupus anticoagulant antibodies were positive in 3/567 (0.5%) and 3/567 (0.5%), respectively. VTE events, bleeding complications and postoperative living donors liver transplantation-related complications were comparable among the three donor groups (P>0.05). One donor in the normal donor group developed pulmonary embolism, but none of the donors in either borderline or high-risk group developed VTE. The mean length of ICU and total hospital stay were comparable. No donor mortality was observed in all donor groups. Conclusions: Due to thrombophilia testing directed VTE prophylaxis, VTE events were comparable in normal, borderline and high-risk thrombophilia donor groups, but more evaluations are required to determine the lower safe levels for various thrombophilia parameters including PC, PS and AT-III before surgery among living donor candidates.

The Application of Existing Risk Assessment Models (RAMS) to Predict the Occurrence of Venous Thromboembolic Events among Patients with Classic Hodgkin Lymphoma.

Background: A majority of patients included in risk assessment models (RAMs) developed to predict venous thromboembolic events (VTE) in lymphoma were non-Hodgkin lymphoma. Our study aims to evaluate the incidence and predictors of VTE, utilizing different RAMs, in patients with classic Hodgkin lymphoma (cHL) treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). Methods: Adult patients with cHL, treated and followed at our center, were included. Correlations between different variables, Khorana score, and thrombosis in lymphoma (ThroLy) RAMs with VTE were examined using Fisher's exact test and logistic regression analysis. Results: A total of 321 patients were included, with a median age of 29 (range: 18-83) years. Of them, 169 (52.6%) had advanced-stage disease. Combined modality treatment was given to 169 (52.6%) patients. A total of 52 (16.2%) patients had relapsed or refractory disease. VTE were reported in 15 (4.7%) patients and were mostly during the administration of first-line (n = 8, 53.3%), or salvage chemotherapy (n = 6, 40.0%). There was no correlation between a Khorana score > 2 (p = 0.689) or ThroLy score > 3 (p = 0.335) and VTE. Older age (p = 0.014) and relapsed or refractory disease (p = 0.003) significantly correlated with VTE. Conclusions: VTE are uncommon in cHL. The commonly used RAMs failed to predict VTE. However, older age and relapsed or refractory disease significantly increased this risk.

[Optimal prevention of VTE in cancer surgery patients with impaired renal function]. / Vybor optimal'nogo resheniya v profilaktike VTEO u onkokhirurgicheskikh patsientov so snizhennoi funktsiei pochek.

Despite notable progress in the prevention of venous thromboembolic complications (VTE) and its widespread use in recent decades, mortality in cancer patients from VTE is still second only to the main disease. Some features and limitations in cancer patients, such as a decrease in kidney function and platelet count, an increased risk of bleeding, and the difficulty of monitoring the adequacy and safety of thromboprophylaxis, as well as the use of aggressive chemotherapy, determine the need for more effective and safer ways to solve the problem of VTE. Also, in the case of surgical interventions in such patients, the need for preoperative thromboprophylaxis raises new challenges for doctors. The article presents a review of the issue using a clinical case.

Factors Associated with Venous Thromboembolism Development in Patients with Traumatic Brain Injury.

BACKGROUND: Venous thromboembolic (VTE) events are a major concern in trauma and intensive care, with the prothrombotic state caused by traumatic brain injury (TBI) increasing the risk in affected patients. We sought to identify critical demographic and clinical variables and determine their influence on subsequent VTE development in patients with TBI. METHODS: This was a cross-sectional study with data retrospectively collected from 818 patients with TBI admitted to a level I trauma center in 2015-2020 and placed on VTE prophylaxis. RESULTS: The overall VTE incidence was 9.1% (7.6% deep vein thrombosis, 3.2% pulmonary embolism, 1.7% both). The median time to diagnosis was 7 days (interquartile range 4-11) for deep vein thrombosis and 5 days (interquartile range 3-12) for pulmonary embolism. Compared with those who did not develop VTE, patients who developed VTE were younger (44 vs. 54 years, p = 0.02), had more severe injury (Glasgow Coma Scale 7.5 vs. 14, p = 0.002, Injury Severity Score 27 vs. 21, p < 0.001), were more likely to have experienced polytrauma (55.4% vs. 34.0%, p < 0.001), more often required neurosurgical intervention (45.9% vs. 30.5%, p = 0.007), more frequently missed ≥ 1 dose of VTE prophylaxis (39.2% vs. 28.4%, p = 0.04), and were more likely to have had a history of VTE (14.9% vs. 6.5%, p = 0.008). Univariate analysis demonstrated that 4-6 total missed doses predicted the highest VTE risk (odds ratio 4.08, 95% confidence interval 1.53-10.86, p = 0.005). CONCLUSIONS: Our study highlights patient-specific factors that are associated with VTE development in a cohort of patients with TBI. Although many of these are unmodifiable patient characteristics, a threshold of four missed doses of chemoprophylaxis may be particularly important in this critical patient population because it can be controlled by the care team. Development of intrainstitutional protocols and tools within the electronic medical record to avoid missed doses, particularly among patients who require operative interventions, may result in decreasing the likelihood of future VTE formation.

Predisposing Factors and Incidence of Venous Thromboembolism among Hospitalized Patients with Sickle Cell Disease.

Though patients with sickle cell disease (SCD) are at risk of developing venous thromboembolism (VTE), clear estimates of its incidence and predisposing factors in hospitalized SCD patients are not available. Therefore, this issue was addressed to facilitate an early diagnosis and initiate appropriate prophylactic and treatment strategies. A retrospective observational study was conducted on patients with SCD who were admitted to an academic center in Saudi Arabia over a 10-year period. We identified 1054 admissions of 394 patients with SCD. Of the 3% of patients identified with VTE, 50% experienced pulmonary embolism (PE), 34.3% exhibited deep vein thrombosis (DVT), 6.3% exhibited cerebral vein thrombosis, and 9.4% showed other forms of VTE. In pregnant SCD patients, 6.4% developed a VTE event during their hospital admission. Of the risk factors, high white blood cell count, length of stay, and presence of any additional risk factor for VTE was associated significantly with higher risk of VTE. In our study, this risk seems to be much lower, which is likely attributed to the use of VTE prophylactic strategies implemented in our center. Nevertheless, further studies are needed to establish the ideal prophylactic strategy in patients with SCD.

[Risk factors for venous thromboembolic complications in elderly and senile patients with diabetes mellitus planned for spinal surgery.]

The search for literature sources in domestic and foreign databases showed the absence of works devoted to the study of risk factors for venous thromboembolic events (VTE) in patients of the older age group with diabetes mellitus who are planned to undergo surgical interventions on the spine, which was the impetus for this study. The aim of the study was to study the risk factors for VTE in elderly and senile patients with diabetes mellitus who are scheduled for spinal surgery. A single-center retrospective study included 119 elderly and senile patients (64 men, 55 women, mean age 74,2±6,5 years) who underwent various surgical interventions on the spinal column. According to the binary logistic regression model, the following parameters are statistically significantly associated with the development of VTEC in the studied group of respondents: age of patients over 75 years (p=0,048), HbA1C levels over 7,5% (p=0,007) and D-dimer over 0,5 mg /l FEU (p=0,034), as well as high risk (5 points or more) of VTE according to Caprini scale (p=0,012). In order to reduce the incidence of VTE in elderly and senile patients with diabetes mellitus who are planned to perform surgical interventions on the spine, it is necessary to verify the above clinical and laboratory parameters in the early stages of hospitalization.

Using machine learning and big data for the prediction of venous thromboembolic events after spine surgery: A single-center retrospective analysis of multiple models on a cohort of 6869 patients.

Objective: Venous thromboembolic event (VTE) after spine surgery is a rare but potentially devastating complication. With the advent of machine learning, an opportunity exists for more accurate prediction of such events to aid in prevention and treatment. Methods: Seven models were screened using 108 database variables and 62 preoperative variables. These models included deep neural network (DNN), DNN with synthetic minority oversampling technique (SMOTE), logistic regression, ridge regression, lasso regression, simple linear regression, and gradient boosting classifier. Relevant metrics were compared between each model. The top four models were selected based on area under the receiver operator curve; these models included DNN with SMOTE, linear regression, lasso regression, and ridge regression. Separate random sampling of each model was performed 1000 additional independent times using a randomly generated training/testing distribution. Variable weights and magnitudes were analyzed after sampling. Results: Using all patient-related variables, DNN using SMOTE was the top-performing model in predicting postoperative VTE after spinal surgery (area under the curve [AUC] =0.904), followed by lasso regression (AUC = 0.894), ridge regression (AUC = 0.873), and linear regression (AUC = 0.864). When analyzing a subset of only preoperative variables, the top-performing models were lasso regression (AUC = 0.865) and DNN with SMOTE (AUC = 0.864), both of which outperform any currently published models. Main model contributions relied heavily on variables associated with history of thromboembolic events, length of surgical/anesthetic time, and use of postoperative chemoprophylaxis. Conclusions: The current study provides promise toward machine learning methods geared toward predicting postoperative complications after spine surgery. Further study is needed in order to best quantify and model real-world risk for such events.

Venous Thromboembolism Rates Have Not Decreased in Elective Lumbar Fusion Surgery from 2011 to 2020.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: This study aimed to (1) evaluate for any temporal trends in the rates of VTE, deep venous thrombosis (DVT), pulmonary embolism (PE), and mortality from 2011 to 2020 and (2) identify the predictors of VTE following lumbar fusion surgery. METHODS: Annual incidences of 30-day VTE, DVT, PE, and mortality were calculated for each of the operation year groups from 2011 to 2020. Multivariable Poisson regression was utilized to test the association between operation year and primary outcomes, as well as to identify significant predictors of VTE. RESULTS: A total of 121,205 patients were included. There were no statistically significant differences in VTE, DVT, PE, or mortality rates among the operation year groups. Multivariable regression analysis revealed that compared to 2011, operation year 2019 was associated with significantly lower rates of DVT. Age, BMI, prolonged operation time, prolonged length of stay, non-home discharge, anterior fusion, smoking status, functional dependence, and chronic steroid use were identified as independent predictors of VTE following lumbar fusion. Female sex, Hispanic ethnicity, and outpatient surgery setting were identified as protective factors from VTE in this cohort. CONCLUSIONS: Rates of VTE after lumbar fusion have remained mostly unchanged between 2011 and 2020. Older age, higher BMI, longer operation time, prolonged length of stay, non-home discharge, anterior fusion, smoking, functional dependence, and steroid use were independent predictors of VTE after lumbar fusion, while female sex, Hispanic ethnicity, and outpatient surgery were the protective factors.

Risks of cardiovascular toxicities associated with ALK tyrosine kinase inhibitors in patients with non-small-cell lung cancer: a meta-analysis of randomized control trials.

BACKGROUND: Anaplastic lymphoma kinases (ALK) tyrosine kinase inhibitors (TKIs) are effective and safe targeted therapies used in advanced ALK-positive non-small cell lung cancers (NSCLC). However, ALK-TKIs associated cardiovascular toxicities in patients with ALK-positive NSCLCremain incompletely characterized. We conducted the first meta-analysis to investigate this. RESEARCH DESIGN AND METHODS: To determine the cardiovascular toxicities associated with these agents, we carried out a meta-analysis comparing ALK-TKIs with chemotherapy and a meta-analysis comparing crizotinib with other ALK-TKIs. Statistical analysis was conducted to calculate the RRs and 95% confidence intervals (CIs) by using either random effects or fixed-effect models according to the heterogeneity of the included studies. RESULTS: A total of 11 studies (2855 patients) were included. ALK-TKIs ranked to have more severe cardiovascular toxicities than chemotherapy (RR 5.03, 95% CI 1.97-12.84, P = 0.0007) . Compared with other ALK-TKIs, increased risks of cardiac disorders and VTEs associated with crizotinib were found (cardiac disorders RR 1.75, 95% CI 1.07-2.86, P = 0.03; risk of VTEs RR 3.97, 95% CI 1.69-9.31, P = 0.002; respectively). CONCLUSION: ALK-TKIs were associated with higher risks of cardiovascular toxicities. Special attention should be given to the risks of cardiac disorders and VTEs related to crizotinib therapy.

Prevalence, risk, and outcomes of venous thromboembolic events in kidney transplant recipients: a nested case-control study.

INTRODUCTION: Thromboembolism is more common in kidney transplant recipients (KTRs) than in the general population. Studies evaluating arterial and venous thromboembolism (VTE) in KTRs are scarce and the magnitude and risk factors are mostly undefined. METHODS: A nested control study was conducted from January 1, 2007, to December 31, 2019. Adult KTRs who were detected to have VTE events during this period were included. The primary outcome was to assess the prevalence of VTE in this population. Secondary outcomes were the assessment of the time to occurrence of the thromboembolic events after transplantation and assessing the risk factors and patient survival. For each subject studied, 4 controls were matched from the data set. RESULTS: Amongst 2158 patients, 97 (4.5%) were found to have VTE. The median follow-up time was 3.9 years (6-156 months). A total of 101 VTE events were recorded. The most common site of VTE was the lower limb deep vein thrombosis in 79 patients (0.03%)).In multivariate Cox regression analysis, serum creatinine of more than 3 mg/dl [HR 1.30, 95% CI (1.03-1.38)] was independently associated with increased VTE risk. Patients who developed a VTE had higher mortality as compared to patients who did not develop VTE. No increased risk of graft failure was found in VTE patients. CONCLUSION: This study suggests that kidney transplantation surgery is a moderate risk factor for VTE, and VTE is associated with higher morbidity and mortality. However, prospective studies are needed to establish a definite role of VTE in outcomes in KTRs.

Fondaparinux Sodium: Recent Advances in the Management of Thrombosis.

Fondaparinux sodium is a chemically synthesized selective factor Xa inhibitor approved for the prevention and treatment of venous thromboembolic events, that is, deep vein thrombosis, pulmonary embolism, and superficial vein thrombosis, in acutely ill (including those affected by COVID-19 or cancer patients) and those undergoing surgeries. Since its approval in 2002, the efficacy and safety of fondaparinux is well demonstrated by many clinical studies, establishing the value of fondaparinux in clinical practice. Some of the advantages with fondaparinux are its chemical nature of synthesis, minimal risk of contamination, 100% absolute bioavailability subcutaneously, instant onset of action, a long half-life, direct renal excretion, fewer adverse reactions when compared with direct oral anticoagulants, and being an ideal alternative in conditions where oral anticoagulants are not approved for use or in patients intolerant to low molecular weight heparins (LMWH). In the last decade, the real-world use of fondaparinux has been explored in other conditions such as acute coronary syndromes, bariatric surgery, in patients developing vaccine-induced immune thrombotic thrombocytopenia (VITT) and in pregnant women with heparin-induced thrombocytopenia (HIT), or those intolerant to LMWH. The emerging data from these studies have culminated in recent updates in the guidelines that recommend the use of fondaparinux under various conditions. This paper aims to review the recent data and the subsequent updates in the recommendations of various guidelines on the use of fondaparinux sodium.

Dose-dependent effects of red blood cell transfusion and case mix index on venous thromboembolic events in spine surgery.

BACKGROUND AND OBJECTIVES: Venous thromboembolic (VTE) events represent a major source of morbidity and mortality in spine surgery. Our goal was to assess whether a dose-response relationship exists between red blood cell (RBC) transfusion and postoperative VTE events among spine surgery patients. MATERIALS AND METHODS: A total of 786 spine surgery patients at a single institution who received at least 1 RBC unit perioperatively were included (2016-2019). Patients were stratified based on RBC transfusion volume: 1-2 units (39.3%), 3-4 units (29.4%), 5-6 units (15.9%) and ≥7 units (15.4%). Subgroup analyses were performed after stratification by case mix index, a standardized surrogate for patients' disease severity and comorbidities. Multivariable regression was used to assess risk factors for the development of postoperative VTE events. RESULTS: The overall VTE event rate was 2.4% (n = 19). A dose-response relationship was seen between RBC transfusion volume and VTE events (1-2 units: 0.97%, 3-4 units: 1.30%, 5-6 units: 3.20%, ≥7 units: 7.44%; p < 0.01). Similar dose-response relationships were seen between case mix index and VTE events (1.00-3.99: 0.52%, 4.00-6.99: 2.68%, ≥7.00: 9.00%; p < 0.01). On multivariable regression, larger RBC transfusion volumes (adjusted odds ratio [OR] 1.18 per RBC unit, 95% confidence interval [CI] 1.07-1.29; p < 0.01) and higher case mix index scores (adjusted OR 1.39 per unit increase, 95% CI 1.14-1.69; p < 0.01) were associated with an increased risk of thrombosis. CONCLUSION: Larger RBC transfusion volumes and higher case mix index scores were associated with an increased risk of VTE events. Physicians should be aware of how these dose-response relationships can influence a patient's risk of developing thrombotic complications postoperatively.

Timing and Type of Venous Thromboembolic Chemoprophylaxis Is Associated with Acute Traumatic Brain Injury Outcomes.

Venous thromboembolic (VTE) prophylaxis in acute traumatic brain injury (TBI) is a controversial topic with wide practice variations. This study examined the association of VTE chemoprophylaxis with inpatient mortality and VTE events among isolated TBI patients. This was a retrospective cohort study of 87 trauma centers within a large hospital system in the United States analyzing 23,548 patients with isolated TBI, 7977 of whom had moderate-to-severe TBI. Primary outcomes were inpatient mortality and VTE events. The control group received no chemoprophylaxis. Other groups received low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), and combined LMWH and UFH chemoprophylaxis. Multi-variable regression accounted for confounders. Outcomes were stratified by timing of administration, body mass index (BMI), and TBI type. Patients without VTE prophylaxis had the least VTE events. LMWH had the lowest mortality for both all-isolated and moderate-to-severe isolated TBI populations at adjusted odds ratio (aOR) 0.24 (95% confidence interval [CI], 0.14-0.43) and aOR 0.25 (95% CI, 0.14-0.44), respectively. Clinically significant progression of TBI was lowest among the LMWH group (0.1%; p value, 0.001). After stratifying by timing of VTE chemoprophylaxis, only patients with subdural hematoma and LMWH between 6 and 24 h (N = 62), as well as patients with ≥35 BMI and LMWH between 6 and 24 h (N = 65) or >24-48 h (N = 54), had no VTE events. VTE chemoprophylaxis timing may have prevented VTE in certain subgroups of isolated TBI patients. Though VTE chemoprophylaxis did not prevent VTE for most TBI patients, LMWH VTE chemoprophylaxis was associated with reduced mortality.

Anterior approach lumbar fusions cause a marked increase in thromboembolic events: Causal inferences from a propensity-matched analysis of 1147 patients.

OBJECTIVE: Anterior lumbar fusions are thought to be associated with elevated venous thromboembolic event (VTE) rates, but the magnitude of this increase in VTE is not well described. The objective of this study was to quantify any increase in VTE caused by anterior approach lumbar fusion. METHODS: 1147 consecutive lumbar fusions performed at our institution over a six-year period were identified, and clinical and demographic data were collected. K-nearest neighbor propensity score matching and propensity score adjusted regression were performed. Patients undergoing anterior versus posterior approach lumbar fusions were matched according to age, body mass index, sex, VTE history, estimated blood loss, length of surgery, transfusion, selection for postoperative intensive care unit (ICU) admission, comorbid disease burden, and use of chemoprophylactic anticoagulation. RESULTS: Anterior approach surgery (OR=4.29, p < 0.001), a history of VTE (OR=8.67, p < 0.001), age (OR=1.53, p = 0.014), length of surgery (OR=1.16, p = 0.044), and selection for postoperative ICU admission (OR=4.60, p = 0.005) were independently associated with VTE on multivariable regression. 1058 anterior or posterior approach fusion patients were matched. After matching, overall bias was reduced by 71.0 %, no covariates remained significantly different between groups, and propensity scores were well balanced between populations (Rubin's B≤0.25, 0.5 ≤Rubin's R≤2.0). Significantly more patients in the anterior group underwent lower extremity duplex ultrasonography (LED) (36.9 % vs. 14.8 %, OR=3.36 [2.38, 4.76], p < 0.0001), and a statistically insignificantly higher proportion of LEDs were positive among patients in the anterior group (23.2 % vs. 13.2 %, OR=1.99 [0.92, 4.25], p = 0.108). After matching, the rate of VTE was 8.6 % for the anterior group and 1.3 % for the posterior group, with anterior approach surgery causing an increase in VTE by 7.2 % (95 % CI [2.28 %, 12.16 %], p = 0.004). CONCLUSION: Among patients undergoing lumbar fusions, anterior approach surgery causes an increase in VTE by 7.2%, which is a multifold increase in the proportion of patients with thromboembolic complications.

Thromboembolic safety of norethisterone vs levonorgestrel in combined oral contraceptive users: a pooled analysis of 4 large prospective cohort studies.

BACKGROUND: Norethisterone (acetate) and levonorgestrel are marketed globally as components of combined oral contraceptives. Although guidelines recommend both as first-line combined oral contraceptives, no direct, comparative safety studies are available. OBJECTIVE: We directly compared the thromboembolic event risk associated with the use of norethisterone acetate-containing and levonorgestrel-containing combined oral contraceptives. STUDY DESIGN: Data regarding the cohorts of interest, norethisterone/norethisterone acetate (ethinylestradiol ≤30 µg) and levonorgestrel (ethinylestradiol ≤30 µg), were retrieved from a pooled dataset comprising 4 prospective, noninterventional, active-surveillance cohort studies in 14 European countries, the United States, and Canada, with similar study design but differing medication cohorts. Baseline characteristics and parameters of reproductive, contraceptive, and medical history were summarized using descriptive statistics. Propensity score subclassification was applied to balance baseline parameters between cohorts. Time-to-event analysis of venous thromboembolic events was performed on the basis of the extended Cox model to calculate crude and adjusted hazard ratios, including 95% confidence intervals. The time of venous thromboembolic events was censored at the end of the observation period for women who did not have an event. Women who dropped out or were lost to follow-up without reported venous thromboembolic events were censored at the time they last confirmed that they did not have an event. RESULTS: The pooled dataset included 235,437 combined oral contraceptive users who were followed up for a total of 571,163 women years. Among these, 40,142 women were users of norethisterone/norethisterone acetate (ethinylestradiol ≤30 µg), and 39,098 women were users of levonorgestrel (ethinylestradiol ≤30 µg), contributing 61,976 and 84,816 women years of observation, respectively. The observed prevalence of prognostic factors at baseline showed typical features of US and European combined oral contraceptive users. Both cohorts showed a similar, low rate of thromboembolic events, and we could exclude a 1.5-fold increased venous thromboembolism risk for norethisterone/norethisterone acetate relative to levonorgestrel (adjusted hazard ratio, 0.73; 95% confidence interval, 0.48-1.11). CONCLUSION: These data confirm the similar risk profiles of norethisterone/norethisterone acetate and levonorgestrel regarding thromboembolic events in routine combined oral contraceptive use of around 80,000 women from Europe and the United States/Canada. The analysis provides reassurance for both combined oral contraceptive users and clinicians regarding the safety of oral contraceptives and potentially opens discussion on norethisterone acetate as a potential gold standard therapy in clinical and postmarket research alongside levonorgestrel-combined oral contraceptives.

Effect of Intermittent Pneumatic Compression in Addition to Pharmacologic Prophylaxis for Thromboprophylaxis in Hospitalized Adult Patients: A Systematic Review and Meta-Analysis.

Venous thromboembolic events (VTE) are frequent complications in hospitalized patients and a leading cause of preventable death in hospital. Pharmacologic prophylaxis is a standard of care to prevent VTE in patients at risk, the additional value of intermittent pneumatic compression (IPC) is uncertain. We aimed to evaluate the efficacy of adding IPC to pharmacologic prophylaxis to prevent VTE in hospitalized adults. DATA SOURCES: We searched the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, and the International Clinical Trials Registry Platform from inception to July 2022. STUDY SELECTION: We included randomized controlled trials comparing the use of IPC in addition to pharmacological thromboprophylaxis to pharmacological thromboprophylaxis alone in hospitalized adults. DATA EXTRACTION: Meta-analyses were performed to calculate risk ratio (RR) of VTE, deep venous thrombosis (DVT), and pulmonary embolism (PE). We assessed the risk of bias using the Cochrane Risk of Bias Tool for Randomized Trials, Version 2 and the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. DATA SYNTHESIS: We included 17 trials enrolling 8,796 participants. The IPC was mostly applied up to the thigh and pharmacological thromboprophylaxis was primarily low-molecular-weight heparin. Adjunctive IPC was associated with a decreased risk of VTE (15 trials, RR = 0.53; 95% CI [0.35-0.81]) and DVT (14 trials, RR = 0.52; 95% CI [0.33-0.81]) but not PE (seven trials, RR = 0.73; 95% CI [0.32-1.68]). The quality of evidence was graded low, downgraded by risk of bias and inconsistency. Moderate and very low-quality evidence, respectively, suggests that adjunctive IPC is unlikely to change the risk of all-cause mortality or adverse events. Subgroup analyses indicate a more evident apparent benefit in industry-funded trials. CONCLUSIONS: Results indicate low-quality evidence underpinning the additional use of IPC to pharmacological thromboprophylaxis for prevention of VTE and DVT. Further large high-quality randomized trials are warranted to support its use and to identify patient subgroups for whom it could be beneficial.

Recurrence rate of venous thromboembolic events in granulomatosis with polyangiitis.

Objective: The incidence of first-time venous thromboembolic events (VTEs) is high in granulomatosis with polyangiitis (GPA). The incidence of recurrent VTEs is unknown. We aimed to describe the recurrence rate of second VTEs in patients with GPA. Methods: Retrospective chart review was performed in patients with GPA and at least one VTE at a single centre from 2002 to 2016. Inclusion criteria were 1990 ACR criteria or 2012 Revised International Chapel Hill nomenclature for GPA, at least two follow-up visits, at least one VTE during the study period, and VTE occurrence after or within 3 months before GPA diagnosis. Second VTE event-free survival rates were estimated. Results: Out of 147 patients initially screened for GPA and with at least one VTE, 84 met inclusion criteria. Median age at first VTE was 57 years. Incidence rate for second VTE was 8.4 events per 100 patient-years (95% CI: 5.7, 12.3). Eighty-three point three per cent of first VTEs and 57.7% of second VTEs occurred when disease was active (P < 0.001). Renal involvement and constitutional symptoms at the time of first VTE were associated with VTE recurrence. Conclusion: GPA has a high rate of VTE recurrence compared with the reported data in the general population with unprovoked VTE. Our results suggest that VTE in GPA is a recurrent co-morbidity, not always during active vasculitis, and more so in those with renal involvement and constitutional symptoms at the time of first VTE.

Factor XI Inhibition for the Prevention of Venous Thromboembolism: An Update on Current Evidence and Future perspectives.

During the past decade, emergence of direct oral anticoagulants (DOACs) has drastically improved the prevention of thrombosis. However, several unmet needs prevail in the field of thrombosis prevention, even in the DOACs' era. The use of DOACs is still constrained and the drugs cannot be administered in every clinical scenario, such as an increased anticoagulant-associated bleeding risk, particularly in some specific populations (cancer - notably those with gastrointestinal or genitourinary cancer - and frail patients), the impossibility to be used in certain patients (eg, end-stage kidney failure during hemodialysis, pregnancy and breastfeeding), and their lack of efficacy in certain clinical scenarios (eg, mechanical heart valves, triple-positive antiphospholipid syndrome). Efforts to find a factor that upon antagonization prevents thrombosis but spares haemostasis have resulted in the identification of coagulation factor XI (FXI) as a therapeutic target. After briefly recapitulating the role of factor XI in the balance of haemostasis, we propose a narrative review of the key data published to date with compounds targeting factor XI to prevent thrombosis as well as the main ongoing clinical studies, opening up prospects for improving the care of patients requiring thrombosis prevention.