Venous thromboembolism in adrenocortical carcinoma: a retrospective analysis.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of death in patients with cancer. Limited data exist about VTE in patients with adrenocortical carcinoma (ACC). The primary objective of this study was to identify the prevalence of VTE in a cohort of patients with ACC. Secondary objectives were to determine the impact of VTE events on overall survival (OS) and to describe the characteristics of VTE in patients with ACC. PATIENTS AND METHODS: We retrospectively reviewed data from 289 patients with ACC cared for at a major referral center from February 2010 to June 2022. RESULTS: VTE prevalence was 18.7% (54 events). Thirty patients (55.6%) had pulmonary embolism (PE); 12 patients (22.2%) had deep vein thrombosis (DVT); and 12 patients (22.2%) had both PE and DVT. VTE occurred after ACC diagnosis in 50 patients (92.6%) including 44 patients (88%) with stage 3 or 4 ACC. VTEs were CTCAE grade ≤2 in 32 cases (59.3%), grade 3 in 17 (31.5%), and grade 4 in 2 (3.7%). Thirteen patients (24%) died within 6 months after VTE diagnosis, although there was no statistically significant association between VTE and overall survival. CONCLUSION: Despite the potential to underestimate the prevalence of VTEs, we found a high frequency of VTE events in patients with ACC. A majority of VTEs occurred in the context of advanced ACC and we observed high short-term mortality. Further studies are needed to validate our findings and investigate mechanisms associated with VTE in ACC.

Successful management of VTE with essential thrombocythemia and cavernous transformation of the portal vein in early pregnancy: a case report.

Due to the thrombohemorrhagic potential of essential thrombocythemia, pregnancy complicated by essential thrombocythemia should be recognized as a risk factor for obstetric complications. Here, we report the case of a patient with essential thrombocythemia with two significantly different pregnancy outcomes. Her first pregnancy (at 30 years of age) ended with an uneventful term delivery. However, the patient progressed to cavernous transformation of the portal vein in the period between her two pregnancies and subsequently experienced deep venous thrombosis during the first trimester of her second pregnancy (at 36 years of age). The patient's platelet count during pregnancy was within the normal range, so she ignored previous instances of essential thrombocytosis (at 26 years of age). The patient's main symptom was unrelieved pain in her leg. After that, she was successfully treated with anticoagulant throughout her entire pregnancy, resulting in a term vaginal delivery. This case highlights the importance of assessing pregnant patients with essential thrombocythemia according to their risk stratification. Specifically, risk assessments for potential pregnancy complications should take into account advanced maternal age and a previous history of thrombosis. Patients with essential thrombocythemia should be encouraged to participate in preconception counseling for risk assessment and to initiate prophylactic anticoagulation as soon as possible.

Comparative analysis of venous thromboembolic complications in diverse groups of orthopaedic patients.

INTRODUCTION AND OBJECTIVE: Venous thromboembolism (VTE) is one of the most important and life-threatening complications in orthopaedic surgery. According to current scientific reports, there are several variables that can affect the severity of CVD, including the site of the pathology or the type of treatment implemented. The aim of the study was to analyze the risk of VTE depending on the location of the pathology, as well as to evaluate the impact of surgical treatment compared to conservative management. MATERIAL AND METHODS: Analysis of laboratory results and clinical picture of 276 patients hospitalized for orthopaedic reasons, admitted between January 2008 - December 2019, with suspected pulmonary embolism (PE). RESULTS: Among patients diagnosed with PE, the most common location of the disease was in the lower limb 59/116 (50.9%), followed by the pelvis location - 22/116 (19.0%), the spine - 19/116 (16.4%), disseminated lesions in oncological patients - 12/116 (10.3%), and a group of pathologies in the upper limb - 4/116 (3.5%). Significant statistical differences were found between the incidence of PE and the diagnosis of pathology in the lower limb and the pelvis. In the group of patients, there was no statistically significant relationship between the incidence of PE associated with surgical treatment, compared to conservative management. CONCLUSIONS: The group with the highest risk of VTE were lower limb and pelvic pathologies. The results are largely consistent with numerous reports treating the risk of CVD among orthopaedic patient populations.

[Maternal mortality due to venous thromboembolism in France 2016-2018]. / Mortalité maternelle par thromboembolie veineuse en France 2016­2018.

Pregnancy and the post-partum period represent a thromboembolic risk situation, with pulmonary embolism (PE) remaining one of the leading causes of direct maternal deaths in developed countries. Between 2016 and 2018 in France, twenty maternal deaths were caused by venous thromboembolic complications (VTE), yielding a Maternal Mortality Ratio (MMR) of 0.9 per 100,000 live births (95%CI 0.6-1.3), with no change compared to the periods 2013-2015 or 2010-2012. Among these 20 deaths, 1 death was related to cerebral thrombophlebitis, and the remaining 19 were due to PE. Regarding the timing of death, 2 deaths occurred after an early termination of pregnancy, 40% (8/20) during an ongoing pregnancy, and 50% (10/20) in the post-partum period. Among the 20 VTE deaths, 20% (4/20) occurred outside of a healthcare facility (at home or in a public place). Among the nineteen cases with documented BMI, seven women had obesity (37%), three times more than in the population of parturients in France (11.8%, ENP 2016). Among the nineteen PE deaths and the case of cerebral thrombophlebitis, eleven were considered preventable, six possibly preventable (35%), two probably preventable (12%), and three preventability undetermined. The identified preventability factors were inadequate care and the patient's failure to interact with the healthcare system. From the case analysis, areas for improvement were identified, including insufficient consideration of major and minor risk factors, the early initiation of appropriate prophylactic treatment, and the absence of fibrinolysis in cases of s refractory cardiac arrest due to suspected PE.

Circulating miR-let7a levels predict future diagnosis of chronic thromboembolic pulmonary hypertension.

Distinct patterns of circulating microRNAs (miRNAs) were found to be involved in misguided thrombus resolution. Thus, we aimed to investigate dysregulated miRNA signatures during the acute phase of pulmonary embolism (PE) and test their diagnostic and predictive value for future diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH). Microarray screening and subsequent validation in a large patient cohort (n = 177) identified three dysregulated miRNAs as potential biomarkers: circulating miR-29a and miR-720 were significantly upregulated and miR-let7a was significantly downregulated in plasma of patients with PE. In a second validation study equal expression patterns for miR-29a and miR-let7a regarding an acute event of recurrent venous thromboembolism (VTE) or deaths were found. MiR-let7a concentrations significantly correlated with echocardiographic and laboratory parameters indicating right ventricular (RV) dysfunction. Additionally, circulating miR-let7a levels were associated with diagnosis of CTEPH during follow-up. Regarding CTEPH diagnosis, ROC analysis illustrated an AUC of 0.767 (95% CI 0.54-0.99) for miR-let7a. Using logistic regression analysis, a calculated patient-cohort optimized miR-let7a cut-off value derived from ROC analysis of ≥ 11.92 was associated with a 12.8-fold increased risk for CTEPH. Therefore, miR-let7a might serve as a novel biomarker to identify patients with haemodynamic impairment and as a novel predictor for patients at risk for CTEPH.

Risk of Venous Thromboembolic Events After Surgery for Cancer.

Importance: The risks and benefits of thromboprophylaxis therapy after cancer surgery are debated. Studies that determine thrombosis risk after cancer surgery with high accuracy are needed. Objectives: To evaluate 1-year risk of venous thromboembolic events after major cancer surgery and how these events vary over time. Design, Setting, and Participants: This register-based retrospective observational matched cohort study included data on the full population of Sweden between 1998 and 2016. All patients who underwent major surgery for cancer of the bladder, breast, colon or rectum, gynecologic organs, kidney and upper urothelial tract, lung, prostate, or gastroesophageal tract were matched in a 1:10 ratio with cancer-free members of the general population on year of birth, sex, and county of residence. Data were analyzed from February 13 to December 5, 2023. Exposure: Major surgery for cancer. Main Outcomes and Measures: The main outcome was incidence of venous thromboembolic events within 1 year after the surgery. Crude absolute risks and risk differences of events within 1 year and adjusted time-dependent cause-specific hazard ratios (HRs) of postdischarge events were calculated. Results: A total of 432 218 patients with cancer (median age, 67 years [IQR, 58-75 years]; 68.7% women) and 4 009 343 cancer-free comparators (median age, 66 years [IQR, 57-74 years]; 69.3% women) were included in the study. The crude 1-year cumulative risk of pulmonary embolism was higher among the cancer surgery population for all cancers, with the following absolute risk differences: for bladder cancer, 2.69 percentage points (95% CI, 2.33-3.05 percentage points); for breast cancer, 0.59 percentage points (95% CI 0.55-0.63 percentage points); for colorectal cancer, 1.57 percentage points (95% CI, 1.50-1.65 percentage points); for gynecologic organ cancer, 1.32 percentage points (95% CI, 1.22-1.41 percentage points); for kidney and upper urinary tract cancer, 1.38 percentage points (95% CI, 1.21-1.55 percentage points); for lung cancer, 2.61 percentage points (95% CI, 2.34-2.89 percentage points); for gastroesophageal cancer, 2.13 percentage points (95% CI, 1.89-2.38 percentage points); and for prostate cancer, 0.57 percentage points (95% CI, 0.49-0.66 percentage points). The cause-specific HR of pulmonary embolism comparing patients who underwent cancer surgery with matched comparators peaked just after discharge and generally plateaued 60 to 90 days later. At 30 days after surgery, the HR was 10 to 30 times higher than in the comparison cohort for all cancers except breast cancer (colorectal cancer: HR, 9.18 [95% CI, 8.03-10.50]; lung cancer: HR, 25.66 [95% CI, 17.41-37.84]; breast cancer: HR, 5.18 [95% CI, 4.45-6.05]). The hazards subsided but never reached the level of the comparison cohort except for prostate cancer. Similar results were observed for deep vein thrombosis. Conclusions and Relevance: This cohort study found an increased rate of venous thromboembolism associated with cancer surgery. The risk persisted for about 2 to 4 months postoperatively but varied between cancer types. The increased rate is likely explained by the underlying cancer disease and adjuvant treatments. The results highlight the need for individualized venous thromboembolism risk evaluation and prophylaxis regimens for patients undergoing different surgery for different cancers.

Impacto del confinamiento durante la pandemia de COVID-19 en la prevalencia de la enfermedad tromboembólica venosa / Impact of strict confinement during the COVID-19 pandemic on the prevalence of venous thromboembolic disease

Objetivo: comparar la frecuencia de eventos tromboembólicos agudos en pacientes atendidos en urgencias de un hospital comarcal durante las primeras semanas de la pandemia de COVID-19 del año 2020 respecto al año anterior.Material y métodos: estudio retrospectivo en pacientes mayores de 40 años atendidos en urgencias del Hospital de Riotinto (Huelva) desde el 15 de marzo al 30 de abril de los años 2019 y 2020. La recogida de información se llevó a cabo a partir de una revisión de historias clínicas y el cuestionario de recogida de datos contenía variables clínicas y sociodemográficas.Resultados: se incluyeron 1.245 pacientes. Edad media: 71,2 años (desviación estándar [DE]: 13,7) y un 51,1% eran mujeres. En 2019 se atendieron a 797 mayores de 40 años y en 2020 fueron 448, suponiendo un descenso del 43,79%. La prevalencia de embolismo pulmonar fue superior en 2020 respecto a 2019 (1,6% frente a 0,4%; p = 0,024). La frecuencia de eventos trombóticos venosos fue superior también en 2020 respecto a 2019 (1,35% frente a 0,4%; p = 0,054). La prevalencia global de la enfermedad tromboembólica venosa con variable compuesta (tromboembolismo pulmonar + trombosis venosa) fue significativamente superior en 2020 frente a 2019 (2,9% frente a 0,8%; p = 0,003). Ningún paciente fue diagnosticado de COVID-19 y tromboembolismo.Conclusiones: en el período de confinamiento durante la pandemia hubo un incremento del número de eventos tromboembólicos agudos en adultos, tanto de tromboembolia pulmonar como de trombosis venosa profunda respecto al año previo. (AU)

Aim: to compare the frequency of acute thromboembolic events in patients visited in the casualty department of a regional hospital during the first few weeks of the COVID-19 pandemic in 2020 with the same period of previous year.Material and methods: retrospective study of patients aged over 40 years of age treated in the casualty department of Hospital de Riotinto (Huelva) from 15 March to 30 April 2019 and same period of 2020. The information was collected from a review of medical records. The data collection questionnaire contained clinical and sociodemographic variables.Results: a total of 1245 patients were included. Mean age was 71.2 (SD:13.7) years old and 51.1% were women. In 2019, 797 patients aged over 40 years of age were treated, while in 2020, the patients seen were 448, which represented a decrease of 43.79%. The prevalence of pulmonary embolism was higher in 2020 compared to 2019 (1.6% vs. 0.4%; P=0.024). The frequency of venous thrombotic events was also higher in 2020 compared to 2019 (1.35% vs. 0.4%; P=0.054). The overall prevalence of venous thromboembolic disease with composite variable (pulmonary thromboembolism + venous thrombosis) was statistically significantly higher in 2020 versus 2019 (2.9% versus 0.8%; P=0.003). None of our patients were diagnosed with COVID-19 and thromboembolism.Conclusions: during the period of confinement during the pandemic there was an increase in the number of acute thromboembolic events in adults, both PE and VTE compared to the previous year.(AU)

Acute inferior vena cava thromboembolism in pregnancy.

A multigravida in her late 20s was diagnosed with inferior vena cava thrombosis (IVCT) and PE at 26 weeks of pregnancy after a routine prenatal care visit. The patient denied any diseases that could cause IVCT, as well as the presence of any symptoms. Progressive thrombocytopenia was diagnosed in the period until the implantation of the inferior vena cava filter (IVCF). Due to a rupture of foetal membranes and chorioamnionitis, labour was induced at 32 weeks of pregnancy. The IVCF remained in place and anticoagulants were continued through the postpartum period for up to 6 months.

Effectiveness and safety of prophylactic anticoagulation among hospitalized patients with inflammatory bowel disease.

ABSTRACT: Hospitalized patients with inflammatory bowel disease (IBD) are at increased risk of venous thromboembolism (VTE). We aimed to evaluate the effectiveness and safety of prophylactic anticoagulation compared with no anticoagulation in hospitalized patients with IBD. We conducted a retrospective cohort study using a hospital-based database. We included patients with IBD who had a length of hospital stay ≥2 days between 1 January 2016 and 31 December 2019. We excluded patients who had other indications for anticoagulation, users of direct oral anticoagulants, warfarin, therapeutic-intensity heparin, and patients admitted for surgery. We defined exposure to prophylactic anticoagulation using charge codes. The primary effectiveness outcome was VTE. The primary safety outcome was bleeding. We used propensity score matching to reduce potential differences between users and nonusers of anticoagulants and Cox proportional-hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The analysis included 56 194 matched patients with IBD (users of anticoagulants, n = 28 097; nonusers, n = 28 097). In the matched sample, prophylactic use of anticoagulants (vs no use) was associated with a lower rate of VTE (HR, 0.62; 95% CI, 0.41-0.94) and with no difference in the rate of bleeding (HR, 1.05; 95% CI, 0.87-1.26). In this study of hospitalized patients with IBD, prophylactic use of heparin was associated with a lower rate of VTE without increasing bleeding risk compared with no anticoagulation. Our results suggest potential benefits of prophylactic anticoagulation to reduce the burden of VTE in hospitalized patients with IBD.

Increase in venous thromboembolism in SARS-CoV-2 infected lung tissue: proteome analysis of lung parenchyma, isolated endothelium, and thrombi.

AIMS: COVID-19 pneumonia is characterized by an increased rate of deep venous thrombosis and pulmonary embolism. To better understand the pathophysiology behind thrombosis in COVID-19, we performed proteomics analysis on SARS-CoV-2 infected lung tissue. METHODS: Liquid chromatography mass spectrometry was performed on SARS-CoV-2 infected postmortem lung tissue samples. Five protein profiling analyses were performed: whole slide lung parenchyma analysis, followed by analysis of isolated thrombi and endothelium, both stratified by disease (COVID-19 versus influenza) and thrombus morphology (embolism versus in situ). Influenza autopsy cases with pulmonary thrombi were used as controls. RESULTS: Compared to influenza controls, both analyses of COVID-19 whole-tissue and isolated endothelium showed upregulation of proteins and pathways related to liver metabolism including urea cycle activation, with arginase being among the top upregulated proteins in COVID-19 lung tissue. Analysis of isolated COVID-19 thrombi showed significant downregulation of pathways related to platelet activation compared to influenza thrombi. Analysis of isolated thrombi based on histomorphology shows that in situ thrombi have significant upregulation of coronavirus pathogenesis proteins. CONCLUSIONS: The decrease in platelet activation pathways in severe COVID-19 thrombi suggests a relative increase in venous thromboembolism, as thrombi from venous origin tend to contain fewer platelets than arterial thrombi. Based on histomorphology, in situ thrombi show upregulation of various proteins related to SARS-CoV-2 pathogenesis compared to thromboemboli, which may indicate increased in situ pulmonary thrombosis in COVID-19. Therefore, this study supports the increase of venous thromboembolism without undercutting the involvement of in situ thrombosis in severe COVID-19.

Altered whole blood thrombin generation and hyperresponsive platelets in patients with pancreatic cancer.

BACKGROUND: Thromboembolic disease is a major complication in patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often have altered blood cell counts, which are associated with venous thromboembolism (VTE) development. The high thrombotic risk in patients with PDAC may be partially caused by procoagulant blood cells. OBJECTIVES: The aim of this study was to compare blood cell-dependent coagulation between patients with PDAC (n = 18) and healthy controls matched for age and sex (n = 18). METHODS: Thrombin generation (TG) was measured in whole blood (WB) and plasma. The capacity of platelets to release granules (PGRCs) was measured in WB. We explored the occurrence of thromboembolic events in patients with PDAC during a 6-month follow-up. RESULTS: Patients showed an increased endogenous thrombin potential in WB compared with controls. This difference was not observed in plasma, indicating a procoagulant effect of blood cells. Both in WB and plasma, the lag time was prolonged in patients compared with controls. Patients had hyperresponsive platelets, with a shorter time to peak granule release. Of the 18 patients with PDAC, 4 developed a venous thromboembolism (22%) and 1 developed an arterial thrombosis (6%). A shorter lag time in WB, but not in plasma, and an increased PGRC were associated with thromboembolic events. CONCLUSION: Patients with PDAC have an increased and delayed WB TG coagulation profile compared with controls. A shorter lag time in WB TG and increased PGRC are associated with the incidence of thromboembolic events. Platelets appear to be key players in thrombosis development. Measuring hemostasis in WB could improve thrombosis risk estimation in patients with PDAC.

Cancer-associated splanchnic vein thrombosis: Clinical implications and management considerations.

Splanchnic vein thrombosis (SVT), a thrombosis which involves the portal, mesenteric, and splenic veins, and the Budd-Chiari syndrome, represents an uncommon type of venous thromboembolism (VTE). Like with deep vein thrombosis of the lower extremities and pulmonary embolism, ample evidence suggests a significant association between SVT and cancer, particularly intra-abdominal solid malignancies (e.g. hepatobiliary and pancreatic cancers) and myeloproliferative neoplasms (MPN). Clinical symptoms of SVT in cancer patients can be ambiguous, and frequently attributed to the primary cancer itself. Alternatively, SVT may be asymptomatic and detected incidentally during cancer staging or follow-up evaluations. SVT can also precede the diagnosis of cancer and has been associated with poorer outcomes in patients with liver or pancreatic cancers. Therefore, an unprovoked SVT warrants a thorough evaluation for an underlying malignancy or MPN. Cancer-associated SVT carries a high risk of VTE extension, recurrence and bleeding. Extended anticoagulant treatment is often required in the absence of a high bleeding risk. Guidelines suggest treatment with either low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs), although available data on the safety and effectiveness of DOACs in these patients is limited. This comprehensive review outlines the epidemiology, pathogenesis, risk factors, and diagnosis of cancer-associated SVT and underscores the importance of comprehensive patient evaluation and evidence-based management.

Clinical prediction tool to identify children at risk of pulmonary embolism.

INTRODUCTION: The diagnosis of pediatric pulmonary embolism (PE) is often delayed due to non-specific symptoms, and clinical prediction tools designed for adults are unsuitable for children. This study aimed to create a PE predictive model and to evaluate the reported tools in the Thai pediatric population. MATERIALS AND METHODS: A multi-center retrospective study from 4 university hospitals included children ≤18 years of age undergoing computed tomography pulmonary angiogram from 2000 to 2020 with the suspicion of PE. Patients' clinical presentations and risk factors of venous thromboembolism (VTE) were compared between the PE-positive and PE-negative groups. Significant risk factors from univariate and multivariate logistic regression were included to create a clinical prediction tool. The performance of the model was demonstrated by sensitivity, specificity, area under the curve (AUC), Hosmer Lemeshow test, ratio of observed and expected outcomes and bootstrapping. RESULTS: Of the 104 patients included, 43 (41.3 %) were grouped as PE-positive and 61 (58.7 %) as PE-negative. Five parameters, including congenital heart disease/pulmonary surgery, known thrombophilia, previous VTE, nephrotic syndrome and chest pain showed significant differences between the two groups. Score ≥ 2 yielded a 74.4 % sensitivity and a 75.4 % specificity with an AUC of the model of 0.809. The model performance and validation results were within satisfactory ranges. CONCLUSION: The study created a clinical prediction tool indicating the likelihood of PE among Thai children. A score ≥2 was suggestive of PE.

Drug-Drug Interactions in the Treatment of Cancer-Associated Venous Thromboembolism with Direct Oral Anticoagulants.

Venous thromboembolism (VTE) is a frequent complication of cancer, and management of cancer-associated thrombosis (CAT) is challenging due to increased risks of bleeding and recurrent VTE. Recent trials have shown an acceptable efficacy and safety of direct oral anticoagulants (DOACs) in the treatment of CAT compared to low-molecular weight heparin. Although DOACs provide an effective and convenient treatment option in CAT, the need to assess the risk of drug-drug interactions (DDI) with antineoplastic therapies poses a barrier to their use in clinical practice. With the aim of supporting the assessment of CAT patients for treatment with DOAC, this review provides a comprehensive overview of the compatibility of antineoplastic therapies with the individual DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban). Using several data sources, we characterized 100 widely used antineoplastic agents with regard to their effect on p-glycoprotein and cytochrome P450, both important in the transport and elimination of DOACs. This enabled us to evaluate 400 "DOAC-antineoplastic agent"-pairs regarding their likelihood to interact (unlikely, potential, or likely), ultimately leading to clinical recommendations on the appropriateness of concomitant use for each pair. A potential or likely DDI was identified for 12% of the evaluated pairs. For nearly all antineoplastic agents, at least one DOAC was considered compatible.

Efficacy and Safety of Warfarin for the Treatment of Venous Thromboembolism　- A Multicenter Prospective Observational Cohort Study in Japan (AKAFUJI Study).

BACKGROUND: A large-scale prospective study of the efficacy and safety of warfarin for the treatment of venous thromboembolism (VTE) has not been conducted in Japan. Therefore, we conducted a real-world prospective multicenter observational cohort study (AKAFUJI Study; UMIN000014132) to investigate the efficacy and safety of warfarin for VTE.Methods and Results: Between May 2014 and March 2017, 352 patients (mean [±SD] age 67.7±14.8 years; 57% female) with acute symptomatic/asymptomatic VTE were enrolled; 284 were treated with warfarin. The cumulative incidence of recurrent symptomatic VTE was higher in patients without warfarin than in those treated with warfarin (8.7 vs. 2.2 per 100 person-years, respectively; P=0.018). The cumulative incidence of bleeding complications was not significantly different between the 2 groups. The mean prothrombin time-international normalized ratio (PT-INR) during warfarin on-treatment was <1.5 in 180 patients, 1.5-2.5 in 97 patients, and >2.5 in 6 patients. The incidence of bleeding complications was significantly higher in patients with PT-INR >2.5, whereas the incidence of recurrent VTE was not significantly different between the 3 PT-INR groups. The cumulative incidence of recurrent VTE and bleeding complications did not differ significantly among those in whom VTE was provoked by a transient risk factor, was unprovoked, or was associated with cancer. CONCLUSIONS: Warfarin therapy with an appropriate PT-INR according to Japanese guidelines is effective without increasing bleeding complications, regardless of patient characteristics.

Venous Thromboembolism Among People With HIV: Design, Implementation, and Findings of a Centralized Adjudication System in Clinical Care Sites Across the United States.

BACKGROUND: People with HIV (PWH) are at increased risk for venous thromboembolism (VTE). We conducted this study to characterize VTE including provoking factors among PWH in the current treatment era. METHODS: We included PWH with VTE between 2010 and 2020 at 6 sites in the CFAR Network of Integrated Clinical Systems cohort. We ascertained for possible VTE using diagnosis, VTE-related imaging, and VTE-related procedure codes, followed by centralized adjudication of primary data by expert physician reviewers. We evaluated sensitivity and positive predictive value of VTE ascertainment approaches. VTEs were classified by type and anatomic location. Reviewers identified provoking factors such as hospitalizations, infections, and other potential predisposing factors such as smoking. RESULTS: We identified 557 PWH with adjudicated VTE: 239 (43%) had pulmonary embolism with or without deep venous thrombosis, and 318 (57%) had deep venous thrombosis alone. Ascertainment with clinical diagnoses alone missed 6% of VTEs identified with multiple ascertainment approaches. DVTs not associated with intravenous lines were most often in the proximal lower extremities. Among PWH with VTE, common provoking factors included recent hospitalization (n = 134, 42%), infection (n = 133, 42%), and immobilization/bed rest (n = 78, 25%). Only 57 (10%) PWH had no provoking factor identified. Smoking (46%), HIV viremia (27%), and injection drug use (22%) were also common. CONCLUSIONS: We conducted a robust adjudication process that demonstrated the benefits of multiple ascertainment approaches followed by adjudication. Provoked VTEs were more common than unprovoked events. Nontraditional and modifiable potential predisposing factors such as viremia and smoking were common.

Cellular Components Contributing to the Development of Venous Thrombosis in Patients with Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of cancer and has a poor prognosis. Patients with PDAC are at high risk of developing thromboembolic events, which is a leading cause of morbidity and mortality following cancer progression. Plasma-derived coagulation is the most studied process in cancer-associated thrombosis. Other blood components, such as platelets, red blood cells, and white blood cells, have been gaining less attention. This narrative review addresses the literature on the role of cellular components in the development of venous thromboembolism (VTE) in patients with PDAC. Blood cells seem to play an important role in the development of VTE. Altered blood cell counts, i.e., leukocytosis, thrombocytosis, and anemia, have been found to associate with VTE risk. Tumor-related activation of leukocytes leads to the release of tissue factor-expressing microvesicles and the formation of neutrophil extracellular traps, initiating coagulation and forming a scaffold for thrombi. Tissue factor-expressing microvesicles are also thought to be released by PDAC cells. PDAC cells have been shown to stimulate platelet activation and aggregation, proposedly via the secretion of podoplanin and mucins. Hypofibrinolysis, partially explained by increased plasminogen activator inhibitor-1 activity, is observed in PDAC. In short, PDAC-associated hypercoagulability is a complex and multifactorial process. A better understanding of cellular contributions to hypercoagulability might lead to the improvement of diagnostic tests to identify PDAC patients at highest risk of VTE.

Tranexamic Acid Demonstrates Efficacy without Increased Risk for Venous Thromboembolic Events in Cranial Neurosurgery: Systematic Review of the Evidence and Current Applications in Nontraumatic Pathologies.

BACKGROUND: The cautionary stance normally taken towards tranexamic acid (TXA) is rooted in concerns regarding its complication profile, namely its purported risk for venous thromboembolic events (VTEs). In the present review, we intend to bring increased attention to TXA as a remarkably valuable tool that does not appear to increase the risk for VTE when used as indicated in select patients. METHODS: We queried three databases to identify reporting use of TXA during nontraumatic cranial neurosurgery procedures (excluded traumatic brain injury). Data gathered included VTE complications, deep venous thrombosis, use of allogeneic blood transfusions, estimated blood loss, and operative duration. RESULTS: Twenty-eight studies were deemed eligible for inclusion in the present meta-analysis, including nine studies on surgical resection of intracranial neoplasms, ten studies on aneurysmal subarachnoid hemorrhage, and nine studies on craniosynostosis. In brain tumor surgery, TXA appears to successfully reduce blood loss without predisposing patients to VTE or seizure (P < 0.01). However, it does not appear to reduce rates of vasospasm in aneurysmal subarachnoid hemorrhage (P = 0.27), and its administration is not associated with clinically meaningful differences in long term neurological outcomes. For pediatric patients undergoing craniosynostosis procedures, TXA similarly reduces blood loss (P < 0.01). Nonetheless, low dosing protocols should be used because they appear effective and the effects of high dose TXA in children have not been studied. CONCLUSIONS: TXA is an effective hemostatic agent that can be administered to reduce blood loss and transfusion requirements for a wide range of neurosurgical applications in a broad spectrum of patient populations.

Real life results of direct-acting oral anticoagulants recommended-dose in obese vs normal-weight patients with venous thromboembolism.

BACKGROUND: There is scarce evidence on the effectiveness and safety of recommended-dose direct acting oral anticoagulants (DOACs) in obese patients with venous thromboembolism (VTE). MATERIAL AND METHODS: We used the data in the RIETE registry to compare the rates of VTE recurrences and major bleeding during long-term therapy with DOACs at recommended doses in patients with body mass index ≥30 kg/m2 (obese) vs. those with BMI 18.5-24.9 kg/m2 (normal weight). We performed regression models with competing risks for death. RESULTS: From January 2013 through October 2022, 2885 obese patients and 2676 with normal weight in RIETE received rivaroxaban (n = 3020), apixaban (n = 1754), edoxaban (n = 636) or dabigatran (n = 151). Median age was 63 years and 52 % were female. At baseline, obese patients were more likely to have diabetes (18.6 % vs. 8.4 %), hypertension (51.9 % vs. 31.4 %) or pulmonary embolism (67.7 % vs. 61 %), and less likely to have renal insufficiency (5.3 % vs. 16 %) or anaemia (21.8 % vs. 28 %%). During anticoagulation (median, 147 vs. 101 days), the obese had a similar rate of VTE recurrences (1.71 vs. 2.14 events per 100 patients-years; hazard ratio (HR): 0.81; 95 % CI: 0.49-1.34) or major bleeding (1.45 vs. 1.76 per 100 patients-years; HR: 0.91; 95 % CI: 0.52-1.59) than those with normal weight. These findings persisted after multivariable analysis (recurrent VTE, HR: 0.80; 95 % CI: 0.48-1.32; major bleeding, HR: 1.11; 95 % CI: 0.60-2.07). CONCLUSION: The use of DOACs at recommended doses in obese patients with VTE was associated with similar rates of VTE recurrences or major bleeding than in patients with normal weight.

Association of eGFR and Albuminuria with Venous Thromboembolism.

BACKGROUND: CKD has been implicated as a risk factor of venous thromboembolism, but the evidence is limited to relatively healthy populations. The objective of this study was to discern whether parameters of kidney function and damage are associated with the occurrence of venous thromboembolism after hospitalization. METHODS: We conducted a retrospective study including 23,899 and 11,552 adult individuals hospitalized within Geisinger Health System and New York University (NYU) Langone Health from 2004 to 2019 and 2012 to 2022, respectively. A Poisson model was used to evaluate adjusted incidence rates of venous thromboembolism according to eGFR and albuminuria categories in each cohort. Cox proportional hazards models were used to analyze associations of eGFR and urinary albumin-to-creatinine ratio (UACR) with venous thromboembolism, and hazard ratios (HRs) were meta-analyzed across cohorts. RESULTS: Both lower eGFR and higher UACR were associated with higher risks of venous thromboembolism. In the Geisinger cohort, the incidence of venous thromboembolism after hospital discharge ranged from 10.7 (95% confidence interval [CI], 9.2 to 12.6) events per 1000 person-years in individuals in G1A1 (eGFR >90 ml/min per 1.73 m 2 and UACR <30 mg/g) to 27.7 (95% CI, 20.6 to 37.2) events per 1000 person-years in individuals with G4-5A3 (eGFR <30 ml/min per 1.73 m 2 and UACR >300 mg/g). A similar pattern was observed in the NYU cohort. Meta-analyses of the two cohorts showed that every 10 ml/min per 1.73 m 2 reduction in eGFR below 60 ml/min per 1.73 m 2 was associated with a 6% higher risk of venous thromboembolism (HR 1.06 [95% CI, 1.02 to 1.11], P = 0.01), and each two-fold higher UACR was associated with a 5% higher risk of venous thromboembolism (HR 1.05 [95% CI, 1.03 to 1.07], P < 0.001). CONCLUSIONS: Both eGFR and UACR were independently associated with higher risk of venous thromboembolism after hospitalization. The incidence rate was higher with greater severity of CKD. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_12_14_CJN0000000000000352.mp3.