Hipertensión pulmonar y leiomiomas uterinos, ¿existe relación causal? Serie de casos y revisión fisiopatológica / Pulmonary Hypertension and Uterine Leiomyomas, Is there a Causal Relationship? Case Series and Pathophysiological Review

Introducción: Los leiomiomas uterinos son un tipo de neoplasia benigna de frecuente aparición en mujeres de edad reproductiva, relacionados con enfermedad tromboem- bólica venosa. Este vínculo surge del efecto producido por la compresión de fibromas que genera estasis venosa en la región pelviana. Sin embargo, este pareciera no ser el único factor que lo relaciona con el desarrollo posterior de hipertensión pulmonar, sino que su presencia es gatillo de una serie de fenómenos que influyen sobre la vasculatu - ra pulmonar y también a nivel sistémico. Método: Revisión de una serie de casos (seis) atendidos en nuestra unidad, seguido de una revisión sobre la relación entre leiomio- mas y distintas formas de hipertensión pulmonar con una revisión desde la fisiopatología. Resultado y conclusiones: Encontramos sustento bibliográfico en los múltiples caminos fisiopatológicos que relacionan los mediadores vasculares comunes, que parecieran ser el punto clave en la relación entre estas dos patologías.

Introduction: Uterine leiomyomas are a type of benign neoplasm that frequently appears in women of reproductive age, related to venous thromboembolic disease. This link arises from the effect produced by the compression of fibroids, which generates venous stasis in the pelvic region. However, this seems not to be the only factor that re- lates it to the subsequent development of pulmonary hypertension, but rather its presence is a trigger for a series of phenomena that influence the pulmonary vasculature and also at a systemic level. Method: Review of a series of cases (six) cared for in our unit, followed by a review on the relationship between leiomyomas and different forms of pulmonary hypertension with a review from the pathophysiology. Result and conclusions: We found bibliographic support in the multiple pathophysiological paths that relate the common vascular mediators, which appear to be the key point in the relationship between these two pathologies.

Tromboprofilaxis entrauma / Thromboprophylaxis in Trauma Santiago Castañeda Palacio1

Introducción: Las lesiones traumáticas son una de las principales causas de morbilidad y mortalidad en todo el mundo. Los pacientes que sufren traumatismos tienen riesgo de estados de hipercoagulación y aumentan el riesgo de sufrir enfermedad tromboembólica venosa. La tromboprofilaxis hace referencia a cualquier intervención usada para prevenir el desarrollo del tromboembolismo venoso como son la trombosis venosa profunda y el tromboembolismo pulmonar. Objetivo: Realizar una revisión sobre los principales mecanismos de tromboprofilaxis y sus principales esquemas en relación con el trauma ortopédico. Métodos: Se realizó una búsqueda de artículos de investigaciones originales en las bases de datos MEDLINE, EMBASE, Lilacs y Science Direct. Se seleccionaron palabras claves y términos del MeSH relacionados con anticoagulantes, tromboembolismo venoso, y embolismo pulmonar entre otros. La mayoría de bibliografía utilizada tuvo un rango de publicación no mayor a 5 años. Conclusiones: Los pacientes que sufren traumas tienen riesgo de sufrir estados de hipercoagulación y aumentan el riesgo de una enfermedad tromboembólica venosa. Con el fin de prevenirla se utilizan en la tromboprofilaxis distintos medicamentos, como heparinas de bajo peso molecular, y dispositivos de compresión(AU)

Introduction: Traumatic injuries are one of the leading causes of morbidity and mortality worldwide. Up to six million people die due to this cause. Trauma patients are at risk for hypercoagulable states and are at increased risk for venous thromboembolic disease. Thromboprophylaxis refers to any intervention used to prevent the development of venous thromboembolism such as deep vein thrombosis and pulmonary thromboembolism. Objective: To carry out a practical review of the main mechanisms of thromboprophylaxis and its main schemes in relation to orthopedic trauma. Methods: A search for original research articles was conducted in MEDLINE, EMBASE, Lilacs, and Science Direct databases. The keywords and MeSH terms related to anticoagulants, venous thromboembolism, and pulmonary embolism were selected among others. Most of the bibliography used had a publication range of no more than 5 years. Conclusions: Patients who suffer trauma are at risk of hypercoagulable states and these increase the risk of venous thromboembolic disease. In order to prevent it, different drugs are used in thromboprophylaxis, such as low molecular weight heparins, among others, as well as other compression devices(AU)

Combined Effect of MTHFR C677T and PAI-1 4G/5G Polymorphisms on the Risk of Venous Thromboembolism in Chinese Lung Cancer Patients.

Venous thromboembolism (VTE) is a common and potentially fatal complication in cancer patients. Although several genetic risk factors related to thrombophilia have been identified, their contributions for the occurrence of VTE in cancer patients have conflicting results. The aim of this study was to evaluated the gene polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor-1 (PAI-1) 4G/5G in lung cancer patients, with and without VTE, and the combined effect on the risk of VTE. 92 lung cancer patients diagnosed with VTE (VTE group) and 122 lung cancer patients without VTE (non-VTE group) were enrolled in the study. The gene polymorphisms were analyzed by the method of polymerase chain reaction-restriction fragment length polymorphism. Gene mutation of factor V Leiden was not detected both in non-VTE group and VTE group. The frequency of MTHFR C677T homozygous mutation in VTE group was 25.00%, higher than that in the non-VTE group without statistical difference. It was found that the PAI-1 4G4G genotype is associated with a higher risk of VTE (OR: 2.62, 95%CI: 1.19-5.75). Interestingly, the interaction between MTHFR C677T and PAI-1 4G/5G polymorphisms showed that the coexistence of the 2 homozygous mutation could further increase the risk of VTE. In conclusion, PAI-1 4G/5G polymorphism may be an increased risk factor for VTE among lung cancer patients in Chinese population. The homozygous MTHFR C677T mutation may be not a risk factor for VTE but increases the risk, accompanied with PAI-1 4G5G genotype.

Prophylaxis and treatment of COVID-19 related venous thromboembolism.

COVID-19 pneumonia has been associated with high rates of thrombo-embolic complications, mostly venous thromboembolism (VTE), which is thought to be a combination of conventional VTE and in situ immunothrombosis in the pulmonary vascular tree. The incidence of thrombotic complications is dependent on setting (intensive care unit (ICU) versus general ward) and the threshold for performing diagnostic tests (screening versus diagnostic algorithms triggered by symptoms). Since these thrombotic complications are associated with in-hospital mortality, all current guidelines and consensus papers propose pharmacological thromboprophylaxis in all hospitalized patients with COVID-19. Several trials are ongoing to study the optimal intensity of anticoagulation for this purpose. As for the management of thrombotic complications, treatment regimens from non-COVID-19 guidelines can be adapted, with choice of anticoagulant drug class dependent on the situation. Parenteral anticoagulation is preferred for patients on ICUs or with impending clinical deterioration, while oral treatment can be started in stable patients. This review describes current knowledge on incidence and pathophysiology of COVID-19 associated VTE and provides an overview of guideline recommendations on thromboprophylaxis and treatment of established VTE in COVID-19 patients.

Solid Tumor Complicated With Venous Thromboembolism: A 10-Year Retrospective Cross-Sectional Study.

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT) occurs more frequently in cancer patients than in the general population. A retrospective cross-sectional study was carried out in patients with solid tumor complicated with VTE admitted to the Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 1st, 2008 and December 31th, 2017. The incidence of VTE in hospitalized cancer patients was 1.8%, twice the incidence of VTE in hospitalized non-cancer patients. The annual incidence of cancer-associated VTE in our center varied between 1.6% in 2015 and 0.4% in 2009 with an overall average incidence of 1.3% over the research decade. BMI values of 549(67.7%) cancer patients were within the normal range, but none of patients had BMI greater than 35 kg/m2. 747(92.1%) cancer patients had ECOG PS score ≤ 2 and 481(59.3%) had distant metastasis. Patients with pancreatic, bladder, ovarian and endometrial cancer had the highest incidence of VTE. Upper extremity DVT (47.2%) was more common in cancer patients and might be closely associated with CVC (74.9%), while lower extremities DVT (36.1%) intended to PE development (15.0%). The annual incidence rates showed a fluctuating and upward trend over the research decade. VTE occurrence was closely related to tumor stage, tumor site, catheterization and anti-neoplasm therapy in cancer patients.

Screening for Cancer in Patients with Acute Venous Thromboembolic Disease.

Active cancer causes approximately 25% of all acute events of venous thromboembolism (VTE). While most of the cancer diagnoses are known or clinically apparent at the time of VTE, care providers and patients may be worried about the 3 to 8% risk of occult cancer occurring in the year after VTE. Several studies have compared limited to extensive cancer screening after acute VTE, especially with the addition of abdominal computed tomography (CT) or whole-body PET-CT, with the hope to shorten the time to cancer diagnosis and lead to less advanced cancer stages. These studies have not shown improved clinical outcomes with an extensive screening, and have led to current recommendations of limited screening for cancer in patients with acute VTE, including unprovoked cases. Several risk assessment models have been developed to identify patients at greatest risk of occult cancer, however, with low discriminative performances and no current clinical usefulness. Some clinical situations may empirically deserve a more thorough cancer screening, such as unprovoked upper extremity deep vein thrombosis (DVT), bilateral leg DVT, descending leg DVT, or recurrent VTE during anticoagulation.

Pharmacologic Thromboprophylaxis Other Than Aspirin Is Associated With Increased Risk for Procedural Intervention for Arthrofibrosis After Anterior Cruciate Ligament Reconstruction.

PURPOSE: To compare rates of procedural intervention for arthrofibrosis following anterior cruciate ligament reconstruction (ACLR) among patients who were not prescribed any pharmacologic thromboprophylaxis compared with patients who were prescribed aspirin and to patients who were prescribed other agents. METHODS: A search of a national insurance claims database was performed to identify all patients who underwent ACLR from 2007 to 2017 who were active within the database at a minimum of 6 months before and 18 months after their surgery. The primary outcome studied was a subsequent procedure for arthrofibrosis, manipulation under anesthesia, and lysis of adhesions (MUA/LOA). Patients who filled a prescription for aspirin, low-molecular weight heparin, direct factor Xa inhibitors, fondaparinux, and warfarin within 2 days after their surgery were included and those who filled a prescription within 3 months before surgery were excluded. Thromboprophylaxis status was defined as no thromboprophylaxis, aspirin, and any agent other than aspirin. Logistic regression analysis was performed to determine the association between prophylaxis status and MUA/LOA. RESULTS: Of the 14,081 patients in our final surgical population, 191 patients had MUA/LOA and 13,890 patients did not. In total, 499 patients were prescribed pharmacologic prophylaxis. Rates of MUA/LOA across groups were 1.3% in the group with no thromboprophylaxis, 1.9% in the group prescribed aspirin, and 4.3% in the group prescribed any agent other than aspirin. Only the group prescribed an agent other than aspirin was significantly associated with subsequent procedure for arthrofibrosis (odds ratio 2.6, 95% confidence interval 1.3-4.8, P = .004). CONCLUSIONS: Patients who were prescribed a pharmacologic agent other than aspirin had a 2.6 times greater likelihood of requiring a procedural intervention for arthrofibrosis following ACLR compared with patients who were not prescribed a thromboprophylaxis agent LEVEL OF EVIDENCE: III, Retrospective Cohort Study.

Cerebral venous sinus thrombosis associated with spontaneous heparin-induced thrombocytopenia syndrome after total knee arthroplasty.

Spontaneous heparin-induced thrombocytopenia (HIT) syndrome, characterized by clinical and serologic features of HIT despite the absence of proximate heparin exposure, can be triggered by total knee arthroplasty (TKA). A 56-year-old female receiving aspirin thromboprophylaxis post-TKA presented with aphasia and thrombocytopenia on post-operative day 11. Imaging studies revealed cerebral venous sinus thrombosis (CVST) and intravenous bivalirudin was initiated. Her serum tested strong-positive for IgG anti-PF4/polyanion complexes and serotonin-release assay in the presence and absence of heparin; strong-positive IgG-specific chemiluminescent immunoassay; and moderate-positive latex immunoturbidimetric assay. Two 65 g doses of IVIG were administered. With the improvement of her platelet count, she was transitioned from bivalirudin to warfarin. At one-year follow-up, she remained free of recurrent thrombosis and neurologically stable with a normal platelet count. Previous reports of post-TKA spontaneous HIT syndrome include venous/arterial thrombosis and adrenal hemorrhage, and this report of CVST expands the clinical spectrum of this rare complication of orthopedic surgery.

Venous thrombosis epidemiology, pathophysiology, and anticoagulant therapies and trials in severe acute respiratory syndrome coronavirus 2 infection.

OBJECTIVE: Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus confers a risk of significant coagulopathy, with the resulting development of venous thromboembolism (VTE), potentially contributing to the morbidity and mortality. The purpose of the present review was to evaluate the potential mechanisms that contribute to this increased risk of coagulopathy and the role of anticoagulants in treatment. METHODS: A literature review of coronavirus disease 2019 (COVID-19) and/or SARS-CoV-2 and cell-mediated inflammation, clinical coagulation abnormalities, hypercoagulability, pulmonary intravascular coagulopathy, and anticoagulation was performed. The National Clinical Trials database was queried for ongoing studies of anticoagulation and/or antithrombotic treatment or the incidence or prevalence of thrombotic events in patients with SARS-CoV-2 infection. RESULTS: The reported rate of VTE among critically ill patients infected with SARS-CoV-2 has been 21% to 69%. The phenomenon of breakthrough VTE, or the acute development of VTE despite adequate chemoprophylaxis or treatment dose anticoagulation, has been shown to occur with severe infection. The pathophysiology of overt hypercoagulability and the development of VTE is likely multifactorial, with evidence supporting the role of significant cell-mediated responses, including neutrophils and monocytes/macrophages, endothelialitis, cytokine release syndrome, and dysregulation of fibrinolysis. Collectively, this inflammatory process contributes to the severe pulmonary pathology experienced by patients with COVID-19. As the infection worsens, extreme D-dimer elevations, significant thrombocytopenia, decreasing fibrinogen, and prolongation of prothrombin time and partial thromboplastin time occur, often associated with deep vein thrombosis, in situ pulmonary thrombi, and/or pulmonary embolism. A new phenomenon, termed pulmonary intravascular coagulopathy, has been associated with morbidity in patients with severe infection. Heparin, both unfractionated heparin and low-molecular-weight heparin, have emerged as agents that can address the viral infection, inflammation, and thrombosis in this syndrome. CONCLUSIONS: The overwhelming inflammatory response in patients with SARS-CoV-2 infection can lead to a hypercoagulable state, microthrombosis, large vessel thrombosis, and, ultimately, death. Early VTE prophylaxis should be provided to all admitted patients. Therapeutic anticoagulation therapy might be beneficial for critically ill patients and is the focus of 39 ongoing trials. Close monitoring for thrombotic complications is imperative, and, if confirmed, early transition from prophylactic to therapeutic anticoagulation should be instituted. The interplay between inflammation and thrombosis has been shown to be a hallmark of the SARS-CoV-2 viral infection.

Patterns and predictors of thromboembolic events among patients with gastric cancer.

Patients with gastric cancer are at higher risk for venous thromboembolic events (VTE). Majority of such patients are treated in ambulatory settings where thromboprophylaxis is not routinely offered. In this study, we report on VTE rates and search for predictors that may help identify patients at higher risk to justify VTE-prophylaxis in ambulatory settings. Patients with pathologically-confirmed gastric adenocarcinoma were retrospectively reviewed for VTE detected by imaging studies. Clinical and pathological features known to increase the risk of VTE were studied. Khorana risk assessment model was applied on patients receiving chemotherapy. A total of 671 patients; median age 55 years, were recruited. VTE were diagnosed in 150 (22.4%) patients, including 42 (28.0%) pulmonary embolism and 18 (12.0%) upper extremity deep vein thrombosis (DVT). Majority (> 80%) developed VTE while in ambulatory settings and none had been on thromboprophylaxis. Rate was higher (27.1%) among 365 patients with metastatic compared to 16.7% among 306 patients with nonmetastatic disease, p = 0.001. Patients with metastatic disease who received multiple lines of chemotherapy (n = 85) had significantly higher rate of VTE compared to those who received a single line; 48.2% versus 19.4%, p < 0.001. Among the whole group, Khorana risk score, age, gender, smoking and obesity had no impact on VTE rates. Patients with metastatic gastric cancer, especially when treated with multiple lines of chemotherapy, are at a significantly higher risk of VTE. Khorana risk score had no impact on VTE rates. Thromboprophylaxis in ambulatory patients with metastatic gastric cancer worth studying.

An Update on Venous Thromboembolism Rates and Prophylaxis in Hip and Knee Arthroplasty in 2020.

Patients undergoing total hip and knee arthroplasty are at high risk for venous thromboembolism (VTE) with an incidence of approximately 0.6-1.5%. Given the high volume of these operations, with approximately one million performed annually in the U.S., the rate of VTE represents a large absolute number of patients. The rate of VTE after total hip arthroplasty has been stable over the past decade, although there has been a slight reduction in the rate of deep venous thrombosis (DVT), but not pulmonary embolism (PE), after total knee arthroplasty. Over this time, there has been significant research into the optimal choice of pharmacologic VTE prophylaxis for individual patients, with the objective to reduce the rate of VTE while minimizing adverse side effects such as bleeding. Recently, aspirin has emerged as a promising prophylactic agent for patients undergoing arthroplasty due to its similar efficacy and good safety profile compared to other pharmacologic agents. However, there is no evidence to date that clearly demonstrates the superiority of any given prophylactic agent. Therefore, this review discusses (1) the current prevalence and trends in VTE after total hip and knee arthroplasty and (2) provides an update on pharmacologic VTE prophylaxis in regard to aspirin usage.

Dynamics of D-dimer in non-small cell lung cancer patients receiving radical surgery and its association with postoperative venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) occurs at a high rate after lung cancer surgery and can be attributed to various clinical risk factors. Here, we aimed to determine whether early detection of perioperative D-dimer and risk-stratified cutoff values would improve the diagnostic efficacy of VTE. METHODS: In this case-control study, D-dimer results were acquired from 171 non-small cell lung cancer (NSCLC) patients preoperatively and at the first, third, and fifth day after surgery. VTE was confirmed by Doppler ultrasonography and computer tomography pulmonary angiography (CTPA). Repeated measures ANOVA was used to analyze how D-dimer changed with time and the effects of risk factors on D-dimer levels. We then compared sensitivity, specificity and negative predictive value, using both adjusted and unadjusted cutoff values. RESULTS: VTE occurred in 23 patients (13.5%) of the study population. D-dimer levels increased unsustainably after lung cancer surgery (P < 0.001) due to a trough on the third day, and patients who had undergone thoracotomy (P < 0.001) and those at a more advanced tumor stage (P = 0.037) had higher D-dimer levels. Area under the curve of D-dimer was greatest on the third day (0.762 [P < 0.001, 95% CI: 0.643-0.882]). Applying stratified cutoff values improved the specificity in the video-assisted thoracoscopy surgery (VATS) (P = 0.004) and thoracotomy groups (P < 0.001). CONCLUSIONS: D-dimer levels elevated with fluctuation in NSCLC patients after surgery. Surgical options and tumor stages had an impact on D-dimer levels. With regard to VTE diagnosis, stratified cutoff values by these two factors showed better accuracy compared with a collective one.. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: The changing pattern of perioperative D-dimer levels in NSCLC patients who received surgical therapy in a major teaching hospital in Beijing, China was revealed. WHAT THIS STUDY ADDS: Risk-stratified D-dimer cutoff values adjusted to surgical methods and disease stages would benefit the exclusion of postoperative venous thromboembolism.

Resting heart rate and incident venous thromboembolism: the Multi-Ethnic Study of Atherosclerosis.

Objective: Venous thromboembolism (VTE) is associated with significant morbidity and mortality. Resting heart rate (RHR), which may be modifiable through lifestyle changes, has been shown to be associated with cardiovascular disease risk and with inflammatory markers that have been predictive of VTE incidence. Methods: We examined whether RHR is also associated with VTE incidence independent of these risk factors. We studied 6479 Multi-Ethnic Study of Atherosclerosis participants free from clinical VTE at baseline who had baseline RHR ascertained by 12-lead ECG. VTE events were recorded from hospital records and death certificates using International Classification of Diseases (ICD)-9 and ICD-10 codes. We categorised RHR as <60, 60-69, 70-79 and ≥80 bpm. We used Cox hazard models to determine the association of incident VTE by RHR. Results: Participants had mean (SD) age of 62 (10) years and RHR of 63 (10) bpm. RHR was cross-sectionally correlated with multiple inflammatory and coagulation factors. There were 236 VTE cases after a median follow-up of 14 years. Compared with those with RHR<60 bpm, the HR (95% CI) for incident VTE for RHR≥80 bpm was 2.08 (1.31 to 3.30), after adjusting for demographics, physical activity, smoking, diabetes and use of atrioventricular (AV)-nodal blockers, aspirin and anticoagulants, and remained significant after further adjustment for inflammatory markers (2.05 (1.29 to 3.26)). Results were similar after excluding those taking AV-nodal blocker medications. There was no effect modification of these associations by sex or age. Conclusion: Elevated RHR was positively associated with VTE incidence after a median of 14 years; this association was independent of several traditional VTE and inflammatory markers.

Analysis of patent, unstented lower extremity vein segment diameters in 266 patients with venous disease.

OBJECTIVE: The objective of this study was to characterize the average maximum diameters of widely patent lower extremity vein segments in patients with underlying venous disease and the demographic factors that affect these diameters. METHODS: Maximum axial diameters of each deep vein segment from the diaphragm to the knee were measured from computed tomography venography studies for all patients who underwent venous stent placement during a 20-year period at a single quaternary venous referral institution. Limbs containing only widely patent, unstented vein segments without variant anatomy were identified for inclusion. The final analysis involved diameter measurements from 870 imaging studies of 266 patients. Multivariate linear regression was used to identify factors associated with vein segment diameters. RESULTS: Average vein segment diameters ranged from 7.8 mm for the left and right femoral veins to 27.9 mm for the long axis of the suprarenal inferior vena cava. Multivariate linear regression demonstrated that women had larger IVC, common iliac vein, and external iliac vein diameters, whereas men had larger common femoral veins. Laterality, height, weight, and sex also had statistically significant associations with the diameters of select vein segments. CONCLUSIONS: This study provides an estimate of the average diameters of widely patent deep vein segments in the lower extremities from the diaphragm to the knees in patients with underlying venous disease and characterizes covariates that significantly affect vein diameter. These findings may help interventionalists better select devices for endovascular intervention.

Retrospective Evaluation of Venous Thromboembolism Prophylaxis in Elderly, High-Risk Trauma Patients.

BACKGROUND: Venous thromboembolism (VTE) risk increases with age. Scarce data exist for patients age ≥65 y. This study evaluated VTE incidence in elderly, high-risk trauma patients receiving unfractionated heparin (UFH) or enoxaparin chemoprophylaxis. MATERIALS AND METHODS: This retrospective, single-center, cohort study included trauma patients age ≥ 65 y with risk assessment profile (RAP) ≥ 5 who received UFH or enoxaparin chemoprophylaxis. The primary outcome was VTE incidence requiring therapeutic anticoagulation. An age-modified RAP (RAP-AM) was calculated as RAP without age distribution points. Logistic regression analyses were performed to identify independent predictors for VTE development and chemoprophylactic agent selection. Bleeding incidence compared packed red blood cells utilized. RESULTS: A total of 1090 patients were included (UFH, n = 655; enoxaparin, n = 435). VTE occurred in 39 (3.6%) patients with no difference between groups in proximal deep vein thrombosis (2.1% versus 3.0%, P = 0.52) or pulmonary embolism (1.2% versus 1.4%, P = 0.96). Weight ≥125 kg (OR 4.12, 95% CI 1.06-16.11) and RAP-AM ≥ 5 (OR 6.52, 95% CI 2.65-16.03) were independently associated with VTE development. Increasing age (OR 1.04, 95% CI 1.03-1.06), initiation ≤ 24 h (OR 2.17, 95% CI 1.66-2.84) and creatinine clearance ≤ 30 mL/min (OR 1.61, 95% CI 1.17-2.21) were independent predictors of receiving UFH whereas increasing ISS (OR 0.97, 95% CI 0.95-0.99) was associated with receiving enoxaparin. CONCLUSIONS: VTE incidence may be similar for high-risk, elderly trauma patients receiving UFH and enoxaparin chemoprophylaxis. Further research is necessary to determine noninferiority of UFH to enoxaparin in this patient population.

Thrombosis: Risk Factors Among Pediatric Patients With Cancer.

BACKGROUND: Thrombosis is the formation of a blood clot, or thrombus, inside of a blood vessel. Pediatric patients with cancer are at a higher risk of developing a thrombus because of their underlying disease, as well as their treatment and supportive care. Thrombosis can lead to significant morbidity, such as pulmonary embolism, in pediatric patients with cancer. OBJECTIVES: The purpose of this study is to identify risk factors for developing a thrombus among pediatric patients with cancer, along with treatment and prevention protocols. This study also examines the clinical nurse's role in preventing thrombosis and caring for pediatric patients who present with thrombosis. METHODS: The thrombosis literature was reviewed to identify risk factors, treatment regimens, and strategies for prevention. FINDINGS: Thrombosis in pediatric patients with cancer requires management of potential complications so that cancer treatment may continue.

[Tissue factors and venous thromboembolism in cancer patients].

Malignant tumor is one of the important acquired risk factors of venous thromboembolism (VTE). As the transmembrane receptor of coagulation factor Ⅶ and activated coagulation factor Ⅶa in vivo, tissue factor is the main initiator of exogenous coagulation. Tissue factor positive particles expressed and released by tumor cells enter the circulation and mediate thrombosis in patients with surgical treatment and distant tumor metastasis; the enhanced procoagulant activity of tissue factor after chemotherapy makes many cancer patients more likely to develop thromboembolic disease. Tissue factors can also be used to predict the risk of VTE in patients with pancreatic cancer, colorectal cancer and ovarian cancer.This article summarizes the role of tissue factor in VTE of cancer patients at different treatment stages, and further clarifies the relationship between tissue factor and the risk of VTE in cancer patients.

Pathologic up-regulation of TNFSF15-TNFRSF25 axis sustains endothelial dysfunction in unprovoked venous thromboembolism.

AIMS: The pathogenetic mechanisms underlying unprovoked venous thromboembolism (uVTE) are largely unknown. In this study, we investigated the molecular mechanisms involved in uVTE pathogenesis by using ex vivo expanded endothelial colony-forming cells (ECFCs), which represent a valuable non-invasive tool for the assessment of endothelial function. METHODS AND RESULTS: We isolated and expanded ECFCs from the peripheral blood of uVTE patients and observed that these cells underwent earlier senescence and showed lower growth rate compared with ECFCs obtained from healthy donors. Through microarray expression profiling, we demonstrated that 2905 genes were differentially expressed between patients and controls. Among them, the anti-angiogenic cytokine TNF superfamily member 15 (TNFSF15) and its death-receptor TNFRSF25 were up-regulated in uVTE ECFCs, and this finding was validated by RT-qPCR. TNFSF15 up-regulation was confirmed at the protein level in ECFC supernatants, and the in vivo relevance of these findings was further corroborated by demonstrating that also the plasmatic levels of TNFSF15 are increased in uVTE patients. After proving that exogenous TNFSF15 exerts pro-apoptotic and anti-proliferative activity on control ECFCs, we demonstrated through blocking experiments that TNFSF15 up-regulation contributes to impaired survival and proliferation of uVTE ECFCs. CONCLUSION: By providing evidence that TNFSF15 impairs ECFC functions crucial to endothelial repair, and that uVTE patients have increased TNFSF15 levels both ex vivo and in vivo, the results of this study suggest that pathologic up-regulation of TNFSF15-TNFRSF25 axis may contribute to uVTE pathogenesis, and may represent the target for novel therapeutic strategies aimed at preventing recurrences in uVTE patients.

Biomarkers of Cancer-Associated Thromboembolism.

Venous thromboembolism is known to be associated with an increase in morbidity and mortality in patients with malignancy. Predictive laboratory biomarkers of venous thromboembolism (VTE) have long been sought after to improve outcomes and help guide clinical decision making. Previously studied biomarkers include C reactive protein (CRP), tissue factor expressing microparticles (TF MP), D-dimer, soluble P-selectin (sP-selectin), plasminogen activator inhibitor 1 (PAI-1), factor VIII, platelet count, and leukocyte counts. This chapter will focus on these possible biomarkers for cancer-associated thrombosis (CAT) with particular emphasis on the pathophysiology behind thrombosis formation as well as data from clinical studies in patients with malignancy. The incorporation of the above biomarkers into risk assessment tools to predict CAT will also be reviewed, as will risk factors for recurrent VTE in patients with malignancy. Further studies are ongoing to develop readily available biomarkers that can be incorporated into future risk assessment models with the goal of reducing morbidity and mortality due to cancer-associated thrombosis.

Postoperative venous thromboembolism and mortality in patients with pancreatic surgery.

BACKGROUND AND OBJECTIVES: Pancreatic cancer is strongly associated with thrombosis. We investigated early postoperative venous thromboembolism (PVTE) mortality among patients with pancreatic surgery and compared outcomes in adenocarcinoma pancreatic cancer (ACPC) to non-adenocarcinoma pancreatic neoplasm (NACPN). METHODS: We analyzed a prospectively collected database of patients who underwent pancreatic cancer or neoplasm-related surgery. As NACPN is underrepresented in other studies, we selected NACPN patients and a random sample of ACPC patients. PVTE was defined as VTE occurring within 3 months of surgical intervention. Statistical analysis was performed using Cox proportional hazards regression. RESULTS: A total of 441 pancreatic surgery patients were included, with 331 ACPC and 110 NACPN. Median follow-up was 449 days during which 90 (20.4%) patients developed VTE. PVTE occurred in 53 (12.0%) patients, including 41 (12.4%) ACPC patients and 12 (10.9%) NACPN patients. Those with PVTE had 60% higher mortality rate. A multivariable analysis found that PVTE is an independent predictor of increased mortality (HR Adj, 1.6; 95% CI, 1.1-2.2; P < .01). The mortality impact was not consistent between ACPC (HR, 3.2; 95% CI, 1.3-7.9) and NACPN groups (HR, 1.3; 95% CI, 0.9-1.8). CONCLUSIONS: Postoperative venous thromboembolism is an independent predictor of increased mortality in pancreatic surgery, specifically in adenocarcinoma pancreatic cancer surgery.