Reduced calf muscle pump function is a risk factor for venous thromboembolism: a population-based cohort study.

The calf muscle pump is a major determinate of venous return in the legs but has not been studied as a risk factor for venous thromboembolism (VTE). A population-based cohort study of Olmsted County, Minnesota residents was performed using calf pump function (CPF) measurements from venous plethysmography studies from 1998 to 2015. Patients with a history of VTE were excluded. Nursing validated VTE outcomes from the Rochester Epidemiology Project were identified after the index study date, and patients with reduced CPF (rCPF) were compared with patients with normal CPF. A total of 1532 patients with recorded CPF (28% air and 72% strain gauge plethysmography) were included; 591 (38.5%) had normal CPF, 353 (23.0%) had unilateral rCPF, and 588 (38.3%) had bilateral rCPF. Any VTE occurred in 87 patients (5.7%) after a median follow-up of 11.7 years (range, 0-22.0 years). Comparing patients with bilateral reduced to bilateral normal CPF, the unadjusted hazard ratio (HR) for incident VTE was 2.0 (95% confidence interval [CI], 1.2-3.4) and after adjusting for age, BMI, and Charlson Comorbidity Index, the HR was 1.68 (95% CI, 0.98-2.89). The adjusted HR for ipsilateral deep vein thrombosis was evaluated in 3064 legs comparing legs with reduced to normal CPF and was 1.71 (95% CI, 1.03-2.84). Mortality was significantly higher in both the bilateral (P < .001) and unilateral (P < .001) rCPF groups compared with normal CPF. Our results demonstrate that CPF is a risk factor for VTE in an otherwise low-risk ambulatory population and might be a useful component in risk stratification models.

Causal effect of renal function on venous thromboembolism: a two-sample Mendelian randomization investigation.

Whether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10-8) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.

COVID-19 and Respiratory System Disorders: Current Knowledge, Future Clinical and Translational Research Questions.

The severe acute respiratory syndrome coronavirus-2 emerged as a serious human pathogen in late 2019, causing the disease coronavirus disease 2019 (COVID-19). The most common clinical presentation of severe COVID-19 is acute respiratory failure consistent with the acute respiratory distress syndrome. Airway, lung parenchymal, pulmonary vascular, and respiratory neuromuscular disorders all feature in COVID-19. This article reviews what is known about the effects of severe acute respiratory syndrome coronavirus-2 infection on different parts of the respiratory system, clues to understanding the underlying biology of respiratory disease, and highlights current and future translation and clinical research questions.

Clinical characteristics and outcomes of patients with venous thromboembolism according to diagnosis on weekends versus on weekdays.

There are uncertainties on the influence of the days of diagnosis in a week (weekends versus weekdays) on clinical outcomes in patients with acute venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT). The COMMAND VTE registry is a multicenter cohort study enrolling 3027 consecutive patients with acute symptomatic VTE. The current study population consisted of 337 patients diagnosed on weekends and 2690 patients diagnosed on weekdays. We compared the clinical characteristics, management strategies and 30-day outcomes between the 2 groups. The patients diagnosed on weekends more often presented with PE (72% vs. 55%, P < 0.001), and with more severe hemodynamic condition for PE patients. The patients diagnosed on weekends more often received initial parenteral anticoagulation therapy and thrombolysis than those diagnosed on weekdays. The cumulative 30-day incidence of all-cause death was not significantly different between the two groups among PE patients (diagnosis on weekends: 6.2% vs. diagnosis on weekdays: 6.5%, P = 0.87), as well as among DVT patients (0.0% vs. 1.5%, P = 0.24). The most frequent cause of deaths was fatal PE in both groups among PE patients. The risks for recurrent VTE and major bleeding at 30-day were not significantly different between the 2 groups among PE patients, nor among DVT only patients. In conclusion, the VTE patients diagnosed on weekends presented more often with PE, and with more severe condition for PE patients. Nevertheless, the risk for 30-day mortality was not significantly different between patients diagnosed on weekends and on weekdays.

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.

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.

Oral Contraceptives and Venous Thromboembolism: Focus on Testing that May Enable Prediction and Assessment of the Risk.

Combined oral contraceptives (COCs) induce several changes in the levels of coagulation factors. The levels of procoagulant factors are often increased, while levels of anticoagulant factors are decreased. Fibrinolysis is also affected, even if the effect seems to be more counterbalanced by opposite regulation of profibrinolytic and antifibrinolytic factors. These effects on hemostasis are more pronounced with third- or fourth-generation COC compared with second-generation COC. Venous thromboembolism (VTE) risk increases when multiple risk factors, including genetic and environmental, are present simultaneously. COC use causes changes in coagulation that modify the prothrombotic state induced by preexisting hemostatic alterations in a supra-additive manner. Therefore, testing appears to be of importance not only before implementing COC but also to monitor any potential thrombogenicity induced by COC therapy. Inherited genetic factors, such as factor V Leiden, G20210A prothrombin mutation, antithrombin, protein C or protein S deficiencies, non-O blood group, as well as CYP2C9*2 and the rs4379368 mutations, have all been identified as genetic predictive risk factors of VTE in women. Nevertheless, the screening of these genetic biomarkers is not capable of assessing the phenotypic expression of the risk. This review will focus on the different options for screening the thrombogenic status in this population. Specific attention will be given to the endogenous thrombin potential-based activated protein C resistance, a test aiming at assessing the thrombogenicity induced by hormonal therapies and inherited or acquired thrombophilia.

Reduced Physical Activity Levels in Children after a First Episode of Acute Venous Thromboembolism.

OBJECTIVE: To assess physical activity in children following acute venous thromboembolism (VTE), examine predictors of reduced physical activity and its relationship to post-thrombotic syndrome. STUDY DESIGN: Using a case-control study design, we enrolled 44 children with acute VTE, and compared physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire and health-related quality of life at 3 and 6 months after diagnosis relative to 44 age- and sex-matched controls. We assessed post-thrombotic syndrome scores using the Manco-Johnson Instrument to measure symptoms and signs attributed to sequelae of DVT in cases. RESULTS: The physical activity of VTE cases was decreased at 3 months after diagnosis (36.6 ± 29.0 vs 56.8 ± 25.0; P = .002), but the differences disappeared at 6 months (57.5 ± 39.0 vs 56.8 ± 25.0; P = .60) relative to controls. At 3 and 6 months after diagnosis, overall, 70% and 50% of VTE cases were below their pre-VTE physical activity levels; providers did not address physical activity in the majority. In multivariable analysis, physical activity of cases was lower by 32 points for completely veno-occlusive thrombosis at diagnosis, 11 points for a diagnosis of pulmonary embolism relative to DVT, and increased by 0.72 points for every unit increase in health-related quality of life score. Physical activity at 3 months after diagnosis did not predict the short-term risk of post-thrombotic syndrome. CONCLUSIONS: VTE limits physical activity in children in the first 3 months after the acute event, but the differences were nonexistent at 6 months. Only 50 percent of VTE survivors resume their pre-VTE physical activity levels within 6 months after diagnosis.

Trends of venous thromboembolism risk before and after diagnosis of gout: a general population-based study.

OBJECTIVE: To estimate the overall risk and the temporal trend of venous thromboembolism (VTE), deep vein thrombosis (DVT), and pulmonary embolism (PE) before and after gout diagnosis in an incident gout cohort compared with the general population. METHODS: We conducted a matched cohort study using a province-wide population-based administrative health database in Canada. We calculated incidence rates (IRs) and multivariable adjusted hazard ratios (HRs) for the risk of VTE, DVT and PE before and after gout diagnosis. RESULTS: Among 130 708 incident individuals with gout (64% male, mean age 59 years), 2071 developed VTE, 1377 developed DVT and 1012 developed PE. IRs per 1000 person-years for gout were 2.63, 1.74 and 1.28 compared with 2.03, 1.28 and 1.06 for non-gout, respectively. The fully adjusted HRs (95% CI) for VTE, DVT and PE were 1.22 (1.13, 1.32), 1.28 (1.17, 1.41) and 1.16 (1.05, 1.29). For the pre-gout period, the fully adjusted HRs (95% CI) were 1.51 (1.38, 1.64), 1.55 (1.40, 1.72) and 1.47 (1.31, 1.66) for VTE, DVT and PE. During the third, second and first years preceding gout, the fully adjusted HRs for VTE were 1.44, 1.56 and 1.62. During the first, second, third, fourth and fifth years after gout, the fully adjusted HRs were 1.63, 1.29, 1.33, 1.28 and 1.22. Similar trends were also seen for DVT and PE. CONCLUSION: Increased risks of VTE, DVT and PE were found both before and after gout diagnosis. The risk increased gradually before gout, peaking in the year prior to diagnosis, and then progressively declined. Gout-associated inflammation may contribute to venous thrombosis risk.

How I use catheter-directed interventional therapy to treat patients with venous thromboembolism.

Patients who present with severe manifestations of acute venous thromboembolism (VTE) are at higher risk for premature death and long-term disability. In recent years, catheter-based interventional procedures have shown strong potential to improve clinical outcomes in selected VTE patients. However, physicians continue to be routinely faced with challenging decisions that pertain to the utilization of these risky and costly treatment strategies, and there is a relative paucity of published clinical trials with sufficient rigor and directness to inform clinical practice. In this article, using 3 distinct clinical scenario presentations, we draw from the available published literature describing the natural history, pathophysiology, treatments, and outcomes of VTE to illustrate the key factors that should influence clinical decision making for patients with severe manifestations of deep vein thrombosis and pulmonary embolism. The results of a recently completed pivotal multicenter randomized trial are also discussed.

Acute pulmonary embolism unmasking underlying chronic thromboembolic pulmonary hypertension and iliac vein compression syndrome.

We describe the case of a 72-year-old gentleman who was referred to our institution for management of cardiogenic shock from a massive pulmonary embolism. Right heart catheterization revealed a low cardiac index and markedly elevated pulmonary pressures, suggested long-standing venous thromboembolic (VTE) disease that evolved into chronic thromboembolic pulmonary hypertension (CTEPH). The patient was cannulated to veno-arterial extra-corporeal membrane oxygenation and eventually treated with pulmonary embolectomy and thromboendarterectomy. Subsequently discovered inferior vena cava clot and left iliac deep vein thrombosis were treated with suction and mechanical thrombectomy. Intravascular ultrasound of the left lower extremity venous system identified iliac vein compression syndrome (IVCS) as the culprit of the patient's VTE and CTEPH. A left iliac stent was placed and the patient was discharged on Warfarin for anticoagulation. The case illustrates the rapidly expanding armamentarium for VTE treatment and proposes IVCS as a new, potentially underrecognized risk factor for CTEPH.

High Rate of Fibrinolytic Shutdown and Venous Thromboembolism in Patients With Severe Pelvic Fracture.

BACKGROUND: Trauma patients with pelvic fractures have a high rate of venous thromboembolism (VTEs). The reason for this high rate is unknown. We hypothesize that fibrinolysis shutdown (SD) predicts VTE in patients with severe pelvic fracture. METHODS: Retrospective chart review of trauma patients who presented with pelvic fracture from 2007 to 2017 was performed. Inclusion criteria were injury severity score > 15, abdomen/pelvis abbreviated injury scale >/= 3, blunt mechanism, admission citrated rapid thrombelastography (TEG). Fibrinolytic phenotypes were defined by fibrinolysis on citrated rapid TEG as hyperfibrinolysis, physiologic lysis, and SD. Univariate analysis of TEG measurements and clinical outcomes, followed by multivariable logistic regression (MV) with stepwise selection, was performed. RESULTS: Overall, 210 patients were included. Most patients (59%) presented in fibrinolytic shutdown. VTE incidence was 11%. There were no significant differences in fibrinolytic phenotypes or other TEG measurements between those who developed VTE and those who did not. There was a higher rate of VTE in patients who underwent pelvic external fixation or resuscitative thoracotomy. On MV, pelvic fixation and resuscitative thoracotomy were independent predictors of VTE. CONCLUSIONS: In severely injured patients with pelvic fractures, there was a high rate of VTE and the majority presented in SD. However, we were unable to correlate initial SD with VTE. Ultimately, the high rate of VTE in this patient population supports the concept of implementing VTE chemoprophylaxis measures as soon as hemostasis is achieved.

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.

Implementation of automatic data extraction from an enterprise database warehouse (EDW) for validating pediatric VTE decision rule: a prospective observational study in a critical care population.

Multiple clinical risk prediction tools for hospital acquired venous thromboembolism (HA-VTE) have been developed. The objectives of this study were to develop and assess the feasibility of data extraction from Electronic Medical Records (EMR) from an enterprise database warehouse (EDW) and to test the validity of a previously developed Pediatric Clot Decision Rule (PCDR). This single-center prospective observational cohort study was conducted between March 2016 and March 2017 and included eligible patients admitted to the intensive care units. Risk score was calculated using the PCDR tool. Sensitivity, specificity, positive and negative predicted value (PPV and NPV) were calculated based on a cut-point of 3. A total of 2822 children were eligible for analysis and 5.1% (95% CI 4.2-6.2) children had a PCDR score of 3. Children with PCDR score of ≥ 3 had a 3 times higher odd of developing VTE compared to those with scores < 3 (OR 3.1; 95% CI 1.93-4.80; p < 0.001). The model performance showed that at the cutoff point of ≥ 3, both the specificity and sensitivity of the PCDR in predicting VTE was 69% and NPV of 98%. We successfully demonstrated using our EDW to populate a research database using an automatic data import. A PCDR score of ≥ 3 was associated with VTE. Collaboration through large registries will be useful in informing practices and guidelines for rare disorders such as pediatric VTE.

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.

[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.

Frequency, Predictors, and Impact of Combined Antiplatelet Therapy on Venous Thromboembolism in Patients With Symptomatic Atherosclerosis.

BACKGROUND: Observational studies suggest that symptomatic atherosclerosis may be associated with risk of venous thromboembolism (VTE). Prior randomized studies have demonstrated a significant reduction in recurrent VTE with aspirin monotherapy. Whether VTE risk is associated with more severe symptomatic atherosclerosis and more intensive antiplatelet therapy reduces VTE risk beyond aspirin monotherapy is unknown. METHODS: TRA2P-TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction) (vorapaxar) and PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) (ticagrelor) were blinded, randomized placebo-controlled trials of antiplatelet therapy for the prevention of ischemic events in stable patients with symptomatic atherosclerosis. Two blinded vascular specialists systematically identified symptomatic venous thromboembolic events in both trials. RESULTS: Of 47 611 patients with stable vascular disease followed for 3 years in both studies there were 343 VTE events in 301 patients (Kaplan-Meier rate at 3 years, 0.9% for placebo). The risk of VTE was independently associated with age, body mass index, polyvascular disease, chronic obstructive pulmonary disease, and malignancy. The burden of atherosclerosis manifested as an increasing number of symptomatic vascular territories was associated with a graded increase in the 3-year rates of VTE (0.76% for 1, 1.53% for 2, and 2.45% for 3 territories). More intensive antiplatelet therapy (vorapaxar and ticagrelor pooled) significantly reduced the risk of VTE by 29% compared with background antiplatelet therapy, from 0.93% to 0.64% at 3 years (hazard ratio, 0.71; 95% confidence interval, 0.56-0.89; P=0.003). CONCLUSIONS: The rate of VTE in patients with atherosclerosis is ≈0.3% per year while on treatment with ≥1 antiplatelet agent, with increased risk independently associated with the number of symptomatic vascular territories. More intensive antiplatelet therapy reduces the risk of VTE. These data suggest a relationship between atherosclerosis burden and VTE risk, and they support inclusion of VTE as a prospective end point in long-term secondary prevention trials evaluating the risks and benefits of antiplatelet therapies in patients with atherosclerosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01225562.

Obstructive sleep apnoea and venous thromboembolism: pathophysiological links and clinical implications.

Obstructive sleep apnoea (OSA) and pulmonary embolism (PE) remain major health issues worldwide. Data from pathophysiological studies suggest that both intermittent hypoxia and sleep fragmentation are associated with increased blood coagulability, endothelial dysfunction and venous stasis. There is growing evidence that OSA is potentially prevalent in and a risk factor for PE. Conversely, patients with acute PE have two to four times greater risk of moderate-to-severe OSA. The role of continuous positive airway pressure (CPAP) treatment in improving clinically meaningful outcomes in PE patients remains unclear, although some authors have suggested that CPAP could improve the hypercoagulability state and normalise circadian alterations in some of the coagulation molecules, as observed in patients with OSA. Emerging research highlights the complex interdependent relationships between OSA and PE, emphasising the need for rigorous, well-powered trials that address the impact of OSA and its treatment on the prevention and management of PE. Undoubtedly, these will require closer collaboration between the sleep medicine and clinical/venous thromboembolism communities.

Management of moderate and severe traumatic brain injury.

Traumatic brain injury (TBI) is a common disorder with high morbidity and mortality, accounting for one in every three deaths due to injury. Older adults are especially vulnerable. They have the highest rates of TBI-related hospitalization and death. There are about 2.5 to 6.5 million US citizens living with TBI-related disabilities. The cost of care is very high. Aside from prevention, little can be done for the initial primary injury of neurotrauma. The tissue damage incurred directly from the inciting event, for example, a blow to the head or bullet penetration, is largely complete by the time medical care can be instituted. However, this event will give rise to secondary injury, which consists of a cascade of changes on a cellular and molecular level, including cellular swelling, loss of membrane gradients, influx of immune and inflammatory mediators, excitotoxic transmitter release, and changes in calcium dynamics. Clinicians can intercede with interventions to improve outcome in the mitigating secondary injury. The fundamental concepts in critical care management of moderate and severe TBI focus on alleviating intracranial pressure and avoiding hypotension and hypoxia. In addition to these important considerations, mechanical ventilation, appropriate transfusion of blood products, management of paroxysmal sympathetic hyperactivity, using nutrition as a therapy, and, of course, venous thromboembolism and seizure prevention are all essential in the management of moderate to severe TBI patients. These concepts will be reviewed using the recent 2016 Brain Trauma Foundation Guidelines to discuss best practices and identify future research priorities.

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.