A systematic review of the timing of therapeutic anticoagulation in adult patients with acute traumatic brain injury: narrative synthesis of observational studies.

Traumatic brain injury (TBI) presents complex management scenarios, particularly in patients requiring anticoagulation for concurrent conditions such as venous thromboembolism (VTE) or atrial fibrillation (AF). A systematic search of PubMed/MEDLINE, Embase, and the Cochrane Library databases was conducted to identify relevant studies. Inclusion criteria encompassed studies assessing the effects of anticoagulation therapy on outcomes such as re-hemorrhage, hematoma expansion, thrombotic events, and hemorrhagic events in TBI patients with subdural hematomas (SDH). This systematic review critically addresses two key questions: the optimal timing for initiating anticoagulation therapy and the differential impact of this timing based on the type of intracranial bleed, with a specific focus on subdural hematomas (SDH) compared to other types. Initially screening 508 articles, 7 studies met inclusion criteria, which varied in design and quality, precluding meta-analysis. The review highlights a significant knowledge gap, underscoring the lack of consensus on when to initiate anticoagulation therapy in TBI patients, exacerbated by the need for anticoagulation in the presence of VTE or AF. Early anticoagulation, particularly in patients with SDH, may elevate the risk of re-hemorrhage, posing a clinical dilemma. Evidence on whether the type of intracranial hemorrhage influences outcomes with early anticoagulation remains inconclusive, indicating a need for further research to tailor management strategies effectively. This review underscores the scarcity of high-quality evidence regarding anticoagulation therapy in TBI patients with concurrent conditions, emphasizing the necessity for well-designed prospective studies to elucidate optimal management strategies for this complex patient population.

Duration of anticoagulation of venous thromboembolism.

Venous thromboembolism (VTE) is a common, serious condition that requires anticoagulation for at least three months to prevent recurrence and long-term complications. After this initial period, the decision to continue or stop anticoagulation depends on the balance between the risk of recurrent VTE and the risk of bleeding. Established guidelines suggest short-term anticoagulation for VTE caused by transient factors and indefinite anticoagulation for recurrent or cancer-associated VTE. However, for a first unprovoked VTE, decision-making remains challenging. Current predictive scores for recurrence and bleeding are not sufficiently reliable, and the safety and efficacy of reduced-dose anticoagulation remain unclear. In the future, precision and patient-centred medicine may improve treatment decisions in this area.

Evaluating the Risk of Venous Thromboembolism in Transfeminine and Gender Diverse People: A Retrospective Analysis.

OBJECTIVE: The risk of venous thromboembolism (VTE) with feminizing gender-affirming hormone therapy is an area of concern. This analysis aimed to assess whether gender-affirming hormone therapy and other potential risk factors are associated with VTE in transfeminine and gender diverse individuals. METHODS: We conducted a chart review of 2126 transfeminine and gender diverse adults receiving care within a large urban health system. The primary outcomes were the prevalence of VTE and odds ratios for the association of VTE with insurer, use of estrogen, and select comorbidities. RESULTS: A history of VTE was documented in 0.8% of the cohort. Those with a history of VTE were older (P < .001), more often self-identified as Hispanic or Black compared to White or Asian (P < .05) and were more likely to have Medicaid or Medicare (P < .01) when compared to those without a history of VTE. The prevalence of hyperlipidemia (P < .001), diabetes mellitus (P < .05), and hypercoagulable conditions (P < .001) were all greater in the positive VTE group. Hyperlipidemia (P < .001), diabetes mellitus (P < .05), and insurer (P < .05) were associated with increased odds of VTE in univariate analyses. None of the exposure variables analyzed were associated with VTE when controlling for age, race, and the number of comorbidities. CONCLUSIONS: The prevalence of VTE in our cohort was lower than previously observed. VTE was not associated with any one risk factor, including estrogen use, when controlling for age, race, and the number of comorbidities. Those of advanced age and those with multiple cardiometabolic comorbidities may benefit from increased surveillance and mitigation of modifiable risk factors.

Direct Oral Anticoagulants in Antiphospholipid Syndrome-Associated Venous Thromboembolism: Real World Evidence.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in patients with antiphospholipid syndrome-associated venous thromboembolism (APS-VTE) remain uncertain. We aimed to evaluate efficacy and safety of DOACs in patients with APS-VTE. METHODS: Using the Korean Health Insurance Review and Assessment Service database, we retrospectively identified all APS-VTE cases. We examined the VTE recurrence, arterial thrombosis, death and bleeding in patients who received DOACs compared with warfarin for therapeutic anticoagulation. RESULTS: Of all the VTE cases (n = 84,916) detected between 2014 and 2018, patients with APS-VTE (n = 410) accounted for 0.48%. Most patients with APS-VTE (73%) were aged < 60 years. The recurrent VTE occurred in 8 of 209 patients (3.8%) who received DOACs and in 7 of 201 (3.5%) who received warfarin (relative risk [RR], 1.099; 95% confidence interval [CI], 0.41-2.98; P = 1.000). The arterial thrombosis (ATE) occurred in 8 of 209 patients (3.8%) who received DOAC and in 20 of 201 (10%) who received warfarin (RR, 0.385; 95% CI, 0.17-0.85; P = 0.024). The composite outcomes of VTE recurrence, ATE, or mortality were significantly lower in patients (9.1%) on DOAC than in those (16.3%) on warfarin (RR, 0.537; 95% CI, 0.32-0.91; P = 0.028). The bleeding outcome occurred in 7 of 209 (3.4%) patients in the DOACs group and 7 of 201 (3.5%) patients in the warfarin group (RR, 0.96; 95% CI, 0.34-2.69; P = 0.840). CONCLUSION: In patients with APS-VTE, DOACs group showed comparable rates of recurrent VTE, bleeding, and deaths, but a significantly lower incidence of ATE and composite outcomes compared with the warfarin group in Korea.

Intensive care treatment in acute pulmonary embolism in Germany, 2016 to 2020: a nationwide inpatient database study.

Background: Pulmonary embolism (PE) is a potentially life-threatening condition. Admission and treatment in the intensive care unit (ICU) is an important element in critically ill PE patients. Objectives: We aimed to identify risk factors for ICU admission and differences in patient profiles regarding risk factors and comorbidities between PE patients who had to be admitted to an ICU and those who were treated in a normal ward without ICU. Methods: We used the German nationwide inpatient sample to analyze all hospitalizations of PE patients in Germany from 2016 to 2020 stratified for ICU admission. Results: Overall, 484,859 hospitalized PE patients were treated in German hospitals from 2016 to 2020. Among these, 92,313 (19.0%) were admitted to ICU. Patients treated in ICU were younger (69.0 [IQR, 58.0-78.0] vs 72.0 [IQR, 60.0-80.0] years; P < .001) and had higher prevalence of cardiovascular risk factors and comorbidities. In-hospital case fatality rate was elevated in PE patients treated in ICU (22.7% vs 10.7%; P < .001), and ICU admission was independently associated with increased in-hospital case fatality (odds ratio [OR], 2.54; 95% CI, 2.49-2.59; P < .001). Independent risk factors for ICU admission comprised PE with imminent or present decompensation (OR, 3.30; 95% CI, 3.25-3.35; P < .001), hemodynamic instability (OR, 4.49; 95% CI, 4.39-4.59; P < .001), arterial hypertension (OR, 1.20; 95% CI, 1.18-1.22; P < .001), diabetes mellitus (OR, 1.16; 95% CI, 1.14-1.18; P < .001), obesity (OR, 1.300; 95% CI, 1.27-1.33; P < .001), surgery (OR, 2.55; 95% CI, 2.50-2.59; P < .001), stroke (OR, 2.86; 95% CI, 2.76-2.96; P < .001), pregnancy (OR, 1.45; 95% CI, 1.21-1.74; P < .001), heart failure (OR, 1.74; 95% CI, 1.71-1.77; P < .001), atrial fibrillation/flutter (OR, 1.69; 95% CI, 1.66-1.73; P < .001), chronic obstructive pulmonary disease (OR, 1.21; 95% CI, 1.18-1.24; P < .001), and renal failure (OR, 1.92; 95% CI, 1.88-1.95; P < .001). Conclusion: ICU treatment is an important element in the treatment of PE patients. Besides hemodynamic compromise, cardiovascular risk factors, stroke, pregnancy, and cardiopulmonary as well as renal comorbidities were independent predictors of ICU admission. Necessity of ICU admission was afflicted by increased case fatality.

Incidence and risk factors for thromboembolic events in pediatric-onset inflammatory bowel disease: A French population-based study.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at higher risk of thromboembolic events (TE). In pediatric-onset IBD, more data on incidence and risk factors of venous (VTE) and arterial events (ATE) at the population level are needed to guide thromboprophylaxis. METHODS: All patients aged ≤ 16 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 1988 and 2011 in the prospective EPIMAD population-based registry were followed until 2013. Every TE occurring during the follow-up period was included. RESULTS: A total of 1,344 patients were included: 1,007 with CD and 337 with UC, and a median diagnosis age of 14.3 years. After a median follow-up of 8.3 years, 2 (0.15 %) ATE and 15 (1.1 %) VTE occurred at median age of 20.4 years. The global incidence rate of thromboembolic events was 1.32 per 1000 person-years. Periods of active disease (HR=8.4, p = 0.0002), the 3-month-period following surgery (HR=16.4, p = 0.0002) and hospitalization (HR=21.7, p < 0.0001) were found to be associated with an increased risk of VTE. A lower rate of VTE was found in patients treated with 5-aminosalicylates (HR=0.1, p = 0.002). CONCLUSION: The risk of TE was low in this population. VTE were strongly associated with active disease, surgery and hospitalization.

Clinical characteristics and thrombophilia associated gene variants in Egyptians with unprovoked venous thromboembolism: three centers experience.

BACKGROUND: Thrombophilias are characterized by excessive venous and arterial thrombosis at regular or unusual sites. It may result from inherited, acquired, or a combination. Hereditary thrombophilia (HT) is detected in 30-40% of patients with thromboembolism. Venous/arterial thrombosis is considered a multifactorial disorder, some patients may have more than one risk factor which may be transient or permanent. OBJECTIVES: Assess the clinical characteristics of patients with unprovoked thromboembolic events and the role of inherited thrombophilia as a causative or additive risk factor. METHODS: 210 consecutive adult patients with unprovoked thromboembolic events were reviewed in hematology units at three tertiary Egyptian centers between September 2022 and September 2023. The diagnosis of thromboembolic events was confirmed by clinical and radiological findings. Laboratory screening for thrombophilia-associated. RESULTS: Among our patients, 53(25.2%) patients presented with isolated DVT, followed by portal vein thrombosis, 32(15.2%) had a pulmonary embolism, and sagittal sinus thrombosis was developed in 23(10.9%) patients. CONCLUSION: Younger people who experience spontaneous thromboembolism run the chance of having hereditary thrombophilia; the more mutations discovered, the higher the risk of thrombosis; the lower leg and deep vein thrombosis were the most common sites. Lastly, MTHFR C677T was the most common polymorphism in Egyptians, detected in almost half of the cases.

Development of an assay using a modified coagulation factor V to measure protein S activity.

BACKGROUND: Protein S (PS) is an anticoagulant that functions as a cofactor for activated protein C and the tissue factor pathway inhibitor. PS deficiency is a risk factor for venous thromboembolism. PS activity is commonly measured using clot-based assays involving fibrin and thrombin production, but improvements are needed. OBJECTIVES: To develop a new assay for measuring plasma PS activity by quantifying the amount of activated coagulation factor (F)V cleaved by activated protein C. METHODS: We designed a recombinant, modified FV (FVm) that mimicked FVa. We analyzed 160 purposively selected plasma samples from the Biobank of the National Cerebral and Cardiovascular Center. RESULTS: The assay using mixed normal and PS-deficient plasma detected FVm cleavage in a PS concentration-dependent manner. The correlation between PS activity, measured using the FVm cleavage assay, and free PS antigen levels was relatively weak. We then sequenced all exons of PROS1 from 47 subjects with <60% activity in either the FVm cleavage assay or the clot-based assay. Nonsynonymous variants were identified in 12 of 24 subjects with <60% activity in both assays and in 2 of 7 subjects with <60% activity in the FVm cleavage assay alone. No variants were identified in 16 subjects with <60% activity in the clot-based assay alone. Unlike the clot-based assay, the FVm cleavage assay was not affected by the presence of rivaroxaban in the plasma. CONCLUSION: An assay using the FVm substrate may be less susceptible to interference and provide a more accurate evaluation of plasma PS activity than clot-based assays.

Venous thromboembolism prophylaxis prescribing patterns for patients with orthopedic trauma: a clinical vignette survey.

Background: A recent clinical trial suggested aspirin is a viable alternative to enoxaparin for venous thromboembolism (VTE) prophylaxis in patients after orthopedic trauma. The initial impact of these findings on VTE prophylaxis prescribing is unknown. The study aimed to evaluate stated VTE prophylaxis prescribing patterns among clinicians who treat patients after orthopedic trauma. Methods: For this clinical vignette survey, we recruited surgeons and advanced practice providers who prescribed VTE prophylaxis to patients with orthopedic trauma across 40 states. Clinicians were shown seven clinical vignettes describing hypothetical patients with orthopedic trauma based on their fracture type, treatment, VTE risk factors, additional injuries and health insurance status. We assessed the stated VTE prophylaxis medications prescribed in-hospital and at discharge, patient factors associated with changes in medication prescribing preferences and practice variation by specialty and provider training. Results: Among the 287 respondents, the median age was 43 years (IQR, 38-50), and 154 (weighted average, 63%) were men. For in-hospital VTE prophylaxis, enoxaparin was prescribed in 83% of the presented scenarios, and aspirin was prescribed in 13% (p<0.001). At discharge, aspirin was prescribed more frequently than enoxaparin (50% vs 41%, p<0.001). Healthcare providers with an aspirin discharge preference were 12% more likely to switch to enoxaparin if the patient had additional VTE risk factors, such as obesity (95% CI 4% to 19%, p=0.005). Conclusions: Despite new clinical evidence, in-hospital VTE prophylaxis prescribing practices for patients with orthopedic trauma remain consistent with those reported a decade ago. However, compared with historical data, clinicians have significantly increased their preference for aspirin for thromboprophylaxis at discharge-unless the patient has additional thromboembolic risk factors. Level of evidence: 5-expert opinion.

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Cushing syndrome (CS) is an endocrine-metabolic disorder characterized by hypercortisolism. Elevated cortisol levels can induce a hypercoagulable state, increasing the risk of venous thromboembolism (VTE). Both pituitary-origin Cushing disease (CD) and adrenal-origin non-adrenocorticotropic hormone (ACTH)-dependent CS are primarily treated with surgery. The dual impact of surgery and the underlying disease further elevates the risk of VTE, potentially leading to pulmonary embolism, which poses a severe threat to patient survival. Additionally, CS patients in a hypercoagulable state have a higher incidence of cardiovascular diseases and VTE, and even mortality compared with the general population. Untreated active CS patients have a 17.8-fold increased risk of VTE compared to the general population. In recent years, the relationship between the hypercoagulable state in CS and VTE has garnered increasing attention from clinicians. A better understanding of the clinical epidemiological characteristics, pathophysiological mechanisms, and clinical prevention and treatment of VTE and pulmonary embolism in CS can provide valuable references for the standardized use of prophylactic anticoagulant therapy in CS patients.

Impact of Estetrol Combined with Drospirenone on Blood Coagulation and Fibrinolysis in Patients with Endometriosis: A Multicenter, Randomized, Open-Label, Active-Controlled, Parallel-Group Study.

Venous thromboembolism is a serious safety concern in women using combined oral contraceptives; ethinyl estradiol (EE) is widely used as an estrogen. Estetrol (E4) is a native estrogen with selective tissue activity and exclusively produced by the fetal liver. This study used a multicenter, randomized, open-label, active-controlled, parallel-group design to evaluate the effects of E4 combined with drospirenone (DRSP) on coagulation and fibrinolysis in Japanese patients with endometriosis. Participants were randomized to receive either E4 15 mg/DRSP 3 mg or EE 20 µg/DRSP 3 mg for 12 weeks. E4/DRSP and EE/DRSP were administered orally once a day in a cyclic regimen, ie, 24-day active use followed by a 4-day hormone-free period, and a flexible extended regimen, respectively, and blood coagulation and fibrinolysis markers were measured. The effect on coagulation and fibrinolysis was considerably less in the E4/DRSP group than in the EE/DRSP group. Major anticoagulant proteins, protein S (free, total) and tissue factor pathway inhibitor (free), were reduced following EE/DRSP treatment. Consequently, thrombin generation determined by the activated protein C sensitivity ratio was increased by approximately 4-fold in the EE/DRSP group than in the E4/DRSP group. Eventually, the fibrinolysis cascade was triggered to compensate for disturbed coagulation, and D-dimer levels were 4.7-fold higher in the EE/DRSP group than in the E4/DRSP group. This study demonstrated that the effect of E4/DRSP on the blood coagulation and fibrinolysis cascades was significantly less than that of EE/DRSP in participants with endometriosis, a disease of women of advanced and reproductive age (jRCT2080225090, https://jrct.niph.go.jp/en-latest-detail/jRCT2080225090).

Dual direct oral anticoagulant therapy in challenging thrombosis: a case series.

Background: While anticoagulation therapy is highly effective at treating venous thromboembolism, some patients can develop rapidly progressive thrombosis in multiple organs or sites despite therapeutic anticoagulation. Effective strategies to manage life-threatening thrombosis in these patients are elusive. Objectives: We describe our experience using dual direct oral anticoagulant (DOAC) therapy with a factor (F)Xa inhibitor (such as rivaroxaban or apixaban) and a FIIa inhibitor (dabigatran) for refractory cases of thrombosis. Methods: A retrospective chart review of all patients treated with simultaneous dabigatran and an oral FXa inhibitor at our institution was conducted. We included all patients over the age of 18. The study was approved by the University of British Columbia Research Ethics Board (REB number: H23-02575). Results: Eight patients were included. All patients initiated standard therapeutic anticoagulation upon diagnosis of acute venous thromboembolism with a median of 3 breakthrough thrombotic events prior to dual DOAC use. Five patients had a positive heparin-induced thrombocytopenia screen, but only 2 had heparin-induced thrombocytopenia confirmed on serotonin release assay testing. There were no recurrent deep vein thrombosis, pulmonary embolism, or bleeding events during dual DOAC use. Most patients ultimately transitioned to a single oral FXa inhibitor. Conclusion: Dual DOAC therapy may be a useful strategy for managing challenging thrombosis cases resistant to conventional anticoagulation. Further research is warranted to validate these findings and explore the broader applicability of dual DOAC therapy in challenging thrombotic scenarios.

Psychological aspects in young people with venous thromboembolic disease, preliminary report.

BACKGROUND: The decline in the mental well-being of young adults following an episode of venous thromboembolism may be related to the uncertainty of long-term health and fear of recurrence. In recent years, post-pulmonary embolism syndrome has gained acceptance, however, less attention has been given to the psychological impact on young patients after venous thromboembolism. This study explores the prevalence, type, and severity of psychological disorders of patients following venous thromboembolism. METHODS: A retrospective observational cohort study was performed of over 18-year-old patients diagnosed with venous thromboembolism followed in the Vascular Medicine Service at Hospital Privado de Córdoba, Argentina from July 2020 to October 2021. Due to the COVID-19 pandemic, virtual interviews were conducted using two pre-established questionnaires administered by the same psychiatrist. The first questionnaire gathered personal data, clinical history, and mental health information, while the second, evaluated mood disorders using the Mini International Neuropsychiatric Interview. Patients with a positive MINI score underwent further assessment using the Hamilton Scale. Patients were considered young if ≤45 years. RESULTS: A total of 50 patients were assessed, 56 % were women, and 54 % were ≤45 years. Major depression was documented in 11 (22 %) patients, eight (72 %) in the younger group, and three (28 %) in the older group. Eight (16 %) patients had an anxiety disorder, four in the younger group, and ten (20 %) patients had post-traumatic stress disorder, seven (70 %) of the younger patients. Generalized anxiety disorder was identified in 20 (40 %) patients with similar proportions in both groups. CONCLUSION: Psychological and emotional symptoms are common following an episode of venous thromboembolism. Post-traumatic stress disorder and depression appear to be numerically more prevalent in the young.

COVID-19 and postoperative complications after plastic surgery procedures: More than just hypercoagulability.

BACKGROUND: Although plastic surgery procedures generally demonstrate less than 2% incidence of venous thromboembolism (VTE) outcomes, the post-COVID era data remain elusive. This study sought to elucidate the relationship between COVID-19 infection and the risk of VTE outcomes across plastic surgery procedures. METHODS: Plastic surgery procedures were identified in the 2012-2022 National Surgical Quality Improvement Program databases. The outcomes of interest were the postoperative occurrence of VTE, defined as deep vein thrombosis (DVT) or pulmonary embolism (PE), and postoperative complication. Propensity score matching was used to 1) compare overall rates of VTE between the pre-pandemic era and pandemic era cohorts and 2) compare rates of VTE and overall postoperative complications in cases with and without COVID-19 diagnosis in the years 2021-2022 (p < 0.05). RESULTS: Overall, 269,006 plastic surgery cases were identified, comprising general breast (76%) and trunk (9.4%) procedures. Non-breast free tissue transfer cases were associated with the highest rates of DVT (1.3%) and trunk procedures with the highest rates of PE (0.7%). After propensity score matching, the overall rate of VTE after the onset of the COVID-19 pandemic was not significantly different from the pre-pandemic era (p = 0.40). In a separately matched cohort, COVID-19 diagnosis did not significantly predict the risk for VTE (p = 0.48) but did significantly predict the risk for overall postoperative complications (p < 0.001). CONCLUSIONS: Although COVID-19 diagnosis itself did not predict the risk of VTE in matched analysis, it significantly predicted the overall postoperative complications. Future studies may further investigate the effects of COVID-19 infection over longer periods of follow-up.

Impact of an updated venous thromboembolism prophylaxis guideline in critically ill trauma patients on rates of venous thromboembolisms.

INTRODUCTION: The objective of this analysis was to evaluate differences in incidence of venous thromboembolisms (VTE) in critically ill trauma patients between pre- and post-implementation of updated VTE prophylaxis guidelines. METHODS: This was a pre-post analysis of critically ill trauma patients receiving pharmacologic VTE prophylaxis. Trauma patients were included if they had an intensive care unit admission during their hospitalization. The primary outcome was incidence of detected VTE and was analyzed using a Chi-Squared test. A multivariate analysis assessed the effects of guideline implementation on VTE development when controlling for confounders. RESULTS: There were 220 patients included. There was a significant increase in low molecular weight heparin use in initial (p â€‹= â€‹0.003) and final (p â€‹= â€‹0.004) prophylactic regimens between groups. There was no significant difference in VTE incidence between the pre and post groups (6.3% vs 1.9%, p â€‹= â€‹0.10). The multivariate analysis showed guideline implementation was independently associated with an 88% reduced odds of VTE (p â€‹= â€‹0.04). CONCLUSION: This analysis suggests the updated VTE prophylaxis guideline implementation was associated with a trend toward reduced VTE development among critically ill trauma patients.

Accurately identifying incident cases of venous thromboembolism in the electronic health record: Performance of a novel phenotyping algorithm.

BACKGROUND: Accurate identification of incident venous thromboembolism (VTE) for quality improvement and health services research is challenging. The purpose of this study was to evaluate the performance of a novel incident VTE phenotyping algorithm defined using standard terminologies, requiring three key indicators documented in the electronic health record (EHR): VTE diagnostic code, VTE-related imaging procedure code, and anticoagulant medication code. METHODS: Retrospective chart reviews were conducted to assess the performance of the algorithm using a random sample of phenotype(+) and phenotype(-) diagnostic encounters from primary care practices and acute care sites affiliated with five hospitals across a large integrated care delivery system in Massachusetts. The performance of the algorithm was evaluated by calculating the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity, using the phenotype(+) and phenotype(-) diagnostic encounters sample and target population data. RESULTS: Based on gold-standard manual chart review, the algorithm had a PPV of 95.2 % (95 % CI: 93.1-96.8 %), NPV of 97.1 % (95 % CI: 95.3-98.4 %), sensitivity of 91.7 % (95 % CI: 90.8-92.6 %), and specificity of 98.4 % (95 % CI: 98.1-98.6 %). The algorithm systematically misclassified a low number of specific types of encounters, highlighting potential areas for improvement. CONCLUSIONS: This novel phenotyping algorithm offers an accurate approach for identifying incident VTE in general populations using EHR data and standard terminologies, and accurately identifies the specific encounter and date of diagnosis of the incident VTE. This approach can be used for measurement of incident VTE to drive quality improvement, research to expand the evidence, and development of quality metrics and clinical decision support to improve the diagnostic process.

Hyperglycemia and Venous Thromboembolism.

Patients with diabetes mellitus (DM) have chronically increased blood glucose and multiple physiologic alterations that place them at elevated risk for vascular disease. Traditionally, this vascular risk has mainly referred to chronic atherosclerosis and embolic arterial disease. Retrospective studies have suggested an increased risk of a pulmonary embolism (PE) and deep vein thrombosis (DVT), collectively termed venous thromboembolism (VTE), in patients with DM, but this association has been difficult to demonstrate with comorbidities such as obesity in meta-analysis. Clinical studies have demonstrated worse outcomes for patients with DM who suffer from VTE. In vitro studies show multiple physiologic abnormalities with chronic inflammation, endothelial dysfunction, dysfunction in the coagulation cascade, as well as other changes that drive a vicious cycle of hypercoagulability. Aggressive medical management of DM can improve vascular outcomes, and some anti-hyperglycemic therapies may modify VTE risk as well. Anticoagulation strategies are similar for patients with DM, but with some added considerations, such as high rates of comorbid renal dysfunction. More research is needed to definitively categorize DM as a risk factor for VTE and elucidate specific therapeutic strategies.

Antibodies and complement are key drivers of thrombosis.

Venous thromboembolism (VTE) is a common, deadly disease with an increasing incidence despite preventive efforts. Clinical observations have associated elevated antibody concentrations or antibody-based therapies with thrombotic events. However, how antibodies contribute to thrombosis is unknown. Here, we show that reduced blood flow enabled immunoglobulin M (IgM) to bind to FcµR and the polymeric immunoglobulin receptor (pIgR), initiating endothelial activation and platelet recruitment. Subsequently, the procoagulant surface of activated platelets accommodated antigen- and FcγR-independent IgG deposition. This leads to classical complement activation, setting in motion a prothrombotic vicious circle. Key elements of this mechanism were present in humans in the setting of venous stasis as well as in the dysregulated immunothrombosis of COVID-19. This antibody-driven thrombosis can be prevented by pharmacologically targeting complement. Hence, our results uncover antibodies as previously unrecognized central regulators of thrombosis. These findings carry relevance for therapeutic application of antibodies and open innovative avenues to target thrombosis without compromising hemostasis.

Higher Incidence of Venous Thromboembolism in Anterolateral Approach in Lateral Position Compared to Anterolateral Supine and Direct Anterior Approaches in Minimally Invasive Total Hip Arthroplasty.

INTRODUCTION: Venous thromboembolism (VTE) remains a major complication after total hip arthroplasty (THA), irrespective of the surgical approach. This study investigated the incidence of VTE in patients undergoing THA through intermuscular minimally invasive surgical techniques, which included a direct anterior approach (DAA), an anterolateral approach (AL), and an anterolateral supine approach (ALS), at a single institution. METHODS: A hundred consecutive patients treated with each surgical approach were evaluated. Plasma D-dimer levels one month preoperatively and one day postoperatively, operative time, and intraoperative blood loss were recorded, and the presence of VTE was evaluated based on multidetector-row computed tomography performed the day after surgery. Student's t-test and Pearson's chi-square test or one-way analysis of variance were used in statistical analysis. RESULTS: No differences among the groups in terms of age, height, weight, operative time, intraoperative bleeding, and preoperative and postoperative D-dimer levels were observed. The overall incidence of VTE was 21%. The incidences of VTE were 30% in AL, 17% in ALS, and 16% in DAA, representing a significantly higher rate in AL than in ALS and DAA (P=0.025). The incidences of VTE on the operated side were 19% in AL, 13% in ALS, and 12% in DAA, with no statistically significant differences. The incidences of VTE on the non-operated side were 22% in AL, 9% in ALS, and 8% in DAA; these differences were statistically significant (P=0.0045). DISCUSSION: Results showed that the incidence of VTE was significantly higher in AL than in ALS and DAA, especially for the non-operated side.

Venous thromboembolism prevention program implementation in a community oncology practice: a cohort study.

Background: While national guidelines recommend Venous Thromboembolism (VTE) risk assessment in cancer outpatients and consideration of pharmacologic prophylaxis in high-risk patients, prophylaxis rates are low in community oncology practices. A successful model for guideline implementation (the Vermont Model, VM) is validated in an academic tertiary oncology setting. We undertook an implementation study to determine the success of this model in a multi-site community oncology practice. The study objectives were to: 1) adapt the VM to the community practice setting; 2) implement the adapted VM into practice; and 3) evaluate clinical and implementation outcomes. Methods: The study was carried out in three phases: (1) Pre-implementation, a multidisciplinary team addressed the need to adapt the VM to the local context including electronic medical record (EMR) optimisation and clinician education; (2) implementation of the strategies adapted to the local context, informed by VM and adapted based on stakeholder feedback; (3) prospective evaluation of clinical and implementation outcomes at six months after implementation. Findings: Following creation of a comprehensive initiation roadmap for the adaptation of VM program to the community practice, 302 cancer outpatients initiating new treatment met inclusion criteria over a 6 month implementation period. VTE risk education was provided to 100% of patients, and 98% (296) of patients received a VTE risk assessment. Of 52 patients (18%) who scored as high risk based on a modified Khorana (Protecht) score, 14 (27%) initiated prophylaxis. Barriers to program adaptation included EMR optimization challenges and practice-level responsibility assignment, time constraints, concern about potential drug interactions, and financial & insurance issues. Interpretation: Implementation of a multidisciplinary VTE prevention model in the community-based oncology setting successfully increased VTE education and risk assessment rates. AC prophylaxis rates were modestly increased, highlighting the need to understand and address barriers to anticoagulant prophylaxis prescribing in this setting. Funding: Northern New England Clinical Oncology Society Research Funding Program.