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Objective: Pneumonia, influenza, COVID-19, and other common infections might increase the risk of thrombotic events acutely through an interaction between inflammation and the thrombotic system. The long-term risks of arterial and venous thrombotic events following hospitalisation for COVID-19 and hospitalisation for pneumonia or influenza are unclear., Materials and Methods: In a population-wide cohort of linked Welsh health data of adults, we calculated the incidence of arterial and venous thrombosis after hospitalisation for COVID-19 (2020-2021). We then compared this post-hospitalisation incidence with the incidence prior to COVID-19 hospitalisation in the same individuals, and with the incidence in individuals who were never hospitalised for COVID-19. We then repeated this analysis for hospitalisation for pneumonia or influenza in a separate cohort (2016-2019). We estimated adjusted hazard ratios (aHRs) in separate time periods starting from the date of the first infection that resulted in hospitalisation (day 0, 1 to 7 days, 2 to 4 weeks, 5 to 16 weeks, and 17 to 75 weeks) using time-varying Cox regression. Confounders included age, sex, smoking status, obesity, deprivation (fifths of Welsh Index of Multiple Deprivation), rural or urban setting, care home attendance, Elixhauser comorbidity index, surgery in the last year, medications (e.g. lipid-lowering and antiplatelet/anticoagulant use), hypertension and/or hypertensive medication use, and past medical history of chronic kidney disease, diabetes, chronic obstructive pulmonary disease, dementia, cancer, or any CVD., Results: For the first arterial thrombosis, the aHRs were 3.80 (95 % CI: 2.50-5.77) between days 1-7, 5.24 (4.21-6.51) between weeks 2-4, 2.12 (1.72-2.60) between weeks 5-16, and 1.60 (1.38-1.86) between weeks 17-75 after hospitalisation for COVID-19. The corresponding aHRs after hospitalisation for pneumonia/influenza were: 5.42 (4.35-6.75), 3.87 (3.32-4.49), 1.96 (1.74-2.21), and 1.41 (1.30-1.53). For first venous thrombosis, aHRs were 7.47 (3.56-15.7) between days 1-7, 22.6 (17.5-29.1) between weeks 2-4, 6.58 (4.98-8.68) between weeks 5-16, and 2.25 (1.67-3.02) between weeks 17-75 after hospitalisation for COVID-19. The corresponding aHRs after hospitalisation for pneumonia/influenza were: 15.1 (10.3-22.0), 11.8 (9.23-15.1), 5.80 (4.75-7.08), and 1.89 (1.57-2.29). Excess risk was highest in individuals aged ≥60 years, in whom we estimated 2,700 and 2,320 additional arterial and 1,270 and 840 additional venous events after 100,000 hospitalisations for COVID-19 and pneumonia/influenza, respectively., Conclusions: Both hospitalisation for COVID-19 and pneumonia/influenza increase the risk of arterial and venous thrombosis. Preventative healthcare policies are needed for cardiovascular risk factor management, vaccination, and anticoagulation in high-risk patients with hospitalised or severe infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Disclosures Dr. Whiteley has given expert testimony to UK courts and served on an advisory board for Bayer. Kamlesh Kunti is chair of the ethnicity subgroup of the UK Scientific Advisory Group for Emergencies (SAGE) and is a member of SAGE. The other authors report no conflicts., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The clinical presentation, outcomes, and anticoagulation strategies in patients with lung cancer-associated isolated distal deep vein thrombosis (LC-iDDVT) are not well-defined., Materials and Methods: The study included 593 patients with LC-iDDVT and 260 patients with lung cancer-associated proximal DVT (LC-Proximal DVT). LC-iDDVT was further classified into axial venous thrombosis (AVT; 112 patients) and muscular venous thrombosis (MVT; 481 patients). Cox proportional risk regression models with Fine-Gray tests and competing risk models were employed to evaluate short-term (90-day) and long-term (1-year) outcomes (hazard ratio [HR]; 95 % confidence intervals [CI])., Results: At the 90-day follow-up, patients with MVT had lower adjusted risks of pulmonary embolism (PE; HR = 0.20 [0.07-0.55], p = 0.002) and venous thromboembolism (VTE) recurrence (HR = 0.54 [0.34-0.88], p = 0.013) than those with LC-Proximal DVT. Similar results were observed at the 1-year follow-up. However, adjusted risks for PE (HR = 0.74 [0.29-1.92], p = 0.540; HR = 0.87 [0.42-1.78], p = 0.700) and VTE recurrence (HR = 0.96 (0.54-1.71), p = 0.890; HR = 0.99 [0.63-1.56], p = 0.970) at 90-day and 1-year were not significantly different between patients with AVT and those with LC-Proximal DVT. Among patients with LC-iDDVT, those receiving anticoagulation had reduced risks of VTE recurrence (HR = 0.57 [0.35-0.95], p = 0.030) and DVT deterioration (HR = 0.28 [0.13-0.60], p = 0.001) compared to those without anticoagulation. Moreover, AVT patients on >3 months of anticoagulation had a lower VTE recurrence risk (HR = 0.23 [0.03-0.92], p = 0.038) than those on ≤3 months of anticoagulation., Conclusion: In the context of lung cancer, patients with AVT may have a higher tendency for recurrent thrombosis compared to those with MVT, especially if anticoagulation is refused or given briefly., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Iliac vein stenting is an effective treatment for iliac venous stenosis after percutaneous mechanical thrombectomy. Nevertheless, while some researchers have investigated medical therapy following iliac vein stenting, no consensus has been reached to date., Objectives: To evaluate the effectiveness and safety of anticoagulation plus antiplatelet therapy following iliac vein stent implantation in patients with acute and subacute iliofemoral deep vein thrombosis (DVT)., Materials and Methods: This retrospective study comprised 234 patients: 167 patients in Group 1 with a mean age of 64.3 ± 13.5 years received anticoagulants alone, and 67 patients in Group 2 with a mean age of 60.7 ± 15.4 years received anticoagulation plus antiplatelet therapy. All patients received technically successful percutaneous pharmacomechanical thrombectomy and iliac vein stent implantation, and 61 patients underwent additional catheter-directed thrombolysis. The two groups exhibited comparable demographics, comorbidities, DVT burdens, and procedural details. Through propensity score matching (PSM) analysis, 62 pairs of patients from Group 1 and Group 2 were matched., Results: During a follow-up period of 33.7 ± 16.5 months, the cumulative primary patency rates were 95.1 %, 89.7 % and 88.3 % at one, three and five years in Group 1 compared to 98.8 %, 98.5 % and 98.5 % in Group 2 for the entire cohort (p = 0.042); in the PSM analysis, the rates were 91.9 %, 87.3 % and 87.3 % at one, three and five years in Group 1 versus 98.4 % at one, three and five years in Group 2 (p = 0.039). The cumulative bleeding-free rate was 98.2 % at one, three and five years in Group 1 versus 95.5 %, 93.8 % and 93.8 % at one, three and five years in Group 2 for the entire cohort (p = 0.089), and it was 98.4 % at one, three and five years in Group 1 versus 95.2 %, 93.3 % and 93.3 % (p = 0.156) at one, three and five years in Group 2 in the PSM analysis., Conclusion: Anticoagulation plus antiplatelet therapy significantly improved stent patency, with a non-significant increase in the bleeding rate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Portal vein thrombosis in cirrhotic patients presents a significant clinical challenge. This study aims to (1) explore the impact of anticoagulation therapy on patient outcomes; (2) comparative outcomes in portal vein thrombosis treated between direct oral anticoagulant and Vitamin K Antagonist (VKA)., Materials and Methods: We leveraged the TriNetX database to analyze a cohort comprising 4224 patients with liver cirrhosis and PVT who were treated with anticoagulation, alongside a comparison group of 15,300 patients with the same conditions but not receiving anticoagulation therapy., Results: The anticoagulated group showed a significant reduction in mortality (27.9 % vs. 34.2 %, HR = 0.723, 95 % CI: 0.678-0.770, P < 0.001). When comparing direct oral anticoagulant versus. VKA, in compensated liver cirrhosis, the direct oral anticoagulant group exhibited significantly lower mortality rates compared to VKA (17.7 % vs. 26.5 %, HR = 0.655, 95 % CI: 0.452-0.951, P = 0.025), with no significant difference in liver transplantation rates (4.0 % vs. 4.7 %, P = 0.080). In decompensated liver cirrhosis, the direct oral anticoagulant group exhibited lower mortality compared to the VKA group (23.6 % vs. 30.6 %, HR = 0.732, 95 % CI: 0.629-0.851, P < 0.001), and a higher frequency of liver transplantation was observed in the VKA group (10.6 % vs. 16.0 %, HR = 0.622, 95 % CI: 0.494-0.784, P < 0.001). Hospitalization rates were significantly lower in the direct oral anticoagulant group compared to the VKA group in decompensated cirrhosis (33.4 % vs. 38.3 %, HR = 0.830, 95 % CI: 0.695-0.992, P = 1.937)., Conclusions: Our study offers compelling evidence supporting the use of anticoagulation therapy in liver cirrhosis with portal vein thrombosis. The use of DOACs in patients with both compensated and decompensated liver cirrhosis showed a marked mortality benefit., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interestsor personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Assess the safety and efficacy of anticoagulants in treating isolated superficial vein thrombosis (iSVT)., Materials and Methods: A systematic review was conducted according to PRISMA 2020 guidelines, for randomized controlled trials (RCTs) investigating anticoagulants in the treatment of iSVT. The primary endpoint of thrombotic complications encompassed any incident of iSVT progression/recurrence and the development of new-onset (deep vein thrombosis) DVT or (pulmonary embolism) PE., Results: Eight RCT's and 4721 patients treated once daily with either fondaparinux 2.5 mg, rivaroxaban 10 mg, therapeutic, intermediate, and prophylactic low molecular weight heparin (LMW) were included. While all anticoagulants displayed a statistically significant risk reduction compared to placebo in terms of thrombotic complications and iSVT progression/recurrence, only fondaparinux reduced the risk for DVT/PE. Additionally, fondaparinux exhibited enhanced efficacy in decreasing DVT/PE events relative to prophylactic and therapeutic LMWH. Furthermore, rivaroxaban and fondaparinux demonstrated superior outcomes in terms of preventing thrombotic complications compared to all three dosing regimens of LMWH without significant differences between the two, risk ratio RR 1.00(95%CI:0.51-1.92). SUCRA identified fondaparinux as the most effective treatment regarding thrombotic complications, (SUCRA,91.6) and DVT/PE, (SUCRA,96) and rivaroxaban in terms of iSVT progression/recurrence (SUCRA,94.68). Ultimately and despite certain model limitations, meta-regression analysis suggested a possible trend towards improved outcomes with longer treatment durations for thrombotic complications β = -0.34(95%CI:-16.39to12.23)., Conclusions: Despite inherent limitations such as variations in treatment durations and follow-up periods, this review displayed the efficacy of fondaparinux, rivaroxaban and LMWH in treating iSVT. The improved efficacy of fondaparinux over therapeutic LMWH in terms of DVT/PE outcomes necessitates cautious interpretation underscoring the need for further investigation through adequately powered RCTs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Additionally, no funding or grants were received to support this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is associated with wound healing, cancer-associated fibroblasts, and chronic fibrosing diseases. However, its expression in deep vein thrombosis (DVT) remains unclear. Therefore, this study investigated FAP expression and localization in DVT., Methods: We performed pathological analyses of the aspirated thrombi of patients with DVT (n = 14), classifying thrombotic areas in terms of fresh, cellular lysis, and organizing reaction components. The organizing reaction included endothelialization and fibroblastic reaction. We immunohistochemically examined FAP-expressed areas and cells, and finally analyzed FAP expression in cultured dermal fibroblasts., Results: All the aspirated thrombi showed a heterogeneous mixture of at least two of the three thrombotic areas. Specifically, 83 % of aspirated thrombi showed fresh and organizing reaction components. Immunohistochemical expression of FAP was restricted to the organizing area. Double immunofluorescence staining showed that FAP in the thrombi was mainly expressed in vimentin-positive or α-smooth muscle actin-positive fibroblasts. Some CD163-positive macrophages expressed FAP. FAP mRNA and protein levels were higher in fibroblasts with low-proliferative activity cultured under 0.1 % fetal bovine serum (FBS) than that under 10 % FBS. Fibroblasts cultured in 10 % FBS showed a significant decrease in FAP mRNA levels following supplementation with hemin, but not with thrombin., Conclusions: The heterogeneous composition of venous thrombi suggests a multistep thrombus formation process in human DVT. Further, fibroblasts or myofibroblasts may express FAP during the organizing process. FAP expression may be higher in fibroblasts with low proliferative activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Imaging evaluation of acute deep vein thrombosis (DVT) or post-thrombotic syndrome (PTS) in animal or clinical models is limited to anatomical assessment of the location and extent of thrombi. We hypothesize that Fe-MRI, used to evaluate macrophage content in other inflammatory diseases, can be useful to evaluate the thromboinflammatory features after DVT over time., Methods: Nineteen wild-type CD-1 mice underwent surgical IVC ligation to induce DVT. Mice received either saline or 5 mg/kg of 14E11, a Factor XI inhibitor, before the procedure. Fe-MRI was performed on days 6-7 after ligation to evaluate thrombus volume, perfusion, and macrophage content via T 2 -weighted images. Mice were euthanized at days 3-15 after surgery. The thrombi and adjacent vein walls were excised, weighed, formalin-fixed, and paraffin-embedded for immunohistological analysis. Specimens were stained with specific antibodies to evaluate macrophage content, collagen deposition, neovascularization, and recanalization. Significance was determined using the Mann-Whitney U or Student's t-test., Results: After IVC-ligation in control mice, thrombus weights decreased by 59 % from day 3 to 15. Thrombus volumes peaked on day 5 before decreasing by 85 % by day 13. FXI inhibition led to reduced macrophage content in both thrombi (p = .008) and vein walls (p = .01), decreased thrombus volume (p = .03), and decreased thrombus mass (p = .01) compared to control mice. CCR2+ staining corroborated these findings, showing significantly reduced macrophage presence in the thrombi (p = .002) and vein wall (p = .002)., Conclusions: Fe-MRI T 2 relaxation times can be used to characterize and quantify post-thrombotic changes of perfusion, macrophage content, and thrombus volume over time in a surgical mouse model of venous thrombosis. This approach could lead to better quantification of in vivo inflammation correlating monocyte and macrophage content within resolving thrombi and veins and may serve as a useful tool for research and clinically in the evaluation of the post-thrombotic environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Pulmonary vein thrombosis (PVT) is a rare thromboembolic disease with potential high-risk complications related to arterial embolization, but little is known regarding risk factors and outcomes., Objective: To describe the etiology, management, and clinical course of PVT., Methods: Institutional health records were queried (1/1/2001-12/30/2023) to identify patients ≥18 years of age diagnosed with PVT. Thrombosis, bleeding, respiratory failure, and all-cause mortality were analyzed. Suspected tumor thrombus cases were excluded., Results: 72 patients with PVT were identified (median age 62 years, 50 % female), and PVT was overall rare at 3.1 diagnosed cases per year at our institution. PVT primarily affected a single vein (89 %), most commonly the left upper PV (40 %). Of these, 37 % occurred while on therapeutic anticoagulation. The most common risk factors included cancer (55 %) and related surgical lobectomy (21 %). Extrinsic vein compression (17 %) and recent surgery (19 %) were also common; 19 % were deemed idiopathic. Most patients (76 %) were treated with anticoagulation and frequently indefinite duration (80 %). During a median follow-up of 11.7 months (IQR 39.5 months), serial imaging (available for 68 %) revealed PVT resolution in 64 %. Four-year Kaplan-Meier probability of outcome included: left atrial thrombus (21 %), need for mechanical ventilation (14 %), pneumonia (9 %), and ischemic stroke (9 %). The mortality rate was 46 % with median survival 14 months after PVT diagnosis., Conclusion: PVT is often associated with active malignancy, lobectomy, recent surgery, and extrinsic vein compression; 1 in 5 cases were idiopathic. Notable complications include left atrial thrombus with arterial embolism including stroke. With anticoagulation, most thrombi resolve over time. Mortality rates are high, reflecting the high the prevalence of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: This review aims to compare the performance of available risk assessment models (RAMs) for predicting peripherally inserted central catheter-related venous thrombosis (PICC-RVT) in adult patients with cancer., Methods: A systematic search was conducted across ten databases from inception to October 20, 2023. Studies were eligible if they compared the accuracy of a RAM to that of another RAM for predicting the risk of PICC-RVT in adult patients with cancer. Two reviewers independently performed the study selection, data extraction and risk of bias assessments. A Bayesian network meta-analysis (NMA) was used to evaluate the performance of the RAMs., Results: A total of 1931 studies were screened, and 7 studies with 10 RAMs were included in the review. The most widely used RAMs were the Caprini (4 studies), Padua prediction score (3 studies), Autar (3 studies), Michigan risk score (2 studies) and Seeley score (2 studies). The sensitivity, specificity and accuracy varied markedly between the models. Notably, the Caprini score achieved higher sensitivity than 4 RAMs (Wells, Revised Geneva, modified MRS, MRS). The Michigan risk score had greater specificity than did the other 6 RAMs (Caprini, Autar, Padua, Seeley, the novel RAM, Wells). The predictive accuracy of the MRS is significantly greater than that of the Caprini and Autar RAM., Conclusion: The MRS could be the most accurate RAM for identifying patients at high risk of PICC-RVT. However, as limited studies are available, more rigorous studies should be conducted to examine the accuracy of the Michigan risk score for PICC-RVT in different contexts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background & Aims: Nonselective β blockers (NSBBs) facilitate the development of portal vein thrombosis (PVT) in liver cirrhosis. Considering the potential effect of NSBBs on neutrophils and neutrophil extracellular traps (NETs), we speculated that NSBBs might promote the development of PVT by stimulating neutrophils to release NETs., Materials and Methods: Serum NETs biomarkers were measured, use of NSBBs was recorded, and PVT was evaluated in cirrhotic patients. Carbon tetrachloride and ferric chloride (FeCl 3 ) were used to induce liver fibrosis and PVT in mice, respectively. After treatment with propranolol and DNase I, neutrophils in peripheral blood, colocalization and expression of NETs in PVT specimens, and NETs biomarkers in serum were measured. Ex vivo clots lysis analysis was performed and portal vein velocity and coagulation parameters were tested., Results: Serum MPO-DNA level was significantly higher in cirrhotic patients treated with NSBBs, and serum H3Cit and MPO-DNA levels were significantly higher in those with PVT. In fibrotic mice, following treatment with propranolol, DNase I significantly shortened the time of FeCl 3 -induced PVT formation, lowered the peripheral blood neutrophils labelled by CD11b/Ly6G, inhibited the positive staining of H3Cit and the expression of H3Cit and MPO proteins in PVT tissues, and reduced serum nucleosome level. Furthermore, the addition of DNase I to tissue plasminogen activator (tPA) significantly accelerated clots lysis as compared with tPA alone. Propranolol reduced portal vein velocity in fibrotic mice, but did not influence coagulation parameters., Conclusion: Our study provides a clue to the potential impact of NETs formation on the association of NSBBs with the development of PVT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Mucins released from epithelial tumors have been proposed to play a role in cancer-associated thrombosis. Mucin1 (MUC1) is a transmembrane mucin that is overexpressed in a variety of human malignancies, including breast and pancreatic cancer. We analyzed the association of MUC1 and venous thrombosis in a mouse tumor model and in patients with cancer., Materials and Methods: We used a human pancreatic cancer cell line HPAF-II that expresses a high level of MUC1. We grew HPAF-II tumors in the pancreas of Crl:NU-Foxn1 nu male mice. MUC1 in plasma and extracellular vesicles (EVs) isolated from plasma was measured using an enzyme-linked immunosorbent assay. MUC1 in EVs and venous thrombi from tumor-bearing mice was assessed by western blotting. We measured MUC1 in plasma from healthy controls and patients with stomach, colorectal or pancreatic cancer with or without venous thromboembolism., Results and Discussion: MUC1 was detected in the plasma of mice bearing HPAF-II tumors and was associated with EVs. MUC1 was present in venous thrombi from mice bearing HFAP-II tumors. Recombinant MUC1 did not induce platelet aggregation. Levels of MUC1 were higher in patients with pancreatic cancer compared with healthy controls. In contrast to the mouse model, MUC1 was present in EV-free plasma in samples from healthy controls and patients with cancer. There was no significant difference in the levels of MUC1 in cancer patients with or without VTE. Our data did not find any evidence that MUC1 contributed to VTE in patients with cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: There are few large-scale, population-based studies detailing the risks of thrombosis, hemorrhage, leukemic transformation in patients with myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF)., Methods: We performed a nationwide longitudinal cohort study using the Korean National Health Insurance System (NHIS) database. MPN patients (n = 11,991) and their 1:4 age- and sex-matched controls (n = 47,964) were enrolled. The risk of thrombosis, hemorrhage, leukemic transformation was estimated using a Cox proportional hazards regression, and stratified analyses were performed for related factors., Results: During a median of 7.8 years of follow-up, 30.1 % of MPN patients (3614/11,991) and 19.0 % of the matched controls (9141/47,964) developed arterial thrombosis, 11.6 % of MPN patients (1397/11,991) and 6.4 % of the matched controls (3099/47,964) developed venous thrombosis and 18.7 % of MPN patients (2251/11,991) and 12.1 % of the matched controls (5836/47,964) developed hemorrhage. 4.9 % of MPN patients (597/11,991) and 0.1 % of matched controls (50/47,964) developed leukemia. The overall risk of developing thrombosis, hemorrhage, leukemic transformation was higher in MPN patients (adjusted hazard ratio [aHR] 1.695, 95 % confidence interval [CI]: 1.629-1.765 for arterial thrombosis, aHR 1.963, 95 % CI: 1.838-2.096 for venous thrombosis, and aHR 1.714, 95 % CI: 1.630-1.802 for hemorrhage) than in the controls. Patients with MPNs had a 10-year cumulative incidence of leukemic transformation of 6.2 %., Conclusion: The patients with MPNs have a higher risk of thrombosis, hemorrhage, and leukemic transformation than matched controls. Strategies are warranted to reduce the risk of thrombosis, hemorrhage, and leukemic transformation in MPN patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The role of elevated coagulation factors VIII (FVIII), FIX, FXI for the prediction of recurrent thrombotic events in children after an index non-central venous catheter (non-CVC) related deep vein thrombosis (DVT) remains unclear., Objective: This study investigates the predictive role of FVIII, FIX, and FXI for recurrent thrombosis in children with index non-CVC DVTs, and the mediation effect of FVIII on chronic inflammation and recurrent thrombosis., Methods: Children aged 0-18 years diagnosed with an index non-CVC related DVT (1993-2020) were included in this single-center retrospective cohort study. Plasma levels of FVIII, FIX, FXI were measured cross-sectionally ≥30 days after the acute DVT. The association between the continuous variables FVIII, FIX, FXI and thrombosis recurrence was investigated using uni- and multivariable logistic regression, adjusting for age, sex, and chronic inflammation. Mediation analysis assessed the role of FVIII as a mediator between chronic inflammation and recurrent thrombosis. Ethics approval was obtained., Results: A total of 139 children with an index non-CVC related DVT were included. Thirty-eight (27 %) had a recurrent thrombosis at a median of 237 days (P25-P75 65-657 days) after the index DVT. In uni- and multivariable-analysis, FVIII, FIX or FXI did not predict thrombosis recurrence; However, chronic inflammation was an independent predictor. There was no evidence that FVIII mediated the effect of chronic inflammation on thrombosis recurrence., Conclusion: We found no evidence that elevated FVIII, FIX or FXI predicted thrombosis recurrence, or evidence of a mediating role of FVIII. Underlying chronic inflammation predicted venous recurrent thrombotic events in this cohort., Competing Interests: Declaration of competing interest K.J.B. reports honoraria from Bayer, outside the topic of the current study. The authors A.B., L.B., Y.Z., J.V., N.A., and L.A. declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The multicenter, open-label, randomized clinical trial ONCO DVT compared 3-month and 12-month edoxaban treatment regimens for isolated distal deep vein thrombosis (DVT) and suggested potential benefits of prolonged edoxaban treatment in terms of thrombotic risk. However, the risk-benefit balance of prolonged edoxaban treatment in patients with renal function remains unclear., Objectives: To compare the safety and efficacy of 3-month and 12-month edoxaban treatment regimens in patients with cancer-associated isolated distal DVT and different renal functions., Methods: This pre-specified subgroup analysis of the ONCO DVT study included 601 patients divided into subgroups according to renal function using a 50 mL/min creatinine clearance (Ccr) cutoff. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) and VTE-related death at 12 months and the major secondary endpoint was major bleeding at 12 months., Results: Among the 601 patients, 131 (21.8 %) comprised the renal dysfunction subgroup. The primary endpoint occurred in 6 (9.7 %) and 1 (1.4 %) patients in the 3-month and 12-month edoxaban groups in the renal dysfunction subgroup, respectively, and in 16 (6.6 %) and 2 (0.9 %) patients in the no renal dysfunction subgroup, respectively. The major secondary endpoint occurred in 9 (14.5 %) and 7 (10.1 %) patients in the 12-month and 3-month edoxaban groups in the renal dysfunction subgroup, and in 13 (5.3 %) and 21 (9.3 %) patients in the no renal dysfunction subgroup, respectively., Conclusions: A 12-month edoxaban regiment was superior to a 3-month treatment in terms of thrombotic risk irrespective of renal function. A higher bleeding risk was not identified in patients with renal dysfunction who received prolonged edoxaban treatment., Competing Interests: Declaration of competing interest Dr. Yamashita received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. Dr. Morimoto reports lecturer's fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Pfizer and Tsumura; manuscript fees from Bristol-Myers Squibb and Pfizer; advisory board for Novartis and Teijin. Dr. Nishimoto received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo. Dr. Ogihara received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and research funds from Bayer Healthcare and Daiichi Sankyo. Dr. Dohi received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and research funds from Daiichi Sankyo. Dr. Ikeda N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi Sankyo. Dr. Tsubata received lecture fees from AstraZeneca, Chugai Pharmaceutical, Bristol-Myers Squibb, Kyowa Kirin, Pfizer, Taiho Pharmaceutical, Takeda Pharmaceutical and Daiichi Sankyo, and grant support from Daiichi Sankyo, AstraZeneca and Ono Pharmaceutical. Dr. Ikeda S. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb and Daiichi Sankyo. Dr. Mo received lecture fees from Bayer Healthcare. Dr. Tsujita received significant research grant from AMI Co., Ltd., Bayer Yakuhin, Ltd., Bristol-Myers K.K., EA Pharma Co., Ltd., MOCHIDA PHARMACEUTICAL CO., LTD., and scholarship fund from AMI Co., Ltd., Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Edwards Lifesciences Corporation, Johnson & Johnson K.K., ONO PHARMACEUTICAL CO., LTD., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and honoraria from Amgen K.K., Bayer Yakuhin, Ltd., Daiichi Sankyo Co., Ltd., Kowa Pharmaceutical Co. Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., and belongs to the endowed departments donated by Abbott Japan Co., Ltd., Boston Scientific Japan K.K., Fides-one, Inc., GM Medical Co., Ltd., ITI Co., Ltd., Kaneka Medix Co., Ltd., NIPRO CORPORATION, TERUMO Co, Ltd., Abbott Medical Co., Ltd., Cardinal Health Japan, Fukuda Denshi Co., Ltd., Japan Lifeline Co., Ltd., Medical Appliance Co., Ltd., Medtoronic Japan Co., Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Splanchnic vein thrombosis (SVT), a thrombosis which involves the portal, mesenteric, and splenic veins, and the Budd-Chiari syndrome, represents an uncommon type of venous thromboembolism (VTE). Like with deep vein thrombosis of the lower extremities and pulmonary embolism, ample evidence suggests a significant association between SVT and cancer, particularly intra-abdominal solid malignancies (e.g. hepatobiliary and pancreatic cancers) and myeloproliferative neoplasms (MPN). Clinical symptoms of SVT in cancer patients can be ambiguous, and frequently attributed to the primary cancer itself. Alternatively, SVT may be asymptomatic and detected incidentally during cancer staging or follow-up evaluations. SVT can also precede the diagnosis of cancer and has been associated with poorer outcomes in patients with liver or pancreatic cancers. Therefore, an unprovoked SVT warrants a thorough evaluation for an underlying malignancy or MPN. Cancer-associated SVT carries a high risk of VTE extension, recurrence and bleeding. Extended anticoagulant treatment is often required in the absence of a high bleeding risk. Guidelines suggest treatment with either low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs), although available data on the safety and effectiveness of DOACs in these patients is limited. This comprehensive review outlines the epidemiology, pathogenesis, risk factors, and diagnosis of cancer-associated SVT and underscores the importance of comprehensive patient evaluation and evidence-based management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The frequency of upper extremities vein thrombosis (UEVT) is rising with the increasing use of endovenous devices. These thromboses are particularly common among hospitalized patients. The epidemiology and risk factors for UEVT are poorly understood in a hospitalized population., Objective: To assess the prevalence of UEVT in hospitalized patients and study thrombosis risk factors according to their location., Methods: Prospective evaluation of patients hospitalized in a university hospital with clinical and Doppler ultrasound (DUS) assessment of the upper extremities., Results: Of the 400 patients included, 91(22.8 %) had UEVT including 8 (8.8 %) proximal thrombosis, 32 (35.2 %) arm venous thrombosis and 51 (56.0 %) forearm venous thrombosis; 7 (7.7 %) patients with UEVT had a concomitant symptomatic pulmonary embolism. In this population of hospitalized patients, 40 (10 %) had proximal or arm thrombosis and 51 (12.8 %) forearm thrombosis. All patients with UEVT had a venous catheter and 63 (69.2 %) of UEVT patients had therapeutic or prophylactic anticoagulation at the time of DUS evaluation. In multivariate analysis, peripheral intravenous catheter (PIVC) OR 3.71 [1.90; 7.91] (p < 0.001); MID line OR 3.58 [1.46; 8.91] (p = 0.005) and infection disease OR 2.21 [1.26; 4386] (p = 0.005) were associated with UEVT. Central venous catheter OR 66.24 [12.64; 587.03] was associated with proximal UEVT and MID line OR 12.61 [4.64; 35.77] (p < 0.001) with arm UEVT. Forearm UEVT were associated with PIVCOR 10.71[3.14; 67.37] (p = 0.001); infectious disease OR 2.87 [1.48; 5.60] (p = 0.002), iron infusion OR 3.11 [1.23; 7.47] and hospitalization for postpartum OR 4.37 [0.97; 18.06] (p = 0.04)., Conclusion: One in 5 hospitalized patients suffers from UEVT. Proximal venous thrombosis is uncommon. The presence of a catheter and hospitalization for infection are the factors most frequently associated with UEVT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The RIETE score could be specifically useful for identification of low-risk pulmonary embolism (PE) patients for home treatment. However, the external validation of the RIETE score has been limited., Methods: The COMMAND VTE Registry is a multicenter registry enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). The current study population consisted of 1479 patients with acute PE, who were divided into 2 groups; RIETE scores of 0 (N = 260) and ≥ 1 (N = 1219)., Results: The cumulative 10-day and 30-day incidences of a composite endpoint of all-cause death, recurrent PE, or major bleeding were lower in patients with the RIETE score of 0 than in those with the RIETE score of ≥1 (10-day: 0.4 % vs. 6.7 %, P < 0.001, and 30-day: 0.4 % vs. 10.0 %, P < 0.001). The area under the receiver-operating characteristic curve (AUC) in the RIETE score for the 10-day composite endpoint showed numerically better predictive ability than that in the sPESI score (0.77 vs. 0.73, P = 0.07), and the AUC in the RIETE score for the 30-day composite endpoint showed significantly better predictive ability than that in the sPESI score (0.77 vs. 0.71, P = 0.003)., Conclusions: The RIETE score was well validated in the current large real-world registry. The RIETE score of 0 could identify patients with reasonably low risks of the 10-day and 30-day composite endpoint of all-cause death, recurrent PE, or major bleeding., Competing Interests: Declaration of competing interest Dr. Yamashita received lecture fees from Daiichi-Sankyo, Bristol-Myers Squibb, Pfizer, and Bayer Healthcare. Dr. Morimoto reports lecturer's fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol-Myers Squibb and Kowa; advisory board for Sanofi. Dr. Akao received lecture fees from Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare and Daiichi-Sankyo. Dr. Nishimoto received lecture fees from Daiichi-Sankyo, Bristol-Myers Squibb, Pfizer, and Bayer Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The incidence of splanchnic vein thrombosis (SVT) in cancer patients has increased in recent years and its real clinical significance and management can be challenging. This study aimed to describe the clinical presentation and short-term outcomes of patients with cancer-associated SVT., Material and Methods: This was a retrospective observational study of consecutive patients with cancer-associated SVT diagnosed during the period 2015-2020. The primary objective was to describe the clinical presentation of SVT. Patients were clinically classified into two groups based on the presence of symptoms on SVT diagnosis. The main outcomes were overall and SVT-related mortality, major and non-major bleeding rates, and the thrombosis recurrence rate in the first 30 days of follow-up., Results: This study enrolled 203 patients. Intra-abdominal tumors (76 %) and metastatic disease (68 %) predominated. A total of 79 (39 %) patients without symptoms were diagnosed with SVT during a scheduled radiological test and were classified as "asymptomatic", while 124 (61 %) patients presented some potential SVT symptoms and were considered as "symptomatic". Although the 30-day outcomes showed no significant differences between the two groups, mortality in the asymptomatic group was slightly lower compared to the symptomatic group (3 % vs. 10 %, p = 0.085)., Conclusions: Almost 40 % of cases of cancer-associated SVT are asymptomatic. There were no significant differences in short-term outcomes between the symptomatic and asymptomatic patients. More studies are required to better define long-term management and outcomes in these patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Limited data exist on the risk of venous and arterial thromboembolisms (VTE and ATE) in patients receiving cetuximab plus chemotherapy. We aimed to determine the thromboembolic risk of patients with recurrent/metastatic colorectal cancer (CRC) treated with cetuximab plus chemotherapy compared to chemotherapy alone., Methods: This population-based study used nationwide claims data from the Health Insurance Review and Assessment Service of South Korea from 2013 to 2020. Patients with recurrent/metastatic CRC treated with first-line oxaliplatin- or irinotecan-based doublets with or without cetuximab and no secondary prevention for VTE and ATE were included. Primary outcomes were the occurrence of any thromboembolic events, VTE, and ATE, which were determined using the cumulative incidence method incorporating death as a competing event., Results: We identified 19,723 patients (cetuximab plus chemotherapy, N = 7630; chemotherapy alone, N = 12,093). The cumulative incidence of any thromboembolic events in patients with cetuximab plus chemotherapy was significantly higher than in those receiving chemotherapy alone (6-month, 5.62 % vs. 3.58 %, P < 0.0001). The rates of VTE (6-month, 5.11 % vs. 3.28 %, P < 0.0001) and ATE (6-month, 0.53 % vs. 0.32 %, P = 0.0218) were also higher in patients receiving cetuximab plus chemotherapy. In multivariable analysis, cetuximab plus chemotherapy was independently associated with developing any thromboembolic events (hazard ratio [HR], 1.63; 95 % confidence interval [CI], 1.42-1.87), VTE (HR, 1.62; 95 % CI, 1.40-1.87), and ATE (HR, 1.77; 95 % CI, 1.16-2.71)., Conclusions: Cetuximab with irinotecan- or oxaliplatin-based doublet chemotherapy was associated with an increased risk of any thromboembolic events, VTE, and ATE; further studies are warranted to examine the underlying mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Portal vein thrombosis (PVT) is a rare disease in children and may be complicated by portal hypertension (PH), hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHTN) but their incidence and risk factors are unknown., Methods: An observational, retrospective cohort study of all consecutive children (≤18 years) with PVT treated at the Emma Children's Hospital Amsterdam University Medical Centers between January 1996 and January 2022 was conducted to identify the incidence and risk factors of these post thrombotic complications (PTC) in pediatric patients., Results: In total 43/ 703 thrombosis patients had PVT (boys 72.1 %; mean age 1.3 ± 0.5 years). Overall, 51 % of patients developed PH (n = 22), complicated by PPHTN in one of them. In 16 of 22 patients, PVT presented with portal hypertension. Clinically relevant bleeding due to portal hypertension occurred in 13 (59.1 %) patients with PH. The mean age at the first clinically relevant bleeding was 5.1 ± 5.9 years. Risk factors for the development of PH were lack of complete thrombus resolution (OR 24.3, 95 % CI 1.2-7.0; p = 0.008) and unprovoked VTE (OR, 35.4; 95 % CI 1.4-6.3; p = 0.012). Median time from PVT to PH was 137 days (range: 0 days to 5.04 years)., Conclusion: We demonstrated that half of the patients develop PH after PVT, with a lack of thrombus resolution and unprovoked VTE as independent risk factors. This high incidence underlines the importance of long-term standardized follow-up of patients after PVT and standard screening in patients at risk of PTC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Hereditary antithrombin (AT) deficiency type I causes venous thrombosis due to decreased levels of AT antigen in the blood. We identified one novel and one known abnormal variant in two unrelated Japanese families with venous thrombosis. In this study, we analyzed the mechanism by which these abnormal variants cause type I AT deficiency., Materials and Methods: Wild-type and variant AT expression vectors were constructed and transiently expressed in human embryonic kidney 293 cells, and AT antigen levels and N-glycosylation of cell lysates and culture medium were evaluated by western blot analysis. Subcellular co-localization of AT was also examined using confocal microscopy, and chase experiments with cycloheximide and MG132 were performed to investigate the degradation pathway of AT variants., Results: Genetic analysis identified a novel variant, c.613delC (p.Leu205Trpfs ⁎ 79), and the known variant c.283T>C (p.Tyr95His). These AT variants exhibited significantly reduced extracellular secretion compared with the wild-type; N-glycosylation of the AT protein was normal. Co-localization analysis suggested that the transport of these abnormal AT proteins to the Golgi apparatus was impaired. The c.613delC variant was degraded early by the proteasome, suggesting that the c.283T>C variant is stored in the endoplasmic reticulum (ER)., Conclusions: The AT variants identified here synthesize abnormal AT proteins that exhibit suppressed secretion and impaired transport from the ER to the Golgi apparatus. These results provide clues that could help elucidate the mechanism of type I AT deficiency and facilitate therapy development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) require indwelling central venous catheters. The comparative incidence, risk, and outcome of isolated catheter-related deep venous thrombosis (CR-DVT) versus pulmonary embolism/lower-extremity DVT (PE/LE-DVT) remains unclear., Materials and Methods: We conducted a retrospective cohort study for patients undergoing allo-HSCT from 2006 to 2019. CR-DVT and PE/LE-DVT outcomes were screened using ICD codes and radiology reports and confirmed by medical record reviews. Cox regression models were used to assess the association between thrombotic outcomes and pertinent baseline and time-varying covariates. The impact of thrombotic events within 1-year post-transplant (time-varying) on overall mortality was also assessed., Results: Among 2879 patients, the cumulative incidence of isolated CR-DVT and PE/LE-DVT at 12 months was 4.2 % and 4.8 %, respectively. The strongest time-varying predictor for onset of CR-DVT and PE/LE-DVT was hospitalization inpatient status (HR 3.71 [95 % CI 2.16-6.37] and 3.99 [95 % CI 2.00-7.99], respectively). Other overlapping variables included lymphoma diagnosis and BMI > 35 kg/m 2 , whereas acute GVHD grades 2-4 were found to be significantly associated with risk of PE/LE-DVT but not CR-DVT. After adjusting for baseline variables and acute GVHD, the occurrences of CR-DVT and PE/LE-DVT were both independently associated with increased overall mortality (HR 1.58 [95 % CI 1.23-2.02] and HR 1.53 [95 % CI 1.19-1.97], respectively)., Conclusions: We observed a high incidence of both CR-DVT and PE/LE-DVT with overlapping and unique risk factors. CR-DVT was also associated with increased mortality similar to PE/LE-DVT. Standardized strategies targeting high-risk hospitalization periods may help mitigate the development of thrombotic outcomes post-transplant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: In a recent interventional study of cancer patients with newly diagnosed venous thrombosis (VT), we found a high risk of arterial thrombotic events (AT) during treatment with therapeutic doses of apixaban., Methods: Total 298 cancer patients with VT received apixaban as treatment and secondary prophylaxis for up to 36 months. AT was registered as a serious adverse event, and this is a post hoc analysis of risk factors for AT. Clinical risk factors and concomitant medication were assessed through odds ratios (OR) with 95 % confidence interval using multivariate logistic regression. Biomarkers were assessed by non-parametric testing., Results: AT occurred in 16/298 patients (5.4 %, 95 % confidence interval (CI) 3.1-8.6 %). Median leucocyte count at baseline was higher in patients with AT compared with patients without AT (11 vs. 6.8·10 9 /L, p < 0.01). Clinical factors associated with AT were pancreatic cancer (OR 13.7, 95 % CI 4.3-43.1), ovarian cancer (OR 19.3, 95 % CI 2.3-164.4), BMI <25 percentile (OR 3.1, 95 % CI 1.1-8.8) and previous VT (OR 4.4, 95 % CI 1.4-13.7). Pancreatic cancer had a cumulative incidence of AT of 36 % compared with 0.8 % for all other cancers at 6 months (p < 0.01). Non-steroidal anti-inflammatory drugs (OR 4.9, 95 % CI 1.0-26) and antiplatelet treatment (OR 3.8, 95 % CI 1.2-12.2) were associated with AT., Conclusion: In cancer patients with apixaban treated VT, pancreatic cancer was strongly associated with AT. In addition, ovarian cancer, BMI < 25 percentile, previous VT, antiplatelet treatment, non-steroidal anti-inflammatory drug use and high leucocyte count at baseline were associated with AT. The CAP study is registered with the unique identifier NCT02581176 in ClinicalTrials.gov., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a premalignant plasma cell disorder which despite being clinically silent carries an increased risk of venous thromboembolism (VTE). We conducted a population-based study to investigate the risk of VTE in these patients., Methods: We utilized the National Inpatient Sample (NIS) for the year 2016 to compare the incidence of acute VTE between patients who carry the diagnosis of MGUS and those who don't. We excluded hospitalizations with age < 18 years and those that had a diagnosed lymphoma, leukemia, solid malignancy, or other plasma cell dyscrasia. We utilized the ICD-10-CM coding system to search the database for codes of VTE, MGUS, and other comorbid conditions. Multivariate logistic regression models were used for comparative analysis adjusting for demographic characteristics and comorbidities. Baseline comorbidities were described as frequencies and proportions for categorical variables and as medians with interquartile ranges for continuous variables., Results: A total of 33,115 weighted hospitalizations were included in the MGUS group. These were compared to 27,418,403 weighted hospitalizations without the diagnosis of MGUS. The MGUS group had higher odds of composite venous thromboembolism (adjusted OR 1.33, 95 % CI 1.22-1.44), deep vein thrombosis (adjusted OR 1.46, 95 % CI 1.29-1.65), and pulmonary embolism (adjusted OR 1.22, 95 % CI 1.09-1.37)., Conclusion: Patients with MGUS had increased odds of developing acute venous thromboembolism compared to patients with no history of MGUS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Post thrombotic syndrome (PTS) is a serious complication of deep venous thrombosis (DVT). There were always debates on the efficacy of elastic compression stockings (ECS) in prevention for post thrombotic syndrome., Objective: To assess effects of elastic compression stockings and ECS's wearing time on post thrombotic syndrome after diagnosis of deep venous thrombosis., Methods: PubMed, Cochrane Library, Embase, Web of Science were last searched on 23 November 2022 for studies assessing effects of elastic compression stockings or theirs wearing time on post thrombotic syndrome after diagnosis of deep venous thrombosis., Results: 9 randomized controlled trials were included. Wearing elastic compression stockings was associated with a statistically reduction in the overall post thrombotic syndrome rate (RR 0.73, 95 % CI 0.53 to 1.00; P = 0.05; I 2  = 82 %). No significant difference in severe post thrombotic syndrome rate, recurrent deep venous thrombosis rate, and death rate was seen whether wearing elastic compression stockings or not. The pooled effect of studies comparing different wearing time of elastic compression stockings showed no significant difference in post thrombotic syndrome rate, severe and moderate post thrombotic syndrome rate, recurrent deep venous thrombosis syndrome rate and death rate., Conclusions: Wearing ECS can reduce the risk of developing PTS after DVT and a wearing time of less than or equal to 1 year is comparable to 2 years wearing. The results support ECS's role as a foundation therapy for preventing PTS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Different patient characteristics influence the decision to order diagnostic imaging for deep venous thrombosis (DVT) and pulmonary embolism (PE) in different settings (emergency department (ED), hospital, and office). Diagnostic yield is defined as the proportion of tests that report positive results. We hypothesize different patient characteristics are associated with higher or lower diagnostic yield of imaging for DVT and PE in different settings., Methods: We used Optum Clinformatics™ national claims database (2015-2019) to assess the diagnostic yield of imaging for DVT and PE in three settings: (a) ED discharge, (b) Hospitalized, and (c) Office. We studied the patient characteristics associated with diagnostic yield using logistic regression., Results: Diagnostic imaging for DVT and PE was performed in 1,502,417 and 710,263 visits, respectively. Diagnostic yield for DVT and PE was 9.8 ± 0.1 % and 12.7 ± 0.1 %, respectively in the overall cohort. In the ED discharge, hospitalized, and office settings, diagnostic yield for DVT was 10.4 ± 0.1 %, 16.9 ± 0.1 %, and 6.5 ± 0.1 %, respectively, and that for PE 6.4 ± 0.1 %, 18.7 ± 0.1 %, and 8.8 ± 0.2 %, respectively. Of the patients who underwent imaging for DVT, higher diagnostic yield was more likely with thrombophilia, central venous access, and cancer. Of the patients who underwent imaging for PE, higher diagnostic yield was most likely with thrombophilia, respiratory failure, and heart failure or acute myocardial infarction., Conclusions: In each setting, different patient characteristics influence the diagnostic yield of imaging for DVT and PE and can inform clinical practice. Judicious use of imaging for DVT and PE could reduce costs and avoid exposure to radiation and contrast., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Several DVT risk assessment tools have been developed and validated to stratify the patients. The 2005 and 2010 Caprini risk assessment models (RAMs) proved reliable in detecting deep vein thrombosis (DVT) and are widely used worldwide. Although the 2010 version was recently modified, the 2005 version is still more exact and popular in the surgical population. This study aimed to compare the predictive power of the 2005 and 2010 Caprini RAMs in Chinese orthopedic patients at admission and describe the incidence of DVT during hospitalization., Study Design: This prospective cohort study involved 2733 patients from the Arthritis Clinic and Research Center, Orthopedics and Traumatology Department, Orthopedic Oncology Department, and Spinal Surgery Department of Peking University People's Hospital from September 2018 to January 2019. The DVT risk scores and levels were determined for all patients using the 2005 and 2010 Caprini RAMs at admission. The sensitivity and specificity of the two tools were calculated. The patients were divided into the screened and unscreened groups according to whether or not a Doppler ultrasound (DUS) was performed. Depending upon the DUS results, the patients were divided into the DVT and non-DVT groups. The receiver operation characteristic (ROC) curve and the area under the curve (AUC) were evaluated to compare the predictive power., Results: Eighty-four patients had DVT in the four orthopedic departments, and the incidence of DVT was 3.1 %-17.2 %. The scores between the 2005 and 2010 Caprini RAMs differed (P < 0.001) among orthopedic patients at admission. Among DVT patients, the highest-risk patients accounted for 63.5 % and 52.9 % based on the 2005 and 2010 Caprini RAMs, respectively. The AUCs of the 2005 and 1020 Caprini RAMs were 0.669 ± 0.030 and 0.648 ± 0.032, respectively. There were no significant differences between the two ROC curves (P = 0.164)., Conclusion: The 2005 and 2010 Caprini RAMs showed a similar predictive power in detecting DVT, but neither met the high sensitivity criteria for screening DVT in orthopedic patients. The incidence of DVT in orthopedic patients was relatively high during hospitalization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Residual venous obstruction (RVO) after deep vein thrombosis (DVT) is considered a risk factor of recurrent venous thromboembolism (VTE), arterial events and post-thrombotic syndrome (PTS). We hypothesized thrombo-inflammatory markers might be associated with RVO and clinical outcomes., Materials and Methods: In a DVT cohort with routine RVO-assessment and 5-year follow-up, patients were invited for blood withdrawal after stopping anticoagulants. Thrombin generation potential, coagulation enzyme:inhibitor complexes, soluble platelet markers and clinical markers were measured in platelet-poor plasma. Associations were represented as odds ratio (OR) or hazard ratio (HR) per standard deviation., Results: Patients with RVO (102/306, 33 %) had higher rates of PTS (24 vs. 12 %, p = 0.008), but similar rates of recurrence (16 vs. 15 %, p = 0.91) and arterial events (7 vs. 4 %, p = 0.26). RVO was associated with thrombin peak height (OR 1.40 [1.04-1.88]), endogenous thrombin potential (ETP, OR 1.35 [1.02-1.79]), and CRP (OR 1.74 [1.10-2.75]). Recurrent VTE was associated with ETP (HR 1.36 [1.03-1.81]), FXIa:C 1 -inhibitor (HR 1.34 [1.04-1.72]), thrombin:antithrombin (HR 1.36 [1.16-1.59]), soluble P-selectin (HR 2.30 [1.69-3.11]), soluble glycoprotein VI (sGPVI, HR 1.30 [1.01-1.69]), D-dimer (HR 1.56 [1.31-1.86]), and factor VIII (HR 1.44 [1.15-1.82]). Arterial events were associated with sGPVI (HR 1.80 [1.25-2.59]). PTS was not associated with any marker., Conclusions: Our findings indicate RVO was associated with thrombo-inflammation, but this did not predict clinical outcomes in this setting. Importantly, we found recurrent VTE was associated with ongoing coagulation and platelet activation in patients well beyond the acute phase of DVT. Furthermore, sGPVI indicated an increased risk of arterial events, highlighting the role of platelets in arterial thrombosis following DVT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Human genetic studies based on the Marburg I polymorphism in the factor VII activating protease (FSAP) encoding gene, analysis of FSAP activity in plasma and biochemical characterization of FSAP substrates indicate a possible causal link between FSAP activity and venous thrombosis. We hypothesized that a direct standardized assay to measure FSAP activity in plasma could provide convincing arguments for or against such a potential link. Using Ac-Pro-DTyr-Lys-Arg-AMC as a highly specific and sensitive substrate, histones as a trigger to activate pro-FSAP and plasma-purified active FSAP as a calibrator, we have developed a fluorogenic kinetic assay that reveals the FSAP generating potential in human plasma in real time. This assay is similar to the thrombin generation assay and allows analysis of lag phase, time to peak and velocity, as well as peak FSAP and the endogenous FSAP potential (EFP) of plasma samples. Carriers of the Marburg I polymorphism showed clearly delayed FSAP generation and lower peak FSAP and EFP level. There were no significant differences in all FSAP activity parameters between plasma from patients with a history of venous thrombosis and controls. When excluding Marburg I carriers, which were evenly distributed between groups, delayed FSAP generation significantly correlated with venous thrombosis in postmenopausal women. The novel FSAP activity assay is robust and easy to perform and will be a useful tool for analyzing plasma FSAP activity, also, in other pathophysiological conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: The incidence of venous thromboembolism (VTE) in children is increasing, attributed in part to increased utilization of central venous catheters (CVCs). Children with protein losing disorders (PLDs) and low serum albumin may have an increased incidence of thrombosis. We sought to determine the prevalence of PLDs and hypoalbuminemia at the time of diagnosis of VTE in pediatric patients and its relationship to central venous catheters., Methods: We performed a single institution retrospective study of 65 consecutive hospitalized pediatric patients with an acute VTE. Data collected included clinical diagnoses, type of thrombosis, presence or absence of a CVC, and serum albumin level, if available., Results: Of 65 patients with acute VTE, 51 % (33/65) had catheter-related thrombosis (CRT), including 71 % (19/27) of patients &lt;12 years of age and 37 % (14/38) of patients aged 12 to 23 (P = 0.008). Eleven VTEs occurred in patients with a diagnosis of a PLD; of these, ten (91 %) were CRT and one (9 %) was a non-CRT (P = 0.003). Serum albumin levels obtained within four days of diagnosis of VTE were available for 38 patients. An albumin level below the lower limit of the age-adjusted normal reference range was documented in 27/38 (71 %) patients with VTE compared to 1011/3028 (33 %) of all pediatric patients admitted to the hospital during a two-year period (P &lt; 0.0001). Albumin levels were low in 19/22 (86 %) patients with CRT compared with 8/16 (50 %) patients with non-CRT (P = 0.019)., Conclusion: Low serum albumin levels are highly prevalent among pediatric patients with VTE, especially in those patients with CRT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Cyclin-dependent kinase inhibitors (CDKIs) may increase the risk of thrombotic events of endocrine therapy (ET) in women with hormone-sensitive, HER2-negative advanced breast cancer (BC). Aim of our systematic review is the estimate of the risk of venous and arterial thromboembolism in women with advanced BC treated with CDKIs in phase III randomized controlled trials (RCTs)., Methods: Studies were identified by electronic search of MEDLINE, EMBASE and CENTRAL database until October 2021. Risk of bias was assessed according to Cochrane criteria. Differences in thrombotic outcomes among groups were expressed as pooled odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using both a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I 2 statistic., Results: We included 7 phase III RCTs (4415 patients) for a total of 15 papers (7 were the first published paper and 8 the follow-up papers). Reporting of thrombotic events was at high risk of bias. Women with advanced BC treated with CDKIs and ET had a two to threefold increased risk of venous thromboembolic event (VTE) compared to ET plus placebo arm [OR 2.90 (95% CI 1.32, 6.37; I 2  = 0%) in the main papers and OR 2.20 (95% CI 0.93, 5.20; I 2  = 49%) in the follow-up papers]. Women with advanced BC treated with CDKIs and ET had a non-significant mild increased risk of arterial thromboembolic event compared to ET plus placebo arm [OR 1.22 (95% CI 0.47, 3.18 I 2  = 0%)]., Conclusions: CDKIs in combination with endocrine therapy are associated with a two to threefold higher risk of VTE in comparison to endocrine therapy alone in women with advanced breast cancer, while the risk of arterial events is still to be defined., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Recombinant neorudin (EPR-hirudin, EH) is an inactive prodrug that is converted to its active metabolite, hirudin variant 2-Lys47 (HV2), at the thrombus site. We aimed to investigate the mechanism underlying site-selective bioconversion of EH to HV2 at the thrombus target site and metabolic transformation of EH in patients with deep vein thrombosis (DVT)., Materials and Methods: Metabolites in healthy volunteer plasma and urine after intravenous administration of EH were determined to elucidate how EH was metabolised after releasing HV2 at the target site in patients with DVT. After intravenous administration of EH in rats with venous thrombosis, the concentrations of EH in the blood and thrombus and the antithrombotic activity of EH were measured to predict whether EH could release HV2 at the thrombus site to exert anticoagulant effect in patients with DVT., Results: In healthy volunteers, EH and HV2 were predominantly excreted in the urine. Nine EH metabolites and ten HV2 metabolites truncated at the C-terminal were identified as N-terminal fragments, and these had the same cleavage sites. In rats with venous thrombosis, the area under the curve ratio of HV2 between the thrombus and blood was 29.5. The weight of wet thrombus was decreased with the production of HV2 by the cleavage of EH. The prothrombin time (PT) and prothrombin time (TT) changed proportionally to the concentration of EH and HV2 in the blood., Conclusion: EH selectively accumulates and releases HV2 in the thrombus to exert antithrombotic effects, thus lowering the bleeding risk. Moreover, after conversion, EH may follow the same metabolic profile as that of HV2 in patients with DVT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The value of D-dimer testing for the diagnosis of thrombosis in unusual sites is not properly established and evidence is scarce. We performed a systematic review of the literature., Methods: The search was conducted in MEDLINE and Cochrane Library for papers published in the last 10 years including different presentations of thrombosis in unusual sites. Twenty-three articles were included, from January 1, 2008, to December 31, 2018, comprising 3378 patients with thrombosis in unusual sites (upper extremity deep vein thrombosis, cerebral vein thrombosis and splanchnic vein thrombosis). The Newcastle-Ottawa scale was used to assess the quality of the studies., Results: Two articles were related to upper extremity thrombosis, showing a high sensitivity and negative predictive value for D-dimer testing. Twelve articles concerned cerebral vein thrombosis, concluding that the timing of D-dimer testing was important, and that patients with a shorter duration of symptoms showed higher D-dimer levels. Sensitivity and specificity in these patients ranged from 58% to 97% and from 77% to 97.5%, respectively. Nine articles were related to splanchnic vein thrombosis. One described a population of patients with mesenteric venous thrombosis, and the rest included patients with portal vein thrombosis. The D-dimer testing methods and the proposed cut-off levels were remarkably different among the included studies., Conclusion: D-dimer testing should not be currently recommended for the diagnosis of thrombosis in unusual sites as a first line diagnostic tool. The development of algorithms combining biomarkers such as D-dimer and clinical decision tools could improve the diagnosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Eponyms are honorific terms ascribed to individuals who discovered a sign, test, syndrome, technique, or instrument. Despite some contentions, eponyms continue to be widely ingrained and incorporated into the medical literature and contemporary language. Physical signs are considered unreliable methods alone for detecting deep venous thrombosis (DVT). The accuracy of the majority of these signs is unknown. For those signs that have been studied, there are a number of methodological limitations hindering the ability to draw meaningful conclusions about their accuracy and validity in clinical practice. Nevertheless, some findings when present and used in conjunction with other key signs, symptoms, and aspects of the patients history may be useful in further supporting the clinical suspicion and likelihood of DVT and/or pulmonary embolism (PE) or venothromboembolism (VTE). These signs also provide the means to better recognize the relationship between clinical findings and VTE. The acquisition of historical knowledge about these signs is important as it further enhances our understanding and appreciation of the diagnostic acumen that physicians were required to employ and to diagnose VTE prior to the advent of advanced imaging methods. Described in this paper is a brief overview of thrombosis as enumerated by Rudolf Virchow, and eponymous signs described in the late eighteenth and nineteenth centuries., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Venous thromboembolic events (VTE) occur in more than 5% of hospitalized patients with acute CMV infection. In immunocompetent patients, splanchnic vein thrombosis (SVT) and splenic infarction have been suggested to represent approximately half of the published cases of CMV-associated VTE. We performed a systematic review of the literature with the aim to describe epidemiology, clinical characteristics, treatment, and natural history of CMV-associated SVT in immunocompetent patients., Methods: Studies were identified by a PubMed and Google Scholar electronic database search until January 2018. All published papers describing immunocompetent adults with SVT occurring concomitantly to an acute CMV infection were included., Results: Forty-four patients with CMV-associated SVT were described in 38 papers. Twenty-three patients were male, mean age was 38.1 years (range, 17-68). Symptomatic SVT occurred in 31 patients, incidental SVT in 13 patients. In symptomatic SVT, an acute and severe onset with small bowel or splenic infarction required surgical treatment for resolution in 22.6% of cases. Anticoagulation induced both a favourable clinical outcome and a recanalization of SVT in more than 70% of the remaining cases. In incidental SVT, a favourable clinical outcome and a complete recanalization of SVT by anticoagulation were reported in more than 80% of cases. No patient with CMV-associated SVT died and no SVT recurrence was reported., Conclusions: CMV-associated SVT has probably a favourable clinical course in most patients. Only future, well-designed, prospective studies with an adequate follow-up will allow to confirm the data of published cases., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The prevalence of calreticulin (CALR) mutations in splanchnic vein thrombosis (SVT) varies among studies. The role of routine screening for CALR mutations in SVT patients remains a debate., Aim: To synthesize the prevalence of CALR mutations according to the different types (i.e., Budd-Chiari syndrome [BCS] and portal vein thrombosis [PVT]) and characteristics (i.e., with and without myeloproliferative neoplasms [MPNs] and JAK2V617F mutation) of SVT patients., Methods: Eligible studies were searched by the PubMed and Embase databases. The study quality was assessed according to the STROBE checklist. The proportion of CALR mutations was pooled by using a random-effects model. The heterogeneity and publication bias were calculated., Results: Eleven papers were included. The study quality was moderate to high. The pooled proportion of CALR mutations was 1.21%, 1.41%, and 1.59% in SVT, BCS, and PVT patients, respectively; 1.52%, 1.03%, and 1.82% in these patients without JAK2V617F mutation, respectively; 3.71%, 2.79%, and 7.87% in these patients with MPN, respectively; and 15.16%, 17.22%, and 31.44% in these patients with MPN but without JAK2V617F mutation, respectively. Only the meta-analysis examining the prevalence of CLAR mutations in BCS patients with MPN but without the JAK2V617F mutation showed statistically significant heterogeneity. Statistically significant publication bias was seen only in the meta-analysis examining the prevalence of CALR mutations in SVT patients without the JAK2V617F mutation., Conclusion: Screening for CALR mutations may have a role in SVT patients with a high probability of MPN in whom the JAK2V617F mutation has been excluded., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Post-thrombotic syndrome (PTS) is the most common long-term complication after deep vein thrombosis (DVT) developing in up to 70% of the patients. PTS is diagnosed on the basis of typical symptoms and signs of the lower limb with a previous DVT, but no objective diagnostic test exists. A number of diagnostic scales have been developed primarily for research purposes. An optimal diagnostic test for PTS should be reliable and easy to use, sensitive and specific, able to grade PTS severity, and to identify changes over time. We have identified reports on seven diagnostic scales that have been used for the diagnosis of PTS; the Widmer classification, the Clinical-Etiological-Anatomical-Pathological (CEAP) classification, the Venous Clinical Severity Score (VCSS), the Brandjes scale, the Ginsberg measure, the Villalta scale, and the Patient-reported Villalta scale. The aim of this paper was to review and present the existing diagnostic scales for PTS in adults and their utility in clinical studies., (Copyright © 2017. Published by Elsevier Ltd.)

Factor V Leiden (FVL) is an inherited autosomal dominant condition that is identified in 20%-50% of patients with venous thromboembolic diseases and 5-8% of the population in Canada. People with FVL are often called hypercoagulable, and have a five-fold increase in the risk of venous thrombosis. There is a low prevalence of FVL among patients with fatal pulmonary embolism (PE) and a higher incidence of deep vein thrombosis (DVT) than PE in patients with FVL. This has been referred to as the FVL paradox in thrombosis. We wished to test whether FVL and normal patients are at the same risk of initial thrombus formation, expect FVL patients present with symptomatic DVT while normal patients do not present, because the small asymptomatic DVT in normal patients embolizes to become an asymptomatic PE. Therefore, to explain why patients with FVL are more likely to present with a DVT rather than a PE we will study DVT stability in FVL mice using a modification of our previously published mouse model of venous thrombus stability. Platelets were fluorescently labeled using CD41 fab fragments conjugated to an Alexa Fluor 488. DVT was induced using a ferric chloride saturated filter paper on the femoral vein of female mice. We chose conditions such that only a small thrombus developed in wild type (WT) mice, and then compared them to thrombi in FVL heterozygous (F5L/+) and FVL homozygous (F5L/L) mice. Intravital videomicroscopy recorded embolic events leaving the thrombus and the thrombus sizes every 10 minutes for 2 hours. Lungs were harvested sectioned and stained for presence of PE. Although thrombus size remained small in WT mice, it significantly increased over time in F5L/+ and F5L/L mice. The number of total and large embolic events, and the percent of thrombus that embolized was significantly decreased in F5L/+ and F5L/L mice compared to WT mice. Previously we have correlated increased large embolic events with increased PE burden. FVL mice had significantly reduced PE burden compared to WT mice. Mice with F5L had higher F1.2 levels than in WT, consistent with increased thrombin generation. This suggests that in noncarriers (reflected by WT), a minor insult initially resulting in a small DVT tends to remain small and asymptomatic, due to the embolization. Alternatively, the same insult in people with FVL (reflected by F5L/L) leads to thrombus growth due to less embolization and thus development of symptomatic DVT, but no PE. [ABSTRACT FROM AUTHOR]

Coagulation and inflammatory parameters are mildly altered in children with SARS-CoV-2 (COVID-19) infection, and laboratory evidence of a proinflammatory and procoagulant state has been noted in multisystem inflammatory syndrome in children (MIS-C). It is not clear whether this pediatric condition is related to thrombotic events. With this study we reviewed the literature for thrombotic complications in children with COVID-19 infection and MIS-C. We searched the Medline PubMed Advanced Search Builder, Scopus, Web Of Science, and Google Scholar electronic databases (until 1 January 2021) using the medical subject headings (MeSH) terms and text words (their combinations and truncated synonyms): (THROMBOSIS OR THROMBOPHILIA) AND (CHILD OR CHILDREN OR INFANT) AND (COVID-19 OR SARS-CoV-2). Inclusion criteria were children with COVID-19 or SARS-COV-2 infection. The search was limited to articles published in English. Exclusion criteria were: reviews of published studies, studies published only as abstracts, letters or conference proceedings, discussion papers, animal studies, or editorials. After screening for duplicates, the initial search yielded 86 records: 12 were case reports involving 19 children; comorbidities were absent or mild in 73.7%. The most common site of thrombosis the lung (21%); the most often used drug was heparin (42%). Two studies were an international survey (n = 337 patients) and a large multicenter study (n = 186 patients with MIS-C). The risk of ischemic stroke in SARS-CoV-2 infection (0.82%) and deep venous thrombosis in MIS-C (4.3%) was lower in children than in adults. Thrombodic or thromboembolic events are rare in pediatric patients with COVID-19 infection and MIS-C. Nonetheless, as in adults, a high index of suspicion should be maintained in children with COVID-19 infection or MIS-C, particularly in those with comorbidities predisposing to thrombotic events. • MIS-C is characterized by laboratory evidence of a procoagulant state. • It is not clear whether MIS-C is related to thrombotic events. • Thrombotic events are rare in children with COVID-19 infection or MIS-C. • High index of suspicion for thrombotic events should be maintained in childhood. [ABSTRACT FROM AUTHOR]

Introduction: Deep vein thrombosis (DVT) is a life-threatening complication in intensive care unit (ICU) patients and DVT incidence is used as a marker of quality care. In our ICU an educational program for implementation of DVT prophylaxis and ultrasound screening resulted in a remarkable decrease in DVT incidence which fell from 11.6% to 4.7%. The aim of this paper is to investigate a 4-year long persistent quality improvement of DVT prophylaxis obtained through the implementation of our educational intervention., Methods: The study was composed of three phases: after the first retrospective investigation of DVT incidence and the evidence of the efficacy of the educational program, this third phase investigates the 2-year long sustainability and persistence in the fall of DVT incidence by the adoption of 1) an electronic form for DVT prophylaxis prescription, 2) a nursing protocol for the application of elastic stokes and 3) a personalized form with a check-list dedicated to DVT prophylaxis. Ultrasound DVT screening was performed twice a week by ICU clinicians., Results: The application of DVT prophylaxis was associated with a very low incidence of DVT (2.6%) not entirely attributable to changes in characteristics of enrolled patients and/or to less intensive DVT ultrasound screening when compared to the preceding phases. Mean mechanical ventilation duration and ICU length of stay were short and similar to those of the second phase and ICU mortality did not change., Conclusions: The direct involvement of ICU clinicians and nurses in the application of DVT prophylaxis and in DVT diagnosis markedly contributed to maintain a low DVT incidence over time, despite the high turnover of patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Direct oral anticoagulants (DOACs) have emerged as safe and effective alternatives to Vitamin-K antagonists for treatment and prevention of arterial and venous thrombosis. Due to their novelty, pharmacokinetic DOAC drug-drug interactions (DDIs) that result in clinical adverse events have not been well-documented. This study aims to systematically review reported pharmacokinetic DDIs resulting in clinical adverse events through documented observational evidence to better inform clinicians in clinical practice. A comprehensive literature review of EMBASE, MEDLINE, and Ovid HealthStar was conducted through March 10th, 2020. Two independent reviewers screened and extracted data from eligible articles according to pre-established inclusion and exclusion criteria. Articles reporting bleeding or thrombotic outcomes in non-controlled (observational) settings resulting from suggested pharmacokinetic DOAC DDIs were included. A total of 5567 citations were reviewed, of which 24 were included following data extraction. The majority were case reports (n = 21) documenting a single adverse event resulting from a suspected DOAC DDI, while the remaining papers were a case series (n = 1) and cohort studies (n = 2). The most commonly reported interacting drugs were amiodarone and ritonavir (bleeding), and phenobarbital, phenytoin, and carbamazepine (thrombosis). Bleeding events more often resulted from a combined mechanism (P-glycoprotein AND CYP3A4 inhibition), whereas thrombotic events resulted from either combined OR single P-glycoprotein/CYP3A4 induction. Current literature evaluating the real-world risk of DOAC DDIs is limited to few case reports and retrospective observational analyses. Clinicians are encouraged to continue to report suspected drug interactions resulting in adverse events. • Patients on direct oral anticoagulants (DOACs) can encounter drug interactions. • Drug interactions can alter the amount of DOAC in a patient's system. • Research on DOAC interactions is currently limited and larger studies are required. • Health providers should continue to be cautious with potential DOAC interactions. [ABSTRACT FROM AUTHOR]

Introduction: Deep vein thrombosis (DVT) is one of the common complications of orthopedic surgery. Low molecular weight heparin (LMWH) is a usually used agent for DVT, but it would increase the risk of bleeding. LRRFIP1 has been shown to play an important role in the formation of thrombosis. Therefore, we investigated the effect of LRRFIP1 shRNA lentivirus on DVT in mice., Materials and Methods: Lentiviral Vectors carrying LRRFIP1 shRNA were constructed and transfected into cultured mouse bone marrow cells (BMCs). Male ICR mice were irradiated with a single dose of 9.5 Gy and then were injected with different agents through the tail vein. Stasis venous thrombosis was induced by inferior vena cava (IVC) ligation. Mice were sacrificed on the 1st, 3rd and 7th day post operation and the thrombi were removed, blotted the excess blood on it with filter paper and immediately weighed. P-selectin and d-Dimer were determined by enzyme-linked immunosorbent assay (ELISA)., Results: LRRFIP1 shRNA significantly suppressed the expression of LRRFIP1 in the thrombi. In contrast, low molecular weight heparin (LMWH) and negative shRNA exhibited little effect on the expression of LRRFIP1. LRRFIP1 shRNA, LMWH and negative shRNA inhibited the thrombus formation in vivo significantly. The plasma P-selectin and d-Dimer levels were significantly increased after IVC ligation. LRRFIP1 shRNA significantly decreased the plasma P-selectin and d-Dimer levels. However, LMWH and negative shRNA showed little effects on the levels of plasma P-selectin and d-Dimer., Conclusion: LRRFIP1 shRNA might represent a promising prevention strategy for DVT., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Patients with antiphospholipid antibodies (APLA) are at risk of arterial thromboembolism (ATE) or venous thromboembolism (VTE). The true strength of the association between APLA and first TE is unknown as there are no prospective studies of a large, well-characterized inception cohort of matched patients with and without APLA. Thus, evidence-based treatment recommendations for primary prophylaxis of TE in such patients cannot be made. Optimal therapy of patients with recent TE and APLA remains controversial; although there is no doubt that some such patients have a malignant hypercoagulable state characterized by resistance to "usual intensity" anticoagulation; recent evidence suggests that most such patients are adequately treated with "usual therapy". After warfarin discontinuation, such patients appear to be at increased risk of recurrent TE, as demonstrated in a series of studies of discontinuation of secondary TE prophylaxis in patients with APLA and venous TE (VTE). Because of this increased risk of recurrent TE, after anticoagulants are discontinued, most "experts" recommend extended duration therapeutic dose warfarin for such patients. This paper will briefly review this evidence.

The treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) in pregnant patients is challenging for several reasons. Coumarins can cause embryopathy and other adverse effects in the fetus. Although unfractionated heparin and low-molecular-weight heparins, the cornerstones of initial therapy, are safe for the fetus, they can have significant maternal side effects, including osteoporosis and thrombocytopenia. Because they must be given parenterally, long-term administration is inconvenient. Further, although low-molecular-weight heparins probably cause less maternal osteoporosis and thrombocytopenia than unfractionated heparin, the appropriate dosing regimens for prevention and treatment of thrombosis during pregnancy have not been established. In addition, there is a paucity of reliable information on the incidence of venous thromboembolism and the risk of recurrent thrombosis during pregnancy. This paper briefly reviews the areas of controversy and provides recommendations for the treatment and prophylaxis of acute deep vein thrombosis and pulmonary embolism in pregnant patients.