Association between tunneled catheter placement and catheter-associated deep venous thrombosis in adults with inflammatory bowel disease receiving home parenteral nutrition: A retrospective cohort study.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of thrombosis. They often need parenteral nutrition (PN) requiring intravenous access for prolonged periods. We assessed the risk of deep vein thrombosis (DVT) associated with peripherally inserted central catheters (PICCs) and tunneled catheters for patients with IBD receiving home PN (HPN). METHODS: Using the Cleveland Clinic HPN Registry, we retrospectively studied a cohort of adults with IBD who received HPN between June 30, 2019 and January 1, 2023. We collected demographics, catheter type, and catheter-associated DVT (CADVT) data. We performed descriptive statistics and Poisson tests to compare CADVT rates among parameters of interest. We generated Kaplan-Meier graphs to illustrate longevity of CADVT-free survival and a Cox proportional hazard model to calculate the hazard ratio associated with CADVT. RESULTS: We collected data on 407 patients, of which, 276 (68%) received tunneled catheters and 131 (32%) received PICCs as their initial catheter. There were 17 CADVTs with an overall rate of 0.08 per 1000 catheter days, whereas individual rates of DVT for PICCs and tunneled catheters were 0.16 and 0.05 per 1000 catheter days, respectively (P = 0.03). After adjusting for age, sex, and comorbidity, CADVT risk was significantly higher for PICCs compared with tunneled catheters, with an adjusted hazard ratio of 2.962 (95% CI=1.140-7.698; P = 0.025) and adjusted incidence rate ratio of 3.66 (95% CI=2.637-4.696; P = 0.013). CONCLUSION: Our study shows that CADVT risk is nearly three times higher with PICCs compared with tunneled catheters. We recommend tunneled catheter placement for patients with IBD who require HPN infusion greater than 30 days.

Management of extensive portal vein thrombosis via thrombolysis and thrombectomy without underlying liver disease: A case report.

Portal vein thrombosis (PVT) is a rare condition, particularly in non-cirrhotic patients. Anticoagulation remains the mainstay of the treatment. Extensive PVT can lead to variceal bleeding, ascites, bowel ischemia, and hypersplenism. The role of thrombolysis and thrombectomy in these patients remains unclear. However, there is evidence that local thrombolysis and thrombectomy should be considered in those who remain symptomatic on anticoagulation and are at risk of complications with acute PVT.

Validation of the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) risk scores for venous thromboembolism and bleeding in an independent population.

Background: Multiple guidelines recommend assessment of bleeding and venous thromboembolism (VTE) risk in adult medical inpatients to inform prevention strategies. There is no agreed-upon method for VTE and bleeding risk assessment. Objectives: To validate the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) VTE and bleeding risk scores in an independent population. Methods: In this retrospective study, we calculated the IMPROVE VTE and bleeding risk scores in medical inpatients admitted between 2010 and 2019 at the University of Vermont Medical Center (UVMMC). Patients were followed for in-hospital bleeding events while hospitalized and VTE events while hospitalized and for 3 months after discharge. We assessed calibration of the risk models by comparing the observed incidence of events in the UVMMC and IMPROVE populations across the published risk categories. We also assessed performance of the IMPROVE risk factors after refitting the models in the UVMMC population. Discrimination was assessed using the area under the receiver operating characteristic curve (AUC). Results: VTE occurred in 270 (1.1%) of 23,873 admissions, with 92 (34%) occurring during admission, and bleeding occurred in 712 (4.7%) of 15,240 admissions. When the IMPROVE-VTE risk factors were refitted to the UVMMC data, the AUC was 0.64. When the IMPROVE bleeding risk factors were refitted to the UVMMC data, the AUC was 0.67. The IMPROVE-VTE score tended to overestimate risk at higher scores, and the IMPROVE bleeding score underestimated risk at lower scores and overestimated risk at higher scores. Conclusion: While the refitted IMPROVE VTE and bleeding risk scores had reasonable model fit, the scores were poorly calibrated and did not reliably identify or differentiate patients at risk for VTE and bleeding. Different methods are needed for risk assessment of medical inpatients for VTE and bleeding risk.

The fatty liver index and risk of incident venous thromboembolism: the Tromsø Study.

Background: For the relationship between obesity and venous thromboembolism (VTE), nonalcoholic fatty liver disease (recently termed metabolic dysfunction-associated steatotic liver disease) is of interest given the hepatic role in hemostasis. Objectives: We aimed to assess the association between the fatty liver index (FLI), as a proxy for nonalcoholic fatty liver disease, and VTE risk in a population-based cohort. Methods: Data from the Tromsø 4 (1994-1995) and 6 (2007-2008) surveys were used to calculate the FLI in 9870 participants. All VTEs were recorded up to December 31, 2020. We used Cox regression to estimate hazard ratios for VTE with 95% CIs by FLI groups defined according to clinical cut-offs (<30, 30-59, and ≥60). Because waist circumference and body mass index (BMI) are main determinants for FLI calculation, we assessed the potential contribution of FLI to VTE risk beyond these body fat measures. Results: During a median follow-up of 13.1 years, 507 incident VTEs occurred. Compared with the reference group (FLI < 30), the hazard ratios for VTE were 1.5 (95% CI, 1.1-1.9) and 1.8 (95% CI, 1.4-2.3) for the FLI 30-59 and ≥60 groups, respectively, in models adjusted for age, sex, alcohol intake, educational level, and physical activity. The association of FLI with VTE was no longer observed, with risk estimates close to unity, when participants were stratified by clinical categories of waist circumference and BMI. Conclusion: Higher values of the FLI were associated with a higher VTE risk. This association was explained by waist circumference and BMI, which reflect excessive body fat deposition and are determinants of the FLI.

Cohort study of prediction of venous thromboembolism in emergency department patients with extremity symptoms.

Despite diagnostic algorithms, identification of venous thromboembolism (VTE) in emergency departments (ED) remains a challenge. We evaluated symptoms, background, and laboratory data in 27,647 ED patients presenting with pain, swelling, or other symptoms from the extremities, and identified predictors of VTE diagnosis within one year. Predictors of a clinical decision to perform phlebography, ultrasound, or computer tomography (CT) angiography of pelvic, lower, or upper extremity veins, CT of pulmonary arteries, or pulmonary scintigraphy at the ED or within 30 days, and the results of such investigations were also evaluated. A total of 3195 patients (11.6%) were diagnosed with VTE within one year. In adjusted analysis of patients in whom all laboratory data were available, a d-dimer value ≥ 0.5 mg/l (odds ratio [OR]: 2.602; 95% confidence interval [CI] 1.894-3.575; p < 0.001) at the ED and a previous diagnosis of VTE (OR: 6.037; CI 4.465-8.162; p < 0.001) independently predicted VTE within one year. Of diagnosed patients, 2355 (73.7%) had undergone imaging within 30 days after the ED visit and 1730 (54.1%) were diagnosed at this examination. Lower age (OR: 0.984; CI 0.972-0.997; p = 0.014), higher blood hemoglobin (OR: 1.023; CI 1.010-1.037; p < 0.001), C-reactive protein (OR: 2.229; CI 1.433-3.468; p < 0.001), d-dimer (OR: 8.729; CI 5.614-13.574; p < 0.001), and previous VTE (OR: 7.796; CI 5.193-11.705; p < 0.001) predicted VTE on imaging within 30 days, whereas female sex (OR 0.602 [95% CI 0.392-0.924]; p = 0.020) and a previous diagnosis of ischemic heart disease (OR 0.254 [95% CI 0.113-0.571]; p = 0.001) were negative predictors of VTE. In conclusion, analysis of 27,647 ED patients with extremity symptoms confirmed the importance of well-established risk factors for VTE. Many patients developing VTE within one year had initial negative imaging, highlighting the importance of continued symptom vigilance.

Antiplatelet and Antithrombotic Properties of Compound L-36, a 6H-1,3,4-Thiadiazine Derivative.

Compound L-36, a new derivative of 6H-1,3,4-thiadiazine, was studied in in vitro and in vivo experiments. This compound exhibits high antiplatelet and antithrombogenic activity. In in vitro experiments, compound L-36 by its antiplatelet activity (by IC50) was superior to acetylsalicylic acid by 9.4 times. In in vivo experiments, compound L-36 by its ED50 value was close to the comparison drug. On the model of pulmonary artery thrombosis, compound L-36 ensured better survival of experimental animals than acetylsalicylic acid. Morphological studies showed that compound L-36 effectively attenuated the thrombosis processes in the pulmonary tissue induced by intravenous injection of a thrombogenic mixture (epinephrine and collagen).

Expression of fibroblast activation protein-α in human deep vein thrombosis.

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.

Recurrence in isolated distal DVT after anticoagulation: a systematic review and meta-analysis of axial and muscular venous thrombosis.

OBJECTIVE: To identify recurrent venous thromboembolism (VTE) after discontinuation of anticoagulation in patients with isolated distal deep vein thrombosis based on its anatomic localization (axial or muscular veins). METHODS: Data were sourced from PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases in the time period up to October 2023. The study followed PRISMA guidelines using a registered protocol (CRD42023443029). Studies reporting recurrent VTE in patients with axial or muscular DVT were included in the analysis. RESULTS: Five studies with a total of 1,403 participants were evaluated. The results showed a pooled odds ratio of 1.12 (95% confidence interval 0.77-1.63) between axial and muscular DVT. Heterogeneity was low (I2 = 0%, p = 0.91) and there was no significant difference in the rate of recurrent VTE between axial and muscular DVT in each subgroup. CONCLUSIONS: Muscular and axial DVT showed comparable recurrent VTE rates after anticoagulation. However, uncertainties regarding the possibility of recurrence affecting the popliteal vein or resulting in pulmonary embolism following muscular DVT anticoagulation persisted. Randomized trials in patients with isolated distal DVT are still needed to clarify its prognosis for different anatomical thrombus locations.

Heparin-Induced Hemorrhagic Bullous Dermatosis: A Rare Complication of Unfractionated Heparin.

We present a case of an 82-year-old female with a significant medical history of hypertension and Alzheimer's disease who developed heparin-induced hemorrhagic bullous dermatosis during treatment for a subsegmental pulmonary embolism. The patient was admitted with lower extremity edema and cyanosis, diagnosed with a subsegmental pulmonary embolism, and started on therapeutic doses of unfractionated heparin. On the sixth day of heparin therapy, she developed abdominal bloating and a diffuse exanthematous rash, which progressed to hemorrhagic bullae on the plantar and dorsal aspects of her feet, alongside extensive purpura on her legs. Laboratory findings revealed thrombocytopenia. Multidisciplinary consultations confirmed the diagnosis of heparin-induced hemorrhagic bullous dermatosis. Management included continuing unfractionated heparin with close monitoring, supportive topical treatments, and a subsequent transition to rivaroxaban. The patient's condition improved significantly, and she was discharged in stable condition. This case highlights the importance of recognizing rare adverse reactions to heparin and raises the question of preventive measures or risk factors related to this manifestation.

Genetic evidence for a causal link between gut microbiota and arterial embolism and thrombosis: a two-sample Mendelian randomization study.

Background: Previous research has hinted at a crucial link between gut microbiota and arterial embolism and thrombosis, yet the causal relationship remains enigmatic. To gain a deeper understanding, we aimed to comprehensively explore the causal relationship and elucidate the impact of the gut microbiota on the risk through a two-sample Mendelian randomization (MR) study. Methods: Genetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics for IBS were drawn from a GWAS including 1,076 cases and 381,997 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test. Results: We identified three bacterial traits that were associated with the risk of arterial embolism and thrombosis: odds ratio (OR): 1.58, 95% confidence interval (CI): 1.08-2.31, p = 0.017 for genus Catenibacterium; OR: 0.64, 95% CI: 0.42-0.96, p = 0.031 for genus Dialister; and OR: 2.08, 95% CI: 1.25-3.47, p = 0.005 for genus Odoribacter. The results of sensitivity analyses for these bacterial traits were consistent (P<0.05). Conclusion: Our systematic analyses provided evidence to support a potential causal relationship between several gut microbiota taxa and the risk of arterial embolism and thrombosis. More studies are required to show how the gut microbiota affects the development of arterial embolism and thrombosis.

Septic embolism due to periorbital cellulitis caused by pimple drainage.

Everyone has used homemade pimple drainage at some point in their lives, particularly in their adolescent and early adult years. However, pimple drainage should always be considered a mild medical procedure, especially in cases where the patient has serious skin diseases. We present the case of a 22-year-old female patient who, in the course of her routine, made a home pimple drainage that resulted in periorbital cellulitis and a septic embolism, despite the fact that these types of clinical cases are uncommon in routine medical practice. This case emphasizes how crucial it is to identify periorbital cellulitis early and treat it appropriately in order to stop a septic embolism from developing.

Group A Streptococcal Toxic Shock Syndrome With Portal Vein Thrombosis: A Rare Presentation in Newborns.

Invasive disease due to group A Streptococcus infection results in a large spectrum of clinical manifestations. In the neonatal period, the occurrence is rare and potentially serious. We present a case of a term male newborn on the 9th day of life who was admitted to the emergency room with moaning and poor feeding. The patient was hemodynamically unstable needing mechanical ventilation and inotropic support. Mother and father had clinical symptoms of pharyngitis. Blood samples revealed high serum C-reactive protein and procalcitonin, leucopenia, thrombocytopenia, hyponatremia, hepatic cytolysis, and cholestasis. He started on IV ampicillin, gentamicin, and cefotaxime. Due to an abdominal distension, an ultrasound was done showing a heterogenous hepatic lobe. A color Doppler scan completed the study revealing a left hepatic thrombosis. Enoxaparin was started. The newborn's blood culture and mother's milk were positive for the same strain of group A Streptococcus. Intravenous immunoglobulin and clindamycin were added to the treatment. On day 5 of treatment, inotropic support was ceased and extubation took place on day 6. Neonatologists should be aware of rare complications of group A Streptococcus infection such as thrombotic events.

Recurrent Deep Vein Thrombosis (DVT) and Inferior Vena Cava (IVC) Filter: Should a Computed Tomography (CT) Venogram and Inferior Vena Cavagram Be the Standard of Care?

A pulmonary embolism (PE) is a life-threatening complication of deep vein thrombosis (DVT). Although timely anticoagulation is the first-line treatment for DVT, an inferior vena cava (IVC) filter can be considered when anticoagulation is contraindicated. Unfortunately, IVC filters come with complications of their own, including thrombus formation in or around the filter. An 89-year-old man with a past medical history of coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and prior DVT status post IVC filter implantation five years ago in 2018 presented with hypotension, dizziness, and syncope. Computed tomography angiography (CTA) of the chest showed bilateral PEs. Venous Doppler ultrasound of the bilateral lower extremities was negative for DVT. CT venogram was performed; however, the contrast filling was suboptimal and as such, a venous thrombosis could not be ruled out. Therefore, an inferior vena cavagram was performed through the right common femoral vein and confirmed a large thrombus positioned cephalad to the IVC filter. A thrombectomy was performed and the IVC filter was replaced given the patient was at high risk for venous thromboembolism recurrence and complications.  Although an IVC filter offers some protection from recurrent PEs, it does have risks and complications. As seen in our patient, the IVC filter can be a nidus for the formation of a thrombus which has the risk of dislodging. When evaluating a patient for the source of a PE, it is important to consider prior IVC implant and perform further workups, such as a CT venogram or an inferior vena cavagram, to evaluate for thrombus in or around the filter.

High risk and low prevalence diseases: Cavernous sinus thrombosis.

INTRODUCTION: Cavernous sinus thrombosis (CST) is a serious condition that carries with it a high rate of morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of CST, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: CST is a potentially deadly thrombophlebitic disease involving the cavernous sinuses. The most common underlying etiology is sinusitis or other facial infection several days prior to development of CST, though other causes include maxillofacial trauma or surgery, thrombophilia, dehydration, or medications. Staphylococcus aureus, streptococcal species, oral anaerobic species, and gram-negative bacilli are the most frequent bacterial etiologies. The most prevalent presenting signs and symptoms are fever, headache, and ocular manifestations (chemosis, periorbital edema, ptosis, ophthalmoplegia, vision changes). Cranial nerve (CN) VI is the most commonly affected CN, resulting in lateral rectus palsy. Other CNs that may be affected include III, IV, and V. The disease may also affect the pulmonary and central nervous systems. Laboratory testing typically reveals elevated inflammatory markers, and blood cultures are positive in up to 70% of cases. Computed tomography of the head and orbits with intravenous contrast delayed phase imaging is recommended in the ED setting, though magnetic resonance venography demonstrates the highest sensitivity. Management includes resuscitation, antibiotics, and anticoagulation with specialist consultation. CONCLUSION: An understanding of CST can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

The effectiveness and safety of Rivaroxaban and Edoxaban in the treatment of lower extremity deep vein thrombosis.

INTRODUCTION: Deep vein thrombosis (DVT) is a medical condition characterized by forming a blood clot, or thrombus, in one of the deep veins, typically in the legs. It is a type of venous thromboembolism (VTE), which refers to the formation of blood clots in the veins. It is caused by Virchow's triad (stasis, hypercoagulation, and endothelial injury). OBJECTIVE: Our main objective is to explore the effectiveness and safety of Rivaroxaban and Edoxaban in treating lower extremity deep vein thrombosis. METHODS: We conducted a retrospective study involving 406 patients subjected to DVT treatment using DOACs (Edoxaban and Rivaroxaban) at our hospital. We recruited adult patients (18 years and above) diagnosed with lower extremity deep vein thrombosis and received treatment with either Rivaroxaban or Edoxaban as the primary anticoagulant therapy for DVT. We excluded patients who received treatment with other anticoagulant medications (warfarin heparin) as the primary therapy for DVT. RESULTS: The groups showed statistically significant differences in red blood cell count and haemoglobin levels, with the Edoxaban group having high values. However, the two groups observed no statistically significant differences in creatinine clearance, white blood cell count, platelet count, C-reactive protein, and D-dimer levels. The difference in the incidence of PE between the two groups was statistically significant (P value < 0.001). The Edoxaban group had fewer PE patients than the rivaroxaban group. The reduction in recurrent thrombosis was significantly higher in the rivaroxaban group compared to the Edoxaban group. There were no significant differences in the major bleeding at various sites across the two treatment groups (p > 0.05). CONCLUSION: Rivaroxaban's pharmacokinetic profile includes rapid absorption and a relatively short half-life. It means that once administered, Rivaroxaban quickly reaches its peak concentration in the blood and is subsequently eliminated from the body within a relatively short period. Edoxaban's pharmacokinetic profile may include slower absorption and a longer half-life than Rivaroxaban. It can result in a slower rate of achieving peak concentration and a more prolonged presence in the bloodstream. These results emphasize the need for careful consideration of anticoagulant therapy in patients with underlying cancer and underscore the importance of managing risks while providing adequate anticoagulation to prevent thrombotic events.

Budd-Chiari syndrome associated with congenital afibrinogenaemia reversed after orthotopic liver transplant.

A woman in her mid-20s, a known case of congenital afibrinogenaemia, presented with abdominal pain and distension. She was diagnosed with decompensated liver cirrhosis due to Budd-Chiari syndrome. She underwent deceased donor liver transplantation. Preoperatively, her serum fibrinogen level was undetectable and prothrombin time and international normalised ratio (INR) were unrecordable. Intraoperatively, she was given thromboelastography-guided human fibrinogen concentrate. Postoperatively, her fibrinogen, prothrombin time and INR normalised rapidly. This report summarises the rare occurrence of a complication of hypercoagulability (Budd-Chiari syndrome) in the setting of congenital hypocoagulability (congenital afibrinogenaemia). In this report, we discuss the simultaneous management of these two clinical problems and the curative role of liver transplantation.

[Coagulation and complement crosstalk: molecular mechanisms of complement-mediated diseases].

The complement and coagulation systems are ancestrally related mechanisms of serine protease-induced protein activation. Recent studies have shown that the complement system enhances platelet aggregation by activating platelets and vascular endothelial cells. This system is also involved in the expression of tissue factor, which induces the coagulation reaction. Activated platelets and coagulation factors are also known to activate the complement system. In diseases involving the complement system, such as paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemia, and atypical hemolytic uremic syndrome, excessive activation of this system contributes to complement-mediated thrombosis. The anti-C5 antibody eculizumab has shown a remarkable thromboprophylactic effect in these complement diseases. The recent surge in development of new anti-complement agents has raised expectations for the advancement of treatments and preventive measures for thrombosis associated with complement disorders. This review outlines the crosstalk between these two systems, and describes the mechanisms of several diseases featuring both thrombosis and complement activation.

Implications of von Willebrand Factor in Inflammatory Bowel Diseases: Beyond Bleeding and Thrombosis.

Inflammatory bowel disease (IBD) displays an increased venous and arterial thrombotic risk despite the common occurrence of intestinal bleeding. While some of the mechanisms leading to these thrombotic complications have been studied, other specific changes in the hemostasis profile of IBD patients have been less explored. One such example relates to von Willebrand factor (VWF) whose plasma levels have been reported to be modulated in IBD. Von Willebrand factor is a plasma glycoprotein crucial for hemostatic functions via roles both in platelet function and coagulation. High plasma VWF is a known risk factor for venous thromboembolism. In addition to its canonical roles in hemostasis, VWF is known to be directly or indirectly involved in other vascular processes such as maintenance of endothelial barrier integrity or proliferation of vascular smooth muscle cells. The purpose of this review is to recapitulate and update the existing data about VWF biology in IBD and to highlight its role both in the existing procoagulant phenotype and in vascular alterations that may occur in IBD.

Inflammatory bowel disease (IBD) displays an increased thrombotic risk. Von Willebrand factor (VWF) is increased in IBD and is a risk factor for venous thromboembolism. This review purposes to recapitulate and update the existing data about VWF biology in IBD.

miR-483-5p-Containing exosomes treatment ameliorated deep vein thrombosis­induced inflammatory response.

Peripheral vascular condition, known as deep vein thrombosis (DVT), is a common ailment that may lead to deadly pulmonary embolism. Inflammation is closely connected to venous thrombosis, which results in blood stasis, leading to ischemia and hypoxia, as indicated by research. The objective of this research was to investigate the mechanism by which exosomes derived from adipose stem cells (ADSCs) prevent deep vein thrombosis. Our data showed that Exo-483 effectively reduced the thrombus weight in DVT rats by intravenous injection. Exo-483 decreased the expression of tissue factor (TF) protein, the influx of inflammatory cells into the thrombosed vein wall, and the levels of cytokines in the serum. Furthermore, Exo-483 suppressed the expression of Mitogen-activated protein kinase 1 (MAPK1) and decreased the expression of NLRP3 inflammasomes. In an oxygen-glucose deprivation (OGD) cell model, the tube-forming and migratory abilities of primary human umbilical vein endothelial cells (HUVEC) and EA.hy926 cells were suppressed by Exo-483 pretreatment.Exo-483 is also linked to regulating Dynamin-related protein 1 (DRP1) production downstream of MAPK1.By decreasing the mitochondrial localization and phosphorylation at the S616 site of DRP1, it diminishes the expression of NLRP3 inflammasomes. Moreover, according to Bioinformatics analysis, miR-483-5p was anticipated to target MAPK1. The research conducted by our team revealed that the miR-483-5p exosome derived from ADSCs exhibited anti-inflammatory properties through the modulation of downstream DRP1-NLRP3 expression by targeting MAPK1.The findings of this research propose that miR-483-5p may be regarded as an innovative treatment target for DVT.

A novel factor V compound heterozygous mutation associated with thrombosis (Y1961C; FV-Kanazawa, together with 1982_1983del).

BACKGROUND: ; Factor (F)V is pivotal in both procoagulant and anticoagulant mechanisms. The present report describes a novel F5 mutation in a FV-deficient patient (FV:C 6 IU/dL, FV:Ag 32 IU/dL), complicated with recurrent deep vein thrombosis. The patient demonstrated activated protein C resistance (APCR) with compound heterozygous mutations consisting of FV-Y1961C (FVKanazawa) and FV-1982_1983del. AIM;: To clarify thrombotic mechanisms associated with this FV abnormality. METHODS AND RESULTS: Levels of FV-1982_1983del were below the detection sensitivity in our expression experiments using HEK293T cells, and analyses were targeted, therefore on the FV-Y1961C mutation. APTT-based clotting assays demonstrated that FV-Y1961C exhibited APCR, and that the reduced APC susceptibility in FVa-Y1961C resulted in a marked depression of APC-catalyzed inactivation with delayed cleavage at Arg506 and little cleavage at Arg306 with or without protein (P)S. The APC cofactor activity of FV-Y1961C in APC-catalyzed FVIIIa inactivation promoted by Arg336 cleavage in FVIII was impaired. The binding affinity of FVa-Y1961C to phospholipid membranes was reduced in reactions involving APC/PS-catalyzed inactivation and in prothrombinase activity. Furthermore, the addition of FVa-Y1961C to plasma failed to inhibit tissue factor (TF)-induced procoagulant function. These characteristics were similar to those of FV-W1920R (FVNara) and FV-A2086D (FVBesançon). CONCLUSIONS: ; We identified a compound heterozygous. FV-Y1961C mutation in the C1 domain representing a novel FV mutation (FVKanazawa) resulting in not only APCR due to impaired FVa susceptibility and FV cofactor activity for APC function, but impaired inhibition of TF-induced procoagulant function. These defects in anticoagulant function associated with FV in FV-Y1961C contributed to a prothrombotic state.