Venous Thrombus Research Articles

Growth kinetics of venous tumor thrombus in patients with renal cell carcinoma

Some patients with renal cell carcinoma (RCC) present with venous tumor thrombus (VTT). The extent of the VTT is related to survival, so prompt surgical care is recommended. However, studies evaluating the natural history of VTT in patients with RCC are rare. We sought to evaluate the growth kinetics of VTT in patients with RCC using preoperative cross-sectional images. We identified patients who underwent radical nephrectomy and venous tumor thrombectomy at our institution from 01/2009 to 02/2022. We included those with a minimum of 2 adequate preoperative imaging studies (contrast-enhanced Computerized Tomography (CT), noncontrast Magnetic resonance imaging (MRI), or contrast-enhanced MRI), at least 14 days apart. We measured VTT in each study to calculate growth rate, and evaluated predictors of faster growth (demographics, histology, laterality, tumor diameter, and staging). To assess the relation between clinical variables and VTT growth, we used the Wilcoxon Rank-Sum, Kruskal-Wallis, and Spearman correlation tests. A total of 30 patients were included in the analysis. The median time interval between studies was 33 days. Patients were mostly Caucasian and Males (90% and 70%, respectively). Most patients underwent a CT scan as their initial imaging study (66%), followed with an MRI as second study (73%). The mean venous tumor thrombus growth rate was 0.3 mm/d (standard deviation of 0.5mm), and only rhabdoid/sarcomatoid differentiation showed an association with tumor thrombus growth rate (0.3 vs. 0.63 mm/d, P = 0.038). To the best of our knowledge, this is the first study evaluating the natural growth rate of venous tumor thrombus in patients with renal cell carcinoma. We found that tumor thrombi grew an average of 0.3 mm/d (1.0 cm/month) and that those with sarcomatoid and/or rhabdoid differentiation grew faster (0.63 mm/d). Further studies are needed to validate these results and provide a better understanding of tumor thrombus kinetics.

Composition of thrombi in zebrafish: similarities and distinctions with mammals

BackgroundBlood clots are primarily composed of red blood cells (RBCs), platelets/thrombocytes, and fibrin. Despite the similarities observed between mammals and zebrafish, the composition of fish thrombi is not as well known. ObjectivesTo analyze the formation of zebrafish blood clots ex vivo and arterial and venous thrombi in vivo. MethodsTransgenic zebrafish lines and laser-mediated endothelial injury were used to determine the relative ratio of RBCs and thrombocytes in clots. Scanning electron and confocal microscopy provided high-resolution images of the structure of adult and larval clots. Adult and larval thrombocyte spreading on fibrinogen was evaluated ex vivo. ResultsRBCs were present in arterial and venous thrombi, making up the majority of cells in both circulations. However, bloodless mutant fish demonstrated that fibrin clots can form in vivo in the absence of blood cells. Scanning electron and confocal microscopy showed that larval and adult zebrafish thrombi and mammalian thrombi look surprisingly similar externally and internally, even though the former have nucleated RBCs and thrombocytes. Although adult thrombocytes spread on fibrinogen, we found that larval cells do not fully activate without the addition of plasma from adult fish, suggesting a developmental deficiency of a plasma activating factor. Finally, mutants lacking αIIbβ3 demonstrated that this integrin mediates thrombocyte spreading on fibrinogen. ConclusionOur data showed strong conservation of arterial and venous and clot/thrombus formation across species, including developmental regulation of thrombocyte function. This correlation supports the possibility that mammals also do not absolutely require circulating cells to form fibrin clots in vivo.

Shear wave elastography for lower extremity deep vein thrombosis

Aim. To evaluate the potential of shear wave elastography to determine the duration of lower extremity deep vein thrombosis, the effectiveness of direct anticoagulation and patient management strategy.Material and methods. Duplex lower extremity vein scanning, supplemented by shear wave elastography with determination of the average, minimum and maximum Young's modulus, was performed in 98 patients with acute, subacute and chronic thrombosis of the iliac and femoral veins on days 1, 3 and 6 of hospitalization. Based on the coefficient of determination (R2) of the median Young's modulus of a venous thrombus at different stages of thrombosis, the significance of its changes was assessed. Diagnostic information content of Young's modulus was calculated by comparing with the histological data of 17 blood clots removed during surgery.Results. As the age of both iliac and femoral vein thrombus increased, the median of the maximum, average and minimum Young's modulus at all stages of thrombosis steadily increased (R2=0,99). The median of the average Young's modulus at the acute stage was determined to be <17 kPa; at the subacute stage — in the range of 17-32 kPa and chronic — >32 kPa. According to shear wave elastography, in patients with acute and subacute stages of thrombosis, by the 6th day of anticoagulant therapy, the thrombus stiffness increased (R2=0,91-0,96), while in the chronic thrombosis group only a tendency to decrease was observed. The diagnostic information value of studying a thrombus using shear wave elastography relative to its histological examination turned out to be sufficient for use in clinical practice. In acute femoral vein thrombosis, the indication for radical treatment was the average Young's modulus ≤8,1 kPa, the minimum Young's modulus ≤1,7 kPa (sensitivity, specificity, positive and negative predictive values varied in the range of 64,3-88,9%); in subacute — ≤23,0 kPa and ≤11,3 kPa, respectively (55,6-100%).Conclusion. The results indicate that the diagnostic information value of shear wave elastography indicators is sufficient to determine the stage of lower extremity deep vein thrombosis in clinical practice.

Cannulation Indocyanine Green Method for Strategic Management of Postoperative Arterial Thrombosis after Free Jejunal Flap Transfer

Summary: Indocyanine green (ICG) angiography is widely used in reconstructive surgery to confirm the perfusion of the flap. Here, we report a case in which the use of the “cannulation ICG method” was useful for strategic management of postoperative arterial thrombosis after free jejunal flap transfer. A 64-year-old woman underwent cervical esophagectomy followed by a free jejunal transfer. On postoperative day 3, ischemia of the free jejunum was suspected, and takeback was performed. In the reoperation, re-anastomosis of the artery was planned after the removal of arterial thrombus. However, before re-anastomosis, it was unclear whether there was venous thrombus and whether this jejunum flap was salvageable. To resolve these two questions, we performed the cannulation ICG method. In this method, we injected a mixture of 1.0 mL of ICG and 20 mL of blood into the jejunal artery via 24-gauge cannula. We then evaluated the perfusion of the jejunal flap and monitoring jejunum, and the patency of the venous anastomosis site using a near-infrared fluorescence imaging device (LIGHTVISION; Shimadzu Corporation, Kyoto, Japan). In this case, the whole jejunal flap (including the monitoring jejunum) and venous anastomosis site were highlighted. We determined that there were no venous thrombi and that the entire jejunum was salvageable. After the arterial re-anastomosis, ICG angiography showed good perfusion of the whole jejunum. The postoperative course was uneventful, and the free jejunal flap survived completely. The cannulation ICG method may be effective for determining the surgical method for reoperation due to arterial thrombosis after reconstruction of the free jejunum.

Initial experience in robot-associated radical nephrectomy with inferior vena cava tumor thrombectomy.

Renal cell carcinoma (RCC) is often locally invasive and may extend from the renal vein into the inferior vena cava (IVC) as a venous tumor thrombus (VTT). Radical nephrectomy with IVC tumor thrombectomy (IVC-TT) via an open approach has been shown to carry high morbidity and mortality. Recently, robot-associated radical nephrectomy (RARN) has been developed with the aim of improving the performance and outcomes of surgery for RCC with IVC-VTT. We here present four patients who had right RCC with IVC-VTT and underwent RARN with IVC-TT in Nagasaki University Hospital. All four patients had level II IVC-TT and underwent RARN with IVC-TT using a da Vinci Xi surgical system. The procedure comprised performing the Kocher maneuver, exposing the right renal artery in the aortocaval region dorsal to the left renal vein, exposing, mobilizing, and clipping the IVC, clamping and incising the IVC, and removing the kidney with the VTT en bloc. The mean tumor size was 83.1 (range, 50.1-115.2) mm and the mean length of the VTT within the IVC 41.6 (range, 25.3-44.3) mm. The mean console time was 290 (range, 287-367) minutes and the mean blood loss was 200 (range, 175-260) mL and no patient required blood transfusion. Our initial experience of the procedure of RARN with IVC-TT for level II IVC-VTT is that it is safe and has acceptable perioperative outcomes and complications.

Construction of the prognostic model in non-metastatic renal cancer patients with venous tumor thrombus.

Venous system invasion is a prominent characteristic of local progression in renal cancer and treatment-naïve renal cancer patients with venous tumor thrombus (VTT) gained short natural course and poor prognosis. This study aimed to investigate the efficacy of the surgery and prognostic factors in non-metastatic renal cancer patients with VTT and to construct a nomogram prognostic model. Clinical data of 114 non-metastatic renal cancer patients with VTT who underwent surgical treatment from January 2011 to September 2022 were retrospectively analyzed. In order to find independent risk factors of prognosis, survival analysis was performed via univariate and multivariate Cox regression models and Kaplan-Meier method. Nomogram prognostic model was established to calculate patients' risk scores. Receiver operating characteristic curve and decision curve analysis were conducted to evaluate the efficacy of the prognostic model. A total of 114 patients were included in this study and there were 48, 12, 25, 23, and 6 cases of grade 0-IV VTT. No perioperative death occurred. The 3-year probabilities of overall survival (OS) and 5-year probabilities of OS were 67% and 43.8%, respectively. Multivariate Cox regression analysis revealed that kidney tumor diameter, preoperative lactate dehydrogenase (LDH), and preoperative neutrophils were independent risk factors. Nomogram was constructed to predict prognosis in renal cancer patients with VTT based on above indicators and Mayo VTT grading. The area under the ROC curve of 1-, 2-, 3-, and 5-year OS of the patients were 0.82, 0.67, 0.57, and 0.55 respectively. Surgical treatment enables renal cancer patients with VTT to gain a better prognosis. Kidney tumor diameter, preoperative LDH, and preoperative neutrophils were independent risk factors. The nomogram perfects the Mayo grading, and provides a reliable reference for evaluation of prognosis of renal cancer patients with VTT.

The Mechanism Underlying Lenalidomide-Induced Thrombosis Susceptibility

Introduction: Lenalidomide, a well-established drug for the treatment of multiple myeloma, significantly enhances patients' survival. Previous clinical studies have demonstrated that its main side effect is an increased risk of thrombotic events. However, the underlying mechanism remains unexplored. Therefore, this study aims to elucidate the mechanism and offer insights into the selection of clinical thrombotic prophylaxis drugs. Methods: Firstly, we conducted a retrospective analysis of clinical data from 169 newly diagnosed multiple myeloma patients who received lenalidomide. To confirm the impact of lenalidomide on thrombosis formation, FeCl3-induced thrombosis and deep venous thrombosis models in mice were established. To investigate the effects of lenalidomide on platelet function, both in vivo and in vitro experiments were designed. Results From January 2013 to June 2021, 169 NDMM patients with VRD as the first-line treatment were included in this study. During our follow-up, 8 patients had TEs . TEs included 8 VTE and 1 ATE. There were 7 DVT and 1 PE including in 8 VTE. Among the 8 patients suffering from thrombus, 2 patients did not receive thromboprophylaxis because of low platelet count, and the other 6 patients took aspirin, warfarin and rivaroxaban. Lenalidomide (25 mg/kg, 50 mg/kg, per day) or vehicle (DMSO) for 14 days were administrated for 2 weeks to healthy male mice. Compared with DMSO group, lenalidomide 25 mg/kg group and lenalidomide 50 mg/kg group significantly affected the formation of venous thrombosis , and there were significant statistical differences in both the length ( p=0.002; p=0.0005) and weight ( p<0.0001; p<0.0001) of thrombosis. In contrast, the formation of arterial thrombosis was not affected by lenalidomide administration in vivo, occlusion time of experiment group had control group did not have difference, which is consistent with the low incidence of ATE in clinical practice. To further explore the mechanism, we firstly focused on whether lenalidomide affects platelet function. Compared to baseline data, after taking one cycle of lenalidomide, the mean platelet volume (MPV, p<0.0001), platelet distribution width (PDW, p<0.0001), large platelet ratio ( p<0.0001), platelet hematocrit ( p=0.0005), and fibrinogen ( p=0.0008) of patients increased significantly. To evaluate the effect of lenalidomide on NDMM patient's platelet activation in vitro, we pretreated the washed platelets from NDMM with lenalidomide (5 or 10 um) or DMSO for platelet function assays . There was no difference between the three groups. To clarify the effect of lenalidomide on platelet function and parameters in vivo, lenalidomide (25 mg/kg, once per day), (50 mg/kg, once per day) or DMSO were administrated for 2 weeks to mice . The last dose was taken the night before narcotism, and platelet function was measured the next morning. We found that different from the changes in platelet related parameters in patients, in vivo data of mice showed no significant changes in platelet count , MPV , PDW , large platelet ratio , and platelet hematocrit after taking lenalidomide.Then we prepared washed platelets from mice for functional experiments. There was no difference between the three groups. In order to further explore the impact of lenalidomide on coagulation function in NDMM patients, we compared the coagulation parameters of NDMM patients who were enrolled at the time of diagnosis and after one cycle of taking lenalidomide. We found significant differences in prothrombin time, thrombin time, and prothrombin time ratio ( PTR, p<0.0001), while there was no statistical difference in some changes in activated partial thrombin time ( APTT, p=0.0881). These results may suggest that lenalidomide promotes the formation of venous thrombosis in vivo by influencing the coagulation pathway. Conclusions: The administration of lenalidomide had no significant impact on platelet function, which may affect venous thrombus formation by affecting coagulation. Therefore, anticoagulant drugs may be superior to antiplatelet drugs in the selection of clinical thrombus prophylaxis.

Preoperative moderate to severe anemia is associated with increased postoperative major adverse cardiac and cerebral events and pulmonary complications: a propensity score-matched analysis in hip fracture surgery patients over 80 years old

BackgroundAnemia is a common health problem in the elderly. Preoperative anemia is a risk factor for postoperative outcomes in the elderly for hip fracture. The objective of the study was to explore the relationship between preoperative moderate to severe anemia and postoperative morbidity and mortality in hip fracture patients over 80 years old.MethodsWe performed a retrospective cohort study exploring preoperative moderate to severe anemia and postoperative morbidity and mortality. Patients over 80 years old undergoing hip fracture surgery were included in the study. Data were collected for major adverse cardiac and cerebral events (MACCE), postoperative pulmonary complications (PPCs), in-hospital mortality, delirium, gastrointestinal complication, deep venous thrombus (DVT), acute renal failure, ICU admission, and perioperative transfusion > 2 units rate.ResultsA total of 912 eligible patients were included for unmatched cohort analysis, and 512 patients were included for matched cohort analysis after propensity score matching. Baseline characteristics between the normal to mild anemia and moderate to severe anemia groups were significantly different. More patients in the moderate to severe cohort had a higher ASA classification grade III and female ratio. Patients in the moderate and severe anemia cohorts had more MACCE (unadjusted: odds ratio [OR] 1.968, 96% CI 1.090–3.555, P 0.023; adjusted: OR 1.929, 95% CI 1.014–3.668, P 0.045) and PPCs (unadjusted: OR 2.616, 95% CI 1.442–4.748, P 0.001; adjusted: OR 2.352, 95% CI 1.225–4.516, P 0.010) than patients with normal or mild anemia. However, the transfusion > 2 units rate was not significantly different between the two cohorts (unadjusted: OR 0.967, 95% CI 0.737–1.270, P 0.811; adjusted: OR 0.941, 95% CI 0.693–1.278, P 0.697). The in-hospital mortality, delirium rate, gastrointestinal complication, ICU admission, and DVT were similar. However, the in-hospital mortality was much higher (3.6%, 21/591 vs 1.6%, 5/321) in the moderate to severe anemia cohort. Furthermore, after propensity score-matched analysis, MACCE and PPCs were also significantly increased in the moderate to severe anemia cohort (OR 2.196 & 3.171, 95% CI 1.0794.470 & 1.563–6.436, P 0.027 & 0.001), which were in accordance with the unadjusted and adjusted results in the unmatched cohorts.ConclusionsModerate to severe preoperative anemia (< 11 g/dl) is associated with increased postoperative major adverse cardiac and cerebral events and pulmonary complications. Additionally, in-hospital mortality was not significant but was higher in the preoperative moderate to severe anemia cohort. Preoperative assessment and correction of hemoglobin level to above 11 g/dl might reduce MACCE, PPCs, and in-hospital mortality in hip fracture patients over 80 years old.

Патофізіологічні механізми тромбозу глибоких вен

Deep venous thrombosis is a frequent multifactorial disease and most of the time is triggered by the interaction between acquired risk factors, particularly immobility, and hereditary risk factors such as thrombophilias. The mechanisms underlying deep venous thrombosis are not fully elucidated; however, in recent years the role of venous flow, endothelium, platelets, leukocytes, and the interaction between inflammation and hemostasis has been determined. Alteration of venous blood flow produces endothelial activation, favoring the adhesion of platelets and leukocytes, which, through tissue factor expression and neutrophil extracellular traps formation, contribute to the activation of coagulation, trapping more cells, such as red blood cells, monocytes, eosinophils, lymphocytes. The coagulation factor XI-driven propagation phase of blood coagulation plays a major role in venous thrombus growth, but a minor role in hemostasis. In this work, the main mechanisms involved in the pathophysiology of deep vein thrombosis are described.

Understanding Thrombosis and Hemorrhage in Myeloproliferative Neoplasms through a Nationwide Study

Introduction The incidence of Myeloproliferative Neoplasms (MPNs), including Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PMF) are increased. Thrombosis and hemorrhage are major complications of ET and PV. Leukemic transformation is a rare but fatal complication of MPNs. However, their incidence and risk factors of thrombosis and hemorrhage in a nationwide population are not fully known. Methods This study used nationwide data from the Korean National Health Insurance System (NHIS). We assessed thrombosis, hemorrhage, and leukemic transformation events in a cohort of all 9,779 patients diagnosed with MPNs during 2011-2016. A Big data formed by the NHIS contains demographic, clinical characteristics (smoking, body mass index, dates of birth, last follow up date, gender), health care utilization, treatment medication and health screening for the whole Korean population (Table 1). Results Of total 9,779 patients with MPNs, 5,970 (61.04%) had ET, 2,655(27.2%) PV, 586 (5.9%) PMF, and 568 (5.8%) unspecified MPN (MPN-U). 2,187 (22.4%) patients were diagnosed arterial thromboembolism including cerebral infarction and other thromboembolism during follow-up. And 1,029 (10.5%) patients were diagnosed venous thrombus including pulmonary thromboembolism. 254 (2.6%) patients were diagnosed intracerebral hemorrhage. Secondary leukemia (acute myeloid leukemia (n=482, 4.9%), acute lymphocytic leukemia (n=38, 0.4%), chronic myeloid leukemia (n=423, 4.3%), and chronic lymphocytic leukemia (n=22, 0.2%)) arising from MPNs were noted. Secondary myelofibrosis was noted in 321 (3.3%) patients with MPNs. Multivariate analysis revealed several risk factors for thrombosis and hemorrhage in patients with PV and ET. In patients with PV, age over 60 years (hazard ratio [HR]=2.199, 95% confidence interval [CI]=1.863-2.596, p&amp;lt;0.001), hypertension (HR=1.519, 95% CI=1.269-1.818, p&amp;lt;0.001), and atrial fibrillation/flutter (HR=1.561, 95% CI=1.088-2.241, p=0.016) were identified as significant risk factors for thrombosis. Additionally, age over 60 years (HR=2.896, 95% CI=1.637-5.123, p&amp;lt;0.001) was associated with an increased risk of hemorrhage in patients with PV. In patients with ET, multivariate analysis identified age over 60 years (HR=2.495, 95% CI=2.217-2.809, p&amp;lt;0.001), male sex (HR=1.147, 95% CI=1.034-1.271, p=0.009), hypertension (HR=1.563, 95% CI=1.385-1.764, p&amp;lt;0.001), dyslipidemia (HR=1.216, 95% CI=1.084-1.364, p=0.001), atrial fibrillation/flutter (HR=1.537, 95% CI=1.091-2.165, p=0.014), and hematologic malignancy (HR=1.294, 95% CI=1.097-1.527, p=0.002) as significant risk factors for thrombosis. Moreover, age over 60 years (HR=2.657, 95% CI=1.744-4.048, p&amp;lt;0.001) and hypertension (HR=1.775, 95% CI=1.161-2.713, p=0.008) were found to be significant risk factors for hemorrhage in patients with ET. Conclusions This is the first Korean nationwide study to understand thrombosis and hemorrhage in patients with MPNs. This set of data can be utilized to compare the Asian patients with MPNs to international data and guidelines.

Abstract 109: Endonasal Endoscopic Approach Associated Cerebral Vasospasm and Management: A Case Report

Introduction Endoscopic endonasal approach(EEA) techniques have been increasingly utilized and have been associated with development of cerebrospinal fluid(CSF) leak, meningitis, diabetes insipidus post‐operatively. Cerebral vasospasm following EEA has rarely been described. Here, we describe the clinical course and management of a patient who underwent EEA for encephalocele repair whose course was complicated by postoperative subarachnoid hemorrhage(SAH) and cerebral vasospasm. Methods n/a Results Case Presentation: 40 year old female with past medical history significant for cerebral venous sinus stent on aspirin, CSF rhinorrhea secondary to right nasal encephalocele s/p endoscopic transnasal transethmoidal repair with nasoseptal flap reconstruction and lumbar drain placement eleven days prior presented with speech difficulties and right sided weakness. On exam, patient was noted to have mild right hemiparesis and expressive aphasia. MRI brain showed subacute infarcts in left greater than right frontal lobes, corpus collosum and right anterior perforated substance. MRA head demonstrated multifocal arterial stenosis. In light of postoperative CT head showing SAH in the basilar, perimesencephalic, prepontine cisterns, interhemispheric fissure and right frontal sulci as well as intraventricular hemorrhage in fourth ventricle, her presentation was thought to be secondary to cerebral vasospasm in the setting of postoperative SAH. She was treated with intravenous hydration, permissive hypertension with head of bed in flat position and transferred for further evaluation. On arrival, she continued have mild right hemiparesis and aphasia. Repeat CTA head/neck and CT perfusion showed severe stenosis of bilateral M1 segments and left greater than right A1 segments as well as ischemic penumbra in left ACA/MCA watershed territory. Diagnostic cerebral angiogram showed bilateral severe A1 stenosis and mild to moderate bilateral M1 and supraclinoid ICA stenosis which improved with intra‐arterial verapamil. She was started on nimodipine. Systolic blood pressure was augmented with vasopressors for goal of 150‐180mmHg. Daily TCDs were followed. She developed worsening right leg weakness following day, thus she was taken for repeat diagnostic cerebral angiogram during which time she was re‐administered intra‐arterial verapamil with improvement in vasospasm. After the second treatment, she had improvement in speech and motor strength. Systolic blood pressure goal was gradually normalized. She was noted to have incidental left internal jugular (IJ) vein thrombosis for which anticoagulation was held in the setting of recent neurosurgical procedure and SAH. Workup for vasculitis and hypercoagulability was unrevealing. Lumbar puncture demonstrated 13 WBC/cu mm with lymphocytic predominance(90%), 23 RBC/cu mm, glucose 89mg/dl, protein 30mg/dl. CSF cultures were negative. Pleocytosis in CSF was attributed to recent neurosurgical procedure. Her neurological exam improved to baseline on hospital day(HD) 9.On HD12, she was found to have left common femoral deep venous thrombus in addition to the left IJ thrombus. Anticoagulation with low dose heparin infusion was started which was transitioned to apixaban on discharge. She was discharged home on HD20. Conclusion We report a case of EEA associated with severe multifocal cerebral vasospasm secondary to postoperative SAH that was successfully treated with induced hypertension, oral nimodipine and intra‐arterial verapamil as an adjunct therapy with an excellent outcome.

Apply Anticoagulants after Discharge not Benefit to the Incidence of Symptomatic Thrombus in High-Altitude Areas: A Retrospective Study.

Many guidelines indicate that continuous use of anticoagulant drugs reduces the incidence of venous thrombus (VT), but no studies show the effect on the incidence of symptomatic venous thrombus (SVT) in total knee arthroplasty (TKA) patients after discharge. This study aimed to investigate whether it is necessary to apply anticoagulants to TKA patients after discharge. Patients who met the exclusion criteria requirement, underwent TKA by the same surgical team and received anticoagulant therapy after the operation were eligible for the study. Finally, a total of 567 TKA patients were recruited as participants. The patients were divided into two groups. The patients in group A were taken low molecular heparin for 5-10 days after surgery, which included but was not limited to low molecular weight heparin calcium injection (0.4 mL, ih, Qd), calcium dioxin injection (0.6 mL, ih, Qd), or enoxaparin sodium injection (0.4 mL, ih, Qd), and the patients needed to continue oral anticoagulant drug (10 mg, po, Qd) for 7-21 days after discharge. The patients in group B only took low molecular heparin 5-10 days after surgery and no treatment after discharge. The baseline characteristics of patients, total complications of SVT include lower limb vascular pain (LLVP), lower limb vascular pain no fester (LLVPNF), lower limbs swelling (LLS), lower limb fester (LLF), and death by thrombosis (DT), bleeding and mortality following discharged were compared between two groups. The study showed that the incidence of SVT patients had no significant difference between the two groups (p = 0.489). Moreover, the incidence of LLVP (p = 0.265), LLS (p = 0.84), LLVPNF (p = 0.213), LLF (p = 0.907), DT (p = 0.907), death from other causes, and bleeding (p = 0.323) had no significant differences between the two groups. However, the incidence of SVT in patients with smoking (p = 0.0001 or 0.0011) or drinking (p = 0.0002 or 0.0001) was significantly increased. There is not enough evidence showing that the TKA patients given anticoagulants after discharge had benefits in decreasing the risk of SVT. Furthermore, smoking and drinking would significantly increase the risk of SVT in TKA patients.

Percutaneous treatment of symptomatic deep vein thrombosis in adolescents using large-bore thrombectomy systems.

While large-bore mechanical thrombectomy provides effective venous thrombus removal, often with avoidance of thrombolytics, literature surrounding the application of these devices in pediatric patients is sparse. To report technical success and outcomes following large-bore thrombectomy systems in adolescent patients with deep venous thrombosis. A retrospective review identified all patients less than 18years of age undergoing mechanical venous thrombectomy at a single institution between 2018 and 2022. No patients were excluded. Technical success was defined as extraction of thrombus sufficient to restore unimpeded flow in affected segments. Clinical success was defined as resolution of presenting symptoms. Nine consecutive patients (6 females, 3 males; age range 15-17years) underwent 10 thrombectomy procedures using ClotTriever (n=6; 60%), FlowTriever (n=2; 20%), or both (n=2; 20%). Chronicity of thrombus was categorized as acute (<2weeks) in 6 (60%), subacute (2-6weeks) in 1 (10%), and chronic (>6weeks) in 3 (30%). Distribution of thrombus was lower extremity and/or inferior vena cava (IVC) in 9 (90%) and unilateral axillo-subclavian in 1 (10%). Technical success was achieved in 9 interventions (90%). Clinical success was achieved in 8 patients (88.9%). No patients received thrombolytics. There were no intraprocedural adverse events (AE). Minor complications (Society of Interventional Radiology mild adverse events) were observed in a delayed fashion following 2 interventions (20%). This preliminary experience demonstrated high rates of technical and clinical success with large-bore deep venous thrombectomy in adolescent patients across a range of thrombus chronicity and locations.

A Novel Doppler Flowmetry Shaft for Postoperative Monitoring after Head and Neck Reconstructive Surgery.

Doppler flowmetry is one of the most popular methods of monitoring Doppler signals during reconstructive surgery of the body surface. However, because of the thick and straight structure of the shaft, it is difficult to perform in areas with limited space, such as the oral cavity. We used a new type of Doppler flowmetry shaft to postoperatively monitor the flap in the oral cavity. Compared with conventional Doppler flowmetry, the new type uses a thinner metal probe shaft that can easily be inserted in narrow and limited spaces, such as the oral cavity. Additionally, the tip of the metal probe is gently bent, thereby allowing the Doppler tip to be placed perpendicular to the surface of the skin flap. We used this new type of Doppler flowmetry shaft for 30 patients after head and neck reconstruction using free flap transfer because Doppler signals were difficult to hear using conventional Doppler flowmetry. For all 30 patients, the new Doppler flowmetry shaft was able to monitor free flaps. Vascular thrombosis or vascular spasm occurred in three patients; two patients had inadequate arterial flow caused by vasospasm and arterial thrombus, and one patient had a venous thrombus. These three patients required re-exploration, and all flaps survived. This new type of Doppler flowmetry is simple and noninvasive. Furthermore, it can easily be performed by nonphysician medical personnel, and is useful for monitoring patients after head and neck reconstructive surgery.

PB0594 Factor XI Localization in Human Deep Venous Thrombus and Function of Activated Factor XI on Mural Thrombus Formation Under Low-Shear Condition

PB0594 Factor XI Localization in Human Deep Venous Thrombus and Function of Activated Factor XI on Mural Thrombus Formation Under Low-Shear Condition

PB0284 Resolution Rates of Provoked Venous Thrombus Embolism in Pediatric Patients Managed at a Tertiary Care Center

PB0284 Resolution Rates of Provoked Venous Thrombus Embolism in Pediatric Patients Managed at a Tertiary Care Center

Thrombin-activatable fibrinolysis inhibitor and sex modulate thrombus stability and pulmonary embolism burden in a murine model

BackgroundThrombin-activatable fibrinolysis inhibitor (TAFI) levels are positively correlated with the risk of thrombosis. The mechanism of how TAFI affects venous thromboembolism (VTE) remains uncertain. In addition, the role of sex on the risk of VTE has also been studied. However, their association also remains unclear. ObjectivesTo investigate how TAFI and/or sex affect venous thrombus stability and consequent pulmonary embolism (PE). MethodsFerric chloride-induced thrombi were formed within the femoral veins of male and female wild-type (WT) or TAFI-knockout (Cpb2-/-) mice. Thrombi were imaged over 2 hours using intravital videomicroscopy to quantify embolization and thrombus size over time. Lungs were examined by immunohistochemistry to quantify (a) emboli and (b) fibrin composition of these emboli. ResultsEmbolization events in female mice were higher than in males (7.9-fold in WT and 3.1-fold in Cpb2-/- mice). Although the maximal thrombus sizes were not different across groups, Cpb2-/- mice had thrombi that were, on average, 24% smaller at the end of the 2-hour experiment than WT mice. Loss of TAFI led to a 4.0- and 2.8-fold increase in PE burden in males and females, respectively, while sex had no influence. Pulmonary emboli in Cpb2-/- mice had higher fibrin composition compared with WT mice. ConclusionFemale mice had less stable venous thrombi than male mice, suggesting a higher risk of PE in females with deep vein thrombosis. Mice lacking TAFI had more thrombus degradation and higher PE burden than WT mice. These results confirm the role of TAFI in venous thrombosis.

Lenalidomide Promotes Thrombosis Formation, but Does Not Affect Platelet Activation in Multiple Myeloma.

Lenalidomide, a well-established drug for the treatment of multiple myeloma, significantly enhances patients' survival. Previous clinical studies have demonstrated that its main side effect is an increased risk of thrombotic events. However, the underlying mechanism remains unexplored. Therefore, this study aims to elucidate the mechanism and offer insights into the selection of clinical thrombotic prophylaxis drugs. Firstly, we conducted a retrospective analysis of clinical data from 169 newly diagnosed multiple myeloma patients who received lenalidomide. To confirm the impact of lenalidomide on thrombosis formation, FeCl3-induced thrombosis and deep venous thrombosis models in mice were established. To investigate the effects of lenalidomide on platelet function, both in vivo and in vitro experiments were designed. During the follow-up period, 8 patients developed thrombotic events, including 8 venous and 1 arterial. Further investigation using mice models demonstrated that lenalidomide significantly promoted the formation of venous thrombosis, consistent with clinical findings. To elucidate the underlying mechanism, assays were conducted to assess platelet function and coagulation. We observed that lenalidomide did not have any noticeable impact on platelet function, both in vitro and in vivo, while administration of lenalidomide resulted in significant decreases in prothrombin time, thrombin time, and prothrombin time ratio in patients, as well as a remarkable reduction in tail-bleeding time in mice. The administration of lenalidomide had no significant impact on platelet function, which may affect venous thrombus formation by affecting coagulation. Therefore, anticoagulant drugs may be superior to antiplatelet drugs in the selection of clinical thrombus prophylaxis.

Sustained and intermittent hypoxia differentially modulate primary monocyte immunothrombotic responses to IL-1β stimulation.

Venous thromboembolism (VTE) is a leading cause of preventable deaths in hospitals, and its incidence is not decreasing despite extensive efforts in clinical and laboratory research. Venous thrombi are primarily formed in the valve pockets of deep veins, where activated monocytes play a crucial role in bridging innate immune activation and hemostatic pathways through the production of inflammatory cytokines, chemokines, and tissue factor (TF) - a principal initiator of coagulation. In the valve pocket inflammation and hypoxia (sustained/intermittent) coexist, however their combined effects on immunothrombotic processes are poorly understood. Inflammation is strongly associated with VTE, while the additional contribution of hypoxia remains largely unexplored. To investigate this, we modelled the intricate conditions of the venous valve pocket using a state-of-the-art hypoxia chamber with software-controlled oxygen cycling. We comprehensively studied the effects of sustained and intermittent hypoxia alone, and in combination with VTE-associated inflammatory stimuli on primary monocytes. TF expression and activity was measured in monocytes subjected to sustained and intermittent hypoxia alone, or in combination with IL-1β. Monocyte responses were further analyzed in detailed by RNA sequencing and validated by ELISA. Stimulation with IL-1β alone promoted both transcription and activity of TF. Interestingly, the stimulatory effect of IL-1β on TF was attenuated by sustained hypoxia, but not by intermittent hypoxia. Our transcriptome analysis further confirmed that sustained hypoxia limited the pro-inflammatory response induced by IL-1β, and triggered a metabolic shift in monocytes. Intermittent hypoxia alone had a modest effect on monocyte transcript. However, in combination with IL-1β intermittent hypoxia significantly altered the expression of 2207 genes and enhanced the IL-1β-stimulatory effects on several chemokine and interleukin genes (e.g., IL-19, IL-24, IL-32, MIF), as well as genes involved in coagulation (thrombomodulin) and fibrinolysis (VEGFA, MMP9, MMP14 and PAI-1). Increased production of CCL2, IL-6 and TNF following stimulation with intermittent hypoxia and IL-1β was confirmed by ELISA. Our findings provide valuable insights into how the different hypoxic profiles shape the immunothrombotic response of monocytes and shed new light on the early events in the pathogenesis of venous thrombosis.

The Application of CT Radiomics in the Diagnosis of Vein Wall Invasion in Patients With Renal Cell Carcinoma Combined With Tumor Thrombus.

The objective of this study was to explore the application of radiomics combined with machine learning to establish different models to assist in the diagnosis of venous wall invasion in patients with renal cell carcinoma and venous tumor thrombus and to evaluate the diagnostic efficacy. We retrospectively reviewed the data of 169 patients in Peking University Third Hospital from March 2015 to January 21, who was diagnosed as renal mass with venous invasion. According to the intraoperative findings, 111 patients were classified to the venous wall invasion group and 58 cases in the non-invasion group. ITK-snap was used for tumor segmentation and PyRadiomics 3.0.1 package was used for feature extraction. A total of 1598 features could be extracted from each CT image. The patients were divided into training set and testing set by time. The elastic-net regression with 4-fold cross-validation was used as a dimension-reduction method. After feature selection, a support vector machines (SVM) model, a logistic regression (LR) model, and an extra trees (ET) model were established. Then the sensitivity, specificity, accuracy, and the area under the curve (AUC) were calculated to evaluate the diagnostic performance of each model on the testing set. Patients before September 2019 were divided into the training set, of which 88 patients were in the invasion group and 42 patients were in the non-invasion group. The others were in the testing set, of which 32 patients were in the invasion group and 16 patients were in the non-invasion group. A total of 34 radiomics features were obtained by the elastic-net regression. The SVM model had an AUC value of 0.641 (95% CI, 0.463-0.769), a sensitivity of 1.000, and a specificity of 0.062. The LR model had an AUC value of 0.769 (95% CI, 0.620-0.877), a sensitivity of 0.913, and a specificity of 0.312. The ET model had an AUC value of 0.853 (95% CI, 0.734-0.948), a sensitivity of 0.783, and a specificity of 0.812. Among the 3 models, the ET model had the best diagnostic effect, with a good balance of sensitivity and specificity. And the higher the tumor thrombus grade, the better the diagnostic efficacy of the ET model. In inferior vena cava tumor thrombus, the sensitivity, specificity, accuracy, and AUC of ET model can be improved to 0.889, 0.800, 0.857, 0.878 (95% CI, 0.745-1.000). Machine learning combined with radiomics method can effectively identify whether venous wall was invaded by tumor thrombus and has high diagnostic efficacy with an AUC of 0.853 (95% CI, 0.734-0.948).