Deep Venous Thrombosis Formation Research Articles

Correlation analysis of serum MMP-1 and MMP-2 levels with lower extremity deep venous thrombosis after operation for lower limb fracture

To investigate the relationship between serum matrix metalloproteinase-1(MMP-1) and matrix metalloproteinase-2(MMP-2) and the formation of deep venous thrombosis(LDVT) in lower extremity patients after surgery for lower extremity fracture, and to analyze the value of MMP-1 and MMP-2 in predicting the occurrence of LDVT after lower extremity fracture. From June 2018 to December 2021, 352 patients who planned to receive surgical treatment of lower limb fracture in our hospital were selected as the research objects. Venous blood was collected at 1, 2 and 3 days after surgery, respectively, and serum MMP-1 and MMP-2 levels were detected. The incidence of LDVT during hospitalization was analyzed, and the risk factors of postoperative LDVT in patients with lower limb fracture surgery and the predictive value of MMP-1 and MMP-2 for LDVT were analyzed. LDVT occurred in 40 patients (LDVT group), the incidence of LDVT was 11.36%, and 312 patients did not occurred(no occurred group). The serum levels of MMP-1 and MMP-2 in LDVT group increased gradually after surgery; the serum levels of MMP-1 and MMP-2 in the no occurred group increased slightly after surgery at 2 days and then decreased at 3 days after surgery (P<0.01);the serum levels of MMP-1 and MMP-2 in LDVT group were higher than those in the no occurred group at 2 days and 3 days after surgery (P<0.05). Serum levels of MMP-1 and MMP-2 were positively correlated with serum levels of interleukin-6 (IL-6), IL-8 and tumor necrosis factor -α (TNF-α) in LDVT patients at 2 days and 3 days postoperatively (P<0.05). Operative time, MMP-1 and MMP-2 postoperative 3 days were related to the occurrence of LDVT after lower limb fracture (P<0.01). The area under the curve(AUC) predicted by MMP-1 and MMP-2 postoperative 3 days for LDVT after lower limb fracture was 0.738 and 0.744 respectively, and the AUC predicted by combined MMP-1 and MMP-2 was 0.910, which was higher than that predicted by single indicator(Z=2.819 and 2.025, P<0.05). High levels of MMP-1 and MMP-2 after lower extremity fracture are closely related to the occurrence of LDVT, and 3 d mMP-1 and MMP-2 after surgery maybe used as evaluation indexes for LDVT risk prediction.

Network pharmacological and molecular docking verification of the mechanism of Osteoking in preventing deep vein thrombosis of lower limb.

The aim of this study was to predict the mechanism of Osteoking in preventing deep vein thrombosis (DVT) of the lower limb by network pharmacology and molecular docking. The relevant active components and targets of Osteoking were collected through the TCMSP database, and the relevant disease targets of DVT were collected through the GeneCards, OMIM, and DisGeNET databases. The intersecting gene targets of Osteoking and DVT were obtained using Venny 2.1.0 software. PPI network construction and core target selection using Cytoscape 3.9.0 software. The Metascape database was used for GO and KEGG enrichment analysis of relevant targets. Finally, the molecular docking of the main active components and key targets was carried out. There are 361 potential targets and 71 core targets of Osteoking in preventing deep vein thrombosis of the lower limb. Signal pathways are involved in various diseases such as cancer, diabetic complications, atherosclerosis, and more. Some of the most common pathways include AGE-RAGE signaling pathway and Calcium signaling pathway. Molecular docking results showed that the main active components of Osteoking had relatively stable binding activities with the key targets. Osteoking can play a role through multiple targets and multiple signal pathways to prevent the formation of deep venous thrombosis of the lower limb after fracture.

P66: Incidence of DVT formation in patients requiring temporary mechanical circulatory support for cardiogenic shock

Background: After the 2018 UNOS organ allocation change, temporary mechanical circulatory support (tMCS) has increased in managing acute decompensated heart failure (ADHF) as a bridge to transplant, recovery, or durable VAD. However, patients supported with tMCS are more prone to complications. Deep venous thrombosis (DVT) is one of the most common complications in this patient population. DVT is associated with an increased risk of pulmonary embolism, stroke, chronic venous insufficiency, and increased length of hospital stays. We aimed to identify the incidence of DVT in ADHF patients supported with tMCS. Method: We performed a retrospective review of patients with ADHF who had undergone heart or heart/kidney transplantation between January 2021 and November 2022 at Mayo Clinic in Florida. Patient data were extracted from the electronic health record after IRB approval as exempt for retrospective chart review was obtained. Our primary outcome was DVT during the transplant, diagnosed by venous duplex ultrasonography. Results: 93 patients with ADHF were found during our review period, of which 46 (49%) developed a DVT. The median age was 60 years (53 – 67), with 65% male. All but one DVT was in the upper extremity. Within the DVT population, 75% were hypertensive (p <.001), 64% were diabetic (p =.003), 78% had hyperlipidemia (p<.001), and had elevated mean creatinine of 2.16 vs. 1.55 (p =.04). A total of 44 patients required tMCS, of these, 26 patients developed DVT (59%) which was statistically significant compared to 18 that did not develop DVT while on tMCS, p =.04. The combination of support was as follows: 27 axillary Impella 5.5 alone, 5 VA ECMO without LV vent, 1 VA ECMO with IABP vent, 4 VA ECMO with Impella 5.5 vent, and 7 intra-aortic balloon pumps only. Ischemic cardiomyopathy was not a significant risk for DVT, p =.372. The median ejection fraction was 25% (15 -55). The median LOS was 48 days (31 – 74). Patients with DVT were found to have a significantly lower BMI, 26.4 vs 29.3 (p =.002), as well as a significantly shorter cardiopulmonary bypass time of 187min vs. 296 min (p <.001). Conclusions: We found increased rates of DVT in patients utilizing all forms of tMCS with ADHF. Factors influencing the development of DVT may relate to an overall increased inflammatory state, evidenced by our data showing significant differences in rates of hypertension, diabetes, hyperlipidemia, worse renal function, and sarcopenia. Chronicity of disease, time in the hospital, and the need for more procedures may also influence DVT risk in patients awaiting transplantation or LVAD.

Endothelium-biomarkers for postthrombotic syndrome: a case-control study.

The postthrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT). Increase knowledge on the PTS pathophysiology and novel biomarkers are needed in order to predict PTS development and to improve treatment results. The aim of this study was to analyze novel endothelium-biomarkers for PTS in patients with DVT out of the acute phase. A case-control study was conducted. Inclusion criteria were symptomatic and confirmed DVT patients treated with anticoagulants for at least 3 months. Villalta score was performed at the time of inclusion and used to diagnose and classify the severity of PTS. Plasma inter-cellular adhesion molecule 1 (ICAM-1), P-selectin, fractalkine and vascular endothelial growth factor (VEGF) were quantified using cytometric bead array. Endothelial progenitor cells (EPCs) and circulating endothelial cells (CEC) level were quantified by flow cytometry. Thirty two patients and 61 controls were included. PTS patients showed higher levels of CEC (0.56/μl (0.34-1.5) vs. 0.20/μl (0.11-0.77); P = 0.04) and EPC (0.75/μl (0.38-1.52) vs. 0.09/μl (0.05-0.82); P = 0.0021) compared to no PTS patients. Patients with PTS had significantly higher levels of fractalkine (387.60 pg/ml (222.30-597.90) vs. 98.00 pg/ml (82.30-193.02); P = 0.044) than patients without PTS. Fracktalkine levels showed a strong linear correlation with Villalta score, r = 0.86, P < 0.0001. No differences were observed in P-selectin, ICAM-1 and VEGF between studied groups. The formation and early resolution of DVT are characterized by inflammation and endothelial/platelet activation. We have identified possible novel biomarkers such as CEC, EPC and fractalkine for the development of PTS. These results suggest a possible role of these mediators in the maintenance and worsening of PTS turning them into potential therapeutic targets.

Correlation analysis of Blood TM, TG and D-dimer with deep venous Thrombosis formation in patients after Total Hip Arthroplasty.

To explore the correlation of blood thrombomodulin (TM), triglyceride (TG) and D-Dimer (D-D) with the formation of deep vein thrombosis (DVT) in patients after total hip arthroplasty (THA). A retrospective analysis was carried out focusing on the clinical data of 150 patients with THA who were admitted to Sichuan Provincial Orthopedic Hospital from May 2019 to May 2022 (the study group). These patients were then subdivided into Group-A (46 cases with DVT) and Group-B (104 cases without DVT) according to whether DVT occurred after an operation. Meanwhile, another 70 patients who received physical examination in this hospital in the same period were selected as the control group. Furthermore, the levels of TM, TG, D-D, fibrinogen (Fb) and C-reactive protein (CRP) were compared between the groups. Pearson correlation was used to analyze the relationship between the levels of TM, TG, D-D, Fb, CRP and the formation of DVT. The levels of TM, TG, D-D, Fb and CRP in the study group were significantly higher than those in the control group (p<0.05). The above indicators in Group-A were higher than those in Group-B one day after the operation (p<0.05). Pearson correlation analysis showed that the levels of TM, TG, D-D, Fb and CRP were significantly positively correlated with the formation of DVT. Patients with DVT after THA show an increase in the levels of TM, TG, D-D, Fb and CRP, indicating their diagnostic value for the formation of DVT. Findings in our study suggest that clinical tests of these indicators can be carried out according to the actual situation of patients.

Resistance exercise promotes the resolution and recanalization of deep venous thrombosis in a mouse model via SIRT1 upregulation

BackgroundEarly exercise for acute deep venous thrombosis (DVT) improves the patient’s symptoms and does not increase the risk of pulmonary embolism. However, information about its effect on thrombus resolution is limited. The aim of this study was to investigate the role of resistance exercise (RE) in thrombus resolution and recanalization and determine its underlying mechanisms. MethodsNinety-six C57BL/6 J mice were randomly divided into four groups: Control group (C, n = 24); DVT group (D, n = 24); RE + DVT group (ED, n = 24); and inhibitor + RE + DVT group (IED, n = 24). A DVT model was induced by stenosis of the inferior vena cava (IVC). After undergoing IVC ultrasound within 24 h post-operation to confirm DVT formation, mice without thrombosis were excluded. Other mice were sacrificed and specimens were obtained 14 or 28 days after operation. Thrombus-containing IVC was weighed, and the thrombus area and recanalization rate were calculated using HE staining. Masson’s trichrome staining was used to analyze the collagen content. RT-PCR and ELISA were performed to examine IL-6, TNF-α, IL-10, and VEGF expression levels. SIRT1 expression was assessed using immunohistochemistry staining and RT-PCR. VEGF-A protein expression and CD-31-positive microvascular density (MVD) in the thrombus were observed using immunohistochemistry. ResultsRE did not increase the incidence of pulmonary embolism. It reduced the weight and size of the thrombus and the collagen content. Conversely, it increased the recanalization rate. It also decreased the levels of the pro-inflammatory factors IL-6 and TNF-α and increased the expression levels of the anti-inflammatory factor IL-10. RE enhanced VEGF and SIRT1 expression levels and increased the MVD in the thrombosis area. After EX527 (SIRT1 inhibitor) was applied, the positive effects of exercise were suppressed.ConclusionsRE can inhibit inflammatory responses, reduce collagen deposition, and increase angiogenesis in DVT mice, thereby promoting thrombus resolution and recanalization. Its underlying mechanism may be associated with the upregulation of SIRT1 expression.

The Use of Machine Learning Techniques to Predict Deep Vein Thrombosis in Rehabilitation Inpatients.

Rehabilitation is crucial to recovering patients' dysfunction, improving their life quality, and promoting an early return to their family and society. In China, most patients in rehabilitation units are patients transferred from neurology, neurosurgery, and orthopedics, and most of these patients face problems such as continuously bedridden or varying degrees of limb dysfunction, all of which are risk factors for deep venous thrombosis. The formation of deep venous thrombosis can delay the recovery process and result in significant morbidity, mortality, and higher healthcare costs, so early detection and individualized treatment are needed. Machine learning algorithms can help develop more precise prognostic models, which can be of great significance in the development of rehabilitation training programs. In this study, we aimed to develop a model of deep venous thrombosis for inpatients in the Department of Rehabilitation Medicine at the Affiliated Hospital of Nantong University using machine learning methods. We analyzed and compared 801 patients in the Department of Rehabilitation Medicine using machine learning. Support vector machine, logistic regression, decision tree, random forest classifier, and artificial neural network were used to build models. Artificial neural network was the better predictor than other traditional machine learnings. D-dimer levels, bedridden time, Barthel Index, and fibrinogen degradation products were common predictors of adverse outcomes in these models. Risk stratification can help healthcare practitioners to achieve improvements in clinical efficiency and specify appropriate rehabilitation training programs.

Incidence, predictors, and 30-day outcomes of Clostridioides difficile infection in patients undergoing cystectomy: A national database analysis

Clostridioides difficile infection (CDI) is the second most common health care acquired infection (HAI) and the most common gastrointestinal HAI, with an estimated 365,200 cases reported by the center for disease control in 2017. CDI continues to remain a major cause of inpatient admission and utilization of health care resources. This study aimed to determine the true incidence, risk factors, and outcomes of CDI in patients undergoing cystectomy. We conducted an analysis of patients undergoing cystectomy between 2015 and 2017 using the American college of surgeon National Surgical Quality Improvement Program to study the incidence, risk factors, and 30 day postsurgical outcomes associated with CDI following cystectomy. Developed by the American College of Surgery, this is a nationally validated, risk adjusted, and outcomes based program designed to determine and improve the quality of surgical and postsurgical care. The incidence of CDI following cystectomy was 3.6% in our patient cohort. About 18.8% of patients developed CDI following hospital discharge. None elective surgeries and complete cystectomy procedures had a higher rate of CDI. About 48.4% of patients with CDI had a preceding postoperative infection. Postoperative organ space infections, postoperative renal failure, postoperative sepsis, and septic shock were independently associated with the development of CDI, (all P < 0.05). Patients who developed postoperative CDI during hospitalization had lengthier hospital admissions than those who did not develop a CDI and had a higher risk of deep venous thrombosis formation. A sizable number of patients experience CDIs after cystectomy procedures in the USA, and CDI development is associated with an increase in length of stay and unplanned readmissions. Interventions and initiatives are needed to reduce this burden of disease.

A prospective marker for the prediction of postoperative deep venous thrombosis: Neutrophil extracellular traps.

Deep venous thrombosis (DVT) is a common medical complication in patients with lumbar fractures. The current study aimed to investigate the predictive value of neutrophil extracellular traps (NETs) in postoperative DVT formation in patients with lumbar fractures and to develop a nomogram relating clinical admission information for prediction. Patients who underwent open reduction and pedicle screw internal fixation in the treatment of single-segment lumbar fracture in the Department of Spine Surgery, the First Affiliated Hospital of Nanjing Medical University, from December 2020 to June 2022 were enrolled in this study. Baseline data and laboratory results were collected from enrollees, and the primary study endpoint event was the occurrence of DVT in patients after surgery. Multivariable logistic regression analysis was used to identify risk factors associated with higher odds of DVT after surgery. A nomogram was constructed using the results of the multivariable model. The calibration plot and receiver operating characteristics (ROC) curve were used to show the satisfactory predictive capacity of the model. Of these 393 patients who did not have DVT preoperatively, 79 patients developed it postoperatively, and 314 did not, respectively. Multivariate analysis showed that higher body mass index (BMI) (BMI between 24 and 28: RR = 1.661, 95% CI = 0.891-3.094; BMI ≤28: RR = 5.625, 95% CI = 2.590-12.217; reference: BMI <24), neutrophils (RR = 1.157, 95% CI 1.042-1.285), D-dimer (RR = 1.098, 95% CI 1.000-1.206), and citrullinated histone H3 (CitH3) (RR = 1.043, 95% CI 1.026-1.060) were independent risk factors for postoperative DVT. Using the multivariable analysis, we then constructed a nomogram to predict DVT, which was found to have an area under the curve of 0.757 (95% CI = 0.693-0.820). Calibration plots also showed the satisfied discrimination and calibration of the nomogram. In conclusion, patients with lumbar fractures with postoperative DVT had higher levels of NETs in the circulation preoperatively compared to those without postoperative DVT. Furthermore, based on BMI, D-dimer, neutrophils, and CitH3, we developed a predictive model to predict postoperative DVT incidence in these patients.

Computational Analysis of the Related Factors of Deep Vein Thrombosis (DVT) Formation in Patients Undergoing Hip Fracture Surgery.

A retrospective study was conducted on 51 patients undergoing hip fracture surgery to investigate the factors associated with the formation of deep venous thrombosis (DVT). The independent sample t-test and correlation analysis were used to sort out and analyze the data. The findings are as follows. (1) Different gender samples showed significant differences in the Caprini score and thrombus location. Most DVTs in females are located in the posterior tibial vein and intermuscular veins. The Caprini score of females was significantly higher than that of males. (2) Age displays a positive correlation with DVT, coronary heart disease, hypertension, and different surgical types, respectively. (3) There is a correlation between age and operation duration. (4) Hyperlipidemia and cerebrovascular disease show a positive correlation with DVT. (5) There was a significant negative correlation between the Caprini score and the quantification of D-dimer. This indicates that in this sample, the higher the patients' Caprini score is, the lower the quantitation of D-dimer will be. (6) Hyperlipidemia and cardiac insufficiency show a positive correlation with cerebrovascular disease. Patients with hyperlipidemia and cardiac insufficiency may also suffer from cerebrovascular diseases.

Intraoperative IPC combined with 3M warming instrument to prevent lower extremity deep venous thrombosis in patients undergoing proximal femoral anti rotation intramedullary nailing

To explore the effect of intermittent pneumatic compression(IPC) combined with 3M thermometer on the prevention of deep venous thrombosis(DVT) in patients with femoral intertrochanteric fracture. From March 2016 to August 2019, 127 patients with femoral intertrochanteric fractures who underwent proximal femoral nail antirotation(PFNA) were retrospectively analyzed. They were divided into two groups according to different methods of thrombus prevention and treatment. Among them, 63 patients in group A did not use IPC and 3M thermometer;64 cases in group B were treated with IPC combined with 3M thermometer. Color Doppler ultrasound was used to dynamically monitor the DVT and changes of lower limbs during perioperative period. The venous thrombosis of lower limbs was monitored at 0, 24, 72 h and > 72 h after operation(recheck every 3 days until discharge). Occurrence of DVT of lower limbs after PFNA operation in two groups:there were 5 cases (7.8%) in group B and 20 cases (31.7%) in group A, there was significant difference between two groups (P=0.001). There was no significant difference in lower limb DVT between two groups at 0, 72 and > 72 h after operation(P>0.05), but the formation rate of group A was significantly higher than that of group B at 24 h after operation (P=0.049). There was no significant difference in DVT formation between group A and group B(P>0.05). However, the formation of DVT in group A was significantly higher than that in group B(P=0.012). Intraoperative IPC combined with 3M thermostat can effectively prevent DVT of lower limbs in patients undergoing PFNA surgery.

Peripheral Blood Levels of miR-448 and SIRT1 in Patients with Deep Venous Thrombosis and Their Relationship.

The goal of this study was to investigate the changes in peripheral blood levels of miR-448 and silent information regulator 1 (SIRT1) in patients with deep venous thrombosis (DVT) and to analyze their relationship. A total of 112 patients treated from January 2019 to June 2020 were divided into DVT group (n = 40) and non-DVT group (n = 72). Fasting venous blood was extracted to separate serum and peripheral blood mononuclear cells (PBMCs). Enzyme-linked immunosorbent assay (ELISA) was employed to measure serum SIRT1 protein, and qPCR was utilized to detect miR-448 expression in PBMCs. The clinical data, serum indicators, and expressions of SIRT1 and miR-448 were compared, and the correlations of miR-448 and SIRT1 with DVT were analyzed using a multivariate Cox regression model. TargetScan Release 7.1 was used to predict the possibility of binding sites between miR-448 and SIRT1 mRNA 3'-untranslated region (3'-UTR), and dual-luciferase reporter assay was used to determine the targeting of miR-448 and SIRT1. HeLa cells were divided into overexpression, inhibition, and blank control groups. The cells were harvested 24 hours after transfection, followed by detection of SIRT1 mRNA expression by qPCR and measurement of supernatant SIRT1 protein expression by ELISA. Serum SIRT1 protein level was lower and miR-448 expression in PBMCs was higher in DVT group than those in non-DVT group (p < 0.05). DVT group had a larger number of patients with vascular diseases and history of venous thrombosis than that of non-DVT group (p < 0.05). miR-448 was an independent risk factor for postoperative DVT, and SIRT1 was a protective factor (p < 0.01). There were potential complementary base binding sites between miR-448 and SIRT1 mRNA 3'-UTR. Dual-luciferase reporter assay verified the targeted regulation between miR-448 and SIRT1. HeLa cell SIRT1 mRNA expression and supernatant SIRT1 protein expression were lower in overexpression group while higher in inhibition group than those in blank control group (p < 0.05). Serum SIRT1 protein level decreases while miR-448 expression in PBMCs increases in patients with DVT, and miR-448 inhibits SIRT1 expression through binding to SIRT1 mRNA 3'-UTR with complementary bases, thus inducing inflammatory response to participate in the formation of DVT. Targeting miR-448 to regulate cytokine expression may become an effective target and approach for the treatment of DVT. miR-488 combined with SIRT1 has a high predictive value for the occurrence of DVT.

Analysis of Related Influencing Factors of Deep Vein Thrombosis after Lumbar Internal Fixation and Treatment Strategy.

Lumbar internal fixation is a traditional surgical method for the treatment of degenerative diseases of the lumbar spine. However, due to its large surgical trauma, it easily causes complications such as deep venous thrombosis (DVT) after the operation. DVT refers to the abnormal coagulation of blood in deep veins, blocking the lumen, causing venous blood return disorder, causing venous blood return disorder to cause swelling and pain, which affects the recovery of the patient's lumbar spine function. In severe cases, even complicated pulmonary embolism endangers the life and health of the patient. Therefore, it is extremely important to explore the related influencing factors and effective treatment of DVT. The purpose of this study was to investigate the influencing factors and effective treatment of DVT after lumbar internal fixation. Univariate analysis and multivariate a logistic regression model were used to analyze the related factors affecting DVT after lumbar internal fixation. Conventional treatments such as anticoagulation, promotion of venous blood return, and improvement of limb circulation were given to patients with DVT, and functional exercise was guided to compare the hypercoagulability and hyperviscosity of blood in patients with DVT before and after treatment. The results showed that the incidence of DVT after lumbar internal fixation was related to age, BMI, and bed time. Getting out of bed for functional exercise in time after surgery can effectively prevent the formation of DVT. Preoperative grading examination, intraoperative intervention, postoperative physical exercise, and other preventive guidance can be carried out according to different individuals during the perioperative period to prevent the formation of postoperative DVT.

Incidence of and risk factors for pre-operative deep venous thrombosis in geriatric intertrochanteric fracture patients.

The purpose of this prospective study was to investigate the pre-operative incidence of and risk factors for deep venous thrombosis (DVT) in geriatric intertrochanteric fractures to help facilitate the peri-operative management of them. Data of 1515 geriatric intertrochanteric fracture patients were extracted from a prospective intertrochanteric fractures database according to the inclusion criteria and exclusion criteria. The demographics, fracture characteristics, and pre-operative laboratory indicators of patients were evaluated statistically. The incidence of pre-operative DVT was 10.2% (155 in 1360 patients) in the present study. The rates of proximal DVT, distal DVT, and mixed DVT were 18.1% (28 patients), 56.8% (88 patients), and 25.2% (39 patients), respectively. The percentages of DVT developing in the affected limb, uninjured limb, and bilateral limbs were 74.2% (115 in 55 patients), 16.8% (26 in 155 patients), and 9% (14 in 155 patients), respectively. After the multivariable analysis, the time from injury to surgery (TIS) > 4days [odds ratio (OR) = 1.870, p = 0.001], the number of comorbidities > 2 (OR = 2.124, p = 0.014), and albumin (ALB) < 35g/L (OR = 1.516, p = 0.043), etc. were significantly associated with the development of preoperative DVT in geriatric intertrochanteric fracture patients. Although routine anticoagulant therapy was used to prevent the formation of DVT, the incidence of which was still high. Therefore, pre-operative ultrasound of both lower extremities was advised for pre-operatively, especially for patients with delayed surgery, hypoproteinemia, three or more comorbidities, and a D-dimer level > 1.59mg/L.

Evaluation of ultrasonic intravascular thrombectomy system on a rabbit model in the treatment of deep vein thrombosis

Background/Aim: Advanced treatment options are needed in deep venous thrombosis (DVT), which is a special subgroup of venous disease. We examined this subgroup on an animal model and aimed to evaluate the effects of the ultrasonic intravascular thrombectomy system on vascular endothelial damage. Methods: A total of 24 rabbits in 3 groups were used in the study. DVT was created in the common iliac vein by the administration of intravascular fibrin. One hour passed for DVT formation. The ultrasonic intravascular thrombectomy system and the mechanical thrombectomy system were used separately in the DVT groups. After one hour, samples obtained from the groups were examined histologically. Results: Significantly less endothelial damage was detected in the ultrasonic intravascular thrombectomy system group compared to the mechanical thrombectomy group (P<0.05). Conclusions: Ultrasonic intravascular thrombectomy method minimizes the thrombus load and causes minimal endothelial damage. These findings show that the ultrasonic intravascular thrombectomy method can be used successfully in DVT treatment.

The secret enemy during a flight: Economy class syndrome.

Deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE) are the major causes of morbidity and mortality in immobile patients. There is observational evidence that intercontinental air travel is associated with a high incidence of DVT and PTE during or within 48 hours of long-distance flights. This situation is known as the economy class syndrome and can affect both the cabin crew and passengers. The term "economy class syndrome" refers to the occurrence of thrombotic events that mainly occur in passengers in the economy class of the aircraft during long-haul flights. This syndrome results from several factors related to the aircraft cabin and the passenger, acting together to predispose to excessive blood coagulation, which can result in venous thromboembolism. In this review, we have shared the relationship between air travel and the formation of DVT and PTE.

MiR-296-5p ameliorates deep venous thrombosis by inactivating S100A4.

Deep venous thrombosis is one of the most common venous thromboembolic diseases and has a low cure rate and a high postoperative recurrence rate. Furthermore, emerging evidence indicates that microRNAs are involved in deep venous thrombosis. miR-296-5p is an important microRNA that plays a critical role in various cellular functions, and S100A4 is closely related to vascular function. miR-296-5p is downregulated in deep venous thrombosis patients, and its predicted target S100A4 is upregulated in deep venous thrombosis patients. Therefore, it was hypothesized that miR-296-5p may play a vital role in the development of deep venous thrombosis by targeting S100A4. An Ox-LDL-stimulated HUVEC and deep venous thrombosis mouse model was employed to detect the biological functions of miR-296-5p and S100A4. Dual luciferase reporter assays and pull-down assays were used to authenticate the interaction between miR-296-5p and S100A4. ELISA and Western blotting were employed to detect the protein levels of thrombosis-related factors and the endothelial-to-mesenchymal transition (EndMT)-related factors. The miR-296-5p levels were reduced, while the S100A4 levels were enhanced in deep venous thrombosis patients, and the miR-296-5p levels were negatively correlated with the S100A4 levels in deep venous thrombosis patients. miR-296-5p suppressed S100A4 expression by targeting the 3' UTR of S100A4. MiR-296-5p knockdown accelerated ox-LDL-induced HUVEC apoptosis, oxidative stress, thrombosis-related factor expression, and EndMT, while S100A4 knockdown antagonized these effects in ox-LDL-induced HUVECs. S100A4 knockdown reversed the effect induced by miR-296-5p knockdown. Moreover, the in vivo studies revealed that miR-296-5p knockdown in deep venous thrombosis mice exacerbated deep venous thrombosis formation, whereas S100A4 knockdown had the opposite effect. These results indicate that elevated miR-296-5p inhibits deep venous thrombosis formation by inhibiting S100A4 expression. Both miR-296-5p and S100A4 may be potential diagnostic markers and therapeutic targets for deep venous thrombosis.

Inhibition of Neutrophil Extracellular Trap Release through the Disruption of PAD4 Leads to Decreased Neutrophil and Platelet Accumulation at Sites of Venular Vascular Injury in a Murine Model of Heparin-Induced Thrombocytopenia

Neutrophil extracellular traps (NETs) are webs of decondensed nuclear DNA decorated with histones that facilitate microbial killing but also promote thrombosis. NET release is dependent on chromatin decondensation mediated by the enzyme peptidylarginine deiminase (PAD) 4 that is expressed predominantly in granulocyte nuclei and citrullinates histone arginine residues, reducing their positive charge, and decreasing their affinity for DNA. Mice deficient in PAD4 are incapable of NET release and have been found to be protected from deep venous thrombosis formation. We have shown that PF4 physically compacts released NETs, causing them to become resistant to DNase digestion. Moreover PF4/NETs bind to heparin-induced thrombocytopenia (HIT)-specific antibodies further stabilizes PF4/NET complexes, enhancing their endonuclease resistance. We therefore speculated that these immunogenic and longer-lasting NETs may contribute to the prothrombotic nature of HIT. To investigate this hypothesis, we used CRISPR technology to disrupt Exon 2 of the Padi4 gene in embryos obtained from mice transgenic for human CXCL4 and FCGR2A, termed “HIT mice”, that have previously been found to develop thrombocytopenia and thrombosis when exposed to the monoclonal HIT-like antibody, KKO. We studied clot formation after cremaster vessel laser injury in PAD4-/- compared toPAD4+/+ HIT mice, quantifying both neutrophil and platelet accumulation. We initially noted PAD4+/+ HIT mice treated with KKO had a significant increase in neutrophil thrombus incorporation 5 minuntes and 60 minutes following venule (but not arteriole) laser injury, compared to mice injected with the isotype control antibody, TRA [8.5±1.3(n=31) vs. 3.1±1.0(n=11), p=0.026 at 5 minutes, 20.1±2.2(n=46) vs. 7.5±1.8(n=17) p=0.002 at 60 minutes). Compared to TRA, KKO infusion also led to a significant increase in venule thrombus platelet volumes 60 minutes following laser injury (p=0.0035, Figure 1). Although KKO exposed PAD4-/- mice had similar thrombus platelet volumes and neutrophil thrombus infiltration compared to PAD4+/+ animals 5 minutes after injury, by 60 minutes, the PAD4-/- animals had significantly smaller platelet volumes (p<0.004, Figure 1) and significantly fewer incorporated neutrophils (p<0.007, Figure 1). To determine if the rise in platelet volumes and increase in neutrophil-thrombus infiltration in HIT was the result of chemokine release by activated platelets, we treated PAD4+/+ mice with the CXCR2 antagonist sch527123 prior to HIT induction. We observed that these mice had a marked reduction in the number of neutrophils in their thrombi, but no decrease in platelet volumes. These findings suggest that PAD4-mediated NET release plays a unique role in the prothrombotic nature of HIT, enhancing neutrophil recruitment while also augmenting platelet accumulation through a chemokine-independent mechanism. We therefore propose that NET release is important for the venular prothrombotic nature of HIT. Furthermore, inhibition of NET-release prevents thrombus growth more effectively than the blockade of chemokine-based neutrophil-platelet interactions and merits further investigation as a treatment strategy in HIT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

ASAIO 2021 Annual Meeting Abstracts.

Study: Deep venous thrombosis (DVT) is said to be the most preventable cause of death in hospitals today (Centers for Disease Control, February 2020). This silent killer most frequently starts in the lower extremities as a small thrombus that initially forms in a valve pocket located behind a venous valve leaflet. Failure to initiate preventative measures to reduce the risk of DVT can result in the development of life-threatening pulmonary emboli (PE) and chronic venous insufficiency (CVI). These risks are currently exacerbated by the current SARS-CoV-2 pandemic that has increased the frequency of DVT formation and PE in patients through mechanisms that are not fully understood. The current study is using artificial intelligence (AI) and machine learning (ML) to evaluate changes in blood rheology, venous blood flow, and venous valve configuration that can lead to increased risk of DVT, PE, and CVI. Methods: In our model, AI/ML is used to evaluate previously recorded images of normal and abnormal cadaver veins and venous valves. Using these data, we can predict that previous DVT formation produced the observed leaflet damage and will increase the risk of CVI and future DVT formation. The contribution that changes in blood rheology could make to venous blood flow abnormality will also be assessed. We leverage the latest advances in image processing to quantify the valve leaflet geometry with respect to the susceptibility to recurrent DVT. Results: Based on this data, AI/ML will predict, on a patient-by-patient basis, the probability of deep venous thrombosis formation. This will allow healthcare professionals to determine when preventative measures are most appropriate. It will also allow physicians to assess whether a patient has an increased risk of developing a future DVT and/or CVI insufficiency. With this information patient care can be improved and the debilitating and life-threatening complications of DVT can be substantially reduced.

Low-molecular-weight heparin calcium attenuates the tourniquet-induced ischemia-reperfusion injury in rats

Ischemia-reperfusion injury (IRI) is a common postoperative complication of the tourniquet used surgery; low-molecular-weight heparin calcium (LMWH) is frequently used postoperatively to prevent the formation of deep venous thrombosis. However, subcutaneous hemorrhage can usually be seen in patients who underwent lower limb surgery, especially in total knee arthroplasty, the influence of LMWH on IRI remains controversial. In this experiment, we designed an animal model to observe the influence of LMWH on the skeletal muscle injury induced by tourniquets. Sprague-Dawley (SD) rats underwent either 2 h of unilateral hindlimb ischemia or anesthesia alone, at different time points of reperfusion interval, animals received either 4mg/kg LMWH or normal saline subcutaneously twice a day. The levels of inflammatory markers in serum, the expression of apoptosis proteins, as well as histological examination of skeletal muscles, were detected at 48-h reperfusion. We found that the injury of skeletal muscle and the systemic inflammatory response was less severe in LMWH-treated animals, indicating that LMWH could attenuate the tourniquet-induced IRI. In conclusion, LMWH given postoperatively after limb surgery may be clinically beneficial.