Femoral Vein Injury Research Articles

Risk Factors for Venous Thromboembolism and Eventual Amputation in Traumatic Femoral and Iliac Vein Injuries: A Trauma Quality Improvement Program Analysis.

Iliac and femoral venous injuries represent a challenging dilemma in trauma surgery with mixed results. Venous restoration of outflow (via repair or bypass) has been previously identified as having higher rates of VTE (venous thromboembolism) compared to ligation. We hypothesized that rates of VTE and eventual amputation were similar whether restoration of venous outflow vs ligation was performed at initial operation. Patients in the 2019-2021 National Trauma Data Bank with iliac and femoral vein injuries were abstracted and analyzed. The primary outcomes of interest were in-hospital lower extremity amputation and VTE. A total of 2642 patients with operatively managed iliac and femoral vein injuries were identified VTE was found in 10.8% of patients. Multivariable logistic regression was performed and identified bowel injury, higher ISS, older age, open repair, and longer time to VTE prophylaxis initiation as independent predictors of VTE. Amputation was required in 4.2% of patients. Multivariable logistic regression identified arterial or nerve injury, femur or tibia fracture, venous ligation, percutaneous intervention, fasciotomy, bowel injury, and higher ISS as independent factors of amputation. Venous restoration was not an independent predictor of VTE. Venous ligation on index operation was the only modifiable independent predictor of amputation identified on regression analysis.

Kaolin-loaded carboxymethyl chitosan/sodium alginate composite sponges for rapid hemostasis

There are several factors that contribute to the mortality of people who suffer from unmanageable bleeding. Therefore, the development of rapid hemostatic materials is necessary. Herein, novel rapid hemostatic composite sponges were developed by incorporation of kaolin (K) into carboxymethyl chitosan (CMCS)/sodium alginate (SA) via a combination of methods that includes ionic crosslinking, polyelectrolyte action, and freeze-drying. The CMCS/SA-K composite sponges were cross-linked with calcium ions provided by a sustained-release system consisting of D-gluconolactone (GDL) and Ca-EDTA, and the hemostatic ability of the sponges was enhanced by loading the inorganic hemostatic agent-kaolin (K). It was demonstrated that the CMCS/SA-K composite sponges had a good porous structure and water absorption properties, excellent mechanical properties, outstanding biodegradability, and biocompatibility. Simultaneously, they exhibited rapid hemostatic properties, both in vitro and in vivo. Significantly, the hemostatic time of the CMCS/SA-K60 sponge was improved by 82.76 %, 191.82 %, and 153.05 %, compared with those of commercially available gelatin sponges in the rat tail amputation, femoral vein, and liver injury hemorrhage models respectively, indicating that its hemostatic ability was superior to that of commercially available hemostatic materials. Therefore, CMCS/SA-K composite sponges show great promise for rapid hemostasis.

Abstract 9850: Predictors of Inpatient Mortality for Patients Admitted With Traumatic Femoral Artery Injury

Introduction: Femoral artery injury (FAI) after trauma is one of the most common vascular injuries evaluated in Trauma Centers. Data at the national level are lacking. Methods: We used Nationwide Inpatient Sample (NIS) data for 2016-2019 in our cross-sectional study. First, we extracted all cases older than 18-years that include the diagnosis of FAI. Then, we kept only the observations with a primary diagnostic category suggestive of trauma or cases that have a concurrent presence of trauma-related diagnoses. Baseline characteristics were evaluated as well as predictors of inpatient mortality. Exclusion criteria included transferred out cases and elective admissions. Appropriate survey and domain analyses were applied to obtain and study national estimates using SAS 9.4. Results: We identified 3,850 weighted admissions that contain a diagnosis of traumatic FAI. The mean age of surviving patients was 37-years (84% were male) in comparison to the mean age of 45-years (80% were male) for non-survival (p<0.0001). African American patients represented the majority (40%), followed by Caucasians (36%). Most patients were of low socioeconomic status (47%) and receiving Medicaid (37%). In-patient mortality was high, 9.5%, and more than 75% of death was within a week of admission. Although documentation of associated femoral vein, nerve, or femur injuries was not statistically significant, age >40-years, presence of comorbidities (especially cirrhosis), and intubation (indicating critical illness with acute respiratory failure or low Glasco-coma scale) were associated with inpatient mortality (p<0.0001). Lower extremity amputation (BKA/ AKA) was associated with higher mortality (not statistically significant). Neither open nor percutaneous femoral artery procedures (individually or combined) were associated with favored outcomes. On the other hand, thigh procedures on musculoskeletal tissues (muscles, fascia, femur) were associated with higher survival. The Area Under the Curve (AUC) of our model was 0.84. Conclusions: Our study suggests that young African American males are more likely to have traumatic FAI. Independent mortality predictors are age, Elixhauser comorbidities, and femur, muscular, soft tissues, and fascia procedures.

Percutaneous edge-to-edge repair for systemic tricuspid valve regurgitation in patients with congenital heart disease: the first descriptive cohort

Abstract In patients with congenital heart diseases (CHD) systemic tricuspid regurgitation (STR) is frequent. Here, we report our experience with percutaneous edge-to-edge repair (PETER) in a series of 12 CHD patients with STR using the MitraClip system. Twelve patients (median age = 35 years, 83% males) with severe STR (ccTGA (n=5), asTGA (n=3), SV (n=4)), at high-risk for surgical treatment, gave informed consent for treatment using PETER. The XTR MitraClip device (Abbott, Santa Clara, CA) was used. At baseline, 7/12 patients were in NYHA functional class ≥ III. Standard femoral venous access was successfully used in 10/12 patients. In SV patients, the systemic valve was accessed directly through the right atrium (n=2), after a Fontan conduit puncture (n=1), or after direct atrial surgical access (n=1). In TGA patients, either transseptal (ccTGA patients, n=4) or transbaffle (asTGA patients, n=3) puncture was performed (4). Mitraclip devices were successfully implanted in 11/12 patients (Figure 1). One procedural complication was reported for a patient with SV in whom a septal leaflet rupture occurred following clip release, leading to severe STR; the patient died from refractory cardiac failure one week later. Peri-procedural complications included one case of left femoral vein injury and one case of atrial flutter treated by catheter ablation. After a median follow-up of 12-months (range 1–25) following device implantation, no death had occurred. The patients had significant reduction in STR (from severe to moderate in 10/11 patients) and clinically improved (10/11 patients were in NYHA class I or II). To conclude, percutaneous edge-to-edge therapy of STR in CHD patients is feasible, safe and effective to reduce STR and SRV dilatation. This reduction is associated with a significant clinical improvement. Funding Acknowledgement Type of funding sources: None.

Biocompatible Hemostatic Sponge Exhibiting Broad-Spectrum Antibacterial Activity.

Hemorrhage during accidents or surgery is a significant challenge that can contribute to mortality. This is further aggravated due to bacterial infections at the injured site. Therefore, rapid application of a hemostatic and antibacterial material is highly necessary as a pretreatment for patients' survival. Herein, we have developed a hemostatic sponge (Hemobac) through amide crosslinking of gelatin and an N-(2-hydroxy) propyl-3-trimethylammonium chitosan (HTCC)-silver chloride nanocomposite (QAm1-Ag0.1) to mitigate bacterial infections, while aiding hemostasis. This Hemobac sponge completely eradicated (∼4-5 log) a wide range of Gram-positive and Gram-negative bacteria encompassing various clinical isolates within 6 h. The antihemorrhagic ability of Hemobac was ascertained through SEM images, which exhibited the presence of agglomerated blood cells onto the sponge with a significantly low blood-clotting index value (∼23 ± 1). Notably, Hemobac reduced the blood loss by ∼70-80% in the liver puncture model and femoral vein injury model in mice, displaying its improved hemostatic ability over a marketed gelatin-based sponge. Negligible hemolytic activity (∼6%) and retained healthy morphology of mammalian cells were observed upon exposure to the Hemobac sponge. Minimal immune response was noticed at the Hemobac-treated wound in mice through histopathology analysis. Collectively, these findings indicate that this biocompatible Hemobac sponge can stop the bleeding instantaneously and combat bacterial infections.

Traumatic Femoral Artery Injuries and Predictors of Compartment Syndrome: A Nationwide Analysis

BackgroundThe femoral artery is commonly injured following lower extremity trauma. If not identified early and addressed properly, it can lead to compartment syndrome (CS) and limb amputation. The aim of this study is to examine traumatic femoral artery injuries and identify risk factors for the development of lower extremity CS. MethodsAdult (≥18 years) patients who presented with traumatic femoral artery injuries were identified in the Trauma Quality Improvement Program 2017. Patients were stratified into two groups, those with evidence of lower extremity compartment syndrome (CS) and those without CS (NCS), for comparison. Multivariate regression analysis was performed. ResultsA total of 1,297 adult trauma patients with femoral artery injury were identified. Mean age was 36 ± 15 y, 86% were male, and 68% had penetrating injuries. Median extremity abbreviated injury scale (AIS) was 3 [3,4], and median injury severity score (ISS) was 27 [22-41]. 68 (5.2%) patients were diagnosed with CS of the lower extremity, 66 (97.1%) of those patients underwent fasciotomy and one (1.5%) patient eventually had an amputation. On multivariate regression analysis, concomitant femoral vein, femoral nerve, and popliteal artery injuries and early need for blood transfusions were independent risk factors for the development of CS (OR 3.1, 3.8, 4.3, and 2.5 respectively). ConclusionsCS following traumatic femoral artery injury is a relatively common finding. Physicians must maintain a high index of suspicion and should consider prophylactic fasciotomy in the setting of combined femoral vein and nerve injuries, combined popliteal artery injury, and multiple blood transfusions.

Surgical management of chronic pelvic instability following periacetabular osteotomy nonunion.

Periacetabular osteotomy (PAO) is an established treatment for symptomatic acetabular dysplasia in skeletally mature individuals without arthritis. Pelvic nonunion and associated stress fractures are under-reported. Nonunited stress fractures can cause continued buttock pain and pelvic instability. The aim of this study is to report on our experience managing patients with ongoing pain following nonunion of PAO. 8 patients presented to a tertiary referral pelvic service with symptomatic PAO nonunion between 2015-2018. All patients underwent open reduction internal fixation of the superior pubic ramus nonunion, with ipsilateral iliac autograft, at an average of 48.1 (15-82) months following initial osteotomy. Demographic and perioperative data were recorded. Follow-up was on average to 9.9 months, once union was confirmed radiographically. All patients were female and average age was 31.8 (18-41) years. In 7/8 (87.5%) patients a modified Stoppa approach was successfully utilised. 1 patient required an ilioinguinal approach due to the amount of rotational correction. All patients went on to union at the superior pubic ramus and reported improvement in mechanical symptoms. 5/8 (62.5%) patients were noted to develop union of the posterior column or inferior pubic ramus stress fracture indirectly. 2/8 (25%) patients developed progression of intra-articular pain, despite restoration of pelvic stability. 1 patient required intraoperative transfusion due to femoral vein injury. There were no other complications seen in this series. To our knowledge, this is the largest case series of surgically managed PAO nonunion. Pelvic instability resulting from nonunion and stress fracture can be satisfactorily addressed by mobilising, grafting and plating the nonunion at the superior pubic ramus. The modified Stoppa approach is suitable in most cases, allowing excellent exposure whilst minimising the insult to soft tissues. The altered anatomy of the pelvis following PAO should be anticipated to reduce the risk to nearby neurovascular structures.

Mussel-inspired degradable antibacterial polydopamine/silica nanoparticle for rapid hemostasis

High-performance hemostasis becomes increasingly essential in civilian and military trauma. However, available topical hemostats still exist various drawbacks and side-effects. Herein, a silica nanoparticle coated with polydopamine (PDA/SiNP) with good degradability, antibacterial performance was developed for hemorrhage control. PDA/SiNP formed a porous network via lyophilization and rendered material with phenol hydroxyls, aminos, proper hydrophobicity, promising for further cells aggregation and inducing clotting. The degradation behaviors in vitro indicated that the weight loss of PDA/SiNP could attain approximately 40% just after 24 h. All results demonstrated that clotting time of blood was shortened by nearly 150 s for PDA/SiNP compared with that of commercial Celox in vitro hemostasis. PDA/SiNP could significantly accelerate coagulation by activating the extrinsic pathway of the coagulation cascade, adhering platelets and aggregating erythrocytes. Therefore, not only the PDA/SiNP achieved adequate hemostasis with low exothermic effects, but also blood loss was remarkably reduced in the femoral artery and vein injury, liver injury models. Importantly, PDA/SiNP exhibited long-lasting inhibition of Escherichia coli even after 208 h. Also, the hemolysis of PDA/SiNP with low cytotoxicity was much lower, while erythrocytes maintained regular morphology. Thus, amorphous nanoscale PDA/SiNP provided a new avenue for design of silica hemostats and nonmetallic ion antimicrobial.

An isolated femoral vein injury caused by bull horn

Introduction Bullhorn injuries have rarely been documented in the literature. Most of the articles are related to the injuries occurred during bullfighting shows and bull-running festivals. Bullfighting is still a popular and uniquely cultural tradition of many Ibero-American countries (Spain, Portugal, Mexico etc.).

Prevention and treatment of vascular complications of inguinal hernia repair

Objective To explore the prevention and treatment of complications of vascular injury after inguinal hernia repair. Methods The retrospective cross-sectional and descriptive study was adopted. The clinical data of 22 patients with vascular injury after inguinal hernia repair who were admitted to the First Affiliated Hospital of Chongqing Medical University between June 2005 and March 2016 were collected. Observation indicators included: (1) the vascular complications after inguinal hernia repair: vascular injury, peritoneal interstitial hemorrhage or hematoma formation, thrombosis and vascular embolization, (2) treatment, (3) follow-up. Patients were followed up by telephone interview at 15 days after discharge up to April 2016, and conditions of patients, recovery of symptoms and subsequent pharmacotherapy were detected. Results (1) The vascular complications after inguinal hernia repair: of 22 patients, peritoneal interstitial hemorrhage or hematoma formation was detected in 8 patients (vascular injury of corona mortis in 2 patients, inferior epigastric artery injury in 3 patients and unexplained peritoneal interstitial hemorrhage in 3 patients), femoral vein injury in 3 patients, femoral artery injury in 1 patient, deep vein thrombosis of the double lower limbs in 8 patients (including 2 with pulmonary embolism) and femoral and popliteal artery embolism in 2 patients. (2) Treatments: 20 of 22 patients had good therapeutic effect, 1 patient with arterial embolism received timely treatment avoiding the necrosis of limbs, 1 ischemic necrosis of partial toes and the other patients had good effect through vascular repair or construction. One patient with inferior epigastric artery injury and 1 with femoral vein injury died of hemorrhagic shock. (3) Follow-up: 20 of 22 patients were followed up for 2 weeks, with good conditions. Patients′ hemorrhage had been improved. The symptoms of patients with deep vein thrombosis and arterial embolism of lower limbs didn′t become obviously aggravated, and they took the medicine as medical advice. Conclusion The different treatments are conducted according to the occuring characteristics of vascular complications, with better outcomes. Key words: Inguinal hernia; Hernia repair; Iatrogenic injury; Vascular injury; Therapy

An Unusual Case of Isolated Femoral Vein Injury After Bull Gore

Animal related injuries are frequently reported in countries where the bulls are used for traditional show events like bullfighting and bull-running as well as in countries where the farming and livestock rearing is predominantly practiced. Although, they are rare among other penetrating traumas, they often tend to be mortal. They have a unique pattern of injury mechanism. Bull gore injuries frequently target the perineal, abdominal and inguinal regions. An isolated femoral vein injury which is caused by an inguinal bull gore with a massive hemorrhage is unusual and it has not been reported in the available literature. In this paper, successfully treated a male patient from the villages of Kars district, who presented with an isolated femoral vein injury after bull gore was presented.

Platelet-like particles for wound-triggered hemostasis in patients at high risk for bleeding during cardiac surgery

Event Abstract Back to Event Platelet-like particles for wound-triggered hemostasis in patients at high risk for bleeding during cardiac surgery Riley Hannan1, Byungwook Ahn2, 3, 4, Wilbur Lam3, 4, Andrew Lyon5, Nina Guzzetta3, 4, Thomas H. Barker2, 4 and Ashley Brown6 1 University of Virginia, United States 2 Georgia Institute of Technology, Biomedical Engineering, United States 3 Children’s Healthcare of Atlanta, United States 4 Emory University, United States 5 Chapman University, Schmid College of Science and Technology, United States 6 North Carolina State University and University of North Carolina at Chapel Hill, Biomedical Engineering, United States Introduction: Neonates born with congenital cardiac defects often undergo complex corrective surgery requiring cardiopulmonary bypass (CPB) within a few days following birth. CPB is known to contribute significantly to surgery associated bleeding through induction of massive hemodilution, thrombocytopenia and platelet dysfunction; these bleeding risks are exacerbated in neonates due to preexisting platelet dysfunction and an immature coagulation system. CPB greatly hinders platelet function; therefore, materials that recapitulate platelet hemostatic functions could be utilized as an alternative to transfusion of adult blood products for augmentation of clotting in patients post-CPB. We have recently developed platelet-like-particles (PLPs) created from highly deformable microgels conjugated to molecularly evolved wound-targeting motifs which enable specific and high affinity binding to the provisional matrix protein fibrin[1]. These PLPs are capable of recapitulating a number of functions of natural platelets, including augmentation of clotting of adult plasma in vitro, decreased bleeding times in vivo in rodent models of traumatic injury, specific homing to injury sites and clot contraction. Here, we characterize the ability of PLPs to augment clotting in CPB-patient plasma samples in vitro and in vivo in a rat model of impaired platelet activity. Materials and Methods: Ultra-low crosslinked (ULC) poly(N-isopropylacrylamide) (pNIPAM) microgels containing 95% pNIPAM and 5% acrylic acid (AAc) were produced through precipitation polymerization. PLPs were produced by conjugating fibrin-specific single domain variable fragment antibodies to ULC microgels through EDC/NHS coupling. Clotting was assessed in vitro in patient platelet poor plasma (PPP) samples collected from neonatal cardiac surgery patients at baseline, post-CPB (+/- PLPs) and post transfusion through an endothelialized microfluidics device that mimics the microenvironment of microcirculation[2]. Fibrin microarchitecture was analyzed using confocal microscopy. Clotting was assessed in vivo in a rodent platelet deficiency model, which mimics the gross dysfunction of platelets in pediatric cardiac patients. To induce platelet hyporeactivity, male Sprague Dawley rats received a daily oral gavage of aspirin (5 mg/kg) for seven days. On the seventh day, bleeding times following induction of a femoral vein injury were assessed in animals receiving intravenous administration of PLPs or saline. Results and Discussion: In vitro clotting experiments in an endothelialized microfluidic device demonstrate minimal clotting in post-CPB PPP alone, while the addition of PLPs induces significant fibrin formation (Figure 1A). To determine the effect of PLPs on fibrin network microstructure, confocal microscopy was performed; incorporation of PLPs into post-CPB PPP results in a denser fibrin network compared to post-CBP PPP alone or samples collected post-transfusion (Figure 1B). In an in vivo model of platelet hyporeactivity, PLPs significantly decreased bleeding following injury compared to control animals (Figure 1C). Conclusions: PLPs enhance clot formation in neonatal patient samples in vitro and decrease bleeding times in vivo in a rodent model of platelet dysfunction. These results highlight the utility of PLPs for treatment of postsurgical bleeding in coagulopathic neonatal patients. 1R21EB019068, NIH/NIBIB

Bevacizumab promotes venous thromboembolism through the induction of PAI-1 in a mouse xenograft model of human lung carcinoma.

BackgroundAn increased incidence of venous thromboembolism (VTE) is associated with anti-vascular endothelial growth factor (VEGF) treatment in cancer. However, the mechanism underlying this effect remains elusive. In this study, we examined the effect of bevacizumab, a humanized monoclonal antibody against VEGF-A, on VTE in a murine xenograft A549 cell tumor model.MethodsInferior vena cava stenosis model and FeCl3-induced saphenous vein thrombosis model were performed in a mouse xenograft models of human lung adenocarcinoma.ResultsWe found that treatment with bevacizumab significantly increased the thrombotic response to inferior vena cava obstruction and femoral vein injury. Plasminogen activator inhibitor (PAI-1) expression in tumors, plasma, and thrombi was significantly increased by bevacizumab. However, bevacizumab did not enhance VTE in PAI-1-deficient mice, suggesting that PAI-1 is a major mediator of bevacizumab’s prothrombotic effect. VEGF inhibited expression of PAI-1 by A549 cells, and this effect was neutralized by bevacizumab, suggesting that bevacizumab increases PAI-1 expression in vivo by blocking the inhibitory effect of VEGF on PAI-1 expression by tumor cells. Pharmacological inhibition of PAI-1 with PAI-039 blocked bevacizumab-induced venous thrombosis.ConclusionCollectively, these findings indicate that PAI-1 plays a role in VTE associated with antiangiogenic therapy and the inhibition of PAI-1 shows efficacy as a therapeutic strategy for the prevention of bevacizumab-associated VTE.

The Clot Thickens…

Ultra-deformable synthetic platelets stop bleeding in minutes.

Venous injuries in pediatric trauma: Systematic review of injuries and management.

Diagnosis of vascular injury in pediatric trauma is challenging as clinical signs may be masked by physiologic compensation. We aimed to (1) investigate the prevalence of noniatrogenic pediatric venous injuries, (2) discuss options in management of traumatic venous injury, and (3) investigate mortality from venous injury in pediatric trauma. Our objective was to provide the practicing clinician with a summary of the published literature and to develop an evidence-based guide to the diagnosis and management of traumatic venous injuries in children. A systematic review of published literature (PubMed) describing noniatrogenic traumatic venous injury in the pediatric population (<17 years) was performed according to PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses] guidelines. Data were retrieved systematically under the following headings: Study Design, Population Demographics (dates of recruitment, mean age, mechanism of injury), Diagnostic Approach, Vessel Injured, Management (operative technique), and Mortality. Thirteen articles were included in this systematic review. In total, 508 noniatrogenic traumatic venous injuries were reported in children between the year 1957 and present day. Mechanisms of injury included blunt trauma from seat belt-related injury and fall from height or penetrating trauma from gunshot and foreign object. Injury to the inferior vena cava was most frequently reported, followed by femoral vein and internal jugular injuries. Primary repair was the most frequently reported technique for surgical repair (38%), followed by ligation (25%) and end-to-end anastomosis (15%). Mortality in pediatric trauma patients who had venous injury was reported as 0% to 67% in published series, highest in the series in which the most frequently reported injury was of the inferior vena cava. Traumatic venous injury in the pediatric population is uncommon but may be associated with significant morbidity and mortality. Intra-abdominal venous injuries are associated with high mortality from exsanguination. Early diagnosis and intervention are therefore essential in such cases. Systematic review, level IV.

Compartment Syndrome following Open Femoral Fracture with an Isolated Femoral Vein Injury Treated with Acute Repair.

Acute compartment syndrome is a surgical emergency and its diagnosis is more difficult in obtunded or insensate patients. We present the case of a 34-year-old woman who sustained a Gustilo-Anderson grade III open midshaft femur fracture with an isolated femoral vein injury treated with direct repair. She developed lower leg compartment syndrome at 48 hours postoperatively, necessitating fasciotomies. She was subsequently found to have a DVT in her femoral vein at the level of the repair and was started on therapeutic anticoagulation. This case highlights the importance of recognition of isolated venous injuries in a trauma setting as a risk factor for developing compartment syndrome.

Absence of hematopoietic tissue factor pathway inhibitor mitigates bleeding in mice with hemophilia

Tissue factor pathway inhibitor (TFPI) blocks thrombin generation via the extrinsic blood coagulation pathway. Because the severe bleeding in patients with hemophilia occurs from deficiency of intrinsic blood coagulation pathway factor VIII or IX, pharmacological agents that inactivate TFPI and, therefore, restore thrombin generation via the extrinsic pathway, are being developed for treatment of hemophilia. Murine models of combined TFPI and factor VIII deficiency were used to examine the impact of TFPI deficiency on bleeding and clotting in hemophilia. In breeding studies, Factor VIII null (F8(-/-)) did not rescue the embryonic death of TFPI null (Tfpi(-/-)) mice. Tfpi(+/-) did not alter the bleeding phenotype of F8(-/-) mice. However, total inhibition of intravascular TFPI through injection of anti-TFPI antibody mitigated tail vein bleeding. Interestingly, tail blood loss progressively decreased at doses greater than needed to totally inhibit plasma TFPI, suggesting that inhibition of a sequestered pool of TFPI released at the injury site mitigates bleeding. Because TFPI is sequestered within platelets and released following their activation, the function of platelet TFPI was examined in F8(-/-) mice lacking hematopoietic cell TFPI that was generated by fetal liver transplantation. Blood loss after tail transection significantly decreased in Tfpi(+/-);F8(-/-) mice with hematopoietic Tfpi(-/-) cells compared with Tfpi(+/-);F8(-/-) mice with Tfpi(+/+) hematopoietic cells. Additionally, following femoral vein injury, Tfpi(+/-);F8(-/-) mice with Tfpi(-/-) hematopoietic cells had increased fibrin deposition compared with identical-genotype mice with Tfpi(+/+) hematopoietic cells. These findings implicate platelet TFPI as a primary physiological regulator of bleeding in hemophilia.

FcγRIIa Enhances Thrombus Growth in Vitro and in Vivo

Abstract 191Outside-in signal transduction is one of several autocrine amplification loops that platelets employ to stabilize and consolidate a platelet thrombus following their adhesion to each other or to components of the extracellular matrix. Binding of soluble fibrinogen to activated integrin αIIbβ3 on the platelet surface, or binding of αIIbβ3 to platelet-immobilized fibrinogen, initiates an outside-in signaling cascade that results in the activation of integrin β3-associated Src family kinases, which in turn phosphorylate tyrosine residues within the cytoplasmic domain of the immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor protein, FcγRIIa. “Activation” of FcγRIIa sets off a cascade of events that result in the assembly and activation of other key signaling intermediates, including the tyrosine kinase Syk and phospholipase Cγ2(PLCγ2), through its lipase activity, generates lipid products that support a multitude of cellular activation responses, including cytoskeletal rearrangements leading to platelet shape change and spreading, secretion of platelet granules, and activation of additional cell surface integrins. We have previously shown that either antibody-mediated or genetic disruption of the functional interaction between integrin αIIbβ3 and FcγRIIa blocks tyrosine phosphorylation of FcγRIIa, Syk, and PLCγ2, and inhibits platelet spreading on immobilized fibrinogen. The physiological significance of FcγRIIa in supporting platelet thrombus formation, however, remains unknown. To further explore the importance of FcγRIIa in platelet function, we compared the relative ability of wild-type FcγRIIa-negative and transgenic FcγRIIa-positive (FcγRIIaTGN) murine platelets to support thrombosis and hemostasis in a number of well-accepted models of platelet function. FcγRIIaTGN platelets exhibited increased tyrosine phosphorylation of Syk and PLCγ2 and increased spreading upon interaction with immobilized fibrinogen. FcγRIIaTGN platelets also retracted a fibrin clot faster than did wild-type FcγRIIa-negative platelets. When anti-coagulated whole blood was perfused over a collagen-coated flow chamber under conditions of arterial shear, the rate and extent of adhesion, aggregation, and thrombus formation was significantly increased for FcγRIIaTGN platelets compared to their wild-type murine counterparts. Addition of Fab fragments specific for FcγRIIa to whole blood derived from either humans or FcγRIIaTGN mice strongly inhibited thrombus formation in the arterial in vitro flow chamber assay. Finally, to examine the in vivo relevance of FcγRIIa, mice were subjected to two models of vascular injury: electrolytic injury of the femoral vein and laser injury of cremaster arterioles. In both in vivo models, FcγRIIaTGN mice displayed increased thrombus formation compared with their wild-type, FcγRIIa-negative counterparts. Taken together, these data establish FcγRIIa as a physiologically-important functional conduit for αIIbβ3–mediated outside-in signaling, and suggest that modulating the activity of this novel integrin/ITAM pair might be effective in controlling thrombosis. Disclosures:No relevant conflicts of interest to declare.

Handlebar injury to femoral vein: case report and review

Handlebar injury varies from minor trauma to life-threatening visceral and vascular damage resulting in a significant morbidity among children. Femoral vein injuries secondary to handlebar trauma are rare but potentially serious. Venous continuity should be restored and several techniques for repair of femoral injuries have been described. We reported a case of femoral vein injury secondary to handlebar trauma in a child and we described techniques used for its repair.

Domain I of β2-glycoprotein I: its role as an epitope and the potential to be developed as a specific target for the treatment of the antiphospholipid syndrome

Antiphospholipid syndrome (APS) represents one of the most common acquired causes of thrombophilia and recurrent miscarriages. The only treatment of proven benefit is anticoagulation, often required at high intensity and life-long duration. This therapy can be associated with side effects such as bleeding and is not always effective. Hence, there remains a need for safer, targeted and ideally more effective therapies. Antiphospholipid antibodies (aPL) are pathogenic and promote thrombosis. Independent groups, including our own, have show that the major epitopes that pathogenic aPL targets lie within domain I of the protein beta2-glycoprotein I (beta2GPI). This review focuses on the evidence presented thus far which characterizes the immunodominant epitopes within domain I, demonstrating that the epitope is a conformational one centred around residues R39-G43 and also involving other residues within domain I, such as residues D8 and D9. The hypothesis is proposed that a recombinant domain I molecule, and a recombinant mutant domain I with enhanced aPL binding properties, may be used as an inhibitor of aPL binding and thus inhibit aPL-induced pathogenicity. In vivo proof-of-concept studies within the murine femoral vein injury model are presented supporting this hypothesis, and the rationale as well as potential benefits and problems of employing such an approach to treat APS are discussed.