Femoral Deep Venous Thrombosis Research Articles

TILE pilot trial study protocol: Tinzaparin Lead-in to Prevent the Post-Thrombotic syndrome study protocol

IntroductionThe post-thrombotic syndrome (PTS) is a form of chronic venous insufficiency due to a prior ipsilateral deep venous thrombosis (DVT). This is a frequent complication that develops in 20%–50% of...

Successful treatment of lupus anticoagulant hypoprothrombinemia syndrome with rituximab

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare acquired bleeding disorder secondary to development of antibodies against prothrombin protein, in the presence of antiphospholipid antibodies. We describe the case of a 13-year-old girl who presented with severe menorrhagia and symptomatic anemia. Labs indicated anemia, thrombocytopenia, elevated PT and aPTT, high-titer inhibitor on mixing studies, positive ANA and anti-dsDNA antibodies, along with a triple-positive antiphospholipid antibody panel. Given additional systemic manifestations, systemic lupus erythematosus was diagnosed. High dose steroids and hydroxychloroquine subsequently started. Her clinical course was complicated by femoral deep venous thrombosis and post renal biopsy retroperitoneal hematoma. Further workup revealed low prothrombin level and the diagnosis of lupus anticoagulant hypoprothrombinemia syndrome. In view of suboptimal response to initial immunosuppressive therapy, rituximab was added to her regimen, leading to an improvement in clinical symptoms and resolution of hypoprothrombinemia. She remains recurrence free 5 years from the event.

Deep venous thromboses complicating central vascular access for renal replacement therapy in a tertiary health centre of a developing country

Background/objectives: Central venous cannulation remains an important process in haemodialysis practises world-wide. The study is designed to determine the prevalence of central access deep venous thrombosis (DVT) and its associated risk factors in the studied population.
 Methods: A prospective observational study of kidney disease patients who underwent haemodialysis between January 2021 and December 31st2021 was carried out. Socio-demographic and clinical data were extracted using structured pro-forma. Data was analyzed using SPSS version 20.
 Results: Of the 98 patients that underwent haemodialysis, 36 (36.8%) were male and 62 (63.2%) were female. Mean age was 48.3±16.7 years. Fifteen (15.3%) had acute kidney injury while 83 (85.0%) had chronic kidney disease. All the patients had emergency dialysis totaling508 sessions. Femoral vein was the most frequently used vascular access (95%) while other vascular access accounted for the remaining (5%). Femoral DVT was seen in 8 (8.2%) patients with majority having CKD (8.4%) .
 Conclusion: Iliofemoral DVT was most common (P=0.537). Statistically significant association was observed between occurrence of femoral DVT and AKI (P<0.02).

The Importance of Early Thrombus Removal

Historically, anticoagulation has been the primary treatment for acute lower extremity deep venous thrombosis (DVT) with or without thrombolysis. Despite large amounts of clinical research data supporting an ‘open vein hypothesis’, which favours early thrombus removal, clinicians have been hesitant to take this option due to a historically high risk of major bleeding and a few notable studies that failed to show any meaningful benefit. The ATTRACT trial failed to show the benefit of using pharmacomechanical catheter-directed thrombolysis (PCDT) for iliofemoral and femoropopliteal DVT but did result in more bleeding. However, the CaVent study before it revealed a significant reduction in post-thrombotic syndrome (PTS) for patients with iliofemoral and femoral DVT after long-term follow-up past 24 months that grew over time. Since these trials, there have been significant advancements in magnetic resonance and CT venography, intravascular ultrasound (IVUS), venous stenting and thrombectomy catheters meaning there is little to no need for adjunct thrombolytics. Results from ongoing research such as CLEAR-DVT reflect the advances in modern technology.

Use of Defibrotide in Patients with COVID-19 Pneumonia; Results of the Defi-VID19 Phase 2 Trial

Background: The clinical spectrum of COVID-19 ranges from pauci-symptomatic forms to severe disease characterized by respiratory failure requiring mechanical ventilation and intensive care unit (ICU) management, as well as multisystem involvement characterized by sepsis, organ dysfunction and death. Treatment of COVID-19 is not standardized, and respiratory failure from ARDS is the leading cause of mortality; in-hospital mortality at 28-days in our tertiary care center in Lombardia, northern Italy was 23% during the first wave in 2020(Ciceri et al. 2020). Endothelial damage and thrombo-inflammation have been identified as common to both COVID-19 pathophysiology and veno-occlusive disease (VOD/SOS). Defibrotide (DF) has endothelial-protective properties, with pro-fibrinolytic, anti-thrombotic, anti-ischemic, anti-inflammatory, and anti-adhesive activity, but no significant systemic anticoagulant effects and is approved for the treatment of severe VOD/SOS.Aim: A prospective, multicenter, phase II, single-arm, open label trial (DEFI-VID19, NCT04335201) was conducted in patients (pts) with COVID-19 ARDS to evaluate the efficacy of DF in addition to best available therapy per institutional guidelines. The primary endpoint was respiratory-failure rate (RFR) defined as progression of respiratory failure, i.e. severe gas transfer deficit (PaO2/FiO2<200 mmHg), need of ICU or death at day+14 from treatment start. Secondary endpoints included overall survival (OS) at 28 days, duration of hospitalization and safety.A sample size of 50 pts was calculated to detect an absolute reduction of 20% in RFR at day+14, assuming a failure rate in non-treated pts of 70% (alpha=5%, power=90%, two-sided test). Pts received DF intravenously at 6.25 mg/kg/dose by 2-hour infusion repeated every 6 hours. Expected treatment duration was 14 days, with earlier discontinuation if clinical improvement occurred. LMWH at prophylactic dose was allowed. Approval was provided by the National IRB for COVID-19 trials at Institute Spallanzani (Rome) and by the Italian Agency for Drug (AIFA). All patients provided written informed consent.Results: Overall, 52 pts were enrolled from September 2020 to April 2021; 48 were evaluated for efficacy and safety; 4 pts were excluded due to screen failure (n=2) or withdrawal of informed consent at day 2 after defibrotide was initiated (n=2). Median age was 60.5 years (range 53-71); 35 pts (73%) were male and 65% had comorbidities, with high blood pressure, obesity and COPD most common. Two pts had pre-existing diagnoses of non-Hodgkin lymphoma. Median time from onset of COVID-19 symptoms and from Sars-COV2 PCR by nasal swab to enrollment were 8 (range 7-10) and 3 days (range 1-6), respectively. All pts were hospitalized and scale 5 of 8-category ordinal scale by WHO criteria, requiring noninvasive ventilation with CPAP or high-flow oxygen, with a median P/F ratio of 211 (range 134-275) mmHg. At treatment start, the median and (range) lymphocyte counts, LDH, CRP, ferritin, D-dimer and IL-6 were 0.7 (0.5-0.9) x 10e9/L; 404 (291-491) U/L; 49 (22-97) mg/L; 823 (363-1088) ng/ml; 0.44 (0.28-1.29) µg/mL and 20 (11-32), respectively.Median treatment duration was 8.5 days (range 6-11). Overall, 13/48 pts (27%) discontinued the treatment due to clinical worsening and/or need of further therapies: 9 pts experienced progressive respiratory failure and 6 of those were transferred to ICU for IOT (one pt required ECMO), and 4 required full anticoagulation due to pulmonary embolism (n=1), ischemic stroke (n=1), and femoral deep venous thrombosis (n=2). All pts who completed the treatment 35/48 (73%) were discharged with no need of oxygen support. Overall, 14 SAEs have been reported in a median time of 6 days (range 2-10): all unrelated to DF. No pts experienced hemorrhagic events. The incidence of RFR at day 14 was 25 (+/- 6)%, and at day 28, 27 (+/- 6) %. Probability of OS at day 28 was 89 (+/-4) %, at day 60 83 (+/- 5)%. Overall, 8 pts died from COVID-19 -related complications. No pts required re-admission after hospital discharge (median 14 days) or died after discharge.Conclusion: Treatment with DF in pts with grade 5 WHO COVID 19 ARDS does not induce bleeding, and is associated with rapid restoration of respiratory function (73% of pts). Notably, no oxygen support was needed at discharge and a 1-month OS rate of 89% was observed, which is higher than historical controls (77%) treated in the same setting. DisclosuresRichardson: Takeda: Consultancy, Research Funding; AbbVie: Consultancy; Karyopharm: Consultancy, Research Funding; AstraZeneca: Consultancy; Oncopeptides: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Protocol Intelligence: Consultancy; Secura Bio: Consultancy; Regeneron: Consultancy; Celgene/BMS: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Janssen: Consultancy; Sanofi: Consultancy. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Carlo-Stella: Incyte: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Research Funding; AstraZeneca: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Oncology: Honoraria; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees.

THE PARADOXICAL PRESENTATION OF PRE-ECLAMPSIA WITH DIFFUSE ALVEOLAR HEMORRHAGE AND VENOUS THROMBOSIS AS CLINICAL MANIFESTATIONS OF ANTIPHOSPHOLIPID SYNDROME

TOPIC: Pulmonary Manifestations of Systemic Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Antiphospholipid Syndrome (APS) is an autoimmune disorder clinically defined by the presence of antiphospholipid antibodies (aPL), history of arterial or deep venous thrombosis (DVT), and/or repeat episodes of early pregnancy loss. Due to the increased risk for thrombosis, often overlooked is a rare and seemingly paradoxical association between APS and diffuse alveolar hemorrhage (DAH) - a disorder characterized by non-localized alveolar bleeding. Rare manifestation of APS presenting with preeclampsia, DAH, and DVT offers a variety of multi-disciplinary challenges. CASE PRESENTATION: A 34-year-old G6P3 woman at 28 weeks gestation with a remote history of pulmonary embolism (PE), presented to the Emergency Department with a two-day history of dyspnea and hemoptysis. Exam was remarkable for sinus tachycardia, grade 3 systolic murmur at the apex, and increased work of breathing with bilateral pulmonary rhonchi. Computed tomography (CT) scan demonstrated centrally predominant opacities without signs of PE. Bronchoscopy was significant for diffusely hemorrhagic airways with progressively hemorrhagic serial lavage aliquots. Emergent delivery was performed in the setting of Preeclampsia while high-dose steroids were administered for DAH. The patient returned to baseline over the next 3 days without returning signs of hemoptysis. Lupus anticoagulant was positive but PT and PTT were both normal. Steroids were discontinued and therapeutic enoxaparin was started for a possible novel diagnosis of APS.Six days later, she reexhibited hemoptysis. Repeat CT revealed bilateral alveolar infiltrates consistent with the recurrence of DAH. Disproportionate left lower extremity edema and a femoral vein DVT were also discovered. Anticoagulation was again withheld, high-dose steroids were re-started, and an inferior vena cava filter was placed. Repeat lupus anticoagulant testing was positive. In addition, the dilute russell viper venom time (DRVV) was prolonged in the setting of normal PT/PTT, confirming APS diagnosis. She recovered within five days and was prescribed warfarin for chronic anticoagulation, glucocorticoids were tapered, while rituximab infusions were initiated as glucocorticoid-sparing therapy. DISCUSSION: This case highlights challenges associated with the diagnosis and management of rare simultaneous manifestations of APS. In particular, the management of DAH in this scenario is unique because unlike the glucocorticoid-responsive antibodies of ANCA-associated vasculitides, aPL are not known to cause alveolar capillaritis; therefore, the role of steroids is unclear. CONCLUSIONS: Chronic anticoagulation is an absolute requirement for long-term management of APS. Yet as this case exemplifies, in the case of concomitant DAH, administration of glucocorticoids, and subsequently glucocorticoid-sparing immunosuppression is recommended as the safest approach to avoid life-threatening hemorrhage. REFERENCE #1: Cartin-Ceba R, Peikert T, Ashrani A, Keogh K, Wylam ME, Ytterberg S, Specks U. Primary antiphospholipid syndrome-associated diffuse alveolar hemorrhage. Arthritis Care Res (Hoboken). 2014 Feb;66(2):301-10. doi: 10.1002/acr.22109. PMID: 23983016. REFERENCE #2: Stoots SA, Lief L, Erkan D. Clinical Insights into Diffuse Alveolar Hemorrhage in Antiphospholipid Syndrome. Curr Rheumatol Rep. 2019 Sep 6;21(10):56. doi: 10.1007/s11926-019-0852-7. PMID: 31493005; PMCID: PMC7102334. REFERENCE #3: Janowiak P, Sieminska A, Porzezinska M, Smolenska Z, Suchanek H, Jassem E. Difficulties in the treatment of recurring diffuse alveolar hemorrhage accompanying primary antiphospholipid syndrome: a case report and literature review. Adv Respir Med. 2018;86(3). doi: 10.5603/ARM.2018.0020. PMID: 29960279. DISCLOSURES: No relevant relationships by Eric Knott, source=Web Response no disclosure on file for Eric Lang; No relevant relationships by Claudia Saborit, source=Web Response

THE CLOT THICKENS: DOES THE JOHNSON & JOHNSON COVID-19 VACCINE INCREASE THE RISK OF THROMBUS IN A HYPERCOAGULABLE STATE?

TOPIC: Pulmonary Vascular Disease TYPE: Fellow Case Reports INTRODUCTION: The 2019 coronavirus disease (COVID-19) has hematologic manifestations in addition to respiratory. COVID-19 is associated with a state of hypercoagulability. Evidence shows correlation with degree of hypercoagulability and severity of disease. Patients with severe COVID-19 were reported to have venous and arterial thrombi causing organ dysfunction and death. There was an urgent need for vaccination against SARS-CoV-2. Companies, including Johnson & Johnson (J&J), have released their vaccine. Recently, the Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) reported six cases of cerebral venous sinus thrombosis, which led to a pause in J&J vaccine administration. We present a case of a woman with antiphospholipid syndrome (APS) who developed acute deep venous thrombosis (DVT) after receiving the J&J vaccine while therapeutic with warfarin. CASE PRESENTATION: Ms G is a 54-year-old black woman with history of APS and severe COVID-19 infection. Prior APS panel for lupus anticoagulant antibody (Ab) on initial and repeat testing was positive. Anticardiolipin and beta-2 glycoprotein Ab were negative. Her complication from APS included chronic left lower extremity DVT since 2018. She was compliant with warfarin. She received the J&J vaccine twenty days prior to the present visit. Fifteen days after receiving the vaccine, she developed bilateral lower extremity swelling and calf pain, left worse than right. On exam, vital signs were within normal limits. She had 1+ non-pitting edema and tenderness in her left calf, worse compared to the right. Complete blood count showed platelets 172x10^9/L (ref range: 167-378x10^9/L). INR 3.03, prothrombin time 33 seconds (ref range: 9.8-12.9). COVID-19 IgG titer 8.08 index (S/C) (ref range: 0-1.39). Heparin-induced thrombocytopenia (HIT) screen was negative. Venous doppler ultrasound showed an acute femoral-to-peroneal DVT in the right leg and a chronic femoral DVT in the left leg. Due to recent joint statement by the CDC and FDA advising against heparin in patients with new thrombi after receiving the J&J vaccine due to HIT-like behavior of these thrombi, the patient was treated with rivaroxaban and is currently doing well. DISCUSSION: APS is an autoimmune disease that causes a chronic hypercoagulable state from antiphospholipid antibodies, which make patients prone to develop thrombi. Correlation has been shown between severity of COVID-19 and degree of inflammation. Severe illness leads to generation of excessive inflammatory cytokines and chemokines, endothelial dysfunction, and a host of other pathways to increase risk of thrombosis. CONCLUSIONS: With the recent discovery of the J&J vaccine potentially creating a HIT-like state, the risk of developing DVT in a patient with known hypercoagulable state (such as APS and severe COVID-19) appears elevated. Due to this finding, we recommend caution in giving the J&J vaccine. REFERENCE #1: Abou-Ismail, Mouhamed Yazan et al. "The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management.” Thrombosis research vol. 194 (2020): 101-115. doi:10.1016/j.thromres.2020.06.029 DISCLOSURES: No relevant relationships by David Rutenberg, source=Web Response No relevant relationships by Yumeng Zhang, source=Web Response

Decreased Platelet Count Due to Heparin in Covid-19

COVID-19 (coronavirus disease-2019) infection may be a extremely prothrombotic state, ensuing from a dysregulation of the coagulation cascade. Therefore, thromboprophylaxis is powerfully suggested in these patients, with some consultants even advocating for therapeutic dosing to forestall thromboembolic events. Heparin-induced blood disorder (HIT) may be a well-known complication of heparin therapy. during this article, we tend to report a case of HIT in a patient with COVID-19. A 52-year-old male with history of one week of dry cough and loose stools. He had a positive COVID-19 reverse-transcriptase–polymerase chain reaction. On admission, the platelet count and liver function test were within normal limits. Throughout his hospitalization, he developed a right femoral deep venous thrombosis and was started on therapeutic anticoagulations. Due to worsening respiratory failure, he was intubated and mechanically ventilated. Between days eight and nine of hospitalization, platelet count decreased from 294000 to 89000 cells/μL. He had a high pretest likelihood for HIT with a 4T score of 6 and a positive anti-PF4/ heparin antibody. Heparin drip was interrupted and was switched to Argatroban. The serotinin assay eventually came back positive, that confirmed the diagnosis of HIT.

Efficacy of venous recanalization by non-invasive pulsed ultrasonic cavitation therapy on swine model of acute deep venous thrombosis with 14 days of follow-up

Post thrombotic syndrome is a frequent complication of deep venous thrombosis, associated with high morbidity. Treatments currently available are invasive. Pulsed cavitational ultrasound therapy (PCUT) is a new technique to destroy remotely soft tissue. We demonstrated that PCUT was able to recanalize non-invasively in in-vitro model of human blood clot. We aim to test the safety and efficacy of venous recanalization by non-invasive PCUT in vivo swine model of acute venous thrombosis. All the experiments were performed on White large X Landrace swine. We induced an acute femoral deep venous thrombosis by using endovascular approach combined with local injection of thrombin. A 3 cm length occlusive thrombosis was obtained after 2 hours. Swine were divided in three groups: one with PCUT without follow-up ( n = 11), one with PCUT and follow-up at 14 days ( n = 8), and a control group also followed for 14 days ( n = 5). Acutely and during follow up all swine received curative anticoagulation. To achieve PCUT, a 2.25 MHz transducer (Imasonic©) centered by a linear probe was used and cavitation was obtained in the centre of the vein. Effectiveness of recanalization was evaluated by echo-Doppler and phlebography. Safety was assessed by Doppler ultrasound and by histological analysis of vein, artery and lungs. Among the 24 swine, we obtained 22 occlusive venous thromboses and 2 partials. The median length of the thrombus was 26 ± 4.4 mm. Acutely, thrombosis recanalization was obtained among the 19 swine with PCUT with median treatment duration of 33 min. After a 14-day follow-up, 75% of recanalisation remains permeable vs. 0% of vein permeable in the no therapy group ( P = 0.008). Residual diameter was 2.6 ± 1.2 mm, 50% of the venous diameter. No embolism or pulmonary infarction was observed in all pigs ( Fig. 1 ). We have demonstrated in vivo the safety and the efficacy of PCUT for non-invasive venous recanalization, persistent after 2 weeks.

P2765Efficacy of venous recanalization by noninvasive pulsed cavitational ultrasound therapy on swine model of acute deep venous thrombosis

Abstract Background Post thrombotic syndrome is a frequent complication of deep venous thrombosis and is associated with high morbidity and hospitalization. Treatments currently available are invasive, involve use of endovenous procedures with stents and balloons, and frequently require general anesthesia. Pulsed cavitational ultrasound therapy (PCUT) emerged recently as a new technique to destroy remotely soft tissue. We recently demonstrated that PCUT was able to recanalize non-invasively in in vitro model of acute venous thrombosis (human blood clot). Purpose We aim to test the safety and efficacy of venous recanalization by noninvasive PCUT in vivo swine model of acute venous thrombosis. Methods All the experiments were performed on White large X Landrace swine. We induced an acute femoral deep venous thrombosis by using occlusive balloons introduced from jugular and popliteal vein combined with local injection of 50 IU of human thrombin. A 3 cm length occlusive thrombosis was obtained after 2 hours. Swines were divided in three groups: one with PCUT without follow-up (n=11), one with PCUT and follow-up at 14 days (n=8), and a control group also followed for 14 days (n=5). Acutely and during the follow up all swines received curative anticoagulation. To achieve PCUT, a 2.25 MHz transducer centered by a linear probe was used and cavitation was obtained in the center of the vein (Figure). After manual determination of thrombus location, a robotic arm was used to automatically move the transducer along the thrombus. Effectiveness of recanalization was evaluated by echo-Doppler and phlebography. Safety was assessed by Doppler ultrasound of the insonified area (artery, veins and surrounding tissue) and by histological analysis (local femoral vein and artery and lungs for pulmonary embolism). Results Among the 24 swines, we obtained 22 occlusive venous thromboses and 2 partial. The median length of the thrombus was 26±4.4 mm with vein diameter of 8.5±1.6 mm. Acutely, thrombosis recanalization was systematically obtained among the 19 swine with PCUT with median treatment duration of 33 minutes with residual diameter of 2.9±0.9 mm. No extravasation of contrast material or hematoma was observed after the therapy. After a 14-day follow-up, 75% of recanalisation remain permeable vs. 0% of vein permeable in the no therapy group (p=0.008). Residual diameter was 2.6±1.2 mm, which correspond to 50% of the venous diameter. No vein or artery damage and no embolism or pulmonary infarction was observed in all pigs. Figure 1 Conclusion We have demonstrated in vivo the safety and the efficacy of PCUT for non-invasive venous recanalization, persistent after 2 weeks. Acknowledgement/Funding French society of cardiology

Underutilization of Thrombolytic Therapy for Patients Diagnosed with Acute Deep Venous Thrombosis in the Outpatient Setting

Catheter-directed thrombolysis (CDT) has been shown to be a safe and effective treatment for the management of acute iliofemoral deep venous thrombosis (DVT). The potential benefits of this therapy include more rapid resolution of symptoms and possible reduction in the long-term sequelae. Many patients diagnosed with DVT in the inpatient setting have contraindications to lytic therapy, but less is known regarding the suitability of thrombolysis for outpatients diagnosed with acute DVT. We sought to determine the proportion of patients who were candidates for thrombolytic therapy and referred to a vascular specialist for evaluation. A manual search of an outpatient vascular laboratory associated with a tertiary medical center was performed to identify all patients referred for the purpose of ruling out DVT between January 2013 and December 2014. Vascular laboratory studies conducted for evaluation of venous insufficiency were excluded. The electronic medical records were reviewed to evaluate for contraindications for thrombolysis. Over a 2-year period, there were 689 referrals to the outpatient vascular laboratory for the evaluation of patients with suspected DVT. Of the 689 referrals, 47 (6.8%) were found to have acute DVT, and 66 (9%) were found to have chronic DVT. Of the 47 patients with acute DVT, 41 involved the lower extremities. Fifteen of the 41 patients (37%) with extensive acute iliofemoral DVT had no absolute or major contraindications for CDT. Of these 15 patients, only 33% were referred to a vascular specialist (4 to vascular surgery and 1 to IR). Two patients (13%) agreed to and underwent successful CDT. Although the majority of patients with acute lower extremity DVT diagnosed in the outpatient vascular laboratory were not candidates for thrombolysis, one-third of those who may have benefited from CDT were referred to a vascular specialist to discuss lytic therapy. Given the potential benefits of CDT, it is imperative that patients with acute iliofemoral or extensive femoral DVT be offered an evaluation by a vascular specialist to optimize outcomes after this diagnosis.

Fecal Microbiota Transplant for Severe Complicated Clostridium difficile Infection via a Loop Ileostomy: A Novel Administration Route

Introduction: Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea in healthcare settings. High cure rates of CDI with fecal microbiota transplantation (FMT) have been reported (88 to 100%). Successful delivery of donor fecal material has been described via nasogastric duodenal tube, colonoscopy, physician administered retention enemas and self-administered enemas. To our knowledge there has been no reported case of successful FMT for CDI via a loop ileostomy. Case Report: A 57-year-old women with past medical history of hypertension and type II diabetes mellitus developed diarrhea related to CDI after a hospitalization for pneumonia that had required antibiotics. She was successfully treated with oral vancomycin and intravenous flagyl. Two months later she re-developed diarrhea and was diagnosed with severe complicated CDI. On this second presentation her WBC count was 87 k/uL and a CT abdomen showed pan-colitis. She developed septic shock with multi-organ system failure. She required pressor support, mechanical ventilation and intermittent hemodialysis. She was treated with oral and rectal vancomycin, intravenous flagyl and oral pro-biotics. When she failed to respond, a laparoscopy was done to create a loop ileostomy. She was given vancomycin solution through the ileostomy for about 10 days. She showed some clinical response to this aggressive antibiotic therapy with declining leukocytosis and pressor requirement but remained critically ill and continued to have diarrhea. At this point it was decided to perform a FMT. All her antibiotics were stopped for a 24-hour period prior to instillation of 250 mL of open biome donor feces into her ileostomy. All antibiotics were held for another week after the FMT. Her diarrhea completely resolved. Her subsequent hospital course was complicated by candidal fungemia, multiple drug resistant Pseudomonas aeruginosa empyema and bilateral femoral deep venous thrombosis but she remained free from recurrence of CDI. Two repeat PCR's for C. difficile approximately one and two month after FMT via loop ileostomy remained negative. She has now been discharged from the hospital and is doing well. Conclusion: This is the first ever reported case of successful cure of recurrent severe complicated CDI with FMT through a loop ileostomy. This report demonstrates the versatility of routes through which a successful FMT can be performed.

Differentiation of deep venous thrombosis from femoral vein mixing artifact on routine abdominopelvic CT.

The objective of this study is to assess the performance of qualitative and quantitative imaging features for the differentiation of deep venous thrombosis (DVT) from mixing artifact on routine portal venous phase abdominopelvic CT. This retrospective study included 40 adult patients with a femoral vein filling defect on portal venous phase CT and a Duplex ultrasound (n = 36) or catheter venogram (n = 4) to confirm presence or absence of DVT. Two radiologists (R1, R2) assessed the femoral veins for various qualitative and quantitative features. 60% of patients were confirmed to have DVT and 40% had mixing artifact. Features with significantly greater frequency in DVT than mixing artifact (all p ≤ 0.006) were central location (R1 90% vs. 28%; R2 96% vs. 31%), sharp margin (R1 83% vs. 28%; R2 96% vs. 31%), venous expansion (R1 48% vs. 6%, R2 56% vs. 6%), and venous wall enhancement (R1 62% vs. 0%; R2 48% vs. 0%). DVT exhibited significantly lower mean attenuation than mixing artifact (R1 42.1 ± 20.2 vs. 57.1 ± 23.6 HU; R2 43.6 ± 19.4 vs. 58.8 ± 23.4 HU, p ≤ 0.031) and a significantly larger difference in vein diameter compared to the contralateral vein (R1 0.4 ± 0.4 vs. 0.1 ± 0.2 cm; R2 0.3 ± 0.4 vs. 0.0 ± 0.1 cm, p ≤ 0.026). At multivariable analysis, central location and sharp margin were significant independent predictors of DVT for both readers (p ≤ 0.013). Awareness of these qualitative and quantitative imaging features may improve radiologists' confidence for differentiating femoral vein DVT and mixing artifact on routine portal venous phase CT. However, given overlap with mixing artifact, larger studies remain warranted.

Association between inflammation biomarkers, anatomic extent of deep venous thrombosis, and venous symptoms after deep venous thrombosis.

Inflammation may play a role in pathogenesis of venous thromboembolism, but the nature of this relationship is not yet understood. The objective of this study was to assess whether inflammation marker levels measured at diagnosis of deep venous thrombosis (DVT) and change in levels during the first month after DVT are associated with anatomic extent of DVT and severity of venous signs and symptoms at baseline and 1 month. The BioSOX study is a biomarker substudy of the Compression Stockings to Prevent the Post-Thrombotic Syndrome (SOX) trial, a multicenter, randomized controlled trial that included patients with a first, acute, symptomatic, proximal DVT. Blood samples were collected from participants at baseline and 1 month, and C-reactive protein (CRP), intercellular adhesion molecule 1, interleukin (IL)-6, and IL-10 were measured by established assays. Linear regression was used to assess the association between continuous log-transformed baseline biomarker levels and anatomic extent of DVT, classified as iliac or common femoral DVT vs femoral or popliteal DVT (reference). Proportional odds ordinal logistic regression models were used to analyze the association between biomarker level and Villalta score (as a measure of severity of venous signs and symptoms) at baseline and 1 month. Among 717 patients, 60.2% were male, and the mean age was 55.2 years. There was a significant association between more extensive DVT (common femoral or iliac) and levels of CRP and IL-6 at DVT diagnosis. Median (interquartile range) CRP level was 11.6 mg/L (3.84-39.5) in patients with common femoral or iliac DVT vs 6.86 mg/L (3.11-22) in patients with popliteal or femoral DVT, and median IL-6 level was 6.36 pg/mL (1.09-14.37) vs 4.40 pg/mL (2.35-8.27), respectively. These differences were statistically significant in linear regression analyses. In addition, compared with those in the lowest quartile, each higher quartile of baseline CRP concentration was associated with an odds ratio of 2.89 (1.93-4.33) for having a more severe Villalta category at baseline and 1.98 (1.28-3.08) for having a more severe Villalta category 1 month after DVT. Higher baseline levels of IL-6 were associated with Villalta severity category at baseline (odds ratio, 2.40 [1.61-3.59]). Change in biomarker levels during the first month after DVT was not strongly associated with the 1-month Villalta score. Levels of CRP and IL-6 at DVT diagnosis were associated with thrombotic disease burden, as measured by DVT extent, and severity of DVT symptoms and signs. Further studies are required to more fully elucidate the role of inflammation in DVT and its clinical course.

Real clinical practice of catheter therapy for deep venous thrombosis: periprocedural and 6-month outcomes from the EDO registry.

A recent national study in Japan indicated that 5.8% of deep venous thrombosis (DVT) patients were treated using endovascular procedures, 83% of which included catheter-directed thrombolysis (CDT). However, the details of these endovascular procedures and their outcomes have not yet been fully evaluated. Using DVT data from the EDO registry (EnDOvascular treatment registry) database, a total of 35 symptomatic iliac or femoral DVT patients who received endovascular treatment (54.3% male, age 64.7±15.1) were analyzed. The dominant patient risks were being bedridden (22.9%) and May-Thurner syndrome (25.7%). Approximately 77.1% of patients were treated using an antegrade approach, and CDT and other endovascular procedures were performed in 82.9 and 57.1% of patients, respectively. A periprocedural inferior vena cava (IVC) filter was used in 94.1% of patients, which remained implanted in 37.1 and 20.0% of patients after discharge and 6months after hospitalization, respectively. After 6months of treatment, 2.9% of patients experienced a recurrence of DVT and 5.7% suffered revascularization, but no patient had a recurrence of pulmonary embolism. Subjective symptoms improved in 80.0% of patients, while 2.9% of patients felt worse at 6months after treatment. Postthrombotic syndrome-related symptoms were observed in seven patients (19.4%), and edema was most frequently observed (71.4%). The details of CDT procedures, such as approach site and the removal of the IVC filter, varied among hospitals. Despite improved symptoms, further procedural standardization and data collection should be conducted to reduce complications and improve outcomes.

A Rare Complication of Artificial Urinary Sphincter: Deep Venous Thrombosis Due to Compression of Femoral Vein by Pressure Regulating Balloon

The placement of artificial urinary sphincters (AUSs) is a common procedure for stress incontinence following treatment for prostate cancer. Complications are relatively rare, and the most common reasons for device removal and revision are cuff erosion, infection, and mechanical failure. We present a case of a 66-year-old male with a history of radiation therapy for prostate cancer that developed a deep venous thrombosis (DVT) and pulmonary embolism (PE) following his second AUS due to compression by a pressure regulating balloon (PRB). Compression of the femoral vein was not originally diagnosed as the cause for DVT on initial hospitalization, and there was an additional hospitalization due to worsening symptoms prior to identification of PRB compression. This is the first published case of migrating PRB causing femoral DVT and PE following the placement of a second AUS in an irradiated tissue field, and one of two published cases of DVT due to PRB compression.

Implante de filtro de veia cava com uso de dióxido de carbono como meio de contraste: série de casos

OBJETIVO: Avaliar o resultado do implante de filtro em veia cava inferior empregando angiografia digital por subtração com dioxide de carbono (CO2) como meio de contraste. MÉTODOS: No período de abril de 2010 a fevereiro de 2011, sete pacientes foram submetidos ao implante de filtro na veia cava inferior, utilizando-se CO2 como meio de contraste em subtração digital. Os pacientes apresentaram como critério de inclusão trombose venosa profunda no setor ilíaco-femoral e contraindicação à anticoagulação. RESULTADOS: Foi obtido sucesso técnico em todos os casos, com adequada visualização da veia cava e veias renais, não havendo complicações relacionadas ao uso do CO2 ou ao procedimento. CONCLUSÃO: O implante de filtro de veia cava utilizando o CO2 como meio de contraste é segura e efetiva em pacientes portadores de alergia ao contraste iodado ou com insuficiência renal não dialítica.

Period frequency of iliofemoral venous occlusive disease by Doppler ultrasound and corresponding treatment in a tertiary care facility

Patients with iliofemoral deep venous thrombosis (DVT) are at highest risk for the postthrombotic morbidity including all aspects of the postthrombotic syndrome. Invasive therapies such as catheter-directed thrombolysis (CDT) and/or mechanical thrombectomy with or without angioplasty and stenting and in some cases open operative thrombectomy improves venous patency, venous valve function, and quality of life in patients with acute iliofemoral DVT. What is the current frequency of acute iliofemoral DVT and how aggressively is it being treated? We hypothesize that the 10-year period frequency of iliofemoral DVT among acute DVT cases is greater than previously reported. Further, we hypothesize that thrombus removal to treat acute iliofemoral DVT is little utilized in current practice. Indiana University (IU) vascular laboratory records from January 1, 1998 to December 31, 2008 were searched by CPT code for venous Doppler ultrasound study (n=7240). A random sample based on the IU medical record number of lower extremity Doppler studies was then selected (n=1020) for retrospective chart review. Corresponding clinical information was gathered from the patients' electronic medical record. Acute DVT occurred in 6.8%, and chronic DVT in 8.8% of patients studied (25.7% inpatient, 61.7% female; median age, 56.0 years [range, 4-91 years, 1.1% less than 16 years]). History of previous DVT (33.3%) and cancer (30.4%) were the most common risk factors in patients with acute DVT. Iliofemoral DVT defined as having an iliac or common femoral vein component was identified in 49.3% of acute DVT and in 36.0% of chronic DVT. CDT was utilized in 14.3% and mechanical thrombectomy in 4.8% of acute iliofemoral DVT, and was never used with distal DVT. Warfarin anticoagulation+unfractionated heparin or low-molecular-weight heparin overlap was the most common treatment for acute iliofemoral DVT (100.0%). In 2008, the referral base of our laboratory increased significantly. Acute DVT occurred significantly less often during the 1-year period 2008 (5.3%) than the 10-year period 1998-2007 (7.6%), but iliofemoral+common femoral DVT as a component of acute DVT did not differ significantly. Iliofemoral DVT may be more frequent than previously reported and represents a significant portion of acute DVT. Current recommendations of acute thrombus removal for the treatment of iliofemoral DVT is underutilized suggesting that perhaps greater education of clinicians and patients regarding invasive therapy for iliofemoral DVT is required.

Classification of proximal endovenous closure levels and treatment algorithm

Endovenous closure is a common method to treat saphenous vein incompetence. Despite attempts to prevent it, some patients have extension of thrombus above the ideal site of closure immediately below the epigastric vein. We have developed a classification system for the level of saphenous vein closure to guide further therapy after endovenous treatment. A six-tier classification system was developed, based on thrombus proximity to the epigastric or femoral vein, and an algorithm for treatment, based on level of closure was applied to all patients. Five hundred consecutive patients underwent radio-frequency ablation of the saphenous vein; it was successfully closed in 498 (99.6%) patients. Thirteen patients (2.6%) experienced thrombus bulging into the femoral vein or adherent to its wall, which was treated with anticoagulation. All of these patients had thrombus retraction to the level of the saphenofemoral junction (SFJ) in an average of 16 days with concurrent anticoagulation. No femoral deep venous thrombosis (DVT) occurred in the series. There was a significantly higher rate of proximal thrombus extension in those patients with a history of DVT and those with a great saphenous vein (GSV) diameter of >8 mm (P < .02). A classification system for saphenous endovenous closure which extends above the epigastric vein has been helpful in guiding management. A GSV diameter at the SFJ of >8 mm and a history of DVT results in significantly higher rates of proximal thrombus extension into the femoral vein. A short course of LMWH, until clot retracts back into the saphenous vein, is therapeutic. Management of the patients with thrombus flush with the femoral vein wall still needs to be defined, but the outcome from these patients is generally benign.

Thrombolysis for Acute Lower Extremity Deep Venous Thrombosis in a Tertiary Care Setting

In 2008, the Surgeon General made a Call to Action for the prevention of deep venous thrombosis (DVT), and for the first time, the 2008 American College of Chest Physicians guidelines for treatment of acute lower extremity DVT (ALE DVT) were revised to include thrombolysis as a grade 2B recommendation. Catheter-directed thrombolysis (CDT) therapy for patients with ALE DVT without contraindications can result in more complete clot dissolution than anticoagulation alone and may prevent the long-term sequelae of DVT. We sought to determine the percentage of inpatients with ALE DVT at a tertiary medical center who were candidates for CDT therapy and whether these patients were appropriately offered such treatment. A hospital administrative database search from a tertiary medical center between January 2007 and December 2007 revealed 667 patient admissions associated with a diagnosis of DVT by International Classification of Diseases, Ninth Revision diagnosis codes (451-451.99, 453-453.99). Computerized hospital records were then searched for information regarding medical history, comorbidities, contraindications to thrombolysis, symptoms, imaging findings, and treatment. Of the 667 patient admissions, 157 (24%) had ALE DVT, 31% had upper extremity DVT, 17% carried an old diagnosis DVT, and 28% had venous thromboses in other vessels. Of those 157 patients with ALE DVT, 60 (38%) had proximal iliofemoral or extensive femoral DVT that would be candidates for thrombolysis. Of the 60 patients, only 10 (17%) had no major contraindication thrombolysis. Of these, one was offered CDT but refused treatment, four did not receive consults for thrombolysis; five (9%) were offered CDT and were treated. However, of these 60 patients, 50 (83%) patients had severe illness and major and often multiple contraindications to thrombolysis. Although the majority of patients identified in the 2007 inpatient database with ALE DVT and an absence of contraindications to thrombolysis were appropriately offered CDT therapy, patients in such a tertiary inpatient setting typically have severe medical comorbidities that precluded the use of thrombolysis. Future studies assessing the expanding role of CDT in patients with ALE DVT should focus on outpatient settings or nontertiary care hospitals, where patients are likely to have fewer contraindications to thrombolytic therapy.