Variation in Death Rate After Abdominal Aortic Aneurysmectomy in the United States: Impact of Hospital Volume, Gender, and Age

Annals of Surgery. Apr, 2002  |  Pubmed ID: 11923615

To determine whether high-volume hospitals (HVHs) have lower in-hospital death rates after abdominal aortic aneurysm (AAA) repair compared with low-volume hospitals (LVHs).

Impaired Vasoreactivity Despite an Increase in Plasma Nitrite in Patients with Abdominal Aortic Aneurysms

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Feb, 2002  |  Pubmed ID: 11854736

This investigation was designed to determine whether differences in vasoreactivity occur in patients with abdominal aortic aneurysms (AAAs) as compared with patients with peripheral arterial occlusive disease (PAOD) or individuals (controls) without known vascular disease.

Cost of Routine Screening for Carotid and Lower Extremity Occlusive Disease in Patients with Abdominal Aortic Aneurysms

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Apr, 2002  |  Pubmed ID: 11932675

The burden of clinically relevant noncoronary atherosclerotic occlusive disease in patients with abdominal aortic aneurysms (AAAs) is poorly defined. Furthermore, the cost-effectiveness of routine versus selective preoperative noninvasive examination of the carotid and lower extremity arterial beds has not been established in patients who undergo elective AAA repair.

Pediatric Splanchnic Arterial Occlusive Disease: Clinical Relevance and Operative Treatment

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. May, 2002  |  Pubmed ID: 12021699

Splanchnic arterial occlusive disease is rare in childhood. The purpose of this study was to review the clinical relevance and operative treatment of these lesions in a unique experience from a single institution.

Tissue Loss, Early Primary Graft Occlusion, Female Gender, and a Prohibitive Failure Rate of Secondary Infrainguinal Arterial Reconstruction

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. May, 2002  |  Pubmed ID: 12021705

This study tested the hypothesis that a subset of secondary infrainguinal arterial reconstructions show prohibitive failure rates.

Compression Stockings and Venous Function

Archives of Surgery (Chicago, Ill. : 1960). Sep, 2002  |  Pubmed ID: 12215163

Surgical compression stockings measurably improve venous physiologic mechanisms, and stocking brands do not differ from one another.

Southern Association for Vascular Surgery William J. Von Leibig Award. Inflammation and Intimal Hyperplasia Associated with Experimental Pulmonary Embolism

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Sep, 2002  |  Pubmed ID: 12218985

We tested the hypothesis that a venous thromboembolism to the pulmonary arterial system (pulmonary embolism [PE]) would cause an inflammatory response within the pulmonary arterial (PA) wall marked by elevated cytokines and chemokines and an influx of inflammatory cells.

Endovascular Treatment of Abdominal Aortic Aneurysm is Associated with a Low Incidence of Deep Venous Thrombosis

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Nov, 2002  |  Pubmed ID: 12422100

This study was performed to define the incidence of acute deep venous thrombosis (DVT) after endovascular treatment of abdominal aortic aneurysms (AAAs). Because aortic endograft placement requires prolonged femoral vessel instrumentation, it may be hypothesized that these patients are at increased risk for development of an acute DVT.

P-selectin Inhibition Enhances Thrombus Resolution and Decreases Vein Wall Fibrosis in a Rat Model

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Nov, 2002  |  Pubmed ID: 12422103

The purpose of this study was to compare the efficacy of P-selectin inhibition with standard anticoagulant and thrombolytic therapy in a rodent model of established deep vein thrombosis (DVT).

Clinical Application of Sonographic Elasticity Imaging for Aging of Deep Venous Thrombosis: Preliminary Findings

Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. May, 2003  |  Pubmed ID: 12751855

Aging of deep venous thrombosis is an important and difficult clinical problem. Because it is known that thrombi harden as they mature, we have preliminarily tested sonographic elasticity imaging, a technique that estimates tissue hardness, to age venous thrombi.

Cellular IL-10 is More Effective Than Viral IL-10 in Decreasing Venous Thrombosis

The Journal of Surgical Research. Jun, 2003  |  Pubmed ID: 12888334

Systemic administration of cellular interleukin-10 (cIL-10) and gene transfection of viral interleukin-10 (vIL-10) at thrombus induction decreases vein wall inflammation. Only cIL-10, despite sharing an 84% amino acid sequence homology with vIL-10, decreases thrombosis through mechanisms yet to be determined.

P-selectin Inhibition Decreases Post-thrombotic Vein Wall Fibrosis in a Rat Model

Surgery. Aug, 2003  |  Pubmed ID: 12947342

Post-deep vein thrombosis (DVT) venous insufficiency is a vexing problem despite effective anticoagulation, and is characterized by vein wall fibrosis. This study tested the hypothesis that P-selectin inhibition would decrease post-thrombotic vein wall fibrosis and associated profibrotic mediators.

Factor VIII and Race: a New Dimension in Hypercoagulability

Thrombosis and Haemostasis. Nov, 2003  |  Pubmed ID: 14597967

P-selectin and Leukocyte Microparticles Are Associated with Venous Thrombogenesis

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Nov, 2003  |  Pubmed ID: 14603220

P-selectin inhibition has been found to limit venous thrombosis. We hypothesize that elevated levels of P-selectin will amplify thrombosis, mediated by procoagulant microparticles (MPs).

Neutropenia Impairs Venous Thrombosis Resolution in the Rat

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Nov, 2003  |  Pubmed ID: 14603221

Neutrophil influx is one of the first events in a formed deep venous thrombosis (DVT), but whether these cells are active participants in the resolution process is not clear. This study tests the hypothesis that neutrophils (PMN) are active participants in DVT resolution.

Deep Vein Thrombosis Resolution is Modulated by Monocyte CXCR2-mediated Activity in a Mouse Model

Arteriosclerosis, Thrombosis, and Vascular Biology. Jun, 2004  |  Pubmed ID: 15105284

To determine the role of CXCR2, the receptor for cysteine-X-cysteine (CXC) chemokines, and its primary effector cell, the neutrophil (PMN), on deep venous thrombosis (DVT) resolution.

Deep Vein Thrombosis Resolution is Not Accelerated with Increased Neovascularization

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Sep, 2004  |  Pubmed ID: 15337885

Deep venous thrombosis (DVT) resolution involves fibrinolysis, neovascularization, and fibrosis. We hypothesized that promoting neovascularization would accelerate DVT resolution.

Venous Thromboembolism: Regional Differences in the Nationwide Inpatient Sample, 1993 to 2000

Vascular. Nov-Dec, 2004  |  Pubmed ID: 15895761

Venous thromboembolism (VTE) is a costly complication of hospitalization. The sequelae make it a concern for public health planners. The Nationwide Inpatient Sample (NIS) contains data for hospital discharges in the United States. These data were reviewed to determine their suitability for health policy planning. International Classification of Diseases, Ninth Revision, Clinical Modification codes for VTE were applied to the NIS data. The sample was queried for demographic information, mortality, length of hospital stay, diagnosis, and treatment. The rates were standardized for geographic region and disease acuity. Statistical analysis included descriptive reporting of means and event rates; analysis of variance and logistic regression were used for regional effects and modeling of mortality. Between 1993 and 2000, 636,814 discharges involved VTE (1.2%). This rate was consistent over time and within regions. Regional differences existed in the acceptance of new technology and hospital charges. Mortality varied from 6.3% (Midwest) to 7.9% (Northeast) and was associated with admission type, comorbidities, pulmonary embolism, and discharge from the Northeast region. White race, chronic venous insufficiency, and female gender were protective variables. The NIS data report a consistent mortality rate despite improved therapy. Regional diagnostic, treatment, and economic differences exist. The data are useful for the purposes of public health care planning and stimulating clinical trial questions.

Staging Deep Venous Thrombosis Using Ultrasound Elasticity Imaging: Animal Model

Ultrasound in Medicine & Biology. Oct, 2004  |  Pubmed ID: 15582239

Deep venous thrombi undergo progressive hardening with age. However, the evolution rate remains poorly characterized by both invasive and noninvasive techniques. In a previous study (Emelianov et al. 2002), we demonstrated the potential of ultrasound elasticity imaging to noninvasively detect and age thrombus using a rat-based model. Knowing that thrombi harden over time is useful, but the value of the technique relies on whether the age of a thrombus can be predicted from strain estimates, and how accurate these predictions are. The objective of the present study is to answer these two questions. In the previous study, thrombus elasticity changes were monitored only on day 3, 6 and 9 after surgically induced formation of thrombosis in rat inferior vena cavas. In this study, ultrasound elasticity imaging was performed on two independent groups of rats (16 in total) starting from day 3 through day 10 with more temporal samples through the thrombus maturation process. For each rat, thrombus hardness was quantified at each scan interval by measures of normalized strains and reconstructed relative Young's moduli. In both groups, strain magnitudes exhibit progressive decrease as clots age. The relationship between the normalized strain and the clot age was developed from the first group and evaluated by the second group. Statistical analysis showed that the age estimation accuracy is within 0.8 day. If further research can successfully transfer the animal clot-hardening model to human patients, we believe that elasticity imaging will become a key component of venous compression ultrasound for effective diagnosis and treatment of deep venous thrombosis.

Revision of the CEAP Classification for Chronic Venous Disorders: Consensus Statement

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Dec, 2004  |  Pubmed ID: 15622385

The CEAP classification for chronic venous disorders (CVD) was developed in 1994 by an international ad hoc committee of the American Venous Forum, endorsed by the Society for Vascular Surgery, and incorporated into "Reporting Standards in Venous Disease" in 1995. Today most published clinical papers on CVD use all or portions of CEAP. Rather than have it stand as a static classification system, an ad hoc committee of the American Venous Forum, working with an international liaison committee, has recommended a number of practical changes, detailed in this consensus report. These include refinement of several definitions used in describing CVD; refinement of the C classes of CEAP; addition of the descriptor n (no venous abnormality identified); elaboration of the date of classification and level of investigation; and as a simpler alternative to the full (advanced) CEAP classification, introduction of a basic CEAP version. It is important to stress that CEAP is a descriptive classification, whereas venous severity scoring and quality of life scores are instruments for longitudinal research to assess outcomes.

Gender Differences in Deep Venous Thrombosis in a Rat Model: a Preliminary Study

Comparative Medicine. Feb, 2005  |  Pubmed ID: 15766210

The purpose of this study was to determine whether gender differences have an effect on inflammation and thrombosis in a rat model of venous thrombosis. A thrombus was created in mature female (n = 12) and male (n = 12) Sprague Dawley rats (Rattus norvegicus) by ligating the inferior vena cava (IVC). The IVC containing the thrombus was harvested at 1 and 3 days postligation, weighed, measured, and submitted for immunohistochemical analysis. In addition, hematology was performed at selected time points. There were no statistically significant differences in thrombus mass (mean +/- 1 standard deviation) between female and male rats at 1 (683 +/- 47.7 x 10(-4) versus 660 +/- 112.0 x 10(-4) g/cm) or 3 (683 +/- 83.3 x 10(-4) versus 580 +/- 86.0 x 10(-4) g/cm) days post-ligation. Females had significantly more platelets than did males on day 1 (741 +/- 37.2 versus 523 +/- 55.1 K/microL, P < 0.01). Day 3 males showed significant increases in vein wall neutrophils (18.0 +/- 2.30 versus 11.2 +/- 1.38, P < 0.05), ED-1-positive monocytes (54.4 +/- 16.0 versus 18.7 +/- 5.63, P < 0.05), and circulating white blood cells (15.4 +/- 0.947 x 10(3) versus 10.9 +/- 0.714 x 10(3)/microL, P < 0.01) at post-thrombosis when compared with females. We conclude that although female rats had greater thrombus mass, the male rats demonstrated more inflammatory cells in circulation and in their vein walls. This finding suggests that inflammation plays a role in thrombus resolution.

The Treatment of Deep Venous Thrombosis, Including the Newer Agents

Disease-a-month : DM. Feb-Mar, 2005  |  Pubmed ID: 15900261

Osteomyelitis of the Foot and Toe in Adults is a Surgical Disease: Conservative Management Worsens Lower Extremity Salvage

Annals of Surgery. Jun, 2005  |  Pubmed ID: 15912038

To characterize the national epidemiology of adult osteomyelitis (OM) and, using a single institutions' experience, test the hypothesis that early surgical therapy as compared with antibiotics alone results in an improved chance of wound healing and limb salvage.

Inflammation-dependent Thrombosis

Frontiers in Bioscience : a Journal and Virtual Library. 2005  |  Pubmed ID: 15970530

Vessel wall endothelial damage initiates a local inflammatory response, which promotes a prothrombotic state driven by tissue factor, adhesion molecules, and pro-inflammatory cytokines. Understanding how natural inflammatory mechanisms promote a procoagulant state, may lead to the development of new pharmacological interventions targeted at thrombosis.

L-selectin-mediated Neutrophil Recruitment in Experimental Rodent Aneurysm Formation

Circulation. Jul, 2005  |  Pubmed ID: 15998669

This investigation tested the hypothesis that L-selectin is important in experimental abdominal aortic aneurysm (AAA) formation in rodents.

Vein Wall Remodeling After Deep Vein Thrombosis Involves Matrix Metalloproteinases and Late Fibrosis in a Mouse Model

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Jul, 2005  |  Pubmed ID: 16012463

Deep venous thrombosis (DVT) confers vein wall injury associated with fibrosis and extracellular matrix (ECM) turnover, likely mediated by matrix proteases. This study investigated the expression of proteases and collagen involved in early vein wall remodeling.

Severe Chronic Venous Insufficiency: Magnitude of the Problem and Consequences

Annals of Vascular Surgery. Sep, 2005  |  Pubmed ID: 16034514

The aim of this study was to characterize patients requiring hospitalization for severe chronic venous insufficiency (CVI) at the local and national levels and to analyze factors related to primary amputation. An administrative database (Nationwide Inpatient Sample, 1988-2000) and a single institution (1992-2000) were reviewed using the International Classification of Diseases, 9th ed., Clinical Modification, codes for CVI, excluding phlegmasia and concomitant peripheral vascular occlusive disease codes. Demographics, clinical course, and outcomes were assessed. Descriptive, univariate, and multivariate statistical analyses were used; p < 0.05 was considered significant. Nationally, CVI occurred with a mean incidence of 92/100,000 admissions, of which 55% were women, having a mean age of 65 years and a median length of stay of 7 days. Mean hospital charges were $13,900 and did not change significantly over time. Acute deep vein thrombosis affected 1.3%, amputation was performed in 1.2%, and in-hospital mortality was 1.6% The local cohort included 67 patients with a mean age of 51 years; a majority were men (60%), and 85% were C6 (of Clinical-Etiologic-Anatomic-Pathophysiology [CEAP]). Patients averaged 23 clinic visits and a median of one hospitalization for CVI care over a 44-month follow-up. Twelve patients (18%) underwent a CVI-related amputation (one transmetatarsal amputation, nine below-knee amputations, and two above-knee amputations). They had fourfold more CVI-related hospitalizations, greater preoperative chronic narcotic use than nonamputee patients (85% vs. 58%), but less ongoing wound care needs (25% vs. 89%) (all p values < 0.05). However, no significant difference in long-term mortality, number of clinic visits, duration of symptoms, antibiotic courses, or prior venous-related surgeries was found. In those with amputation, ambulatory status was maintained in 75% at 15-month follow-up. The physiological and economic costs of severe CVI are significant and have not decreased over more than a decade. Amputation for CVI-related nonhealing wounds has a reasonable outcome. Future therapy must focus on prevention of CVI sequelae.

Decreased Venous Thrombosis with an Oral Inhibitor of P Selectin

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Aug, 2005  |  Pubmed ID: 16102635

P-selectin inhibition with protein therapeutics such as antibodies or soluble ligands given intravenously can decrease thrombosis in a mouse ligation model of venous thrombosis. In this study, we hypothesized that oral inhibition of P selectin with a novel oral nonprotein inhibitor (PSI-697) would decrease thrombosis and circulating microparticle populations. This study evaluated the effects on thrombosis and circulating microparticle populations in this murine venous thrombosis model.

The Role of Inflammation in Early and Late Venous Thrombosis: Are There Clinical Implications?

Seminars in Vascular Surgery. Sep, 2005  |  Pubmed ID: 16168886

Venous thrombosis is associated with a significant inflammatory response. Inflammatory cells, adhesion molecules (especially selectins), cytokines, and procoagulant microparticles appear to be associated with the thrombogenic process. Once thrombus forms, inflammatory cells are important to thrombus resolution along with fibrinolytic agents and proinflammatory mediators. Collagen and elastin breakdown by the DVT renders the vein wall stiff and non-compliant. Rapid and complete thrombus resolution should lessen vein wall damage and lessen or prevent the development of chronic venous insufficiency. Understanding the basic biology of thrombogenesis and thrombus resolution is important, as novel therapies to both prevent and treat venous thrombosis and hasten thrombus resolution should result from a better understanding of the basic biological mechanisms.

Correspondence of Ultrasound Elasticity Imaging to Direct Mechanical Measurement in Aging DVT in Rats

Ultrasound in Medicine & Biology. Oct, 2005  |  Pubmed ID: 16223638

Previous ultrasound elasticity imaging experiments supported a generally accepted concept that the hardness of deep venous thrombi increases with thrombus aging. Results also showed that this noninvasive imaging technique can accurately predict thrombus age through strain estimates, in a well-controlled animal study. In the present study, as an alternative means to characterize elastic properties of thrombi, we used a direct mechanical measurement system to estimate Young's modulus of ex vivo thrombi. Unlike conventional indentation tests, the device uses a specific compression geometry for cylindrical tissue specimens. We also proposed an approximation scheme to retrieve Young's modulus from force-displacement measurements made using the device. Finite element simulations and calibrations on tissue-mimicking phantoms validated the system. Then, using two groups of rats with surgically-induced thrombi, we further investigated the correlation between Young's modulus measured ex vivo and elasticity images reconstructed in vivo. This comparison was accomplished by converting the intrathrombus strains measured in the in vivo studies into Young's modulus estimates using a model-based approach. Good agreement between time-dependent Young's modulus estimates observed in vivo and direct measurements of Young's modulus using the mechanical device helps to confirm the ability of elasticity imaging to age deep venous thrombi for efficient treatment.

D-dimer, P-selectin, and Microparticles: Novel Markers to Predict Deep Venous Thrombosis. A Pilot Study

Thrombosis and Haemostasis. Dec, 2005  |  Pubmed ID: 16411411

Current plasma markers for diagnosis of deep venous thrombosis (DVT) allow for exclusion of the diagnosis, but lack adequate specificity to establish the diagnosis. Thus, a prospective study was performed to determine the sensitivity and specificity of plasma assays for D-dimer, soluble P-selectin (P-selectin), and total microparticles in patients with documented DVT by duplex ultrasound. Three groups of individuals were examined: 30 normals; 22 positive for DVT on duplex ultrasound (Group 2); and 21 symptomatic, but negative on duplex ultrasound for DVT (Group 3). Group 1 individuals had D-dimer values of 1.53 +/- 0.12 mg/l and P-selectin values of 0.34 +/- 0.05 ng/mg total protein. Group 2 vs. Group 3 individuals had D-dimer values of 7.57 +/- 2.03 vs. 3.19 +/- 0.79 mg/l, p = 0.02; P-selectin values of 0.98 +/- 0.11 vs. 0.55 +/- 0.08 ng/mg total protein, p < 0.01; and micro-particle values of 129 +/- 17% vs. 99 +/- 12% of control, p = ns. Using a logistic regression model with dichotomous variables, we determined a sensitivity of 73%, specificity of 81%, and accuracy of 77% when combining D-dimer, soluble P-selectin, and total microparticles to differentiate Group 2 from Group 3 patients. Logistic regression using continuous variables yielded similar results (p = 0.05). This study demonstrates that plasma markers for DVT can be developed and achieve moderate sensitivity and specificity in diagnosing DVT. However for clinical applicability, the sensitivity/specificity will need to be improved. These studies also suggest the importance of soluble P-selectin in assessing DVT in humans.

Macrovascular Thrombosis is Driven by Tissue Factor Derived Primarily from the Blood Vessel Wall

Blood. Jan, 2005  |  Pubmed ID: 15339841

Leukocytes and leukocyte-derived microparticles contain low levels of tissue factor (TF) and incorporate into forming thrombi. Although this circulating pool of TF has been proposed to play a key role in thrombosis, its functional significance relative to that of vascular wall TF is poorly defined. We tested the hypothesis that leukocyte-derived TF contributes to thrombus formation in vivo. Compared to wild-type mice, mice with severe TF deficiency (ie, TF(-/-), hTF-Tg+, or "low-TF") demonstrated markedly impaired thrombus formation after carotid artery injury or inferior vena cava ligation. A bone marrow transplantation strategy was used to modulate levels of leukocyte-derived TF. Transplantation of low-TF marrow into wild-type mice did not suppress arterial or venous thrombus formation. Similarly, transplantation of wild-type marrow into low-TF mice did not accelerate thrombosis. In vitro analyses revealed that TF activity in the blood was very low and was markedly exceeded by that present in the vessel wall. Therefore, our results suggest that thrombus formation in the arterial and venous macrovasculature is driven primarily by TF derived from the blood vessel wall as opposed to leukocytes.

A Role for Interleukin-10 in the Assessment of Venous Thromboembolism Risk in Injured Patients

The Journal of Trauma. Jan, 2006  |  Pubmed ID: 16456448

Management of patients with multiple trauma requires prophylaxis for venous thromboembolism (VTE). This involves recognition of the physiologic factors that are associated with VTE risk. Currently, there is no effective strategy for risk assessment. The purpose of this study is to investigate the relationship of serum P-selectin and interleuken-10 (IL-10) with VTE as a possible physiologic marker.

Outcome of Surgical and Endoluminal Intervention for Infrainguinal Bypass Anastomotic Strictures

Vascular and Endovascular Surgery. Jan-Feb, 2006  |  Pubmed ID: 16456601

The objective of this study was to compare the outcomes of percutaneous transluminal angioplasty (PTA) versus open surgical repair of anastomotic strictures affecting infrainguinal bypasses. Anastomotic strictures affecting 39 bypasses in 36 patients were identified among 593 consecutive infrainguinal arterial reconstructions performed between 1994 and 2004. The mean age of affected patients was 65 +/- 2 years (range: 61 to 101 years). The original bypasses, with vein grafts outnumbering prosthetic grafts 2 to 1, were performed for acute (5%) and chronic (54%) limb-threatening ischemia, disabling claudication (28%), or popliteal aneurysms (13%). Anastomotic strictures were first recognized an average of 16 +/- 3 months (range 2 to 92 months) postoperatively. Strictures affected the distal anastomosis in 62% of cases and the proximal anastomosis in 38%. Primary patency, assisted primary patency, secondary patency, and limb salvage were assessed following PTA or open surgical repair of the strictures. Anastomotic strictures were detected following acute (41%) and chronic (18%) limb-threatening ischemia, claudication (13%), or during routine graft surveillance (28%) in asymptomatic patients. Graft thrombosis, occurring in 51% of patients at the time of presentation, was not affected by the site of anastomotic stricture, although prosthetic grafts were affected more than vein grafts (92% vs 31%). Interventions included PTA (67%) and conventional open procedures (33%). The latter included vein patch angioplasty, short interposition grafts, and redo bypasses. The stricture site and bypass material used in the original revascularization did not affect reintervention patency rates. Sixteen (62%) of the endovascular procedures were performed on a graft presenting with thrombosis, while only 4 (31%) were initially treated with operative therapy. Treatment of thrombosed grafts resulted in an 18-month patency of 32% compared to an 80% patency in treating grafts that were not occluded at the time of presentation (p < 0.05). No anastomotic stricture repaired operatively required reintervention, whereas 42% of those treated by PTA required a mean of 1.3 additional reinterventions (p < 0.03). Anastomotic strictures affecting infrainguinal bypass grafts contribute to low patency rates. Outcomes can be significantly improved if these strictures are identified before graft thrombosis. Open surgical repair, compared to PTA, provides improved graft function as evident by fewer subsequent interventions required to maintain graft patency.

Neutrophils Modulate Post-thrombotic Vein Wall Remodeling but Not Thrombus Neovascularization

Thrombosis and Haemostasis. Feb, 2006  |  Pubmed ID: 16493489

Early deep venous thrombosis (DVT) resolution is associated with neutrophil (PMN) influx. This study examined the role of PMNs in thrombus neovascularization and vein wall injury after DVT. A rat model of DVT by inferior vena cava (IVC) ligation was performed with control serum or rabbit anti-rat PMN serum administered perioperatively with sacrifice at 2 and 7 days. At 2 days, neutropenic rats had 1.6-fold larger thrombi (P = .04) and 1.4-fold higher femoral venous pressures by water manometry (P = .008) but no difference in thrombus neovascularization was observed. By 7 days, DVT sizes were similar, but vein wall injury persisted in the neutropenic rats with a 2.0-fold increase in vein wall stiffness by microtensiometry (P < .05), as well as a 1.2-fold increased thickness (P = .04). Collagen and profibrotic growth factors were significantly increased in neutropenic IVC at 7 days (all P < .05). Vein wall and intrathrombus uPA byWestern immunoblotting, and intrathrombus MMP-9 gelatinase activity were significantly less in neutropenic rats than controls (P < .001). Conversely, MMP-2 was significantly elevated in neutropenic IVC at 2 days after DVT. However, neutropenia induced 24 hours after DVT formation resulted in no significant increase in vein wall stiffness or collagen levels at 7 days, despite 1.4-fold larger thrombi (P < .05). These data suggest a critical early role for PMN in post DVT vein wall remodeling.

Experimental Pulmonary Embolism: Effects of the Thrombus and Attenuation of Pulmonary Artery Injury by Low-molecular-weight Heparin

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Apr, 2006  |  Pubmed ID: 16616240

Pulmonary embolism (PE) is a life-threatening condition that is associated with the long-term sequelae of chronic pulmonary hypertension. Prior experimental work has suggested that post-PE inflammation is accompanied by pulmonary artery intimal hyperplasia. This study evaluated the effect of the thrombus and tested the hypothesis that thrombolytic, antiplatelet, and anticoagulant agents would decrease pulmonary injury.

Risk Factors Associated with Venous Thromboembolic Events in Patients with Malignancy

Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. Jun, 2006  |  Pubmed ID: 16651868

Malignancy is a major risk factor for venous thromboembolic events, but not all patients with malignancy develop such events. This study attempts to identify risk factors in patients with malignancy who develop venous thromboembolic events. In the current study, 566 consecutive patients without venous thromboembolic events and 416 patients with, admitted to University of Michigan with malignancy between 1992 and 2000, were identified using International Classification of Diseases-9 Clinical Modification codes. Data on potential risk factors was obtained from the University of Michigan Cancer Registry and the medical record. Univariate and multivariate analysis was used to identify factors associated with venous thromboembolic events and mortality. The mean patient age was 45.6 years with a mean survival of 7.8 years from cancer diagnosis. Venous thromboembolic events were associated with solid tumors (odds ratio 5.0; 95% confidence interval 1.7-14.9; P = 0.004), infection (4.9; 1.2-19.8; P = 0.03), and increasing age (1.05; 1.03-1.08; P < 0.001). While leukopenia (4.2; 1.2-14.6; P = 0.02) was associated with an increased incidence of venous thromboembolic events, neutropenia was not. Sex, type of therapy, and cancer stage were not independently associated with venous thromboembolic events. Survival was decreased in patients with venous thromboembolic events (5.9 versus 9.2 years, P < 0.0001). Solid tumors (3.9; 1.8-8.4; P = 0.001), infection (3.3; 1.1-9.9; P = 0.03), advanced stage (1.6; 1.2-2.1; P = 0.001), and increasing age (1.02; 1.0-1.04; P = 0.01) were associated with decreased survival. Patients with malignancy who have solid tumors, advanced age, infection, and leukopenia have a significantly increased risk of venous thromboembolic events.

Multidetector Computed Tomography for Acute Pulmonary Embolism

The New England Journal of Medicine. Jun, 2006  |  Pubmed ID: 16738268

The accuracy of multidetector computed tomographic angiography (CTA) for the diagnosis of acute pulmonary embolism has not been determined conclusively.

American Venous Forum: The Future is Now!

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Jul, 2006  |  Pubmed ID: 16828451

A Negative Carotid Plaque Area Test is Superior to Other Noninvasive Atherosclerosis Studies for Reducing the Likelihood of Having Underlying Significant Coronary Artery Disease

Arteriosclerosis, Thrombosis, and Vascular Biology. Mar, 2006  |  Pubmed ID: 16357319

Coronary calcium score (CCS), carotid plaque area (CPA), intima-media thickness (IMT), and C-reactive protein (CRP) are independent predictors of cardiovascular prognosis. Although each test may enhance risk stratification, their comparative abilities to screen for underlying coronary stenoses in individual patients is less established.

Targeted Deletion of CCR2 Impairs Deep Vein Thombosis Resolution in a Mouse Model

Journal of Immunology (Baltimore, Md. : 1950). Sep, 2006  |  Pubmed ID: 16920980

CCR2 is required for monocyte recruitment in many inflammatory processes, as well as conferring Th1 lymphokine responses. Deep vein thrombosis (DVT) resolution represents a specific inflammatory response whereby the thrombus must be dissolved for restoration of blood flow. Using a stasis model of DVT in the mouse, we investigated the role of CCR2 on DVT resolution. Genetic deletion of CCR2 (CCR2-/-) was associated with larger thrombi at early and later time points, increased thrombus collagen, fewer thrombus monocytes (F4/80), and significantly impaired neovascularization. IL-2 and IFN-gamma were significantly reduced in early CCR2-/- thrombi, whereas MCP-1 was significantly increased, and Th2 lymphokines were unaffected. Supplementation of CCR2-/- mice with IFN-gamma normalized early thrombus resolution without increasing monocyte influx. Neither Ab depletion of IFN-gamma nor genetic deletion of IFN-gamma impaired early DVT resolution. Early fibrinolysis was not impaired in CCR2-/- mice, but a significant reduction in both matrix metalloproteinase (MMP)-2 and MMP-9 activity was observed. However, only MMP-9 activity was restored with administration of IFN-gamma. We conclude that an early CCR2-dependent Th1 lymphokine response predominates in normal DVT resolution, mediates this in part by MMP-9 activation, but is not solely dependent on IFN-gamma.

Sonographic Elasticity Imaging of Acute and Chronic Deep Venous Thrombosis in Humans

Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. Sep, 2006  |  Pubmed ID: 16929019

The purpose of this study was to assess the ability of sonographic elasticity imaging to distinguish acute from chronic deep venous thrombosis (DVT).

Treatment with an Oral Small Molecule Inhibitor of P Selectin (PSI-697) Decreases Vein Wall Injury in a Rat Stenosis Model of Venous Thrombosis

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Sep, 2006  |  Pubmed ID: 16950445

Vein wall injury after thrombosis is multifactorial but seems dependent on thrombus and local thrombotic and inflammatory mechanisms. We hypothesized that inhibition of vein wall injury through reduction of thrombotic and inflammatory events with P-selectin inhibition and/or low-molecular-weight heparin (LMWH) occurs independently of thrombus resolution in a rat model of venous thrombosis.

Acute Limb Ischemia Associated with Type B Aortic Dissection: Clinical Relevance and Therapy

Surgery. Oct, 2006  |  Pubmed ID: 17011900

The goal of the current study is to characterize the presentation, therapy, and outcomes of acute limb ischemia (ALI) associated with type B aortic dissection (AoD).

Pediatric Renovascular Hypertension: 132 Primary and 30 Secondary Operations in 97 Children

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Dec, 2006  |  Pubmed ID: 17055693

This study was undertaken to characterize the contemporary surgical treatment of pediatric renovascular hypertension.

Diagnostic Pathways in Acute Pulmonary Embolism: Recommendations of the PIOPED II Investigators

The American Journal of Medicine. Dec, 2006  |  Pubmed ID: 17145249

To formulate comprehensive recommendations for the diagnostic approach to patients with suspected pulmonary embolism, based on randomized trials.

Diagnostic Pathways in Acute Pulmonary Embolism: Recommendations of the PIOPED II Investigators

Radiology. Jan, 2007  |  Pubmed ID: 17185658

Results of the National Pilot Screening Program for Venous Disease by the American Venous Forum

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Jan, 2007  |  Pubmed ID: 17210399

This report describes the pilot of a free comprehensive national screening program for venous disease.

Risk Factors and Clinical Impact of Postoperative Symptomatic Venous Thromboembolism

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Feb, 2007  |  Pubmed ID: 17264013

Although common risk factors for venous thromboembolism (VTE) are well known, little data exist concerning the clinical impact of VTE in postoperative patients outside of controlled studies. This study evaluated prospective perioperative demographic and clinical variables associated with occurrence of postoperative symptomatic VTE.

Resolution of Venous Thrombosis Using a Novel Oral Small-molecule Inhibitor of P-selectin (PSI-697) Without Anticoagulation

Thrombosis and Haemostasis. Mar, 2007  |  Pubmed ID: 17334507

P-selectin inhibition has been shown to decrease thrombogenesis in multiple animal species. In this study, we show that a novel oral small-molecule inhibitor of P-selectin, PSI-697, promotes thrombus resolution and decreases inflammation in a baboon model of venous thrombosis. Experimental groups consisted of the following: 1) primates receiving a single oral dose of PSI-697 (30 mg/kg) daily starting three days pre-iliac vein balloon occlusion, and continued for six days; 2) primates receiving a single treatment dose of a low-molecular-weight-heparin (LMWH) (1.5 mg/kg) daily starting one day pre-iliac balloon occlusion, and continued for six days; and 3) primates receiving a single oral dose of a vehicle control daily starting three days pre-iliac vein balloon occlusion, and continued for six days. Animals receiving PSI-697, although thrombosed after balloon deflation, demonstrated greater than 80% vein lumen opening over time, with no opening (0%) for vehicle control (p < 0.01). LMWH opening evident after balloon deflation slightly deteriorated over time compared to PSI-697. PSI-697 therapy also significantly decreased vein wall inflammation determined by magnetic resonance venography (MRV). Importantly, this beneficial opening occurred without measured anticoagulation. Animals receiving PSI-697 demonstrated significantly increased plasma D-dimer levels versus LMWH and control animals six hours post thrombus induction (p < 0.01). This study is the first to demonstrate the effectiveness of oral P-selectin inhibition to modify venous thrombogenesis, increase vein lumen opening, and decrease inflammation in a large animal model.

Iliorenal Bypass: Indications and Outcomes Following 41 Reconstructions

Annals of Vascular Surgery. Jan, 2007  |  Pubmed ID: 17349328

Iliorenal bypass is a nonanatomic means of renal revascularization usually performed in high-risk patients. Its efficacy was assessed in this review of 35 patients (17 males and 18 females, two children and 33 adults) ranging in age 8-84 years, who were subjected to 41 iliorenal bypasses at the University of Michigan Hospital during 1975-2003. Renal artery lesions included arteriosclerosis (n = 20), developmental narrowing (n = 10), arterial fibrodysplasia (n = 3), penetrating trauma (n = 1), and aortorenal dissection associated with Marfan disease (n = 1). All patients had hypertension attributed to their renal artery disease. Twenty patients exhibited renal insufficiency (serum creatinine >1.8 mg/dL). Primary reasons for selecting an iliorenal reconstruction over a more conventional open revascularization included advanced aortic arteriosclerosis (n = 9); prior aortoaortic, aortoiliac, or aortofemoral reconstruction (n = 7); a small aortic aneurysm not justifying aortic surgery (n = 6); prior aortorenal surgery (n = 6); congenital abdominal aortic coarctation (n = 4); a hostile retroperitoneum (n = 2); or compromised cardiac status (n = 1). Eleven patients had prior ipsilateral renal artery interventions. Iliorenal bypasses were to the right kidney (n = 20), the left kidney (n = 9), and bilateral (n = 12). Conduits were saphenous veins (n = 29), synthetic prostheses (n = 11), or direct renal artery-iliac artery reimplantation (n = 1). Initial bypass patency was 93%. Follow-up averaged 7.5 years. Three early and six late graft complications resulted in eight secondary operations. The mean preoperative and postoperative serum creatinine of all 35 patients did not vary (1.9 vs. 1.8 mg/dL), although on an individual basis renal function improved in eight, remained stable in 21, and deteriorated in six patients. The series' mean preoperative blood pressure of 180/97 mm Hg decreased postoperatively to 140/78 mm Hg (P < 0.001). Hypertension was cured in three patients, improved in 27, and became worse in four. Antihypertensive medication numbers decreased postoperatively, from a median of three to two (P < 0.0001). Surgical mortality was limited to one patient succumbing from perioperative intestinal infarction. Iliorenal bypass is an effective means of renal revascularization in patients not amenable to more conventional open or transluminal procedures.

Venous Thromboembolism and Cancer

Current Problems in Surgery. Mar, 2007  |  Pubmed ID: 17437761

Proximate Versus Nonproximate Risk Factor Associated Primary Deep Venous Thrombosis: Clinical Spectrum and Outcomes

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. May, 2007  |  Pubmed ID: 17466793

Although the treatment for acute deep vein thrombosis (DVT) is uniform, the circumstances under which it develops vary widely and may impact outcomes. This study compared clinical features and outcomes in patients who developed a primary DVT associated with a defined risk to those without any proximate risk factor.

Plasmin Inhibition Increases MMP-9 Activity and Decreases Vein Wall Stiffness During Venous Thrombosis Resolution

The Journal of Surgical Research. Oct, 2007  |  Pubmed ID: 17574586

Deep venous thrombosis (DVT) resolution involves the plasmin and the matrix metalloproteinase (MMP) system. This study tested the hypothesis that pharmacological inhibition of the plasmin system would impair DVT resolution and worsen vein wall damage.

CT Venography for Deep Venous Thrombosis: Continuous Images Versus Reformatted Discontinuous Images Using PIOPED II Data

AJR. American Journal of Roentgenology. Aug, 2007  |  Pubmed ID: 17646468

This study was designed to determine whether discontinuous CT of the lower extremities for the detection of deep venous thrombosis (DVT) yields results similar to those of complete helical imaging using cases from the Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II).

Factors Associated with Outcome After Interventional Treatment of Symptomatic Iliac Vein Compression Syndrome

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Oct, 2007  |  Pubmed ID: 17903652

Iliac vein compression syndrome (IVCS) results from compression of the left iliac vein by the overlying right iliac artery against the pelvic brim. In many cases, patients are symptomatic. In symptomatic cases, management consists of angioplasty and stenting. Although therapy is often initially successful, factors associated with long-term outcome have been poorly defined. The purpose of this study was to identify factors associated with stent patency.

CT Venography and Compression Sonography Are Diagnostically Equivalent: Data from PIOPED II

AJR. American Journal of Roentgenology. Nov, 2007  |  Pubmed ID: 17954642

The purpose of this study was to compare the clinical value of CT venography (CTV) after MDCT angiography (CTA) with venous compression sonography for the diagnosis of venous thromboembolism (VTE). The Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) showed that lower extremity imaging detects about 7% more patients requiring anticoagulation than CTA alone.

Fibrotic Injury After Experimental Deep Vein Thrombosis is Determined by the Mechanism of Thrombogenesis

Thrombosis and Haemostasis. Nov, 2007  |  Pubmed ID: 18000610

Vessel wall matrix changes occur after injury, although this has not been well studied in the venous system. This study tested the hypothesis that the thrombus dictates the vein wall response and vein wall damage is directly related to the duration of thrombus contact. To determine the injury response over time, rats underwent inferior vena cava (IVC) ligation to produce a stasis thrombus, with harvest at various time points to 28 days (d). Significant vein wall matrix changes occurred with biomechanical injury (stiffness) peaking at 7-14 d, with concurrent early reduction in total collagen, an increase in early matrix metalloproteinase (MMP)-9 and late MMP-2, and concomitant increase in tumor necrosis factor (TNF)alpha, monocyte chemoattractant(MCP)-1 and tumor growth factor (TGF)beta (all P<0.05). To isolate the effect of the thrombus and its mechanism of genesis, rats underwent 7 d or limited stasis (24 hours), non-stasis thrombosis, or non-thrombotic IVC occlusion (Silicone plug). Vein wall stiffness was increased seven-fold, with a five-fold reduction in collagen, and 5.5- to seven-fold increase in TNFalpha, MCP-1, and TGFbeta with 7 d stasis as compared with controls (all P<0.05). By Picosirus red staining analysis, collagenolysis was significantly greater with 7 d stasis injury (P=0.01) but neither MMP-9 nor MMP-2 activity correlated with injury mechanism. In addition, vein wall cellular proliferation and uPA gene expression paralled the stasis thrombotic injury. Limited stasis, non-stasis thrombosis and non-thrombotic IVC occlusion showed a lesser inflammatory response. These data suggest both a static component and the thrombus directs vein wall injury via multiple mechanisms.

Mapping the Future: Organizational, Clinical, and Research Priorities in Venous Disease

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Dec, 2007  |  Pubmed ID: 18068564

Preface: Acute and Chronic Venous Disease. Current Status and Future Directions

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Dec, 2007  |  Pubmed ID: 18068559

Acute Venous Disease: Venous Thrombosis and Venous Trauma

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Dec, 2007  |  Pubmed ID: 18068560

Acute venous disorders include deep venous thrombosis, superficial venous thrombophlebitis, and venous trauma. Deep venous thrombosis (DVT) most often arises from the convergence of multiple genetic and acquired risk factors, with a variable estimated incidence of 56 to 160 cases per 100,000 population per year. Acute thrombosis is followed by an inflammatory response in the thrombus and vein wall leading to thrombus amplification, organization, and recanalization. Clinically, there is an exponential decrease in thrombus load over the first 6 months, with most recanalization occurring over the first 6 weeks after thrombosis. Pulmonary embolism (PE) and the post-thrombotic syndrome (PTS) are the most important acute and chronic complications of DVT. Despite the effectiveness of thromboembolism prophylaxis, appropriate measures are utilized in as few as one-third of at-risk patients. Once established, the treatment of venous thromboembolism (VTE) has been defined by randomized clinical trials, with appropriate anticoagulation constituting the mainstay of management. Despite its effectiveness in preventing recurrent VTE, anticoagulation alone imperfectly protects against PTS. Although randomized trials are currently lacking, at least some data suggests that catheter-directed thrombolysis or combined pharmaco-mechanical thrombectomy can reduce post-thrombotic symptoms and improve quality of life after acute ileofemoral DVT. Inferior vena caval filters continue to have a role among patients with contra-indications to, complications of, or failure of anticoagulation. However, an expanded role for retrievable filters for relative indications has yet to be clearly established. The incidence of superficial venous thrombophlebitis is likely under-reported, but it occurs in approximately 125,000 patients per year in the United States. Although the appropriate treatment remains controversial, recent investigations suggest that anticoagulation may be more effective than ligation in preventing DVT and PE. Venous injuries are similarly under-reported and the true incidence is unknown. Current recommendations include repair of injuries to the major proximal veins. If repair not safe or possible, ligation should be performed.

Model-based Reconstructive Elasticity Imaging Using Ultrasound

International Journal of Biomedical Imaging. 2007  |  Pubmed ID: 18256732

Elasticity imaging is a reconstructive imaging technique where tissue motion in response to mechanical excitation is measured using modern imaging systems, and the estimated displacements are then used to reconstruct the spatial distribution of Young's modulus. Here we present an ultrasound elasticity imaging method that utilizes the model-based technique for Young's modulus reconstruction. Based on the geometry of the imaged object, only one axial component of the strain tensor is used. The numerical implementation of the method is highly efficient because the reconstruction is based on an analytic solution of the forward elastic problem. The model-based approach is illustrated using two potential clinical applications: differentiation of liver hemangioma and staging of deep venous thrombosis. Overall, these studies demonstrate that model-based reconstructive elasticity imaging can be used in applications where the geometry of the object and the surrounding tissue is somewhat known and certain assumptions about the pathology can be made.

Novel Biomarkers Associated with Deep Venous Thrombosis: A Comprehensive Review

Biomarker Insights. 2008  |  Pubmed ID: 19578498

Primary and recurrent venous thromboembolic disease (VTE, deep venous thrombosis and pulmonary embolism) remain a significant source of morbidity and mortality in the hospitalized patient. Non-specific subjective complaints and lack of specific objective findings related to acute deep venous thrombosis (DVT) and pulmonary embolism (PE) complicate the diagnosis. There remains no single serum marker available to exclusively confirm the diagnosis of VTE. While D-dimer is highly sensitive and useful for diagnostic exclusion, it lacks the specificity necessary for diagnostic confirmation resulting in the need for a variety of additional studies (i.e.: duplex ultrasound, venography, V/Q scanning, helical thoracic and pelvic CT scans and pulmoary angiography). There is evolving research supporting the utility of various plasma markers as novel "biomarkers" for VTE including selectins, microparticles, interleukin-10 and other cytokines. This review attempts to examine recent literature assessing the utility of P-selectin, microparticles, D-dimer, E-selectin, thrombin, interleukins and fibrin monomers in the diagnosis and guidance of therapy for VTE.

Prophylactic P-selectin Inhibition with PSI-421 Promotes Resolution of Venous Thrombosis Without Anticoagulation

Thrombosis and Haemostasis. Feb, 2008  |  Pubmed ID: 18278184

P-selectin inhibition has been evaluated as a therapeutic for prevention and treatment of venous thrombosis. In this study, a novel oral small-molecule inhibitor of P-selectin, PSI-421, was evaluated in a baboon model of stasis induced deep vein thrombosis (DVT). Experimental groups included i) primates receiving a single oral dose of 1 mg/kg PSI-421 two days prior and continued six days after thrombosis (n = 3); ii) primates receiving a single daily subcutaneous dose of 0.57 mg/kg enoxaparin sodium two days prior and continued six days post thrombosis (n = 3); and iii) primates receiving no treatment (n = 3). PSI-421 treated primates had greater percent vein reopening and less vein wall inflammation than the enoxaparin and controls at day 6. Microparticle tissue factor activity (MPTFA) was significantly lower in the animals receiving PSI-421 immediately after thrombosis (T+6 hours day 0) suggesting lower potential for thrombogenesis in these animals. PSI-421 also reduced soluble P-selectin levels versus controls at T+6 hours day 0, day 2 and 6. Experimental animals in any group showed no adverse effects on coagulation. This study is the first to demonstrate a reduction in MPTFA associated with vein reopening and reduced vein inflammation due to oral P-selectin inhibition in a baboon model of DVT.

Vein Wall Re-endothelialization After Deep Vein Thrombosis is Improved with Low-molecular-weight Heparin

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Mar, 2008  |  Pubmed ID: 18295113

Vein wall endothelial turnover after stasis deep vein thrombosis (DVT) has not been well characterized. The purpose of this study was to quantify re-endothelialization after DVT and determine if low-molecular-weight heparin (LMWH) therapy affects this process.

Mechanisms of Venous Thrombosis and Resolution

Arteriosclerosis, Thrombosis, and Vascular Biology. Mar, 2008  |  Pubmed ID: 18296594

Venous thromboembolism is a significant health care problem in the US. In this review, the unique role of inflammation to the venous thrombotic process is emphasized as well as the potential role of abnormalities of fibrinolytic mechanisms to the thrombotic process. Inflammation influences not only thrombogenesis but also thrombus resolution and vein wall remodeling, and these interactions are also discussed. Knowledge of molecular and immunologic mechanisms for venous thrombosis and its resolution should allow for the future development of targeted therapies.

Increasing Awareness About Venous Disease: The American Venous Forum Expands the National Venous Screening Program

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Aug, 2008  |  Pubmed ID: 18572373

To evaluate the results of the expanded National Venous Screening Program (NVSP) as administered by the American Venous Forum.

Endovenous Laser Ablation: Venous Outcomes and Thrombotic Complications Are Independent of the Presence of Deep Venous Insufficiency

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Dec, 2008  |  Pubmed ID: 18829223

We hypothesize that endovenous laser ablation (EVA) therapy is equally successful in improving venous insufficiency symptoms in patients with or without deep venous insufficiency (DVI).

Venous Thromboembolism in Cancer Patients Undergoing Major Surgery

Annals of Surgical Oncology. Dec, 2008  |  Pubmed ID: 18841419

Cancer patients undergoing major abdominal or pelvic surgery are at considerable risk of venous thromboembolism (VTE). The genesis of thromboses in malignancy is complicated, and reflects the interaction and derangement of multiple molecular pathways. Furthermore, the nature and location of the cancer, as well as the type surgery involved, are thought to affect the level of VTE risk. These considerations may therefore affect treatment decisions.

In Brief. Thromboembolic Disease

Current Problems in Surgery. Dec, 2008  |  Pubmed ID: 18984094

Thromboembolic Diseases

Current Problems in Surgery. Dec, 2008  |  Pubmed ID: 18984095

Methods of Prospective Investigation of Pulmonary Embolism Diagnosis III (PIOPED III)

Seminars in Nuclear Medicine. Nov, 2008  |  Pubmed ID: 19331840

In this work, the methods of the Prospective Investigation of Pulmonary Embolism Diagnosis III (PIOPED III) are described in detail. PIOPED III is a multicenter collaborative investigation sponsored by the National Heart, Lung and Blood Institute. The purpose is to determine the accuracy of gadolinium-enhanced magnetic resonance angiography in combination with venous phase magnetic resonance venography for the diagnosis of acute pulmonary embolism (PE). A composite reference standard based on usual diagnostic methods for PE is used. All images will be read by 2 blinded and study-certified central readers. Patients with no PE according to the composite reference test will be randomized to undergo gadolinium-enhanced magnetic resonance angiography in combination with venous phase magnetic resonance venography. This procedure will reduce the proportion of patients with negative tests at no loss in evaluation of sensitivity and specificity.

Leukocyte- and Platelet-derived Microparticles Correlate with Thrombus Weight and Tissue Factor Activity in an Experimental Mouse Model of Venous Thrombosis

Thrombosis and Haemostasis. Apr, 2009  |  Pubmed ID: 19350121

Microparticles (MP) are lipid vesicles from platelets, leukocytes and endothelial cells that are involved in early thrombogenesis. We evaluated a detailed time-course analysis of MPs on thrombogenesis and the associated tissue factor (TF) activity in wild-type, in gene-deleted for E- and P-selectins and with high levels of P-selectin expression after the initiation of venous thrombosis in mice. Inferior vena cava (IVC) ligation was performed on C57BL/6 mice (n = 191, 59 = wild-type [WT], 55 = gene-deleted for E- and P - selectins [knock-outs, EPKO] and 77 = elevated levels of soluble P-selectin, named Delta Cytoplasmic Tail (DeltaCT). Animals were euthanised at various time points to assess MP production, origin and thrombus weight. MPs were re-injected into separate mice at concentrations of 80,000 and 160,000 units, as well as from different ages. In addition, MPs from thrombosed animals were pooled and TF activity quantitated using a chromogenic assay. Thrombus weight correlated negatively with MPs derived from leukocytes, and positively with MPs derived from platelets for WT animals (p < 0.05), while MPs from platelets presented a positive correlation to thrombus weight in the WT and EPKO groups (p < 0.01). Total MPs correlated negatively with thrombus weight in the DeltaCT group (p < 0.05). MP re-injections led to greater thrombus weight, while older MP reinjections tended to form larger thrombus than younger. Finally, TF bearing MPs showed a significant correlation to MP concentrations (R = 0.99). In conclusion, MPs appear to be an important element in venous thrombogenesis.

Microparticle Surface Protein Are Associated with Experimental Venous Thrombosis: a Preliminary Study

Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. Mar-Apr, 2009  |  Pubmed ID: 19028772

Microparticles are small membrane vesicles released from activated cells and are associated with thrombosis and inflammation. Microparticle contain a unique subset of surface protein derived form the parent cell and may be responsible for their diverse biological functions. To identify these proteins, juvenile baboons (Papio anubis, n = 4) underwent iliac vein thrombosis with 6-hour balloon occlusion. Plasma samples were taken at baselines and at 2 days postthrombosis for microparticle analysis. Microparticles were extracted from platelet-poor plasma, digest separately with trypsin and tagged using isobaric tagging for relative and absolute quantitation reagents. The digests were subjected to 2-dimensional liquid chromatographic separation followed by matrix-assisted laser desorption/ionization tandem mass spectrometry. Peak lists were generated and searched against all primate sequences. For protein identity, a minimum of 2 peptides at 95% confidence interval was required. Later, isobaric tagging for relative and absolute quantitation ratios were generated comparing relative protein level of day 2 to baseline. The proteomic analysis was performed twice for each blood sample, totaling 8 experiments. Proteins were considered elevated of depressed if the isobaris tagging for relative and absolute quantitation ratio deviated by 20% changes from normal and a P value less than .05. Significantly, 7 proteins were differentially expressed on day 2 compared to baseline, and appeared in at least 3 animals and regulated in at least 4 experiment. Among these 7 proteins, upregulated proteins include various forms of fibrinogen and alpha-1-antichymotrypsin and downregulated proteins include immunoglobulins. These proteins influence thrombosis and inflammation through hemostatic plug formation (fibrinogen), inhibiting neutrophil adhesion (alpha-1-antichymoptrypsin), and immunoregulation (immunoglobulins). Further studies are needed to confirm the mechanistic role of these proteins in the pathogenesis of venous thrombosis.

Metabolic Consequences of Acute Limb Ischemia and Their Clinical Implications

Seminars in Vascular Surgery. Mar, 2009  |  Pubmed ID: 19298933

Acute limb ischemia is a common medical condition resulting from arterial embolization, in situ thrombosis, trauma, and other causes. The severity of injury is related to the duration of ischemia and the effects of reperfusion. Metabolic consequences of reperfusion injury can be variable, ranging from transient symptoms in the lower extremity to systemic inflammation with multiple organ dysfunction. This article provides an overview of some of the key mediators of reperfusion injury. Additional discussion is focused on the clinical effects of reperfusion in the extremity, as well as the pulmonary, cardiac, and renal organ systems. A better understanding of these processes may result in improved patient outcomes and decreased mortality.

Role of Selectins and Fibrinolysis in VTE

Thrombosis Research. 2009  |  Pubmed ID: 19303502

Venous thromboembolism (VTE) accounts for an estimated 900,000 cases of deep venous thrombosis (DVT) and pulmonary embolism (PE) yearly, resulting in approximately 300,000 deaths [1]. For the past 150 years, Virchow's triad has encompassed the elements of venous thrombogenesis, including stasis, changes in the vessel wall, and thrombogenic changes in the blood. However, in the early 1970s, through the work of Gwendylen Stewart, a relationship between thrombosis and inflammation was suggested. In this review, we will address the role of selectins and fibrinolysis in the process of venous thrombogenesis.

Call to Action to Prevent Venous Thromboembolism

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Jun, 2009  |  Pubmed ID: 19497526

Deep venous thrombosis and pulmonary embolism, together called venous thromboembolism, remain a serious national health problem. Estimates suggest that over 900,000 cases occur in the United States per year, with 300,000 deaths per year. Because of the significant and serious nature of this problem, a workshop was held in May of 2006, which resulted in the Acting U.S. Public Health Service Surgeon General's Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism. On September 15, 2008, Acting Surgeon General, Rear Admiral Steven K. Galson, MD, MPH, and Elizabeth Nabel, MD, Director National Heart, Lung, and Blood Institute, announced the Call to Action. The Call to Action highlights public awareness about the risk factors, triggering events, and symptoms of venous thrombosis and pulmonary embolism, and encourages the development of evidence based practices for screening, prevention, diagnosis, and treatment of venous thrombosis and pulmonary embolism. It is designed to encourage new scientific investigation in an effort to obtain needed evidence to fill in the gaps of knowledge about venous thrombosis and pulmonary embolism. This knowledge should be quickly and easily disseminated to the public and put into practice by health professionals. The Surgeon General's Call to Action represents one of the most important advances in the field of venous thromboembolism and sets the stage for multidisciplinary efforts to combat this serious national health problem.

Aging is Associated with Impaired Thrombus Resolution in a Mouse Model of Stasis Induced Thrombosis

Thrombosis Research. Jan, 2010  |  Pubmed ID: 19616825

To evaluate the effects of aging on venous thrombosis.

A Validation Study of a Retrospective Venous Thromboembolism Risk Scoring Method

Annals of Surgery. Feb, 2010  |  Pubmed ID: 19779324

Validate a retrospective venous thromboembolism (VTE) risk scoring method, which was developed at the University of Michigan Health System and based on the Caprini risk assessment model, and assess the confounding effects of VTE prophylaxis.

Do Galectins Play a Role in Venous Thrombosis? a Review

Thrombosis Research. May, 2010  |  Pubmed ID: 19959209

Galectins are a family of carbohydrate-binding proteins that have a high affinity to galactosides on cell surfaces and extra cellular glycoproteins. They are involved in a variety of biological functions, including modulation of cell apoptosis, cell activation and inflammation. Our laboratory has recently identified galectin-3 binding protein (Gal-3BP) as being up-regulated in a microparticle proteomics analysis for deep venous thrombosis (DVT) patients compared to negative controls. P-selectin, another glycoprotein involved in thrombus propagation, has proven a promising target for DVT management and has been widely studied by our group. Galectins are involved in P-selectin expression and can potentially be implicated in the venous thrombogenesis process. The function of galectins, their role in inflammation and thrombosis as well as their potential implications as a new pharmacological target for DVT management are reviewed in this manuscript.

P-selectin/ PSGL-1 Inhibitors Versus Enoxaparin in the Resolution of Venous Thrombosis: a Meta-analysis

Thrombosis Research. Apr, 2010  |  Pubmed ID: 19962723

P-selectin antagonism has been shown to decrease thrombogenesis and inflammation in animal models of deep venous thrombosis (DVT).

Invited Commentary

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Feb, 2010  |  Pubmed ID: 20141963

Vein Wall Remodeling After Deep Vein Thrombosis: Differential Effects of Low Molecular Weight Heparin and Doxycycline

Annals of Vascular Surgery. Feb, 2010  |  Pubmed ID: 20142002

Venous thrombus resolution sets up an early intense inflammatory reaction, from which vein wall damage results. Tissue response to injury includes matrix metalloproteinase (MMP) activation and extracellular matrix protein turnover. This study sought to determine the effect of exogenous MMP inhibition and its potential attenuation of early vein wall injury.

Proteomics of Microparticles After Deep Venous Thrombosis

Thrombosis Research. Jun, 2010  |  Pubmed ID: 20156641

Microparticles (MP) are submicron size membrane vesicles released from activated cells that are associated with thrombosis and inflammation. MP present diverse biological expressions that may be linked to a unique subset of proteins derived from their origin cells.

Chronic Venous Insufficiency: Current Management of Varicose Vein Disease

The American Surgeon. Feb, 2010  |  Pubmed ID: 20336886

This review encompasses the basic pathophysiology, diagnosis, and current therapies for superficial venous insufficiency.

Thrombogenesis with Continuous Blood Flow in the Inferior Vena Cava. A Novel Mouse Model

Thrombosis and Haemostasis. Aug, 2010  |  Pubmed ID: 20589322

Several rodent models have been used to study deep venous thrombosis (DVT). However, a model that generates consistent venous thrombi in the presence of continuous blood flow, to evaluate therapeutic agents for DVT, is not available. Mice used in the present study were wild-type C57BL/6 (WT), plasminogen activator inhibitor-1 (PAI-1) knock out (KO) and Delta Cytoplasmic Tail (DCT). An electrolytic inferior vena cava (IVC) model (EIM) was used. A 25G stainless-steel needle, attached to a silver coated copper wire electrode (anode), was inserted into the exposed caudal IVC. Another electrode (cathode) was placed subcutaneously. A current of 250 muAmps over 15 minutes was applied. Ultrasound imaging was used to demonstrate the presence of IVC blood flow. Analyses included measurement of plasma soluble P-selectin (sP-Sel), thrombus weight (TW), vein wall morphometrics, P-selectin and Von Willebrand factor (vWF) staining, transmission electron microscopy (TEM), scanning electron microscopy (SEM); and the effect of enoxaparin on TW was evaluated. A current of 250 muAmps over 15 minutes consistently promoted thrombus formation in the IVC. Plasma sP-Sel was decreased in PAI-1 KO and increased in DCT vs. WT (WT/PAI-1: p=0.003, WT/DCT: p=0.0002). Endothelial activation was demonstrated by SEM, TEM, P-selectin and vWF immunohistochemistry and confirmed by inflammatory cell counts. Ultrasound imaging demonstrated thrombus formation in the presence of blood flow. Enoxaparin significantly reduced the thrombus size by 61% in this model. This EIM closely mimics clinical venous disease and can be used to study endothelial cell activation, leukocyte migration, thrombogenesis and therapeutic applications in the presence of blood flow.

Venous Thromboembolic Events in the Rehabilitation Setting

PM & R : the Journal of Injury, Function, and Rehabilitation. Jul, 2010  |  Pubmed ID: 20659721

Venous thromboembolism (VTE) is a disease entity that encompasses both deep venous thrombosis and pulmonary embolism. During the past decade there have been significant advances in the understanding of prophylaxis and treatment of VTE. There is an extensive research base from which conclusions can be drawn, but the heterogeneity within the rehabilitation patient population makes the development of rigid VTE protocols challenging and overwhelming for the busy clinician. Given the prevalence of this condition and its associated morbidity and mortality, we review the evidence for the prevention, identification, and optimal treatment of VTE in the rehabilitation population. Our goal is to highlight studies that have the most clinical applicability for the care of VTE patients from a physiatrist's perspective. At times, information about acute care protocols is included in our discussion because these situations are encountered during the consultation process that identifies patients for rehabilitation needs.

Extracellular DNA Traps Promote Thrombosis

Proceedings of the National Academy of Sciences of the United States of America. Sep, 2010  |  Pubmed ID: 20798043

Neutrophil extracellular traps (NETs) are part of the innate immune response to infections. NETs are a meshwork of DNA fibers comprising histones and antimicrobial proteins. Microbes are immobilized in NETs and encounter a locally high and lethal concentration of effector proteins. Recent studies show that NETs are formed inside the vasculature in infections and noninfectious diseases. Here we report that NETs provide a heretofore unrecognized scaffold and stimulus for thrombus formation. NETs perfused with blood caused platelet adhesion, activation, and aggregation. DNase or the anticoagulant heparin dismantled the NET scaffold and prevented thrombus formation. Stimulation of platelets with purified histones was sufficient for aggregation. NETs recruited red blood cells, promoted fibrin deposition, and induced a red thrombus, such as that found in veins. Markers of extracellular DNA traps were detected in a thrombus and plasma of baboons subjected to deep vein thrombosis, an example of inflammation-enhanced thrombosis. Our observations indicate that NETs are a previously unrecognized link between inflammation and thrombosis and may further explain the epidemiological association of infection with thrombosis.

What is the Optimal Duration of Treatment for DVT? An Update on Evidence-based Medicine of Treatment for DVT

Seminars in Vascular Surgery. Sep, 2010  |  Pubmed ID: 20826296

Venous thromboembolism, including deep venous thrombosis (DVT) and pulmonary embolism, represent a major source of morbidity and mortality today. Incidence of DVT is estimated to be 56 to 160/100,000 population per year. Systemic anticoagulation with low molecular weight heparin or unfractionated heparin with initiation of oral vitamin K antagonist therapy has been shown to be beneficial in preventing pulmonary embolism and reducing extension and recurrence of DVT. The duration of anticoagulation following an episode of DVT is determined by the greatest predictors of recurrence. These include the presence of reversible risk factors, nonreversible risk factors, and no risk factors (idiopathic or unprovoked DVT). Short durations of anticoagulation are only appropriate for calf DVTs in patients with reversible risk factors. Patients with nonreversible risk factors, such as malignancy and certain inherited thrombophilias with a strong family history of venous thromboembolism will require lifelong anticoagulation. Those with proximal DVT due to reversible risk factors require 3 to 6 months of anticoagulation. Patients with idiopathic DVT require reassessment of risk-to-benefit ratio of hemorrhage from oral vitamin K antagonist therapy compared to reducing risk of recurrence and frequently require prolonged oral anticoagulant therapy. Monitoring with d-dimer and serial ultrasounds may offer an individualized approach to therapy.

Reducing Venous Stasis Ulcers by Fifty Percent in 10 Years: the Next Steps

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Nov, 2010  |  Pubmed ID: 20719467

Anticoagulant Treatment for Superficial Venous Thrombosis

Disease-a-month : DM. Oct, 2010  |  Pubmed ID: 20971328

The Sixth Pacific Vascular Symposium: the Venous Ulcer Summit

Arteriosclerosis, Thrombosis, and Vascular Biology. Dec, 2010  |  Pubmed ID: 21084704

Urokinase Plasminogen Activator Independent Early Experimental Thrombus Resolution: MMP2 As an Alternative Mechanism

Thrombosis and Haemostasis. Dec, 2010  |  Pubmed ID: 20886179

Deep-vein thrombosis (DVT) resolution is thought to be primarily a urokinase plasminogen activator (uPA) -dependent mechanism, although observations suggest other non-fibrinolytic mechanisms may exist. We explored the role of matrix metalloproteinase (MMP) -2 and -9 in early DVT resolution in uPA-deficient mice. Male B6/SVEV (WT) and genetically matched uPA -/- mice underwent inferior vena cava (IVC) ligation to create stasis venous thrombi, with IVC and thrombus harvest. Thrombus size was similar between WT and uPA -/- mice at day 4, suggesting early non uPA-dependent resolution. Intrathrombus neutrophils and monocytes were reduced 3- and 3.5-fold in uPA -/- mice as compared with WT. By ELISA, tumour necrosis factor α and interleukin 1β were not altered, while interferon (IFN)γ was significantly elevated in uPA -/- mice. A compensatory increase in thrombus tPA was not observed, plasmin activity was reduced and PAI-1 was elevated 2.5-fold in uPA -/- mice. Active MMP2, but not MMP9, was elevated 3-fold in uPA -/- mice as compared with WT as well as MMP-14, an MMP2 activator. Collagen type IV and fibrinogen were reduced in uPA -/- mice thrombi as compared with WT. IFNγ induces MMP2, and blockade of IFNγ was associated with larger venous thrombi and reduced active MMP2, as compared with WT. Consistently, MMP2 -/- mice had larger VT as compared with WT controls, despite normal thrombus plasmin levels. Taken together, early experimental venous thrombus resolution is independent of uPA, and, in part, inflammatory cell influx. MMP2-dependent thrombolysis is an important compensatory mechanism of venous thrombus resolution, possibly by collagen type IV metabolism, and may represent an exploitable therapeutic avenue.

Von Willebrand Factor-mediated Platelet Adhesion is Critical for Deep Vein Thrombosis in Mouse Models

Blood. Jan, 2011  |  Pubmed ID: 20959603

Deep vein thrombosis (DVT) and its complication, pulmonary embolism, are frequent causes of disability and mortality. Although blood flow disturbance is considered an important triggering factor, the mechanism of DVT initiation remains elusive. Here we show that 48-hour flow restriction in the inferior vena cava (IVC) results in the development of thrombi structurally similar to human deep vein thrombi. von Willebrand factor (VWF)-deficient mice were protected from thrombosis induced by complete (stasis) or partial (stenosis) flow restriction in the IVC. Mice with half normal VWF levels were also protected in the stenosis model. Besides promoting platelet adhesion, VWF carries Factor VIII. Repeated infusions of recombinant Factor VIII did not rescue thrombosis in VWF(-/-) mice, indicating that impaired coagulation was not the primary reason for the absence of DVT in VWF(-/-) mice. Infusion of GPG-290, a mutant glycoprotein Ibα-immunoglobulin chimera that specifically inhibits interaction of the VWF A1 domain with platelets, prevented thrombosis in wild-type mice. Intravital microscopy showed that platelet and leukocyte recruitment in the early stages of DVT was dramatically higher in wild-type than in VWF(-/-) IVC. Our results demonstrate a pathogenetic role for VWF-platelet interaction in flow disturbance-induced venous thrombosis.

The Care of Patients with Varicose Veins and Associated Chronic Venous Diseases: Clinical Practice Guidelines of the Society for Vascular Surgery and the American Venous Forum

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. May, 2011  |  Pubmed ID: 21536172

The Society for Vascular Surgery (SVS) and the American Venous Forum (AVF) have developed clinical practice guidelines for the care of patients with varicose veins of the lower limbs and pelvis. The document also includes recommendations on the management of superficial and perforating vein incompetence in patients with associated, more advanced chronic venous diseases (CVDs), including edema, skin changes, or venous ulcers. Recommendations of the Venous Guideline Committee are based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system as strong (GRADE 1) if the benefits clearly outweigh the risks, burden, and costs. The suggestions are weak (GRADE 2) if the benefits are closely balanced with risks and burden. The level of available evidence to support the evaluation or treatment can be of high (A), medium (B), or low or very low (C) quality. The key recommendations of these guidelines are: We recommend that in patients with varicose veins or more severe CVD, a complete history and detailed physical examination are complemented by duplex ultrasound scanning of the deep and superficial veins (GRADE 1A). We recommend that the CEAP classification is used for patients with CVD (GRADE 1A) and that the revised Venous Clinical Severity Score is used to assess treatment outcome (GRADE 1B). We suggest compression therapy for patients with symptomatic varicose veins (GRADE 2C) but recommend against compression therapy as the primary treatment if the patient is a candidate for saphenous vein ablation (GRADE 1B). We recommend compression therapy as the primary treatment to aid healing of venous ulceration (GRADE 1B). To decrease the recurrence of venous ulcers, we recommend ablation of the incompetent superficial veins in addition to compression therapy (GRADE 1A). For treatment of the incompetent great saphenous vein (GSV), we recommend endovenous thermal ablation (radiofrequency or laser) rather than high ligation and inversion stripping of the saphenous vein to the level of the knee (GRADE 1B). We recommend phlebectomy or sclerotherapy to treat varicose tributaries (GRADE 1B) and suggest foam sclerotherapy as an option for the treatment of the incompetent saphenous vein (GRADE 2C). We recommend against selective treatment of perforating vein incompetence in patients with simple varicose veins (CEAP class C(2); GRADE 1B), but we suggest treatment of pathologic perforating veins (outward flow duration ≥500 ms, vein diameter ≥3.5 mm) located underneath healed or active ulcers (CEAP class C(5)-C(6); GRADE 2B). We suggest treatment of pelvic congestion syndrome and pelvic varices with coil embolization, plugs, or transcatheter sclerotherapy, used alone or together (GRADE 2B).

Longevity and Outcomes of Axillary Valve Transplantation for Severe Lower Extremity Chronic Venous Insufficiency

Annals of Vascular Surgery. May, 2011  |  Pubmed ID: 21549918

To assess the efficacy of axillary vein transplantation in the treatment of severe chronic venous insufficiency (CVI).

Commentary on "Venous Trauma: New Lessons and Old Debates"

Perspectives in Vascular Surgery and Endovascular Therapy. Jun, 2011  |  Pubmed ID: 21810806

Impaired Fibrinolytic System in ApoE Gene-deleted Mice with Hyperlipidemia Augments Deep Vein Thrombosis

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Nov, 2011  |  Pubmed ID: 22119245

BACKGROUND: Hyperlipidemia increases the level of blood plasminogen activator inhibitor-1 (PAI-1) that is responsible for regulating fibrinolysis by inhibiting both urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA). While this fibrinolytic pathway is well known, the role of PAI-1 in venous thrombosis (VT) under hyperlipidemic conditions has not been fully established. We sought to determine the effects of PAI-1 in an in vivo hyperlipidemic model of VT. METHODS: C57BL/6 wild-type (WT) mice, apolipoprotein E gene-deleted mice (ApoE-/-) having hyperlipidemia, and PAI-1 gene-deleted (PAI-1-/-) mice were used in this study. Inferior vena cava (IVC) ligation below the level of the renal veins was performed to create a stasis VT. Endpoints included measuring acute thrombosis (day 2) and chronic thrombosis (days 6 and 14). At euthanasia, blood samples were collected for plasmin and PAI-1 activity. In addition, the IVC and its thrombus were evaluated for thrombus weight (TW), u-PA activity, and differential leukocyte count while the vein wall only was analyzed for monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase (MMP) 2, and MMP-9. RESULTS: Compared to WT at day 2, ApoE-/-mice demonstrated a statistically significant 14% increase in TW (P < .05) and a significant 41% increase in circulating PAI-1 activity (P < .05), while showing a trend of decreased plasmin activity. In addition, TW in ApoE-/-mice was 45% higher than PAI-1-/-mice at day 2 (P < .05), 33% at day 6 (P < .01), and 41% at day 14 (P < .01). ApoE-/-mice exhibited undetectable levels of u-PA in both vein wall and thrombus, compared to WT, at all time points. Also, vein wall MMP-2 was significantly decreased by 64% at day 6 (P < .01) and 58% at day 14 (P < .05). MMP-9 was significantly decreased by 71% at day 2 (P < .01) and 48% at day 6 (P < .01), in ApoE-/-mice compared to WT mice. In addition, in ApoE-/-mice, MCP-1 was significantly decreased by 38% at day 2 (P < .01) and 67% at day 6 (P < .01) vs WT mice. As expected in ApoE mice, following a decrease in MCP-1, monocyte recruitment was significantly decreased at days 6 (P < .01) and 14 (P < .05). CONCLUSIONS: A significant increase of circulating PAI-1 levels in hyperlipidemic mice correlated with an early increase in TW due to impaired fibrinolysis. The undetectable levels of u-PA in ApoE-/-mice correlated to a decrease in vein wall MMP-2, MMP-9, MCP-1, and a decrease in monocyte recruitment diminishing thrombus resolution.

Myeloid Cell Tissue Factor Does Not Contribute to Venous Thrombogenesis in an Electrolytic Injury Model

Thrombosis Research. Dec, 2011  |  Pubmed ID: 22192154

INTRODUCTION: Tissue factor (TF) is a potent initiator of the extrinsic coagulation cascade. The role and source of TF in venous thrombotic disease is not clearly defined. Our study objective was to identify the contribution of myeloid cell TF to venous thrombogenesis in mice. MATERIALS AND METHODS: The mouse electrolytic inferior vena cava model was used to induce thrombosis. The following groups of mice were used (1) TF(flox/flox)LysMCre(+) mice that have reduced TF expression in myeloid cells, (2) TF(flox/flox)LysMCre(-) littermate controls, (3) Wild type mice given a monoclonal anti-mouse TF antibody (1H1) to inhibit TF activity, and (4) Wild type mice given rat IgG. Evaluations at baseline, day 2, and day 6 post thrombosis included thrombus weight, vein wall inflammatory cell migration, vein wall TF mRNA, and plasma D-dimer levels. RESULTS: Inhibition of TF significantly decreased thrombus weight 2days post venous thrombosis. In contrast, TF(flox/flox)LysMCre(+) had no change in thrombus weight when compared to littermate controls. The absence of myeloid cell TF did not affect infiltration of neutrophils or monocytes into the vein wall. TF mRNA expression in the vein wall decreased at 2days but then returned to baseline levels by 6days post thrombosis. D-dimer levels peaked at 2days post thrombosis in mice with or without myeloid cell TF. CONCLUSIONS: TF is important in the formation of venous thrombi in the macrovasculature. However, TF expression by myeloid cells does not significantly contribute to venous thrombogenesis in this model.

Toll-like Receptor 9 Signaling is Critical for Early Experimental Deep Vein Thrombosis Resolution

Arteriosclerosis, Thrombosis, and Vascular Biology. Jan, 2011  |  Pubmed ID: 20966396

Toll-like receptors (TLR) bridge innate immunity and host responses, including inflammation. Sterile inflammation such as a venous thrombus (Vt) may involve TLR signaling, including TLR9.

Postthrombotic Vein Wall Remodeling: Preliminary Observations

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Jan, 2011  |  Pubmed ID: 20869834

Postthrombotic syndrome is characterized by a fibrotic vein injury following deep vein thrombosis (DVT). We sought to quantify the change in vein wall thickness in patients who fail to resolve DVT by 6 months and whether there were differences in blood or plasma levels of inflammatory proteins associated with venous remodeling.

Interleukin-6: a Potential Target for Post-thrombotic Syndrome

Annals of Vascular Surgery. Feb, 2011  |  Pubmed ID: 21131172

Deep vein thrombosis (DVT) and its associated sequelae, post-thrombotic syndrome (PTS), are significant health care problems in the United States. It is estimated that a maximum of 60% of patients diagnosed with DVT develop PTS, which is characterized by extensive perivenous and mural fibrosis. Interleukin-6 (IL-6) has been linked to fibrosis, and high circulating plasma levels have been found to increase the risk of developing DVT. The aim of this study was to elucidate the role of IL-6 in the progression of vein wall fibrosis by using a mouse model of DVT.

Evaluation of Soluble P-selectin As a Marker for the Diagnosis of Deep Venous Thrombosis

Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. Aug, 2011  |  Pubmed ID: 21593019

The combination of D-dimer and Wells score can exclude, but not confirm, the diagnosis of deep venous thrombosis (DVT). Since thrombosis and inflammation are interrelated, we evaluated the combination of soluble P-selectin (sPsel) with other inflammatory biomarkers for the diagnosis of DVT.

The Effect of Abdominal Wall Plication on Intra-abdominal Pressure and Lower Extremity Venous Flow: A Case Report

Journal of Plastic, Reconstructive & Aesthetic Surgery : JPRAS. Mar, 2012  |  Pubmed ID: 21855437

Abdominal wall plication is known to cause increased intra-abdominal pressure (IAP). Whether plication-associated increased IAP causes lower extremity venous stasis, a recognized risk factor for DVT, remains unknown. A 55-year-old woman had a unilateral pedicled TRAM procedure for mastectomy reconstruction. Prior to plication, duplex ultrasound measured proximal femoral vein (PFV) cross-sectional diameter and volume-flow. PFV measurements were repeated immediately after plication and on post-operative days (POD) 1, 2, and 4. Bladder pressure was measured at similar timepoints. PFV volume-flow decreased from 0.22 L/min to 0.16 L/min (73% of baseline) immediately post-plication and reached a nadir of 0.08 L/min (36% of baseline) on POD 2. Bladder pressure increased from 13 mm Hg to 19 mm Hg after plication, and peaked at 31 mm Hg after intra-operative trunk flexion to 30°. Thus, abdominal wall plication was associated with increased intra-abdominal pressure and ultrasound-documented lower extremity venous stasis that persisted for 48 h after surgery.

Inflammation and Thrombosis: New Insights

Frontiers in Bioscience (Scholar Edition). 2012  |  Pubmed ID: 22202081

Vessel wall endothelial damage initiates a local inflammatory response, which promotes a prothrombotic state driven by tissue factor, adhesion molecules, and pro-inflammatory cytokines. Understanding how natural inflammatory mechanisms promote a procoagulant state, may lead to the development of new pharmacological interventions targeted at thrombosis.

Statins, Inflammation and Deep Vein Thrombosis: a Systematic Review

Journal of Thrombosis and Thrombolysis. Jan, 2012  |  Pubmed ID: 22278047

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism. The 2009 JUPITER trial showed a significant decrease in DVT in non-hyperlipidemic patients, with elevated C-reactive protein (CRP) levels, treated with rosuvastatin. The effects of statins on thrombosis are unclear, prompting this literature review. A literature search was performed (1950 to February 2011) with MEDLINE, EMBASE, and PUBMED databases including the following keywords: "statins", "hydroxymethylglutaryl-CoA reductase inhibitors", "VTE", "PE", "DVT", and either "anti-coagulation" or "inflammation". Editorials, reviews, case reports, meta-analysis and duplicates were excluded. Inflammatory biomarkers of DVT, include interleukin (IL)-6, CRP, IL-8, and monocyte chemotactic protein 1 (MCP-1). Statin therapy reduces IL-6 expression of CRP and MCP-1, usually elevated in VTE. Reduction of IL-6 induced MCP-1 has been linked to vein wall fibrosis, promoting post thrombotic syndrome (PTS) and recurrent DVT in patients. Also, our review suggests that the anti-thrombotic effects are likely exhibited through the anti-inflammatory properties of statins. This work supports that statin therapy has the ability to decrease the incidence and recurrence of VTE and the potential to decrease PTS. This is mainly due to the anti-inflammatory effects of statins and may explain why normolipidemic patients, with elevated CRP, appear to have the greatest reduction in VTE. Given their low risk of bleeding, statins have the potential to serve as a safe adjunctive pharmacological therapy to current treatments in select patients with VTE, however further investigations into this concept are needed and essential.

Increased PAI-1 in Females Compared to Males is Protective for Abdominal Aortic Aneurysm Formation in a Rodent Model

American Journal of Physiology. Heart and Circulatory Physiology. Feb, 2012  |  Pubmed ID: 22307671

The serine proteases, along with their inhibitor plasmin activator inhibitor-1 (PAI-1), have been shown to play a role in abdominal aortic aneurysm (AAA) formation. The aim of this study is to determine if PAI-1 may be a protective factor for AAA formation and partially responsible for the gender difference observed in AAAs. Male and female wild type (WT) C57BL/6 and PAI-1 -/- mice, 8-12 weeks of age underwent aortic perfusion with porcine pancreatic elastase. Animals were harvested 14 days following perfusion and analyzed for phenotype, Western blot, and matrix metalloproteinase (MMP) 9 and 2 activity. WT males had an average increase in aortic diameter of 80%, while females only increased 32% (p<0.001). PAI-1 -/- males increased 204% and females 161%, significantly more than their WT counterparts (p<0.001). Western blot revealed 61% higher PAI-1 protein levels in the WT females compared to the WT males (p=0.01). Zymography revealed higher levels of pro MMP2 and active MMP2 in the PAI-1 -/- males and females compared to their WT counterparts. PAI-1 -/- females had significantly higher serum plasmin levels compared to WT females (p=0.003). In conclusion, WT female mice are protected from aneurysm formation and have higher levels of PAI-1 compared to males during experimental aneurysm formation. Additionally both male and female PAI-1 -/- animals develop significantly larger aneurysms than WT animals, correlating with higher pro and active MMP 2 levels. These findings suggest that PAI-1 is protective for aneurysm formation in the elastase model of AAA and plays a role in the gender differences seen in AAA formation.