cerebral Venous sinus thrombosis

Objectives: 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). Methods: Male mice (Mus musculus, n659), 20 to 25 grams, underwent IVC ligation to induce thrombosis. Groups consisted of wild type (WT) C57BL/6 controls, mice with high circulating levels of soluble P-selectin (^CT), P-selectin gene-interrupted knockout mice (PKO), and E-and P-selectin gene-interrupted mice (EPKO). Additional groups were used to evaluate the ability of a P-sel antagonist (rPSGL-Ig) and an antibody directed against PSGL-1 to downregulate the effects of P-sel in^CT mice and WT mice administered soluble P-sel at time of thrombosis. Animals were sacrificed on days 2 and 6 after IVC ligation. Thrombus mass (TM), vein wall morphometrics, and serum leukocyte/platelet microparticles (MPs) were evaluated by means of double-stained fluorescence-activated cell scanning analysis, and soluble P-and E-sel protein determination by ELISA. Results: At days 2 and 6 in phase I of the experiment, significant differences (P < .01) in TM were noted between groups, with^CT animals having the largest thrombi (50% and 57% increase in TM compared to WT at days 2 and 6) while EPKO mice had the smallest thrombi. Statistically, greater levels of neutrophils and total inflammatory cells were noted in the vein walls of^CT animals at day 2 compared with WT and PKO animals. A significant difference was noted between^CT and EPKO for neutrophils, monocytes, and total inflammatory cells, also at day 2. At day 6, the only statistically significant difference was found for monocytes, with a higher number in the^CT animals than in WT animals. The evaluation of MPs revealed that the^CT mice had a mixed leukocyte (MAC-1) and platelet (CD41) MP population that was also present in WT and PKO mice on day 2 and day 6. EPKO mice revealed a primarily platelet-derived MP population. Of interest, the^CT mice with the highest TM showed a high amount of mean channel fluorescence for MAC-1 (phycoerythrin) antibody, indicative of leukocyte MPs.^CT mice revealed statistically higher levels of soluble P-selectin at days 2 and 6. In phase 2, an antibody directed against PSGL-1 was more effective than rPSGL-Ig in decreasing TM and limiting leukocyte-derived MP fluorescence. Conclusions: This study demonstrates that high circulating levels of P-selectin are associated with increased thrombosis, whereas a lack of P-selectin and E-selectin is associated with a lessening of thrombosis. Additionally, leukocyte MPs are associated with venous thrombus formation. These data suggest the importance of selectins to venous thrombogenesis and show that P-selectin and leukocyte-derived MPs should be good targets to limit venous thrombus formation. (J Vasc Surg 2003;38:1075-89.)

Peripherally inserted central catheters (PICC) are widely used to provide central venous access, often in chronically ill patients with long-term intravenous access requirements. There are a number of significant complications related to both insertion and maintenance of PICC lines, including catheter malposition, migration, venous thrombosis, and line fracture. The incidence of these complications is likely to rise as the number of patients undergoing intravenous outpatient therapy increases, with a corresponding rise in radiologist input. This paper provides an overview of the relevant peripheral and central venous anatomy, including anatomical variations, and outlines the complications of PICC lines. Imaging examples demonstrate the range of radiological findings seen in these complications.

Summary. Background: Protein Z (PZ) serves as a cofactor for activated factor X inhibition by the PZ-dependent protease inhibitor. In vivo and in vitro studies aimed at investigating the role of PZ levels in venous thombosis have produced conflicting results. Objectives: We investigated whether reduced PZ levels and PZ gene common variants are associated deep vein thrombosis (DVT). Patients and methods: In 197 patients with DVT and in 197 age-matched and sex-matched controls, PZ plasma levels and gene polymorphisms were evaluated by means of an enzyme-linked immunosorbent assay and direct cycle sequence analysis. Results: Similar PZ levels were found in controls (1.44; SD 0.63 μg mL−1) and in patients (1.44; SD 0.96 μg mL−1). The incidence of PZ levels below the 5.0 (0.52 μg mL−1) or the 2.5 percentile of controls (0.47 μg mL−1) was higher in patients (10.2% and 8.7%, respectively) than in controls {4.1% [odds ratio (OR) 2.7, 95% confidence interval (CI) 1.2–7.3], and 2.0% (OR 4.6, 95% CI 1.5–13.9), respectively}. This relationship was independent of the effect of age, sex, and factor V Leiden and FII A20210 alleles [OR 2.8 (95% CI 1.1–7.3), and OR 4.9 (95% CI 1.4–17.3)]. PZ levels were associated with the intron C G-42A and the intron F G79A polymorphisms in cases (r2 = 0.129) and in controls (r2 = 0.140). However, frequencies of the PZ gene polymorphisms were similar in the two groups and were not associated with very low PZ levels. Conclusions: The present data suggest an association between very low PZ plasma levels and the occurrence of DVT, with PZ gene polymorphisms contributing little to this relationship.

Impaired fibrinolysis as a result of increased plasminogen activator inhibitor-1 (PAI-1) levels in plasma is a common finding in patients with deep vein thrombosis (DVT). A 4G/5G polymorphism in the promoter region of the PAI-1 gene has been reported to influence the levels of PAI-1. The 4G allele was found to be associated with higher plasma PAI-1 activity (act), but contradictory results on the incidence of the 4G allele in DVT patients have been reported. The aim of this study was to analyse whether the PAI-1 promoter 4G/5G genotype increases the risk of venous thrombosis in subjects with thrombophilic defects, and to determine the distribution of the PAI-1 4G/5G genotype and its relation to plasma PAI-1 levels in 190 unrelated patients with DVT in comparison with a control group of 152 healthy subjects. No differences between the 4G/5G allele distribution in the DVT group (0´43/0´57) and in the control group (0´42/0´58) were observed. However, the presence of the 4G allele significantly increased the risk of thrombosis in patients with other thrombophilic defects.

Deep vein thromboses (DVTs) cause significant morbidity and mortality in the general population. Oral anticoagulation therapy may reduce thrombus propagation but does not cause clot lysis and therefore does not prevent postthrombotic syndrome (PTS). Catheter-directed thrombolysis (CDT) can be used to treat DVTs as an adjunct to medical therapy, but there is no consensus defining exact indications. Current evidence suggests that CDT can reduce clot burden and DVT recurrence and consequently prevents the formation of PTS compared with systemic anticoagulation. Appropriate indications include younger individuals with acute proximal thromboses, a long life expectancy, and relatively few comorbidities. Limbthreatening thromboses may also be treated with CDT, although the subsequent mortality remains high. A number of randomized controlled trials are currently under way comparing the longer-term outcomes of CDT compared with anticoagulation alone. Initial reports suggest that venous patency and valvular function are better maintained after CDT. The effectiveness of combined pharmacomechanical thrombectomy and the role of vena cava filters need to be investigated further before strong recommendations can be made. The reported short-term outcomes following catheter-based intervention for DVT are encouraging in selected patients. Further evidence is required to establish long-term benefits and cost-effectiveness. (Arterioscler Thromb Vasc Biol. 2010;30:669-674.)

OBJECTIVES: A case of delayed popliteal artery injury (PA-INJ) onset after total knee arthroplasty (TKA) in a patient under postoperative anticoagulation therapy is reported. The role of anticoagulation both in late PA-INJ presentation and in PA-INJ management is discussed.ReportAn obese 76-year-old woman was presented with a common femoral vein thrombosis coupled with pulmonary embolism five days after TKA. She was immediately placed under anticoagulation therapy. Four days later, during physiotherapy-supervised mobilization, she developed a calf haematoma and large retro-articular pseudoaneurysm. Angiography revealed a minor PA-INJ successively treated with a covered stent-graft. CONCLUSIONS: In cases of initially undetected and staunched TKA-related PA-INJs, postoperative anticoagulation therapy may act as a potential trigger for final arterial rupture during mobilization exercises, followed by acute bleeding; in these cases, endovascular management represents an excellent treatm...

This was a prospective cohort study at Sir Ganga Ram Hospital, a large multispecialty hospital in New Delhi, India. From January 2001 to July 2004, 1,552 consecutive inpatients and outpatients who presented with clinically suspected lower limb DVT were enrolled in the study. ...

Congenital anomalies of the inferior vena cava such as absence or atresia are uncommon vascular defects and result from aberrant development during embryogenesis. We report a case of a young female patient affected by proximal deep venous thrombosis (DVT) complicated by liver and pulmonary embolism; subsequent extensive evaluation revealed the congenital absence of infrarenal inferior vena cava, with emboli probably occurring through collateral veins. Accordingly, in young patients with idiopathic DVT of the lower extremities and pelvic veins, the presence of inferior vena cava abnormalities should always be considered and investigated, together with classic coagulation factors, as a factor predisposing to thromboembolic complications.

The development of venous thromboembolism is influenced by a variety of genetic and environmental risk factors. A few studies have ascertained whether thrombophilic defects are risk factors for venous thromboembolism in Latin American populations with a variable degree of admixture, such as the Colombian population. To address this issue, we conducted a case-control study involving 100 consecutive patients with deep vein thrombosis and 114 healthy controls from the Hospital Universitario San Vicente de Paú l, Medellín, Colombia. Activated protein C resistance (APC resistance) was detected in 25/99 patients vs. 6/114 controls (OR 5 6.08, 95% CI 5 2.23-17.47). Ten of 100 patients carried the factor V Leiden mutation vs. 1/114 controls (OR 5 12.56, 95% CI 5 1.61-267). APC resistance was associated with the factor V Leiden mutation in only 10/25 patients. The prothrombin G20210A mutation was found in 4/100 patients, but none of the controls (P < 0.05). There was no significant difference in the proportion of homozygous carriers of methylenetetrahydrofolate reductase C677T variant among patients and controls. In conclusion, in our studied population, factor V Leiden, APC resistance, and prothrombin G20210A were associated with an increased risk of deep vein thrombosis. However, the frequencies of these thrombophilic defects and of APC resistance associated with factor V Leiden was lower than the corresponding frequencies previously reported for Caucasian populations. Further study is required to assess the influence of ethnicity on thrombophilia. Am. J. Hematol. 81: [933][934][935][936][937] 2006. V V C 2006 Wiley-Liss, Inc.

The aim of this study was to evaluate our experience with the retrievable Cook Celect inferior vena cava (IVC) filter (William Cook, Europe) with regard to insertion, efficiency, ease of retrieval, and any associated complications. A retrospective review was performed of 115 patients (41 female, 74 male, mean age 47.97 years) who underwent Cook Celect IVC filter insertion between December 2005 and October 2007. Filter insertion was successful in all patients. Of the 115 filters inserted, 57 have been successfully retrieved (49.6%) to date. The successful retrieval rate from attempted retrieval was 93.4%. The mean dwell time of successfully retrieved filters was 114.9 days (range 14-267 days). Failed retrievals were due to a thrombosed vena cava (n = 1) and endothelialisation of the filter (n = 3). In the failed retrieval group the mean implantation time was 142 days (range 78-211 days). While this is the first retrospective clinical study on the Cook Celect filter, results to date a...

The use of D-dimer in combination with a clinical decision rule has been widely investigated in pulmonary embolism and deep venous thrombosis. Although it has been shown to be safe in excluding venous thromboembolism, the clinician is often faced with specific situations in which the use of D-dimer is controversial. We review the best available evidence on these patients. We conclude that it is not safe to use D-dimer testing in patients with symptoms of a venous thromboembolism for over 14 days, patients receiving therapeutic heparin treatment and patients with suspected deep venous thrombosis during oral anticoagulant therapy. In these populations the levels of D-dimer can be lower then expected giving rise to false-negative results. It is safe to use D-dimer testing in combination with a clinical decision rule in patients of all ages, patients presenting with a suspected recurrent venous thromboembolism or inpatients with suspected pulmonary embolism. As patients with recurrent venous thromboembolism, elderly patients and inpatients have higher levels of D-dimer, D-dimer testing has a low specificity and the need for additional radiological testing is increased.

Livedo reticularis (LR) is a skin vasculopathy that has been frequently described in patients with anti-phospholipid syndrome (APS) and reported to be present in association with valvular heart pathology and strokes (i.e. Sneddon's syndrome).

Plasminogen activator inhibitor 1 (PAI-1) is the main inhibitor of tissue-type and urokinase-type plasminogen activator. A 4G/5G polymorphism in the promoter region of the PAI-1 gene has been reported to enhance the plasma levels of PAI-1. In particular, the 4G allele (guanosine deletion) has been linked with increased plasma PAI-1 levels, which may lead to impaired activity of the fibrinolytic system, thus increasing the incidence of thrombotic events. The aim of this case-control study was to analyze whether variants of the PAI-1 promotor genotype 4G/4G, 4G/5G and 5G/5G, in particular the 4G/5G-variant, constitute an independent risk factor of cerebral venous thrombosis (CVT). A total of 136 consecutive patients with proven CVT were compared to 1,054 DNA specimens of healthy controls from a population-based cohort. PAI-1 promotor polymorphisms were evaluated using polymerase chain reaction. No significant association of CVT with PAI-1 4G/5G was found in either the additive (OR 1.04; 95 % CI 0.78-1.38) or in the dominant model (OR 1.24; 95 % CI 0.72-2.13). Also, the prevalence of the other genotypes (4G/4G and 5G/5G) in patients was not significantly different from controls. When considering the variants of the PAI-1 promoter genotype in combination with known genetical thrombophilias, no differences were found either. As was expected, the prothrombin (G20210A) genotype was confirmed as an independent risk factor for CVT. We conclude that the 4G allele of the PAI-1 polymorphism does not increase the risk of CVT in adults.

Septic thrombophlebitis (STP) is a complex, cross-disciplinary clinical condition that combines a localized infection with a neighboring venous thrombosis. STP can occur at several possible anatomic sites, such as dural sinuses, jugular vein (Lemierre syndrome), portal vein (pylephlebitis), and pelvic veins. Its high mortality in the preantibiotic era improved considerably with the introduction of modern antibiotics. However, little evidence exists to date to guide its clinical management. The incidence of STP or its risk factors may be increasing, and its mortality may still be considerable. These trends would have far-reaching implications, especially in the setting of increasing resistance to antimicrobial agents. No clinical assessment tools exist to support patient screening or guide treatment in STP. Few interventional studies exist on the efficacy and safety of anticoagulation. Recommendations on its indications, duration, and the agents of choice are mostly based on evidence derived from small observational studies. While all forms of STP pose similar challenges, future research may benefit from the distinction between bacteria-associated, virus-associated, and mycosis-associated thrombophlebitis. Addressing these gaps in evidence would enhance our ability to diagnose this condition and treat patients effectively.

Due to the evolving field of medicine, new research may, in due course, modify the recommendations presented in this document. At the time of publication, every attempt has been made to ensure that the information provided is up to date and accurate. It is the responsibility of the treating physician to determine the best treatment for the patient. The authors, committee members, editors, and publishers cannot be held responsible for any legal issues that may arise from the citation of this statement. Rules of evidence Management of patients with chronic venous disorders has been traditionally undertaken subjectively among physicians, often resulting in less than optimal strategies. In this document, a systematic approach has been developed with recommendations based upon cumulative evidence from the literature. Levels of evidence and grades of recommendation range from Level I and Grade A to Level III and Grade C. Level I evidence and Grade A recommendations derive from scientifically sound randomized clinical trials in which the results are clear-cut. Level II evidence and Grade B recommendations derive from clinical studies in which the results among trials often point to inconsistencies. Level III evidence and Grade C recommendations result from poorly designed trials or from small case series. 1, 2 Meta-analysis Meta-analyses are included in the present document but there should be caution as to their possible abuse. Certain studies may be included in a meta-analysis carelessly without sufficiently understanding of substantive issues, ignoring relevant variables, using heterogenous findings or interpreting results with a bias. 3 It has been demonstrated that the outcomes of 12 large randomized controlled trials were not predicted accurately 35% of the time by the meta-analyses published previously on the same topics. 4 PART I PATHOPHYSIOLOGY AND INVESTIGATION Pathophysiology Changes in superficial and deep veins Varicose veins are a common manifestation of CVD and are believed to result from abnormal dis

It has been recognized, since the first description of the disease, that arterial and venous thrombosis are common in patients with homocysteinuria. Interest in the condition increased with reports from a large number of mainly retrospective studies showing that mildly elevated homocysteine levels are also associated with venous thromboembolism (VTE), thrombotic stroke, and peripheral vascular disease. This association is less strong when populations are studied prospectively. Vitamin supplementation, primarily with folic acid, and to a lesser degree with pyridoxine and vitamin B 12 , is effective in reducing elevated levels of plasma homocysteine. Surprisingly, however, recent prospective intervention studies showed that despite lowering of the homocysteine level with such treatment, there was no impact on the risk of recurrence of venous or arterial disease. Semin Hematol 44:70-76

Background: Thromboprophylaxis for deep vein thrombosis (DVT) after lower-extremity trauma could include rivaroxaban, an oral medication that does not need laboratory monitoring. Objective: To assess rivaroxaban's efficacy in preventing DVTs after pelvic trauma compared to its historical incidence. Materials and Methods: All patients admitted with pelvic fractures in a 12-month period followed a standardized thromboprophylaxis protocol: 1) rivaroxaban 10 mg/day within 24 h of injury or upon hemodynamic stability; 2) pre-operative, post-operative, and 30-day extremity ultrasound; 3) ventilation-perfusion scintigraphy for clinical signs of pulmonary embolus; and 4) a 45-, 90-, and 120-day re-evaluation. Rivaroxaban administration ceased the day of surgery and restarted 12 h postoperatively or upon hemodynamic stability, continuing for 30 days. Excluded patients had severe neurological or hepatosplenic injuries, heparin hypersensitivity, or hemodynamic instability. Results: Of 113 patients assessed, 84 patients (66 males), average age 46.6 years (range 19-69 years), were included. They had isolated pelvic trauma (n = 37), associated lower limb injuries (n = 47), average Injury Severity Score 21.4 (range 16-50), and average Glasgow Coma Scale score 13.6 (range 9-15). Patients receiving thromboprophylaxis soon after their fracture (n = 64) had a lower incidence of DVT than those receiving delayed thromboprophylaxis (n = 20) (p = 0.02). One patient (1.2%) died from a pulmonary embolus; 13 had asymptomatic below-the-knee DVTs. Rivaroxaban did not increase intra-or post-operative bleeding in surgical wounds. Conclusions: DVT incidence after pelvic fractures is reduced by administering antithrombotics within 24 h of injury or, if the patient is hemodynamically unstable, 24 h after stabilization. Rivaroxaban is a safe and effective method of providing this thromboprophylaxis. Ó 2012 Elsevier Inc.

Pacing in neonates and infants continues to be challenging due to size constraints, growth potential, and the need for life long pacing. Indications for permanent pacing in pediatric patients have been difficult to determine due to the lack of data from controlled studies and multicenter trials. Temporary pacing has been useful to restore cardiac output in pediatric patients quickly and efficiently. Methods of temporary pacing include transcutaneous, transesophageal, transvenous, and epicardial. Permanent pacemaker implantation can be accomplished by transvenous or epicardial approaches, but the use of transvenous pacing in neonates and infants offers no advantages over epicardial pacing. Transvenous pacing in infants is often prohibitive due to size and growth constraints as well as the subsequent risk of skin erosion and venous thrombosis. Smaller pulse generators, multiprogrammable features, and steroid-eluting epicardial leads are a few of the technological advances that have made pacing in neonates and infants easier and safer. Data supporting the use of pacing systems in very young patients are sparse. Pacing 'indications' should be viewed as guidelines until such data can be accumulated. ᮊ

Deep venous thrombosis (DVT) is a common complication after orthopaedic hip and knee surgery, and prophylaxis for prevention is often used. Upper extremity DVT is an extremely rare complication after shoulder surgery. Overall, there has been an increased incidence and awareness of upper extremity DVT, and this has been attributed to malignancy and the use of central venous catheters, shunts for dialysis, and transvenous pacemakers. 4 The potential complications arising from upper extremity DVT include post-thrombotic syndrome (pain, stasis pigmentation, and edema), recurrent thromboembolism, and pulmonary embolism. 2,7 In up to one third of patients with an upper extremity DVT, a symptomatic pulmonary embolism may develop, which can be fatal. 1,2,8,10 Accurate diagnosis of an upper extremity DVT requires a high index of suspicion, and early treatment may reduce the risk of thromboembolic complications.

Purpose. – The association of antiphosphatidylethanolamine antibodies (aPE) as the only antiphospholipid antibody with antiphospholipid syndrome (APS) is discussed. The aPE was described as the sole antibody in many cases suggesting APS. aPE was not included in the Sapporo criteria for the classification of APS.Methods. – We investigated the clinical features of 20 patients with aPE only; 17 patients had symptoms potentially

Neurological symptoms are rare manifestations of Behcet&#39;s disease. In this paper, we report cerebral venous thrombosis as the initial presentation of Behcet&#39;s disease in a 40 yearold man. Our patient presented with a six-week history of headache, progressive loss of vision in the right eye and recurrent oral ulcers. Physical examination revealed oral ulcers and posterior synechia in the right eye with loss of light perception. Fundoscopic examination showed evidence of retinal vasculitis. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) of the brain showed superior sagittal, left transverse, and left sigmoid sinus venous thrombosis. A diagnosis of Behcet&#39;s disease was made based on clinical criteria. Treatment with methylpredinsolone, cyclophosphamide, and azathioprine as well as anticoagulation was done with significant clinical improvement.

To present a case of acute mesenteric and portal vein thrombosis treated with thrombolytic therapy in a patient with ulcerative colitis in acute phase and to review the literature on thrombolytic therapy of mesenteric-portal system. Treatment of acute portal vein thrombosis has ranged from conservative treatment with thrombolysis and anticoagulation therapy to surgical treatment with thrombectomy and/or intestinal resection. We treated our patient with intraportal infusion of plasminogen activator and then heparin through a percutaneous transhepatic catheter. Thrombus resolved despite premature interruption of the thrombolytic treatment for neurological complications, which subsequently resolved. Conservative management with plasminogen activator, could be considered as a good treatment for patients with acute porto-mesenteric thrombosis.

Patients undergoing major orthopaedic surgery of the lower extremities are at high risk of developing venous thromboembolism (VTE). Pharmacologic thromboprophylaxis has greatly reduced the likelihood of VTE. The most effective medications are administered once or twice daily by subcutaneous injection, a drug delivery route associated with an increased risk of needlestick injury. Awareness of the potential lethality of needlestick injuries has increased during the past decade, resulting in the development of national safety guidelines from the Occupational Safety and Health Administration on the handling and management of needles and other sharps. This article reviews the potential risks and costs associated with needlestick injury during the administration of VTE prophylaxis in patients undergoing major orthopaedic surgery. The development of novel anticoagulants and accompanying devices to prevent needlestick injury is also discussed.

Background The use of venous thromboembolism prophylaxis after an Achilles rupture is controversial. The rates of reported deep vein thrombosis (DVT) range from 6.3% to 34%. There is no agreement regarding prophylactic therapy after an Achilles tendon rupture. Questions/purposes We determined the overall risk of DVT and pulmonary embolism (PE) after an Achilles tendon rupture and identified potential risk factors including surgery. Patients and Methods We retrospectively reviewed a large healthcare management organization database and identified 1172 patients who had Achilles tendon ruptures.