Summary. Background/objectives: We prospectively measured change in quality of life (QOL) during the 2 years after a diagnosis of deep vein thrombosis (DVT) and evaluated determinants of QOL, including development of the postthrombotic syndrome (PTS). Patients/methods: Consecutive patients with acute DVT were recruited from 2001 to 2004 at eight hospitals in Canada. At study visits at baseline, and 1, 4, 8, 12 and 24 months, clinical data were collected, standardized PTS assessments were performed, and QOL questionnaires were self-completed. Generic QOL was measured using the Short-Form Health Survey-36 (SF-36) questionnaire. Venous disease-specific QOL was measured using the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL/ Sym questionnaire. The change in QOL scores over a 2-year follow-up was assessed. The influence of PTS and other characteristics on QOL at 2 years was evaluated using multivariable regression analyses. Results: Among the 387 patients recruited, the average age was 56 years, two-thirds were outpatients, and 60% had proximal DVT. The cumulative incidence of PTS was 47%. On average, QOL scores improved during follow-up. However, patients who developed PTS had lower scores at all visits and significantly less improvement in QOL over time (P-values for PTS*time interaction were 0.001, 0.012, 0.014 and 0.006 for PCS, MCS, VEINES-QOL and VEINES-Sym). Multivariable regression analyses showed that PTS (P < 0.0001), age (P = 0.0009), proximal DVT (P = 0.01) and inpatient status (P = 0.04) independently predicted 2-year SF-36 PCS scores. PTS alone independently predicted 2-year VEINES-QOL (P < 0.0001) and VEINESSym (P < 0.0001) scores. Conclusions: Development of PTS is the principal determinant of health-related QOL 2 years after DVT. Our study provides prognostic information on patientreported outcomes after DVT and emphasizes the need for effective prevention and treatment of the PTS.

SummaryThe post-thrombotic syndrome (PTS) occurs frequently after deep venous thrombosis (DVT) despite appropriate anticoagulant therapy. A close relationship between inflammation and thrombosis exists. While the inflammatory process at the time of DVT appears to improve thrombus resolution, it may promote destruction of venous valves, valvular reflux and subsequent development of PTS. We prospectively evaluated the association between levels of four cytokines (IL-6, IL-8, IL-10 and MCP-1), two adhesion molecules (ICAM-1 and VCAM-1) and the development of PTS in a well-defined cohort of patients with DVT. The study population consisted of 387 patients with objectively diagnosed symptomatic DVT who were followed for two years to determine the incidence of PTS. At the end of follow-up, plasma samples frozen at the four-month visit in 307 study patients were thawed and analyzed for the above inflammatory markers using the Luminex beads technology. Mean levels of IL-6 were significantly higher in patients with PTS compared to patients without PTS (7.35 pg/ml ± 14.26 [SD] vs. 4.60 pg/ml ± 4.90;p=0.03). Logistic regression analyses showed significant associations between PTS and levels above vs. below the median of IL-6 [odds ratio (OR) 1.66; 95% confidence interval (CI) 1.05, 2.62 (p=0.03)] and ICAM-1 [OR 1.63; 95% CI 1.03, 2.58 (p=0.04)]. None of the other markers showed any association with PTS. Our study suggests the presence of significant associations between markers of inflammation such as IL-6 and ICAM-1 and the development of PTS. Further work is needed to evaluate this relationship and to analyse other candidate markers that could be implicated etiologically in the association between DVT and PTS. If confirmed, this could lead to identification of new therapeutic targets for preventing PTS after DVT.

Background: The post-thrombotic syndrome (PTS) occurs frequently after deep vein thrombosis (DVT) despite appropriate anticoagulant therapy. A close relationship between inflammation and thrombosis exists. While the inflammatory process at the time of DVT appears to improve thrombus resolution, it may promote destruction of venous valves, valvular reflux and subsequent development of PTS. Objective: We prospectively evaluated the association between levels of four cytokines (IL-6, IL-8, IL-10 and MCP-1), two adhesion molecules (ICAM-1 and VCAM-1) and the development of PTS in a well-defined cohort of patients with DVT. Methods: The study population consisted of 387 patients with objectively diagnosed symptomatic DVT who participated in the Venous Thrombosis Outcomes (VETO) Study and were followed for two years to determine the incidence of PTS. For this substudy, plasma samples frozen at the 4 month visit in 307 study patients who consented to provide blood samples were thawed and analyzed for the above inflammatory markers using the Luminex beads technology. Associations between marker levels and development of the PTS during follow-up were evaluated. Results: Mean levels of IL-6 were significantly higher in patients with PTS compared to patients without PTS (7.35 pg/ml ± 14.26 vs. 4.60 pg/ml ± 4.90;p=0.03). Logistic regression analyses showed significant associations between PTS and levels above vs. below the median of IL-6 (OR 1.66; 95% CI 1.05, 2.62 (p=0.03)) and ICAM-1 (OR 1.63; 95% CI 1.03, 2.58 (p=0.04)). None of the other markers showed any association with PTS. Conclusion: Our study suggests the presence of significant associations between markers of inflammation such as IL-6 and ICAM-1 and the development of PTS. Further work is needed to evaluate this relationship and to analyze other candidate markers that could be implicated etiologically in the association between DVT and PTS. If confirmed, this could lead to identification of new therapeutic targets for preventing PTS after DVT.

BackgroundPost thrombotic syndrome (PTS) is a burdensome and costly complication of deep venous thrombosis (DVT) that develops in 20–40% of patients within 1–2 years after symptomatic DVT. Affected patients have chronic leg pain and swelling and may develop ulcers. Venous valve disruption from the thrombus itself or thrombus-associated mediators of inflammation is considered to be a key initiating event for the development of venous hypertension that often underlies PTS. As existing treatments for PTS are extremely limited, strategies that focus on preventing the development of PTS in patients with DVT are more likely to be effective and cost-effective in reducing its burden. Elastic compression stockings (ECS) could be helpful in preventing PTS; however, data on their effectiveness are scarce and conflicting.Methods/DesignThe SOX Trial is a randomized, allocation concealed, double-blind multicenter clinical trial. The objective of the study is to evaluate ECS to prevent PTS. A total of 800 patients with proximal DVT will be randomized to one of 2 treatment groups: ECS or placebo (inactive) stockings worn on the DVT-affected leg daily for 2 years. The primary outcome is the incidence of PTS during follow-up. Secondary outcomes are severity of PTS, venous thromboembolism (VTE) recurrence, death from VTE, quality of life and cost-effectiveness. Outcomes will be evaluated during 6 clinic visits and 2 telephone follow ups. At baseline, 1 and 6 months, blood samples will be obtained to evaluate the role of inflammatory mediators and genetic markers of thrombophilia in the development of PTS (Bio-SOX substudy).DiscussionThe SOX Trial will be the largest study and the first with a placebo control to evaluate the effectiveness of ECS to prevent PTS. It is designed to provide definitive data on the effects of ECS on the occurrence and severity of PTS, as well as DVT recurrence, cost-effectiveness and quality of life. This study will also prospectively evaluate the predictive role of biomarkers that are reflective of putative underlying pathophysiological mechanisms in the development of clinical PTS. As such, our results will impact directly on the care of patients with DVT.Trial RegistrationNCT00143598 and ISRCTN71334751

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SummaryBeta thalassemia is an autosomal recessive disorder characterized by reduced (β + ) or absent (β 0 ) beta-globin chain synthesis. In Lebanon it is the most predominant genetic defect. In this study we investigated the religious and geographic distribution of the β-thalassemia mutations identified in Lebanon, and traced their precise origins. A total of 520 β-globin chromosomes from patients of different religious and regional backgrounds was studied. Beta thalassemia mutations were identified using Amplification Refractory Mutation System (ARMS) PCR or direct gene sequencing.Six (IVS-I-110, IVS-I-1, IVS-I-6, IVS-II-1, cd 5 and the C>T substitution at cd 29) out of 20 β-globin defects identified accounted for more than 86% of the total β-thalassemia chromosomes. Sunni Muslims had the highest β-thalassemia carrier rate and presented the greatest heterogeneity, with 16 different mutations. Shiite Muslims followed closely with 13 mutations, whereas Maronites represented 11.9% of all β-thalassemic subjects and carried 7 different mutations. RFLP haplotype analysis showed that the observed genetic diversity originated from both new mutational events and gene flow from population migration. This study provides information about the types and distribution of β-thalassemia mutations within each religious group and geographic region, which is essential for the implementation of screening and prevention programs.

Sickle cell disease (SCD) is an inherited autosomal recessive disorder of the beta-globin chain. Despite the fact that all subjects with SCD have the same single base pair mutation, the severity of the clinical and hematological manifestations is extremely variable. This study examined for the first time in Lebanon the correlation between the clinical manifestation of SCD and the beta-globin gene haplotypes. The haplotypes of 50 patients diagnosed with SCD were determined using polymerase chain reaction amplification of fragments containing nine polymorphic restriction sites around and within the epsilon-Ggamma-Agamma-psibeta-delta-beta-globin gene complex. Most reported haplotypes were found in our population with the Benin haplotype as the most prevalent one. When the patients were divided according to their HbF levels into three groups (Group A: HbF < 5%, Group B: HbF between 5 and 15%, and Group C: HbF > 15%), surprisingly, the highest levels of HbF were associated with the most severe clinical cases. Our findings suggest that fetal hemoglobin levels are important but not the only parameters that affect the severity of the disease. In addition, the high levels of HbF in patients with CAR haplotypes did not seem to ameliorate the severity of symptoms, suggesting that genetic factors other than haplotypes are the major determinants of increased HbF levels in Lebanon.

Ta ble 1: Patients' hematologic profile according to transfusion regimen