Association of Thrombophilia and Inflammation with Post-Thrombotic Syndrome

Summary

Principal Investigator: M Cushman
Abstract: Deep vein thrombosis (DVT) or pulmonary embolus affect 1-3 per 1000 yearly of the adult population, or nearly 200,000 per year, with an incidence that rises exponentially with age. The burden of venous thrombosis predominantly involves DVT, which is complicated by post-thrombotic syndrome (PTS) in 20- 50% of cases. PTS has a spectrum from mild edema to disabling symptomatic disease with trophic skin changes, chronic pain, and venous skin ulceration. While PTS is thought to occur as a result of damage to the venous valves with resultant reflux or chronic venous obstruction limiting outflow, additional etiologic determinants of PTS have not been extensively studied. We propose a population-based study to evaluate the molecular determinants of chronic peripheral venous disease (CPVD) in a multi-ethnic general population sample, the San Diego Population Study (SDPS). Participants had detailed physical examination and duplex leg ultrasound to establish presence of CPVD based on anatomic and clinical findings. We will address the following hypotheses: 1.Among those with hereditary disorders associated with the hypercoagulable state ("hereditary thrombophilia") there will be an increased risk of deep functional venous disease (DFD) assessed by duplex ultrasound and of superficial venous functional disease (SFD) when it occurs in the absence of DFD and together with clinical features of PTS. 2. There will be an increased risk of DFD or SFD with features of PTS, among participants with higher levels of biomarkers reflecting different aspects inflammation. 3. Given the association of obesity with the risk of CPVD and PTS, there will be an increased risk of DFD or SFD with features of PTS in association with higher levels of biomarkers reflecting adipocyte products. To test these hypotheses phenotypic and genetic molecular biomarkers will be measured in stored biological specimens of the SDPS participants including 370 control participants and 370 cases of CPVD, focusing on post-thrombotic syndrome. Findings will allow hypotheses to be formed concerning etiologic factors in the development of PTS after clinically diagnosed or clinically silent DVT. PTS and CPVD affect -2.5 million people in the United States; 20% develop severe disease with venous ulcers. Resultant disability is estimated at 2 million lost workdays/year and medical costs as $300 million yearly. Findings here can form the basis for development of new therapies to treat, and moreover prevent,PTS.
Funding Period: 2006-05-12 - 2010-03-31
more information: NIH RePORT

Top Publications

  1. pmc Chronic kidney disease and venous thromboembolism: epidemiology and mechanisms
    Keattiyoat Wattanakit
    Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Curr Opin Pulm Med 15:408-12. 2009
  2. pmc Risk factors for peripheral venous disease resemble those for venous thrombosis: the San Diego Population Study
    M Cushman
    Department of Medicine, University of Vermont, Burlington, VT, USA
    J Thromb Haemost 8:1730-5. 2010
  3. pmc Adipokines are associated with lower extremity venous disease: the San Diego population study
    M A Allison
    Department of Family and Preventive Medicine, University of California, San Diego, CA, USA
    J Thromb Haemost 8:1912-8. 2010
  4. pmc Higher soluble P-selectin is associated with chronic venous insufficiency: the San Diego Population Study
    Locke J Bryan
    University of Vermont, Department of Medicine, Colchester, VT 05446, USA
    Thromb Res 130:716-9. 2012
  5. ncbi Efficacy of a short course of complex lymphedema therapy or graduated compression stocking therapy in the treatment of post-thrombotic syndrome
    Chris E Holmes
    Department of Medicine, University of Vermont, Burlington, VT, USA
    Vasc Med 19:42-8. 2014

Detail Information

Publications5

  1. pmc Chronic kidney disease and venous thromboembolism: epidemiology and mechanisms
    Keattiyoat Wattanakit
    Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Curr Opin Pulm Med 15:408-12. 2009
    ..An estimated 13% of Americans have kidney disease. We sought to describe the association of kidney disease with risk of venous thromboembolism and discuss possible mechanisms explaining this association...
  2. pmc Risk factors for peripheral venous disease resemble those for venous thrombosis: the San Diego Population Study
    M Cushman
    Department of Medicine, University of Vermont, Burlington, VT, USA
    J Thromb Haemost 8:1730-5. 2010
    ..Clinically silent deep vein thrombosis (DVT) is common and may cause chronic venous disease that resembles post-thrombotic syndrome...
  3. pmc Adipokines are associated with lower extremity venous disease: the San Diego population study
    M A Allison
    Department of Family and Preventive Medicine, University of California, San Diego, CA, USA
    J Thromb Haemost 8:1912-8. 2010
    ..Obesity is a risk factor for venous disease. We tested the associations between adipokines and the presence and severity of venous disease...
  4. pmc Higher soluble P-selectin is associated with chronic venous insufficiency: the San Diego Population Study
    Locke J Bryan
    University of Vermont, Department of Medicine, Colchester, VT 05446, USA
    Thromb Res 130:716-9. 2012
    ..P-selectin is a cell adhesion molecule shown to play a role in venous thromboembolism. We evaluated whether higher P-selectin is associated with chronic venous insufficiency (CVI)...
  5. ncbi Efficacy of a short course of complex lymphedema therapy or graduated compression stocking therapy in the treatment of post-thrombotic syndrome
    Chris E Holmes
    Department of Medicine, University of Vermont, Burlington, VT, USA
    Vasc Med 19:42-8. 2014
    ..ClinicalTrials.gov Identifier: NCT00633971. ..