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Surveillance for Deep Vein Thrombosis and Pulmonary Embolism

Recommendations from a National Workshop

      Abstract

      Deep vein thrombosis (DVT) and pulmonary embolism (PE), known collectively as venous thromboembolism (VTE), affect an estimated 900,000 people in the U.S. each year, resulting in several hundred thousand hospitalizations and about 300,000 deaths. Despite this substantial public health burden, no systematic collection of VTE-related morbidity and mortality data exists in the U.S. The available information about disease prevalence and incidence consists of estimates based mainly on population-based epidemiologic studies and analysis of hospital discharge or health insurance claims databases. The limited scope of the available data has raised the question of whether a systematic surveillance system for VTE should be established.
      To help answer this question and to make recommendations for the next steps toward better surveillance of VTE, the CDC asked the American Society of Hematology (ASH) to convene a national workshop of stakeholders representing relevant federal agencies, experts in VTE epidemiology and treatment, public health experts in VTE, and patient representatives. These groups were assembled by ASH for a 1-day meeting in Washington DC. The subspecialty experts included representatives from internal medicine, cardiovascular diseases, adult and pediatric hematology, surgery, obstetrics and gynecology, radiology, emergency medicine and trauma care, hospital practice and critical care, and geriatrics. Experts in epidemiology, healthcare quality, and health policy also participated. During the workshop, experts discussed their perspectives on the burden of disease from VTE and its diagnosis, treatment, and prevention.
      The workshop also focused on the advisability and feasibility of establishing systematic surveillance for VTE and included preliminary discussion of the advantages and disadvantages of various approaches. The workshop concluded that (1) improved utilization in clinical practice of existing, proven-effective preventive measures is critical to reducing the disease burden from VTE; (2) systematic surveillance of DVT and PE is needed to provide nationally representative data on the prevalence and annual incidence of DVT and PE in the U.S.; (3) tracking and documenting changes in the incidence of DVT and PE through systematic surveillance will be important to enhance prevention efforts; and (4) the CDC should convene a second group of experts to advise the agency in detail on the strengths, weaknesses, and feasibility of possible approaches to systematic surveillance for DVT and PE.

      Introduction

      Venous thrombosis commonly develops in the deep veins of the leg or the arm. Pulmonary embolism (PE) originates from thrombi in the deep veins of the leg in 90% or more of patients.
      • Moser K.
      • Lemoine J.
      Is embolic risk conditioned by location of deep-venous thrombosis?.
      Other less-common sources of PE include the deep pelvic veins, renal veins, inferior vena cava, right side of the heart, and axillary veins.
      • Raskob G.
      • Hull R.
      • Pineo G.
      Venous thrombosis.
      Most clinically important pulmonary emboli arise from thrombosis of the proximal deep veins of the leg (i.e., popliteal, femoral, or iliac veins).
      • Moser K.
      • Lemoine J.
      Is embolic risk conditioned by location of deep-venous thrombosis?.
      Upper-extremity deep vein thrombosis also may lead to important pulmonary embolism.
      • Prandoni P.
      • Polistena P.
      • Bernardi E.
      • et al.
      Upper-extremity deep-vein thrombosis Risk factors, diagnosis, and complications.
      Deep vein thrombosis (DVT) and/or PE are referred to collectively as venous thromboembolism (VTE).
      The disease burden from VTE is major. Each year, there are an estimated 900,000 patients with clinically evident VTE in the U.S., resulting in an estimated 300,000 deaths from PE.
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      The estimated 600,000 nonfatal cases of VTE result in several hundred thousand primary hospitalizations or extended hospital stays in patients who develop VTE while hospitalized. The direct medical costs for the treatment of patients with nonfatal VTE are estimated to be between 5.8 to 7.8 billion dollars (based on 2004 provider payments).
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      • Spyropoulos A.
      • Lin J.
      Direct medical costs of venous thromboembolism and subsequent hospital readmission rates: an administrative claims analysis from 30 managed care organizations.
      Despite the large disease burden from VTE and the major economic burden, no systematic national surveillance system for VTE currently exists in the U.S. The available information has been based on two population-based epidemiologic studies
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      • Anderson F.A.
      • Wheeler H.B.
      • Goldberg R.J.
      • et al.
      A population-based perspective of the hospital incidence and case-fatality rates of deep-vein thrombosis and pulmonary embolism: the Worcester DVT study.
      • Silverstein M.
      • Heit J.
      • Mohr D.
      • et al.
      Trends in the incidence of deep-vein thrombosis and pulmonary embolism: a 25-year population-based study.
      • Heit J.
      • Melton L.
      • Lohse C.
      • et al.
      Incidence of venous thromboembolism in hospitalized versus community residents.
      • Heit J.
      • O'Fallon W.
      • Petterson T.
      • et al.
      Relative impact of risk factors for deep-vein thrombosis and pulmonary embolism: a population-based study.
      and on limited data from hospital discharge surveys or analysis of healthcare provider claims databases.
      • White R.H.
      • Zhou H.
      • Romano P.
      Incidence of idiopathic deep venous thrombosis and secondary thromboembolism among ethnic groups in California.
      • Hooper W.C.
      • Holman R.
      • Heit J.A.
      • Cobb N.
      Venous thromboembolism hospitalizations among American Indians and Alaskan Natives.
      • White R.
      • Zhou H.
      • Murin S.
      • Harvey D.
      Effect of ethnicity and gender on the incidence of venous thromboembolism in diverse population.
      • Stein P.
      • Beemath A.
      • Olson R.
      Trends in the incidence of pulmonary embolism and deep venous thrombosis in hospitalized patients.
      A growing awareness of VTE as an important public health problem, as concluded by a combined APHA and CDC public health leadership conference in 2003
      American Public Health Association
      Deep-vein thrombosis: advancing awareness to protect patient lives.
      and the Surgeon General's Workshop on DVT in 2006,
      Office of the Surgeon General
      Surgeon General's Workshop on Deep-Vein Thrombosis.
      has raised the question of whether a systematic national approach to surveillance of VTE should be undertaken to provide more generalizable data on disease incidence, refine the current understanding of risk factors and the impact of changes in clinical practice on disease incidence, and provide updated information on the implementation in clinical practice of established preventive measures.
      This article provides a summary of the current understanding of the epidemiology of VTE and communicates the proceedings of a national workshop convened jointly by the CDC and the American Society of Hematology to explore whether more systematic national surveillance of VTE should be undertaken, and to make recommendations for possible next steps in strengthening the surveillance of VTE in the U.S.

      Diagnosis of Deep Vein Thrombosis and Pulmonary Embolism

      Deep vein thrombosis and PE are not separate disorders but a continuous syndrome in which the initial clinical presentation might be either symptoms of DVT (e.g., leg pain, tenderness, and swelling) or symptoms of PE (e.g., shortness of breath, tachypnea, and pleuritic chest pain).
      • Raskob G.
      • Hull R.
      • Pineo G.
      Venous thrombosis.
      All of these clinical features are nonspecific for DVT and PE, however, and each may be caused by several different nonthrombotic conditions. Therefore, diagnostic testing with imaging techniques is required to accurately confirm or exclude the presence of DVT and PE in patients who present with clinical features that suggest the diagnosis.
      • Raskob G.
      • Hull R.
      • Pineo G.
      Venous thrombosis.
      Among patients with symptomatic DVT as the chief presenting complaint, approximately 50% have evidence of PE (mostly asymptomatic) by diagnostic imaging procedures (e.g., radionuclide lung scanning or computed tomography [CT] imaging).
      • Moser K.
      • Lemoine J.
      Is embolic risk conditioned by location of deep-venous thrombosis?.
      • Raskob G.
      • Hull R.
      • Pineo G.
      Venous thrombosis.
      Many of these emboli are asymptomatic. The clinical importance of PE depends on the size of the embolus and the patient's cardiorespiratory reserve. Often, only part of the thrombus embolizes, and 30%–70% of patients with symptomatic PE detected by angiography also have identifiable DVT of the legs.
      • Raskob G.
      • Hull R.
      • Pineo G.
      Venous thrombosis.
      The implication of the relationship between DVT and PE for surveillance is that strategies for diagnosis of VTE should include both tests for detection of PE (lung scanning; computed tomography [CT]; or pulmonary angiography) and tests for DVT of the legs (ultrasound or venography).
      The diagnosis of DVT has become well standardized with the implementation of compression ultrasound imaging.
      • Kearon C.
      • Ginsberg J.
      • Hirsh J.
      The role of venous ultrasonography in the diagnosis of suspected deep-vein thrombosis and pulmonary embolism.
      • Lensing A.
      • Prandoni P.
      • Brandjes D.
      • et al.
      Detection of deep-vein thrombosis by real-time b-mode ultrasonography.
      • Qaseem A.
      • Snow V.
      • Barry P.
      • et al.
      Current diagnosis of venous thromboembolism in primary care: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians.
      The sensitivity and specificity of this method is >95% for DVT involving the proximal deep veins and the major calf veins. Ultrasonography using vein compression as the diagnostic criterion has a very high inter-rater reliability in symptomatic patients. The performance characteristics of ultrasonography in asymptomatic patients are less strong.
      New CT imaging technology, particularly multi-row detector CT, has substantially improved the diagnosis of PE. Multiple studies
      • Perrier A.
      • Bounameaux H.
      Accuracy or outcome in suspected pulmonary embolism.
      • Stein P.
      • Fowler S.
      • Goodman L.
      • et al.
      Multidetector computed tomography for acute pulmonary embolism.
      have defined the diagnostic performance characteristics of CT imaging. The test has overall high specificity, high positive predictive value in patients with high or intermediate probability of PE, and high negative predictive value in patients with intermediate or low clinical probability of PE. The inter-rater reliability of CT imaging for PE is very good among appropriately trained and credentialed radiologists. In settings without access to CT imaging, the diagnosis of PE is more difficult, and in these settings, many patients have nondefinitive test results for establishing or excluding the diagnosis of PE. The current status, gaps in knowledge, and issues of future study design to improve the diagnostic evaluation of patients with suspected PE have been reviewed recently.
      • Stein P.
      • Sostman D.
      • Bounameaux H.
      • et al.
      Challenges in the diagnosis of acute pulmonary embolism.
      Although the simplicity and accuracy of diagnosing DVT and PE have been improved greatly through the recent advances in imaging technology, there is no uniform, generally accepted case definition for either DVT or PE to be used for surveillance. Variation in the application of diagnostic imaging criteria across centers, and in the availability of CT imaging technology may influence the sensitivity and specificity of the diagnosis, and therefore, it has important implications for surveillance of DVT and PE.

      Epidemiology of Deep Vein Thrombosis and Pulmonary Embolism

      The estimated annual incidence of clinically evident VTE (either new or recurrent DVT or PE) in the U.S. ranged from approximately 250,000 cases during 1966–1990
      • Silverstein M.
      • Heit J.
      • Mohr D.
      • et al.
      Trends in the incidence of deep-vein thrombosis and pulmonary embolism: a 25-year population-based study.
      to more than 900,000 cases based on more recent data through 2002 from a population-based incidence study
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      conducted in Olmstead County MN. Based on this more recent data, approximately one third (300,000) of the cases were fatal PE, and the remaining two thirds were nonfatal episodes of DVT or PE. Pulmonary embolism ranks high among causes of death each year in the U.S., leading to 300,000 deaths annually. Although it causes fewer deaths than tobacco (>400,000 deaths), the number of deaths attributable to VTE is similar to the number attributable to poor diet and exercise, and more than each of the next highest–ranked causes, which include infectious diseases, motor vehicle crashes, and alcohol or illicit drug use.
      • Kung H.C.
      • Hoyert D.
      • Xu J.
      • Murphy S.
      Deaths: final data for 2005.
      Of the estimated remaining 600,000 cases of nonfatal VTE each year, approximately 60% are cases of DVT, and 40% are cases of nonfatal PE.
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      Over the past 30 years, the estimated annual incidence
      • Anderson F.A.
      • Wheeler H.B.
      • Goldberg R.J.
      • et al.
      A population-based perspective of the hospital incidence and case-fatality rates of deep-vein thrombosis and pulmonary embolism: the Worcester DVT study.
      • Silverstein M.
      • Heit J.
      • Mohr D.
      • et al.
      Trends in the incidence of deep-vein thrombosis and pulmonary embolism: a 25-year population-based study.
      • Gillum R.F.
      Pulmonary embolism and thrombophlebitis in the United States, 1970–1985.
      • Coon W.W.
      • Willis P.W.
      • Keller J.B.
      Venous thromboembolism and other venous disease in the Tecumseh community health study.
      of VTE has ranged from as low as 44 per 100,000 population to as high as 145 per 100,000. Based on data from the National Hospital Discharge Survey, the estimated incidence in 1985 was 130 per 100,000. The Worcester DVT Study published in 1991 estimated the incidence to be 107 per 100,000.
      • Anderson F.A.
      • Wheeler H.B.
      • Goldberg R.J.
      • et al.
      A population-based perspective of the hospital incidence and case-fatality rates of deep-vein thrombosis and pulmonary embolism: the Worcester DVT study.
      More recently, the study from Olmstead County MN estimated the average annual incidence of VTE over the past 30 years to be 108 per 100,000 among the U.S. white population.
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      • Silverstein M.
      • Heit J.
      • Mohr D.
      • et al.
      Trends in the incidence of deep-vein thrombosis and pulmonary embolism: a 25-year population-based study.
      Specific data on the incidence of VTE in U.S. minority populations are limited. The estimated incidence
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      among African Americans from the Olmstead County study is 78 per 100,000 population. For American Indians/Alaskan Natives, the incidence of hospitalization for VTE has been estimated
      • Hooper W.C.
      • Holman R.
      • Heit J.A.
      • Cobb N.
      Venous thromboembolism hospitalizations among American Indians and Alaskan Natives.
      from the Indian Health Service database to be 33 per 100,000 during the period 1980 through 1996. Using the linked California Patient Discharge Set from 1991 through 1994, White and colleagues calculated the annual incidence of idiopathic VTE among adults for whites, African Americans, Hispanics, and Asians/Pacific Islanders.
      • White R.H.
      • Zhou H.
      • Romano P.
      Incidence of idiopathic deep venous thrombosis and secondary thromboembolism among ethnic groups in California.
      The incidences per 1,000,000 population were 230 for whites, 293 for African Americans, 139 for Hispanics, and 60 for Asians/Pacific Islanders.
      • White R.H.
      • Zhou H.
      • Romano P.
      Incidence of idiopathic deep venous thrombosis and secondary thromboembolism among ethnic groups in California.
      The above data suggest there are important differences in the annual incidence of VTE between whites and minority populations. However, the studies used different methodologies and case definitions (e.g., all VTE versus idiopathic only), and evaluated incidences over different periods of time. Further studies are needed to make firm conclusions.
      Venous thromboembolism is predominantly a disease of older age. The incidence of VTE increases exponentially with age for both men and women.
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      The estimated overall age-adjusted incidence rate is higher for men (114 per 100,000) than it is for women (105 per 100,000).
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      Several independent risk factors for VTE have been established.
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      • Heit J.
      • Melton L.
      • Lohse C.
      • et al.
      Incidence of venous thromboembolism in hospitalized versus community residents.
      • Heit J.
      • O'Fallon W.
      • Petterson T.
      • et al.
      Relative impact of risk factors for deep-vein thrombosis and pulmonary embolism: a population-based study.
      • Geerts W.
      • Bergqvist D.
      • Pineo G.
      • et al.
      Prevention of venous thromboembolism American College of Chest Physicians evidence-based clinical practice guidelines.
      These include advancing patient age; a history of previous VTE; surgery or trauma within the prior 3 to 6 months; hospitalization or nursing home confinement; active cancer; paralysis of the leg; a variety of medical conditions (e.g., myocardial infarction, stroke, systemic lupus erythematosus, inflammatory bowel disease, and multiple hematologic conditions); obesity; venous catheterization; pregnancy and the postpartum period; estrogen use; and a variety of hereditary thrombophilias such as the factor V Leiden gene mutation, activated protein C resistance, and antithrombin deficiency.
      Effective prophylaxis against VTE is available for most high-risk patients.
      • Geerts W.
      • Bergqvist D.
      • Pineo G.
      • et al.
      Prevention of venous thromboembolism American College of Chest Physicians evidence-based clinical practice guidelines.
      For most patient groups, either anticoagulant prophylaxis using subcutaneous low-dose heparin or low-molecular weight heparin, or a mechanical method such as intermittent pneumatic leg compression, are effective for preventing VTE. For selected patients at high risk of bleeding, in whom intermittent compression cannot be applied (e.g., multiple trauma with tibia fracture and head injury), case finding of DVT using repeated testing with ultrasonography may be of benefit. Evidence-based recommendations are available for the prevention of venous thromboembolism in the specific high-risk patient groups.
      • Geerts W.
      • Bergqvist D.
      • Pineo G.
      • et al.
      Prevention of venous thromboembolism American College of Chest Physicians evidence-based clinical practice guidelines.
      However, recent audits of the utilization in clinical practice of recommended, evidence-based preventive measures indicate that thromboprophylaxis is notably under-utilized,
      • Yu H.T.
      • Dylan M.L.
      • Lin J.
      • Dubois R.J.
      Hospitals compliance with prophylaxis guidelines for thromboembolism.
      • Cohen A.T.
      • Tapson V.F.
      • Bergman J.F.
      • et al.
      Venous thromboembolism risk factors and prophylaxis in the acute care setting (ENDORSE study): a multi-national cross-sectional study.
      with 50% or more of patients failing to receive the recommended approach in several of the high-risk groups.
      Of all incident VTE occurring in the community, about 60% are associated with recent hospitalization or nursing home confinement.
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      • Heit J.
      • Melton L.
      • Lohse C.
      • et al.
      Incidence of venous thromboembolism in hospitalized versus community residents.
      • Heit J.
      • O'Fallon W.
      • Petterson T.
      • et al.
      Relative impact of risk factors for deep-vein thrombosis and pulmonary embolism: a population-based study.
      Hospitalized patients have more than a 100-fold increased incidence of acute VTE compared to residents in the community.
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      • Heit J.
      • Melton L.
      • Lohse C.
      • et al.
      Incidence of venous thromboembolism in hospitalized versus community residents.
      • Heit J.
      • O'Fallon W.
      • Petterson T.
      • et al.
      Relative impact of risk factors for deep-vein thrombosis and pulmonary embolism: a population-based study.
      Patient admission to a hospital is therefore an opportune access point to identify patients at risk and to initiate preventive measures. The Agency for Healthcare Research and Quality (AHRQ) identified thrombosis prevention as the top priority among approximately 80 evidence-based practices with the greatest potential to improve the safety of hospitalized patients.
      University of California at San Francisco (UCSF) Evidence–Based Practice Center
      Making healthcare safer: a critical analysis of patient safety practices. Agency for Healthcare Research and Quality—Evidence Report/Technology Assessment # 43.
      Although hospital admission is an opportune point to initiate preventive measures against VTE, preventive measures may need to be continued after hospital discharge because the lengths of stay for many surgeries and medical conditions have been reduced in recent years. For example, although the average length of stay for hip or knee replacement surgery is about 4 days, the period of risk for associated DVT or PE extends to 4–6 weeks after hip or knee replacement,
      • White R.
      • Gettner S.
      • Newman J.
      • et al.
      Predictors of re-hospitalization for symptomatic venous thromboembolism after total hip arthroplasty.
      and randomized trials
      • Geerts W.
      • Bergqvist D.
      • Pineo G.
      • et al.
      Prevention of venous thromboembolism American College of Chest Physicians evidence-based clinical practice guidelines.
      have established the benefit of continuing thromboprophylaxis for 30–35 days postoperatively. Similarly, the benefit of extending preventive measures for 4–6 weeks after surgery to remove cancer has also been established by a clinical trial.
      • Bergqvist D.
      • Agnelli G.
      • Cohen A.
      • et al.
      Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer.
      Of the remaining 40% of incident cases of VTE in the community that are not associated with recent hospitalization or nursing home confinement, active cancer accounts for almost one half, or 20%, of all incident cases.
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      • Heit J.
      • O'Fallon W.
      • Petterson T.
      • et al.
      Relative impact of risk factors for deep-vein thrombosis and pulmonary embolism: a population-based study.
      In approximately 10%, to as many as 20%, of adult patients with VTE, a risk factor is not identified, even after extensive search for associated disorders and a hematologic investigation for thrombophilic conditions.
      The current understanding of the epidemiology of VTE and the estimated annual incidence are based on studies that are several years old. Major factors that are likely to contribute to an increasing incidence of VTE in the U.S. now and in the future are aging of the population; a more extensive use of surgical procedures in older patients; multiple hospital admissions of patients for the care of chronic conditions (e.g., heart failure, stroke, or diabetes); and confinement of an increasing number of patients to long-term care facilities.

      Methodology for Deep Vein Thrombosis and Pulmonary Embolism Surveillance

      The CDC representatives provided an overview
      CDC
      Updated guidelines for evaluating public health surveillance systems: recommendations from the guidelines working group.
      of the development of a disease surveillance system and gave examples of existing CDC surveillance and health information systems and disease registries that might be used as models for the establishment of additional surveillance for DVT and PE. Developing a surveillance system includes defining the specific objectives (e.g., describing the burden of disease, identifying risk factors, evaluating the population impact of prevention and treatment strategies, detecting changes in healthcare practice and the impact on the burden of disease, and identifying research needs). Important steps in creating a surveillance system include developing a case definition, identifying indicators and data sources, and locating partners to undertake surveillance, field testing, collecting and analyzing data, disseminating the findings, and evaluating the system and its impact on the health problem.
      The strengths and limitations of using national databases for disease surveillance were reviewed. National or regional databases that might be useful in DVT and PE include state all-payer discharge data sets (some with linkage to death records); the Healthcare Cost and Utilization Project; Medicare administrative claims and Medicare patient safety monitoring; trauma registries; health plan data; the National Hospital Discharge Survey; and hospital consortium data.
      • Spyropoulos A.
      • Lin J.
      Direct medical costs of venous thromboembolism and subsequent hospital readmission rates: an administrative claims analysis from 30 managed care organizations.
      • DeFrances C.J.
      • Lucas C.A.
      • Buie V.C.
      • Golosinsky A.
      2006 National Hospital Discharge Survey National Center for Health Statistics Reports, No. 5.
      Healthcare Cost and Utilization Project
      Databases and related tools from the Healthcare Cost and Utilization Project (HCUP).
      Three existing programs that could be helpful in surveillance of DVT and PE were summarized. These include the Pregnancy Risk Assessment Monitoring System (PRAMS); the Thrombosis and Hemostasis Centers Research and Prevention Network; and the Paul Coverdell National Acute Stroke Registry.
      The use of existing databases for surveillance of DVT and PE is subject to several limitations.
      • Quan H.
      • Parsons G.
      • Ghali W.
      Validity of information on comorbidity derived from ICD-9-CCM administrative data.
      • Zhan C.
      • Battles J.
      • Chiang Y.
      • Hunt D.
      The validity of ICD-9-CM codes in identifying postoperative deep-vein thrombosis and pulmonary embolism.
      • White R.
      • Brickner L.
      • Scannell K.
      ICD-9-CM codes poorly identified venous thromboembolism during pregnancy.
      These include bias toward documenting surviving cases; inaccuracy of the death certificate for the attribution of PE as a cause of death; secular changes in the diagnostic methods and criteria for VTE and variance in inter-rater reliability of imaging tests; and the relatively low sensitivity, specificity, and predictive value of administrative claims codes for VTE diagnoses. The importance of a shift toward outpatient treatment of VTE has a major impact on the value of hospital discharge databases for surveillance, and linkage of data from emergency department and outpatient practice settings will be critical in a national VTE surveillance system. In addition, proposed changes to the ICD-9-CM and ICD-10 codes for VTE diagnoses might improve the predictive value of DVT and PE codes.

      Perspectives from Clinical Specialties

      The workshop provided the opportunity for representatives of several clinical specialties to exchange perspectives on the impact of VTE.

      Surgery

      The surgical practice perspective underscored three points that might affect VTE surveillance. First, the length of stay for many surgical procedures has been substantially reduced, but the period of risk for development of DVT or PE may extend up to 90 days postoperatively, as is known in the case of some surgeries.
      • White R.
      • Gettner S.
      • Newman J.
      • et al.
      Predictors of re-hospitalization for symptomatic venous thromboembolism after total hip arthroplasty.
      • Bergqvist D.
      • Agnelli G.
      • Cohen A.
      • et al.
      Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer.
      Second, more data are needed to define the risk for DVT or PE associated with procedures thought to be of lower risk (e.g., Achilles tendon repair or certain laparoscopic or arthroscopic procedures) and to determine how the risk in such patients is modified by the presence or absence of other inherited or acquired risk factors. Third, divergent recommendations
      • Geerts W.
      • Bergqvist D.
      • Pineo G.
      • et al.
      Prevention of venous thromboembolism American College of Chest Physicians evidence-based clinical practice guidelines.
      American Academy of Orthopaedic Surgeons
      American Academy of Orthopedic Surgeons clinical practice guideline on prevention of symptomatic pulmonary embolism in patients undergoing total hip or knee arthroplasty.
      for prevention in the same patient groups (e.g., joint replacement surgery) contained within the practice guidelines should be coordinated among the various specialties.

      Obstetrics and Gynecology

      The obstetric and gynecologic practice perspective emphasized three points related to VTE surveillance. First, because of changes in the characteristics of patients, such as increased age of childbearing and increased numbers of pregnancies in patients with underlying medical conditions, additional data are needed on the incidence of DVT and PE among obstetric patients. Second, the risk for VTE associated with modern laparoscopic and/or robotic gynecologic procedures needs to be better defined. Third, more data are needed on the duration of risk for DVT and PE postoperatively because the length of hospital stay following gynecologic surgery has been substantially reduced. More data are needed on the incidence of VTE in women and adolescent girls with a family history of DVT or PE or with a family history of genetic thrombophilia who are taking oral contraceptives. In addition, data are needed on whether evidence-based recommendations for VTE prophylaxis in gynecologic surgery patients are being translated into practice.

      Internal Medicine

      The internal medicine practice perspective emphasized the importance of hospitalization as an independent risk factor for VTE. Hospitalization for acute medical illness accounts for approximately 30% of VTE cases.
      • Heit J.
      • Melton L.
      • Lohse C.
      • et al.
      Incidence of venous thromboembolism in hospitalized versus community residents.
      • Heit J.
      • O'Fallon W.
      • Petterson T.
      • et al.
      Relative impact of risk factors for deep-vein thrombosis and pulmonary embolism: a population-based study.
      The most common independent risk factors for VTE after a hospital stay are increasing patient age and BMI, active cancer, fracture, prolonged immobility, and use of a central venous catheter.
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      • Heit J.
      • Melton L.
      • Lohse C.
      • et al.
      Incidence of venous thromboembolism in hospitalized versus community residents.
      • Heit J.
      • O'Fallon W.
      • Petterson T.
      • et al.
      Relative impact of risk factors for deep-vein thrombosis and pulmonary embolism: a population-based study.
      Despite improvements in the efficacy and safety of pharmacologic prophylaxis and drug regimens, and frequent updates and wide dissemination of evidence-based prophylaxis guidelines, the overall age- and gender-adjusted incidence of VTE has not been reduced substantially during the preceding 25 years.
      • Heit J.
      The epidemiology of venous thromboembolism in the community.
      • Silverstein M.
      • Heit J.
      • Mohr D.
      • et al.
      Trends in the incidence of deep-vein thrombosis and pulmonary embolism: a 25-year population-based study.
      Potential reasons include an increasing prevalence of known thromboembolism risk factors (i.e., an increase in the population or time period at risk); exposure to new unrecognized risk factors; the underuse of effective thromboprophylaxis; and incomplete efficacy of prophylaxis.
      Research should be directed toward developing automated methods (e.g., computerized or other prompt systems, or empiric prophylaxis of all hospitalized patients coupled with an “opt out” system) to improve use of appropriate DVT prophylaxis in the short term, and to identify the patient or recently hospitalized person at high risk for VTE so both in-hospital and extended outpatient prophylaxis can be targeted to patients who will benefit most. A national surveillance system should address the under-recognition of PE as a cause of death because of the low national autopsy rate, especially among the elderly. Such a system should be able to measure changes in the distribution of known risk factors, the incidence of “idiopathic” DVT or PE, the utilization of appropriate thromboprophylaxis, and failures and adverse effects of VTE prophylaxis.

      Pediatrics

      The pediatric practice perspective emphasized the relative lack of rigorous data on all aspects of VTE in children compared with those for adults.
      • Andrew M.
      • David M.
      • Adams M.
      • et al.
      Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE.
      • Van Ommen C.
      • Heijboer H.
      • Buller H.
      • et al.
      Venous thromboembolism in childhood: a prospective two-year registry in the Netherlands.
      The estimated incidence of VTE in children is much lower than that in adults, and it peaks in the neonatal period and in adolescence.
      • Stein P.
      • Kayali F.
      • Olson R.
      Incidence of venous thromboembolism in infants and children: data from the National Hospital Discharge Survey.
      Congenital heart disease, infection, and use of a central venous catheter appear to be the most common risk factors for VTE. Acquired thrombophilia (e.g., transient antiphospholipid antibodies) is relatively common among children who have VTE. Definitive randomized trials of approaches for prevention and treatment of established DVT or PE in children are needed. These trials should focus on high-risk groups of children and should evaluate both the outcome of fatal PE and the prevention of morbidity from nonfatal VTE (e.g., post-thrombotic syndrome of leg pain, swelling, and dependent edema).

      Geriatrics

      The geriatric perspective emphasized the impact of an aging population on the future incidence of VTE. Aging and frailty have been documented as risk factors for VTE.
      • Folsom A.
      • Boland L.
      • Cushman M.
      • Heckbert S.
      • Rosamond W.
      • Walston J.
      Frailty and risk of venous thromboembolism in older adults.
      Long-term care facilities should be given special consideration in the design of surveillance of prevention programs because of their role in the care of the elderly. Special considerations should be given to research designed to improve the risk–benefit profile of anticoagulant drugs in the elderly for either prevention or treatment of established thrombosis.

      Disability

      The disability perspective emphasized immobility as a strong risk factor for VTE. Patients suffering from motor disability (e.g., because of spinal cord injury, spina bifida, or stroke) are at an increased risk for VTE. The burden of DVT and PE in this group is not completely understood, and further study and representation of this risk group in a surveillance system is needed.

      Emergency Medicine

      Emergency medicine and acute trauma care practice perspectives emphasized the importance of obtaining data from emergency departments as a key part of a surveillance program, because patients with VTE present to the emergency department and are often treated as outpatients. Certain emergency departments have standard protocols for outpatient treatment; therefore, if a surveillance system did not include emergency department diagnoses, such patients would be missed by analysis of hospital discharge databases. Other areas of need include evaluation of the benefits of and risks for removable vena-caval filters. Such filters can prevent major PE, and if removed at an appropriate time, can prevent the increased risk for recurrent DVT associated with the permanent vena-caval filter. The potential for “overtesting” for PE using CT angiography in patients at low risk or very low clinical probability is an issue for emergency medicine practice because of the risks of radiation and contrast dye.

      Recommendations

      The current understanding of the epidemiology of VTE supports two major conclusions. First, the improved utilization in clinical practice of proven-effective preventive measures is critical to reducing death and morbidity from VTE. Second, strengthened systematic surveillance of DVT and PE will be important to achieve the following objectives:
      • 1
        to provide a geographically representative measure of the annual incidences of DVT and PE in the U.S.;
      • 2
        to provide a demographically representative measure of the incidence of DVT and PE in the U.S. population;
      • 3
        to determine if differences exist in the incidences of DVT and PE among minority populations, and to determine if DVT or PE are important contributors to health disparities among minority populations;
      • 4
        to determine the incidence of DVT and PE and define the risk factors in selected patient groups representing current clinical practice (e.g., pregnant patients in a population representative of current obstetric practice; patients undergoing various laparoscopic, arthroscopic, or robotic surgical procedures; children; women, especially under-represented minorities with a family history of VTE or genetic thrombophilia; and residents of long-term care facilities);
      • 5
        to evaluate whether evidence-based preventive measures are being appropriately applied in clinical practice;
      • 6
        to detect changes in the incidences of DVT and PE over time and to relate these findings to major national initiatives to increase the use of preventive measures into practice; and
      • 7
        to identify areas for future research on approaches for reducing the disease burden of VTE.
      The above objectives are unlikely to be accomplished by a single surveillance system or approach. A series of focused, targeted surveillance efforts might be useful and appropriate.
      In addition, the CDC should convene a group of experts in VTE epidemiology and diagnosis and in surveillance methodology to provide advice on the scientific approaches to addressing the above objectives of a surveillance system for VTE. In addition, guidance could be provided on how existing systems such as PRAMS (which monitors changes in maternal and child health indicators); National Ambulatory Medical Care Survey (which collects data on ambulatory medical care services); the National Hospital Ambulatory Medical Care Survey (which collects data on the use and provision of ambulatory-care services in hospital emergency departments and outpatient departments); and the Thrombosis and Hemostasis Centers Research and Prevention Network could be leveraged to achieve the objectives.
      Finally, the CDC, in cooperation with relevant partners, should initiate a national campaign to increase public awareness of DVT and PE with two goals: first, to increase awareness of the risk for DVT or PE beyond the issue of travel-related thrombosis, and second, to increase the application of preventive measures in clinical practice by having informed patients engage in discussion of this issue with their physicians and healthcare providers when undergoing surgery or being admitted to a hospital for medical illness.
      American Society of Hematology Workshop on Thrombosis Surveillance participant list:
      Hani K. Atrash, MD, MPH, National Center on Birth Defects and Developmental Disabilities, CDC; Michele G. Beckman, MPH, National Center on Birth Defects and Developmental Disabilities, CDC; Mary Beth Bigley, DrPH, MSN, ANP-C, Office of the Surgeon General; Dale W. Bratzler, DO, MPH, Oklahoma Foundation for Medical Quality; Joseph A. Caprini, MD, FACS, Evanston and Glenview Hospitals; Daniel L. Clarke-Pearson, MD, Department of Obstetrics and Gynecology, University of North Carolina; Sara E. Critchley, MS, RN, National Center on Birth Defects and Developmental Disabilities, CDC; William B. Ershler, MD, National Institute on Aging, NIH; Randolph B. Fenninger, JD, The National Alliance for Thrombosis and Thrombophilia; Mary G. George, MD, MSPH, FACS, National Center for Chronic Disease Prevention and Health Promotion, Division for Heart Disease and Stroke, CDC; Neil A. Goldenberg, MD, PhD, University of Colorado Denver and The Children's Hospital; Lawrence R. Goodman, MD, FACR, Diagnostic Radiology and Pulmonary Medicine and Critical Care, Medical College of Wisconsin; John A. Heit, MD, Cardiovascular Diseases and Hematology Research, Mayo Clinic; W. Craig Hooper, PhD, National Center on Birth Defects and Developmental Disabilities, CDC; Jeffrey Allen Kline, MD, Department of Emergency Medicine, Carolinas Medical Center; James R. Klinger, MD, Brown Medical School and Division of Pulmonary Sleep and Critical Care Medicine, Rhode Island Hospital; Rebecca P. Link, PhD, National Heart, Lung, and Blood Institute, NIH; Nicholas M. Lomangino, MD, Medical Specialties Division, Federal Aviation Administration; Sylvia C. W. McKean, MD, FACP Harvard Medical School and Brigham and Women's Hospital; Traci Heath Mondoro, PhD, National Heart, Lung, and Blood Institute, NIH; Patsy Myers, DrPH, South Carolina Department of Health and Environmental Control; Gary E. Raskob, PhD (co-chair), College of Public Health, University of Oklahoma Health Sciences Center; Art Sedrakyan, MD, PhD, Agency for Healthcare Research and Quality; Roy L. Silverstein, MD (co-chair), Department of Cell Biology, and Department of Hematology, Cleveland Clinic Foundation; Kenneth Simon, MD, MBA, Centers for Medicare and Medicaid Services; Harrison Spencer, MD, MPH, Association of Schools of Public Health; Sharon Sprenger, RHIA, CPHQ, MPA, Division of Quality Measurement and Research, The Joint Commission; Edwin Trevathan, MD, MPH, National Center on Birth Defects and Developmental Disabilities, CDC; Richard H. White, MD, Department of Internal Medicine, UC Davis; Guy Young, MD, Children's Hospital, Los Angeles.
      GER has received consulting fees for advice on clinical drug development from the following companies: Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, Johnson & Johnson, Daiichi Sankyo, Sanofi-Aventis, and Takeda.
      No other financial disclosures were reported by the authors of this paper.

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