Michele G. Beckman

Venous Thromboembolism: A Public Health Concern

Venous thromboembolism (VTE), defined as deep vein thrombosis, pulmonary embolism, or both, affects an estimated 300,000-600,000 individuals in the U.S. each year, causing considerable morbidity and mortality. It is a disorder that can occur in all races and ethnicities, all age groups, and both genders. With many of the known risk factors-advanced age, immobility, surgery, obesity-increasing in society, VTE is an important and growing public health problem. Recently, a marked increase has occurred in federal and national efforts to raise awareness and acknowledge the need for VTE prevention. Yet, many basic public health functions-surveillance, research, and awareness-are still needed. Learning and understanding more about the burden and causes of VTE, and raising awareness among the public and healthcare providers through a comprehensive public health approach, has enormous potential to prevent and reduce death and morbidity from deep vein thrombosis and pulmonary embolism throughout the U.S.

Comparison of characteristics from White‐ and Black‐Americans with venous thromboembolism: A cross‐sectional study

When compared with Whites, Black‐Americans may have a 40% higher incidence venous thromboembolism (VTE) incidence. However, whether other VTE characteristics and risk factors vary by race is uncertain. To compare demographic and baseline characteristics among White‐ and Black‐Americans with VTE, we used data prospectively collected from consecutive consenting adults enrolled in seven Centers for Disease Control (CDC) Thrombosis and Hemostasis Centers from August 2003 to March 2009. These characteristics were compared among Whites (n = 2002) and Blacks (n = 395) with objectively diagnosed VTE, both overall, and by age and gender. When compared with Whites, Blacks had a significantly higher proportion with pulmonary embolism (PE), including idiopathic PE among Black women, and a significantly higher proportion of Blacks were women. Blacks had a significantly higher mean BMI and a significantly lower proportion with recent surgery, trauma or infection, family history of VTE, and documented thrombophilia (solely from reduced factor V Leiden and prothrombin G20210A prevalence). Conversely, Blacks had a significantly higher proportion with hypertension, diabetes mellitus, chronic renal disease and dialysis, HIV, and sickle cell disease. When compared with White women, Black women had a significantly lower proportion with recent oral contraceptive use or hormone therapy. We conclude that Whites and Blacks differ significantly regarding demographic and baseline characteristics that may be risk factors for VTE. The prevalence of transient VTE risk factors and idiopathic VTE among Blacks appears to be lower and higher, respectively, suggesting that heritability may be important in the etiology of VTE among Black‐Americans. Am. J. Hematol. 85:467–471, 2010

Development of a screening tool for identifying women with menorrhagia for hemostatic evaluation

OBJECTIVE A study was conducted to develop a short, easy to administer screening tool useful for stratifying women with unexplained menorrhagia for hemostatic testing for underlying bleeding disorders. STUDY DESIGN One hundred forty-six women with a physician diagnosis of menorrhagia underwent comprehensive hemostatic testing for the diagnosis of bleeding disorders, including von Willebrand disease, platelet dysfunction, and coagulation factor deficiencies. A 12 page questionnaire of bleeding symptoms was administered. Bleeding symptoms with high predictive values for laboratory hemostatic abnormalities were combined and used as single variables to calculate sensitivity, specificity, and positive and negative predictive values in order to develop a short screening tool to identify females for testing and evaluation. RESULTS A combination of 8 questions in 4 categories resulted in a sensitivity of 82% (95%CI 75-90) for bleeding disorders. Adding a pictorial blood assessment chart score > 100 increased the sensitivity of the screening tool to 95% (95%CI 91-99). CONCLUSION These results demonstrate the feasibility of a simple questionnaire based screening tool to identify females for testing and evaluation for bleeding disorders.

The U.S. Thrombosis and Hemostasis Centers pilot sites program

Venous thromboembolism (VTE) is a common disorder associated with significant morbidity and mortality. Despite important advances in understanding the etiology of VTE, delivery of care to patients with thrombosis and thrombophilia is frequently incomplete and highly variable. A comprehensive model of health care has been used successfully to treat and prevent complications for people with hemophilia and other chronic disorders. The effectiveness of an integrated healthcare model for patients with all coagulation disorders has yet to be evaluated. The Division of Hereditary Blood Disorders of the Centers for Disease Control and Prevention (CDC) is collaborating with eight Thrombosis and Hemostasis Centers (pilot sites) to provide health-related services and conduct research directed toward the reduction or prevention of complications of thrombosis and thrombophilia. The initial objectives of the collaboration are to (1) determine the efficacy of integrated multidisciplinary care and prevention services for people with hemostatic disorders, (2) assess unmet needs for service delivery and identify outreach strategies to improve access to care, (3) develop effective messages aimed at disease management and prevention, and (4) foster the development of training programs to enhance provider skills for the delivery of patient care. To address these objectives, the investigators and CDC have developed and implemented a web-based patient registry to follow prospectively service allocation and patient outcomes. Funding for the program began in October 2001. All eight funded centers are affiliated with U.S. medical schools. Principal investigators at the centers are hematologists (five adult, two pediatric) or cardiologists. Faculty in obstetrics-gynecology, surgery, and multiple other specialties are integral to the model of care at the centers. Other critical components at the centers are clinical laboratory services, training programs, research networks, and education and outreach programs. From August 2003 to March 2006, over 2,600 patients were enrolled in the registry, accounting for a total of more than 5,000 visits to the centers. Immediate goals of the data collection at the centers are to characterize patients receiving care at centers and document the state of health services provided. Long-term goals are to evaluate prospectively clinical outcomes for patients receiving multidisciplinary care and prevention services at centers. The network of data collection across centers will facilitate future collaborative clinical and epidemiologic investigations and enhance collective expertise in hemostasis and coagulation disorders.

Predictive accuracy of 29-comorbidity index for in-hospital deaths in US adult hospitalizations with a diagnosis of venous thromboembolism.

Background Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a significant source of mortality and morbidity worldwide. By analyzing data of the 2010 Nationwide Inpatient Sample from the Agency for Healthcare Research and Quality (AHRQ), we evaluated the predictive accuracy of the AHRQ’s 29-comorbidity index with in-hospital death among US adult hospitalizations with a diagnosis of VTE. Methods We assessed the case-fatality and prevalence of comorbidities among a sample of 153,518 adult hospitalizations with a diagnosis of VTE that comprised 87,605 DVTs and 65,913 PEs (with and without DVT). We estimated adjusted odds ratios and 95% confidence intervals with multivariable logistic regression models by using comorbidities as predictors and status of in-hospital death as an outcome variable. We assessed the c-statistics for the predictive accuracy of the logistic regression models. Results In 2010, approximately 41,944 in-hospital deaths (20,212 with DVT and 21,732 with PE) occurred among 770,137 hospitalizations with a diagnosis of VTE. When compared separately to hospitalizations with VTE, DVT, or PE that had no corresponding comorbidities, congestive heart failure, chronic pulmonary disease, coagulopathy, liver disease, lymphoma, fluid and electrolyte disorders, metastatic cancer, other neurological disorders, peripheral vascular disorders, pulmonary circulation disorders, renal failure, solid tumor without metastasis, and weight loss were positively and independently associated with 10%−125% increased likelihoods of in-hospital death. The c-statistic values ranged from 0.776 to 0.802. Conclusion The results of this study indicated that comorbidity was associated independently with risk of death among hospitalizations with VTE and among hospitalizations with DVT or PE. The AHRQ 29-comorbidity index provides acceptable to excellent predictive accuracy for in-hospital deaths among adult hospitalizations with VTE and among those with DVT or PE.

Determinants of venous thromboembolism among hospitalizations of US adults: a multilevel analysis.

Background Venous thromboembolism (VTE) is a significant clinical and public health concern. We evaluated a variety of multilevel factors—demographics, clinical and insurance status, preexisting comorbid conditions, and hospital characteristics—for VTE diagnosis among hospitalizations of US adults. Methods We generated adjusted odds ratios with 95% confidence intervals (CIs) and determined sources of outcome variation by conducting multilevel logistic regression analysis of data from the 2011 Nationwide Inpatient Sample that included 6,710,066 hospitalizations of US adults nested within 1,039 hospitals. Results Among hospitalizations of adults, age, sex, race or ethnicity, total days of hospital stay, status of health insurance, and operating room procedure were important determinants of VTE diagnosis; each of the following preexisting comorbid conditions—acquired immune deficiency syndrome, anemia, arthritis, congestive heart failure, coagulopathy, hypertension, lymphoma, metastatic cancer, other neurological disorders, obesity, paralysis, pulmonary circulation disorders, renal failure, solid tumor without metastasis, and weight loss—was associated independently with 1.04 (95% CI: 1.02−1.06) to 2.91 (95% CI: 2.81−3.00) times increased likelihood of VTE diagnosis than among hospitalizations of adults without any of these corresponding conditions. The presence of 2 or more of such conditions was associated a 180%−450% increased likelihood of a VTE diagnosis. Hospitalizations of adults who were treated in urban hospitals were associated with a 14%−15% increased likelihood of having a VTE diagnosis than those treated in rural hospitals. Approximately 7.4% of the total variation in VTE diagnosis occurred between hospitals. Conclusion The presence of certain comorbidities and hospital contextual factors is associated with significantly elevated likelihood of VTE diagnosis among hospitalizations of adults. The findings of this study underscore the importance of clinical risk assessment and adherence to evidence-based clinical practice guidelines in preventing VTE, as well as the need to evaluate potential contextual factors that might modify the risk of VTE among hospitalized patients.

Differences in thrombotic risk factors in black and white women with adverse pregnancy outcome

INTRODUCTION Black women have an increased risk of adverse pregnancy outcomes and the characteristics of thrombotic risk factors in this population are unknown. The objective of this study was to examine the racial differences in thrombotic risk factors among women with adverse pregnancy outcomes. METHODS Uniform data were collected in women with adverse pregnancy outcomes (pregnancy losses, intrauterine growth restriction (IUGR), prematurity, placental abruption and preeclampsia) referred to Thrombosis Network Centers funded by the Centers for Disease Control and Prevention (CDC). RESULTS Among 343 white and 66 black women seen for adverse pregnancy outcomes, protein S and antithrombin deficiencies were more common in black women. The prevalence of diagnosed thrombophilia was higher among whites compared to blacks largely due to Factor V Leiden mutation. The prevalence of a personal history of venous thromboembolism (VTE) did not differ significantly by race. A family history of VTE, thrombophilia, and stroke or myocardial infarction (MI) was higher among whites. Black women had a higher body mass index, and a higher prevalence of hypertension, while the prevalence of sickle cell disease was approximately 27 fold higher compared to the general US black population. CONCLUSIONS Thrombotic risk factors differ significantly in white and black women with adverse pregnancy outcomes. Such differences highlight the importance of considering race separately when assessing thrombotic risk factors for adverse pregnancy outcomes.

Developing Public Health Surveillance for Deep Vein Thrombosis and Pulmonary Embolism

Deep vein thrombosis (DVT) and pulmonary embolism (PE), collectively known as venous thromboembolism (VTE), are an important and growing public health issue, associated with considerable morbidity and mortality. Presently, there is no national surveillance for DVT and PE. This article provides a summary of an expert workgroup meeting convened January 12, 2010, by the CDC. The purpose of the meeting was to inform CDC on the development of U.S. population-based public health surveillance activities for DVT/PE. Topics discussed included: (1) stakeholders, needs, gaps, and target populations; (2) requirements of surveillance systems; (3) challenges, limitations, and potential barriers to implementation of surveillance activities; and (4) integration of research and education with surveillance activities.

Prevalence of Venous Thromboembolism Among Privately Insured US Adults

V enous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE); DVT refers to the formation of 1 or more blood clots in a large vein, and PE results when a portion of the blood clot breaks loose, travels through the bloodstream, and partially or completely blocks a pulmonary artery. Venous thromboembolism is an important and growing public health concern; however, a national surveillance system for this condition has not been established. Therefore, many of the current estimates of VTE incidence were derived from geographically defined populations, single institutions, or hospital discharge databases. Hospital discharge data are particularly problematic because many patients are treated on an outpatient basis. Administrative data represent a potential source for monitoring VTE trends in the absence of established public health surveillance systems. We used health insurance claims data from a large, privately insured US adult population to estimate the prevalence of VTE during 2005 through 2006 within that population. To account for the potential for misclassification of DVT or PE diagnoses in claims data, we also explored using different algorithms to calculate our estimates.

Characteristics and Risk Factors of Cancer Associated Venous Thromboembolism

INTRODUCTION The objective of this study was to examine the differences in commonly associated characteristics and risk factors of venous thromboembolism (VTE) between patients with and without cancer in a VTE population. MATERIALS AND METHODS Uniform data were collected for patients with a diagnosis of VTE obtaining care at CDC funded Thrombosis Network Centers. Patient characteristics and risk factors were compared in VTE patients with and without cancer. Logistic regression was used to calculate the unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to assess patient characteristics and thrombotic risk factors more frequently identified among VTE patients with cancer compared to those without cancer. RESULTS Between August 2003 and April 2011, 3,115 adult patients with a diagnosis of VTE including 189 (6.1%) patients with active cancer participated in the multi-site thrombosis registry. VTE patients with cancer had a higher prevalence of PE and DVT in unusual sites compared to those without cancer. Thrombophilia was more common among VTE patients without cancer than those with cancer (25.1% vs 10.6%, p<0.001). In adjusted analysis, age group≥45years (OR =5.20, 95% CI, 3.30, 8.18), surgery (OR =1.86, 95% CI, 1.19, 2.91), and hypertension (OR =1.66, 95% CI, 1.15, 2.40) were the VTE risk factors more commonly found among VTE patients with cancer. CONCLUSION The study identified several thrombotic risk factors more likely to be found with cancer associated VTE, which may help to characterize at risk cancer patients and to develop prevention and management strategies in this population.