Traumatic injury is a leading cause of morbidity and mortality in the United States.1 Venous thromboembolism (VTE) is the 4th most common complication in trauma patients, 2 and represents a major source of preventable morbidity and mortality in this population. In patients who survive the initial injury, pulmonary embolism (PE- a subset of VTE) represents the 3rd most common cause of death.3 Low molecular weight heparin (LMWH) anticoagulants are the gold standard for prevention of VTE in this population.4 However, the most effective LMWH is unknown. Although enoxaparin and dalteparin are the two most commonly used LMWHs in trauma patients, there are few studies that have evaluated their comparative effectiveness in this population. In addition, specific factors that may decrease the effectiveness of both agents are poorly understood. The proposal aims to improve VTE prophylaxis in trauma patients through the following broad objectives: 1) Examine the comparative effectiveness of enoxaparin and dalteparin~ 2) Identify patient and treatment factors that predict failure of prophylaxis 3) train the applicant in methods of pharmacoepidemiology as they apply to the critically ill trauma population~ and 4) aid the applicant's evolution to a career in independent investigation. The applicant will leverage the resources of the University of Pennsylvania to achieve the stated objectives. Penn is a major trauma center and maintains a patient registry that contains demographics, injury characteristics, and outcomes for all trauma patients treated at Penn. These data will be linked to information from a local pharmacy database and clinical data warehouse, and the incidence of VTE will be compared in patients given enoxaparin versus dalteparin. In addition, a risk prediction model will be developed to identify patients that develop VTE despite receiving prophylaxis. This prediction tool will be used to target patients that would benefit from additiona prophylaxis strategies in future studies. The applicant will complete these objectives through direct one-on-one mentoring with a senior investigator and through a rigorous didactic training program in research methods. As a result of training provided by the NRSA, the applicant will develop the skills to conduct further research focusing on VTE prevention as part of a K23 career development award. Moreover, the results of the project supported by this F32 award will have an immediate impact on VTE prophylaxis in the trauma population. It will provide data to hospitals that are searching for the most effective agent, and it will identify risk factors for prophylaxis failure. Insights from this research may eventually lead to studies of personalized dosing regimens.

Public Health Relevance

Traumatic injury is a major public health problem, accounting nearly two hundred thousand lost lives each year and billions of dollars in health care expense. Trauma patients are given blood-thinning drugs to prevent blood clots that can after injury, which is a leading cause of death in these patients. Because the most effective drug is unknown, this research project will compare the two drugs that are most commonly used for preventing clots and determine which is most effective.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Sarkar, Rita
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University of Pennsylvania
Biostatistics & Other Math Sci
Schools of Medicine
United States
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Miano, Todd A; Lautenbach, Ebbing; Wilson, F Perry et al. (2018) Attributable Risk and Time Course of Colistin-Associated Acute Kidney Injury. Clin J Am Soc Nephrol 13:542-550
Miano, Todd A; Cuker, Adam; Christie, Jason D et al. (2018) Comparative Effectiveness of Enoxaparin vs Dalteparin for Thromboprophylaxis After Traumatic Injury. Chest 153:133-142
Gutsche, Jacob; Vernick, William; Miano, Todd A et al. (2017) One-Year Experience With a Mobile Extracorporeal Life Support Service. Ann Thorac Surg 104:1509-1515
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