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C-Reactive Protein Predicts Risk of Venous Thromboembolism in Pediatric Musculoskeletal Infection

Amaro, Emilie, MD*; Marvi, Tanya K., MD*; Posey, Samuel L., BS*; Benvenuti, Michael A., MD*; An, Thomas J., MD*; Dale, Kevin M., MD; Lovejoy, Steven A., MD†,‡; Martus, Jeffrey E., MD†,‡; Johnson, Megan E., MD†,‡; Mencio, Gregory A., MD†,‡; Moore-Lotridge, Stephanie N., BS†,§; Thomsen, Isaac P., MD, MSCI‡,∥; Schoenecker, Jonathan G., MD, PhD†,‡,§,¶

Journal of Pediatric Orthopaedics: January 2019 - Volume 39 - Issue 1 - p e62–e67
doi: 10.1097/BPO.0000000000001256
Infection

Background: The rate of venous thromboembolism in children with musculoskeletal infections (MSKIs) is markedly elevated compared with hospitalized children in general. Predictive biomarkers to identify high-risk patients are needed to prevent the significant morbidity and rare mortality associated with thrombotic complications. We hypothesize that overactivation of the acute phase response is associated with the development of pathologic thrombi and we aim to determine whether elevations in C-reactive protein (CRP) are associated with increased rates of thrombosis in pediatric patients with MSKI.

Methods: A retrospective cohort study measuring CRP in pediatric MSKI patients with or without thrombotic complications.

Results: The magnitude and duration of elevation in CRP values correlated with the severity of infection and the development of pathologic thrombosis. In multivariable logistic regression, every 20 mg/L increase in peak CRP was associated with a 29% increased risk of thrombosis (P<0.001). Peak and total CRP were strong predictors of thrombosis with area under the receiver-operator curves of 0.90 and 0.92, respectively.

Conclusions: Future prospective studies are warranted to further define the discriminatory power of CRP in predicting infection-provoked thrombosis. Pharmacologic prophylaxis and increased surveillance should be strongly considered in patients with MSKI, particularly those with disseminated disease and marked elevation of CRP.

Level of Evidence: Level III.

*School of Medicine

§Department of Pharmacology, Vanderbilt University, Nashville, TN

Departments of Orthopaedics and Rehabilitation

Pediatrics

Pathology Microbiology and Immunology

Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN

E.A. and T.K.M. contributed equally.

E.A. and T.K.M. assisted in study concept and design, collected and analyzed patient data, drafted the initial manuscript, conducted statistical analysis, assisted in figure production, and provided critical revisions of the work. S.L.P. assisted in study concept and design, collected patient data, drafted the initial manuscript, and provided critical revisions of the work. M.A.B. and T.J.A. assisted in study concept and design, collected and analyzed patient data, and provided critical revisions of the work. K.M.D., S.A.L., J.E.M., M.E.J., and G.A.M. assisted in study concept and design, oversaw patient care and assisted in the collection of patient data, and provided critical revisions of the work. S.N.M.-L. assisted in study concept and design, assisted with the drafting of the initial manuscript and figure production, and oversaw the submission and review process. I.P.T. assisted in study concept and design, assisted in drafting the initial manuscript, and provided critical revision of the work. J.G.S. directed the study concept and design, oversaw patient care and assisted in the collection of patient data, provided funding and support for completion of this work, assisted in drafting the initial manuscript, provided critical revisions of the work, and oversaw the submission and review process.

Funding for this work was provided by the Caitlin Lovejoy Fund and the Vanderbilt University Medical Center, Department of Orthopaedics and Rehabilitation.

J.G.S. is a member of the Education Advisory Board at OrthoPediatrics. The remaining authors declare no conflicts of interest. Reprints: Jonathan G. Schoenecker, MD, PhD, 4202 Doctors Office Tower, 2200 Children’s Way, Nashville, TN 37232. E-mail: Jon.schoenecker@vanderbilt.edu.

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