Working Diagnosis:
Severe secondary immune thrombocytopenia associated with Epstein-Barr Virus mononucleosis, complicated by splenomegaly and transaminitis.

Treatment:
Admitted to the hospital and started on prednisone 1 mg/kg with close monitoring.

Outcome:
Platelets improved from 3,000 to 37,000 by discharge, with stable hemoglobin and without transfusion. She was discharged on steroids with strict precautions and follow-up arranged with hematology and primary care.
Advised to avoid contact sports, strenuous lifting, and abdominal trauma due to risk of splenic rupture and bleeding. Outpatient hematology follow-up in 1 week planned for a complete blood count monitoring and steroid taper. Clearance for return to athletic activity deferred until platelet recovery exceeds 100,000 and resolution of splenomegaly by primary care sports medicine and hematology. She eventually returned to sport safely.

Author's Comments:
EBV mononucleosis typically presents with fever, pharyngitis, and lymphadenopathy. Hematologic complications are common, but severe thrombocytopenia is rare, in less than 2 percent of cases. Mechanisms include immune-mediated platelet destruction, impaired marrow production, and splenic sequestration. Counts less than 10,000 significantly increase the risk of spontaneous bleeding and are considered a medical emergency. Patients may appear clinically stable despite dangerous cytopenias. Corticosteroids are first-line for EBV-associated ITP, while IVIG or rituximab are second-line. Platelet transfusion is reserved for active bleeding. PCSM providers should monitor athletes for hematologic complications and emphasize activity restrictions given risk of splenic rupture and hemorrhage.

Editor's Comments:
This case highlights the importance of maintaining a high index of suspicion for serious complications in athletes presenting with infectious mononucleosis. While many cases are self-limited, significant thrombocytopenia could easily be overlooked because athletes can appear clinically well despite critically low platelet counts. Concerning symptoms that should trigger prompt workup but are certainly not limited to the presence of petechiae, mucosal bleeding, epistaxis, easy bruising, or other hemorrhagic manifestations. Workup would optimally include a complete blood count and EBV testing.
Severe thrombocytopenia is a medical emergency that requires urgent hematology involvement. Even after treatment is initiated, restricting return to activity plays a significant role in patient outcome. This discussion should involve both the hematology team and primary care sports medicine physician. Return-to-play decisions should account for hematologic recovery and splenic injury risk. Consistent with the 2023 AMSSM Position Statement, contact and collision sports should generally be avoided for at least 3 to 4 weeks after symptom onset, with individualized shared decision-making and consideration of serial ultrasonography when splenomegaly is present.

References:
Raadsen M, Du Toit J, Langerak T, van Bussel B, van Gorp E, Goeijenbier M. Thrombocytopenia in virus infections. J Clin Med 2021;10(4):877.
Chow KU, Luxembourg B, Seifried E, Bonig H. Spleen Size Is Significantly Influenced by Body Height and Sex: Establishment of Normal Values for Spleen Size at US with a Cohort of 1200 Healthy Individuals. Radiology. 2016;279(1):306-313.
Fu H, Cai X, Cui L, et al. The evolution of preexisting primary immune thrombocytopenia after COVID-19 onset: A nationally representative, prospective, multicentre, observational study. Ann Hematol. 2024;103(5):1549-1559.
Putukian, Margot MD; McGrew, Christopher A. MD; Benjamin, Holly J. MD; Hammell, Mary Kitazono MD; Hwang, Calvin E. MD; Ray, Jeremiah W. MD; Statuta, Siobhan M. MD; Sylvester, Jillian MD; Wilson, Kristina MD, MPH. American Medical Society of Sports Medicine Position Statement: Mononucleosis and Athletic Participation. Clinical Journal of Sport Medicine 33(4):p 359-367, July 2023.

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