Background Immune thrombocytopenia (ITP) remains a diagnostic challenge, with many primary and secondary causes that are often difficult to discern. COVID-19 infection and vaccination have been implicated in causing ITP; however, no case of ITP has been documented after receiving multiple uneventful COVID vaccine doses. Here we present a case of ITP presumably secondary to his 5th mRNA COVID-19 booster.

Case Presentation A 76-year-old male with Type 2 Diabetes Mellitus, Hypertension, and Hyperlipidemia, presented to the emergency department for a low platelet count of 8x10^3/uL found on outpatient blood work done at his primary care physician’s office. The patient had received the 5th dose of mRNA COVID-19 vaccine booster 4 days before presentation and developed a rash on bilateral lower extremities the day after receiving the vaccine. On the day of admission, the patient had minorbleeding from the gums. Otherwise, he denied fevers, lymphadenopathy, URI symptoms, epistaxis, hemoptysis, abdominal pain, nausea, vomiting, diarrhea, hematochezia, melena, new medications, or new illness. The patient denied personal or family history of bleeding, clotting or thrombocytopenia. The patient had received 4 doses of the Moderna vaccine in the past without any adverse reaction.

Peripheral smear revealed 1-2 schistocytes, PLASMIC score of 3. Treatment included dexamethasone 40mg daily x 4 days and intravenous immunoglobulin (IVIG) 0.5g/kg x 3 days. The fourth dose of IVIG was held in the setting of acute kidney injury with Creatinine rise 1.1 to 1.4, which improved to 1.3 after IV fluids. The patient did not require transfusion and platelet count improved to 126x10^3/uL on discharge. Of note, the patient developed marginal zone B-cell lymphoma 6 months after his initial presentation.

Discussion This case illuminates the potential for confounding variables and the elusive nature in diagnosing ITP. Recognizing the distinction between primary ITP and secondary ITP is crucial in guiding management and improving patient outcomes. Primary ITP is a diagnosis of exclusion, and typically responds well to steroids and IVIG. Despite this patient’s subsequent diagnosis of marginal zone B-cell lymphoma, he responded well to combination of IVIG and steroid treatment. As secondary ITP induced by lymphoma treatment is usually successful only when underlying disease is controlled, patient’s thrombocytopenia may not be related to lymphoma. Identifying the root cause of thrombocytopenia informs appropriate treatment strategies and management of the patient's overall health. IVIG is an expensive therapy, and its use should be carefully considered to reduce medical expenditure and improve patient outcomes.