A Management Conundrum: Active Infection and Secondary Immune Thrombocytopenia in an Immunocompromised Patient

Introduction/Background/Significance: Immune Thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by platelet count < 100 K/uL. Pathogenesis involves peripheral destruction of platelets with antiplatelet autoantibodies and/or inhibition of platelet production. Primary ITP is a diagnosis of exclusion with no identifiable cause. Secondary ITP can occur from infections (HIV, Hepatitis C), autoimmune diseases, lymphoproliferative disorders, or medications. First-line treatment for ITP is corticosteroids +/- IVIG. In this case, we describe a patient with ITP and acute HIV infection with bacteremia highlighting the challenges of treatment when corticosteroids and other therapies are contraindicated.

Materials and Methods/Case Presentation/Objective: 26-year-old male with history of chronic variable immune deficiency (CVID) on monthly IVIG therapy and warm autoimmune hemolytic anemia (WAIHA) status post splenectomy who presented with weakness, fatigue and non-bloody diarrhea. On presentation, he was profoundly hypotensive with a lactic acidosis and mucosal bleeding. Initial labs showed leukocytosis of 57.8 K/uL, hemoglobin concentration 11.5 g/dL, and platelet count < 2 K/uL (baseline 251 K/uL). The patient was admitted to the intensive care unit for management of septic shock and multiorgan failure requiring vasopressors. Blood cultures grew Streptococcus mitis in 2/2 bottles.

His septic shock resolved, and WBC count improved with antibiotics. His platelet count remained undetectable and he developed iron deficiency anemia. He had ongoing mucosal bleeding requiring daily platelet transfusions. Peripheral blood smear showed hypochromic anemia, no schistocytes, and no evidence of peripheral platelet destruction. Immature platelet fraction (IPF) was reduced. IVIG 1 g/kg was given without improvement of platelets. HIV screening returned positive, with viral load 570,000 copies. The patient was given romiplostim 1 mcg/kg and IPF improved. Highly active antiretrovirals (HAART) were initiated. Platelet count continued to be refractory and romiplostim dose was escalated to 4 mcg/kg. Ultimately, on hospital day 23, his platelet count rose above to 17 K/uL. Despite a rising IPF, the platelet count continued to fluctuate, suggesting ongoing peripheral destruction. He remains on weekly romiplostim 4mcg/kg to maintain a safe platelet count.

Conclusions: This patient had several possible etiologies and risk factors for developing ITP: CVID, HIV, and influenza B. Initially, there was evidence of mixed bone marrow hypoproliferation (low IPF) and peripheral immune-mediated destruction. Our patient did not improve with resolution of underlying bacteremia and initiation of HAART. He had a bone marrow response to romiplostim but continued to have evidence of peripheral destruction of platelets. Our patient was treated with romiplostim with weekly dose-escalations up to 4 mcg/kg to target an appropriate rise in platelets. Platelet counts were able to improve to >30 K/dL, however he continued to have ongoing platelet destruction. Corticosteroids were avoided due to the active infection. Second line therapies for ITP can include splenectomy and rituximab. Our patient already has a history of splenectomy and rituximab was contraindicated due to infection. Overall, this case highlights the challenges and limitations of treatment options available for ITP when trying to avoid corticosteroids and further immunosuppression in an already immunocompromised patient.