Case Presentation: A 71-year-old woman presented with progressive fatigue and two months of dull pain in her proximal extremities. Medical history was significant for depression with psychotic features, well-controlled on fluoxetine and trifluoperazine. Exam demonstrated diffuse non-tender hyperpigmented patches on her back and forearms and proximal extremity tenderness. Labs revealed a hemoglobin (Hb) of 4.1g/dL and platelets (plts) of 1×109/L. Basic chemistries, iron studies, B12, folate, and lactate dehydrogenase were normal. HBV, HCV, HIV, EBV, CMV, and parvovirus serologies were negative. Anti-nuclear antibody (Ab) and complement levels were normal. Radiographs of long bones showed no lytic lesions, and ultrasound demonstrated no hepatosplenomegaly. The patient’s Hb responded appropriately to one unit of packed red blood cells. However, she continued to require plt transfusions every 1-2 days. Her plt Ab was positive, but she failed to improve despite high dose steroids and IVIG. A bone marrow biopsy (BMBx) showed toxic damage and absence of megakaryocytes. Trifluoperazine was then suspected as the inciting cause but the patient failed to improve despite its discontinuation. Given the clinical course and absence of megakaryocytes on BMBx, the patient was diagnosed with acquired pure megakaryocytic aplasia. She is currently undergoing a trial of cyclosporine, but continues to require weekly plt transfusions.
Discussion: Anemia and thrombocytopenia are exceedingly common in hospitalized patients. In severe cases, identification of the cause is critical to management. Our case describes a patient with the rare diagnosis of megakaryocytic aplasia, inconsistently described as acquired pure megakaryocytic aplasia (APMA) or acquired amegakaryocytic thrombocytopenia purpura (AATP). APMA, described only in a few case reports, is identified by severe thrombocytopenia and megakaryocytic aplasia. AATP is a similar diagnostic entity with associated purpuric skin changes. Suggested causes include cytogenetic changes, viral infections, autoimmune diseases, and drugs or toxins. However, in many cases a cause is not identified. While the pathophysiology is unclear, available evidence favors autoimmune mechanisms. Patients with APMA may have IgG Abs to the thrombopoietin receptor and respond to immunosuppressive therapy. Given the paucity of cases, the ideal treatment regimen is unknown. In our patient’s case, the positive plt Ab further complicates her clinical picture as she has both an underproduction of plts due to aplasia and increased peripheral destruction.
Conclusions: APMA and AATP are rare disease syndromes, whose hallmark signs are severe thrombocytopenia and megakaryocyte aplasia on BMBx. While identifying a trigger is critical to address reversible causes, our case illustrates a presentation without identifiable cause and demonstrates the challenges in diagnosing APMA. Our case also highlights the difficulty in treating these syndromes.
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