Unusual Bone Marrow Findings in a Patient with Congenital Amegakaryocytic Thrombocytopenia.

Abstract

BACKGROUND: Congenital Amegakaryocytic Thrombocytopenia (CAMT) is a rare bone marrow failure syndrome that presents with isolated thrombocytopenia within the first year of life. Classic diagnostic bone marrow findings reveal absent or significantly decreased megakaryocytes with otherwise normal marrow cellularity. We present a case of a newborn with CAMT whose initial bone marrow aspirate showed an appropriate number of megakaryocytes.CASE: A caucasian male presented on day-of-life (DOL) 1 with petechiae and a platelet count of 13,000/mcL. Physical exam, WBC count and hemoglobin were otherwise normal. Alloimmune thrombocytopenia evaluation and CMV serology were negative. Platelet transfusions were required almost daily to maintain platelet counts >100,000/mcL in the neonatal period. Tibial bone marrow aspirate performed on DOL 21 revealed normocellular marrow with a normal number of immature megakaryocytes. [Display omitted] Cytogenetics were normal and DNA breakage studies were negative. Beyond 1-month-of-age, platelet counts were maintained >25-30,000/mcL with 1–2 transfusions per week. Repeat bone marrow aspirate and biopsy on DOL 102, from the iliac crest, again was normocellular, but was now significant for marked megakaryocytic hypoplasia.Number of Megakaryocytes Found on Serial Bone Marrow AspiratesAgePatientAge-Matched Control21 days31.6102 days02.14 slides per aspiration site were examined at the feathered edge at 40× magnification. Data is expressed in average number of megakaryocytes/10 hpfMutation analysis of the gene responsible for the thrombopoietin receptor MPL was notable for a homozygous point mutation in exon 3, resulting in a substitution of proline for arginine at amino acid position 102. This missense mutation has been previously associated with CAMT.CONCLUSION: This is the third reported case of normal megakaryocyte numbers found on the initial bone marrow aspirate, in a patient who was later diagnosed with CAMT. CAMT should not be excluded from the differential diagnosis of persistent thrombocytopenia within the first year of life, solely based on normal numbers of megakaryocytes on the initial bone marrow. The presence of immature megakaryocytes may represent early morphological findings in CAMT.