Congenital conditions that cause thrombocytopenia include amegakaryocytic thrombocytopenia, the thrombocytopenia-absent radius syndrome, and Wiskott-Aldrich syndrome; these disorders usually feature isolated thrombocytopenia, whereas patients with Fanconi anemia and dyskeratosis congenita typically include cytopenias in other blood cell lineages. Mutations in genes (FLI1, MYH9, GATA1, ETV6, among others) that cause thrombocytopenia are being identified.
Acquired causes of bone marrow failure (see Chapter 13) leading to thrombocytopenia include, but are not limited to, acquired aplastic anemia, myelodysplastic syndrome (MDS), acquired amegakaryocytic thrombocytopenia (albeit a rare disorder), alcohol, and drugs. Unlike aplastic anemia, MDS is more common among older patients.
See Chapter 13 for symptoms and signs of aplastic anemia. Acquired aplastic anemia typically presents with reductions in multiple blood cell lineages, and the CBC reveals pancytopenia (anemia, thrombocytopenia, and neutropenia). A bone marrow biopsy is required for diagnosis and reveals marked hypocellularity. MDS also presents as cytopenias and can have pancytopenia, but the marrow typically demonstrates hypercellularity and dysplastic features. The presence of macrocytosis, ringed sideroblasts on iron staining of the bone marrow aspirate, dysplasia of hematopoietic elements, or cytogenetic abnormalities (especially monosomy 5 or 7 and trisomy 8) is more suggestive of MDS.
Adult patients with acquired amegakaryocytic thrombocytopenia (rare) have isolated thrombocytopenia and reduced or absent megakaryocytes in the bone marrow, which along with failure to respond to immunomodulatory regimens typically administered in immune thrombocytopenia (ITP), distinguishes them from patients with ITP.
Treatment is varied but may include blood product support, blood cell growth factors, androgens and, in some cases, allogeneic hematopoietic stem cell transplantation.
Patients with severe aplastic anemia are treated with immunosuppressive therapy or allogeneic hematopoietic stem cell transplantation (see Chapter 13).
Treatment of thrombocytopenia due to MDS, if clinically significant bleeding is present or if the risk of bleeding is high, is limited to chronic transfusion of platelets in most instances (Table 14–3). Additional treatment is discussed in Chapter 13.
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