Abstract
Thrombocytopenia and pancytopenia, occurring in patients with Fanconi anemia (FA), are interpreted either as progression to bone marrow failure or as developing myelodysplasia. On the other hand, immune thrombocytopenia (ITP) represents an acquired and often self-limiting benign hematologic disorder, associated with peripheral, immune-mediated, platelet destruction requiring different management modalities than those used in congenital bone marrow failure syndromes, including FA. Here, we describe the clinical course of two independent FA patients with atypical – namely immune – thrombocytopenia. While in one patient belonging to complementation group FA-A, the ITP started at 17 months of age and showed a chronically persisting course with severe purpura, responding well to intravenous immunoglobulins (IVIG) and later also danazol, a synthetic androgen, the other patient (of complementation group FA-D2) had a self-limiting course that resolved after one administration of IVIG. No cytogenetic aberrations or bone marrow abnormalities other than FA-typical mild dysplasia were detected. Our data show that acute and chronic ITP may occur in FA patients and impose individual diagnostic and therapeutic challenges in this rare congenital bone marrow failure/tumor predisposition syndrome. The management and a potential context of immune pathogenesis with the underlying marrow disorder are discussed.
Highlights
Thrombocytopenia and pancytopenia are frequent hematologic manifestations of Fanconi anemia (FA) ascribed to a varying, increasing degree of congenital bone marrow failure and developing myelodysplasia
After mitomycin C-mediated induction of G2 arrest and chromosomal breaks and/or complementation group analysis for FA, genetic testing was performed by means of multiplex ligation-dependent probe amplification (MLPA) and exon-scanning sequencing of genomic DNA of all exons of FANCA and of FANCD2
While in one patient with a FANCA mutation, the immune thrombocytopenia (ITP) started at 17 months of age and showed a chronically persisting course with severe purpura, that responded to intravenous immunoglobulins (IVIG) and synthetic androgen therapy, the other patient had a self-limited course that resolved after a single administration of IVIG
Summary
Thrombocytopenia and pancytopenia are frequent hematologic manifestations of Fanconi anemia (FA) ascribed to a varying, increasing degree of congenital bone marrow failure and developing myelodysplasia. Treatment options range from none (observation) to therapeutic administration of androgens and, in case of transfusion dependence or signs of (pre-) malignancy, e.g., cytogenetic aberrations indicative of clonal evolution, hematopoietic stem cell transplantation. Immune thrombocytopenia (ITP) is observed as an acquired acute and self-limited benign post- or para-infectious or idiopathic cytopenia in otherwise healthy children that, if treatment is required, usually responds well to high-dose intravenous immunoglobulins (IVIG) and/or corticosteroids [4]. Chronic ITP may develop and indicate an underlying immune hematologic disorder [5]. Refractory chronic ITP with bleeding diathesis sometimes requires additional immunosuppressive or thrombopoietin agonist treatment, or splenectomy. We delineate the diagnostic and therapeutic challenges of this previously unnoticed concurrence and discuss potential implications
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