Hematological Abnormalities
Clinically, hematological abnormalities are the most serious symptoms in FA. By the age of 40, 98% of FA patients will have developed some type of hematological abnormality. It is interesting to note, however, the few cases in which older patients have died without ever developing them. Symptoms appear progressively, and often lead to complete bone marrow failure. While at birth, blood count is usually normal, macrocytosis/megaloblastic anemia, defined as unusually large red blood cells, is the first detected abnormality, often within the first decade of life (median age of onset is 7 years). Within the next 10 years, over 50% of patients presenting haematological abnormalities will have developed pancytopenia, defined as abnormalities in two or more blood cell lineages. Most commonly, a low platelet count (thrombocytopenia) precedes a low neutrophil count (neutropenia), with both appearing with relative equal frequencies. The deficiencies cause increased risk of hemorrhage and recurrent infections, respectively.
As FA is now known to affect the DNA repair, and given the current knowledge about dynamic cell division in the bone marrow, it is not surprising to find patients are more likely to develop bone marrow failure, myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). The next sections will detail those pathologies.
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