Hematology: Red Cell Disorders, Anemias, Hemoglobinopathies, and Bone Marrow Failure
Two questions first
Every pediatric anemia question reduces to two: is the marrow responding (reticulocyte index), and is the red cell small, normal, or large (MCV with RDW)? A low reticulocyte count in an anemic child means a production problem - iron deficiency, thalassemia, marrow failure, or transient erythroblastopenia of childhood. A high count means loss or destruction - bleeding, hemolysis, or sequestration.
Microcytic disease
Iron deficiency is the most common cause; ferritin is the best single test but rises as an acute-phase reactant, so pair it with CRP or soluble transferrin receptor when the child is ill. The Mentzer index (MCV divided by RBC count) separates it from thalassemia trait: under 13 favors thalassemia, over 13 favors iron deficiency. Thalassemia trait shows a normal ferritin, a high RBC count, and target cells; iron deficiency shows a high RDW and a low ferritin.
Hemoglobinopathies
Sickle cell disease requires penicillin prophylaxis, pneumococcal vaccination, transcranial Doppler screening, hydroxyurea, and family education about splenic sequestration and acute chest syndrome. Hydroxyurea raises MCV and fetal hemoglobin - macrocytosis on therapy is expected, not a reason to stop. Hereditary spherocytosis presents with elevated MCHC, reticulocytosis, and a negative Coombs test; parvovirus B19 triggers an aplastic crisis. G6PD deficiency causes episodic hemolysis with bite cells and Heinz bodies after oxidative stress.
Marrow failure
Fanconi anemia is confirmed by chromosome breakage studies with diepoxybutane or mitomycin C; Diamond-Blackfan anemia is a pure red cell aplasia with elevated erythrocyte adenosine deaminase that often responds to corticosteroids.
Rule of thumb
Correct the reticulocyte percentage for the degree of anemia before interpreting it; a "normal" 2% is inappropriately low when the hematocrit is 20%.
Trap
A child with iron deficiency and a coexisting inflammatory state may have a normal ferritin - never exclude iron deficiency on ferritin alone in a sick child.