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Overview of Decreased Erythropoiesis

By Evan M. Braunstein, MD, PhD, Assistant Professor of Medicine, Division of Hematology, Department of Medicine, Johns Hopkins School of Medicine

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Anemia (a decrease in the number of RBCs, Hb content, or Hct) can result from decreased RBC production (erythropoiesis), increased RBC destruction, blood loss, or a combination of these factors.

Anemias due to decreased erythropoiesis (termed hypoproliferative anemias) are recognized by reticulocytopenia, which is usually evident on the peripheral smear.

The RBC indices, mainly the mean corpuscular volume (MCV), can narrow the differential diagnosis of deficient erythropoiesis and help determine what further testing is necessary.

Microcytic anemias result from deficient or defective heme or globin synthesis. Microcytic anemias include iron deficiency anemias, iron-transport deficiency anemias, iron-utilization anemias (including some sideroblastic anemias and lead poisoning), and thalassemias (which also cause hemolysis). Patients with microcytic anemias typically require testing of iron stores.

Normocytic anemias are characterized by a normal RBC distribution width (RDW) and normochromic indices. The two most common causes are hypoproliferation due to a deficiency of or inadequate response to erythropoietin (EPO) and anemia of chronic disease. Acquired primary bone marrow disorders such as aplastic anemia, pure red cell aplasia, and myelodysplastic syndrome (MDS) can also present with a normocytic anemia.

Macrocytic anemias can be caused by impaired DNA synthesis leading to megaloblastosis, as occurs with deficiencies of vitamin B12 or folate (see Megaloblastic Macrocytic Anemias). Other causes include chronic alcohol intake (independent of vitamin deficiency), liver disease, myelodysplastic syndrome (MDS), and hemolysis. Some patients with hypothyroidism have macrocytic RBC indices, including some without anemia.

Many anemias have variable findings on the peripheral smear. Anemia of chronic disease may be microcytic or normocytic. Anemias due to myelodysplastic syndromes may be normocytic or macrocytic. Anemias due to endocrine disorders (such as hypothyroidism) or elemental deficiencies (such as copper or zinc) can have variable manifestations, including a normocytic or macrocytic anemia.

Treatment of deficient RBC production depends on the cause.