Pure Red Cell Aplasia

Excerpt

Pure red cell aplasia (PRCA) is a rare disorder that presents with anemia from failure of erythropoiesis. This condition is characterized by normocytic, normochromic anemia with associated reticulocytopenia and absent or infrequent erythroblasts in the bone marrow. PRCA is distinct from aplastic anemia in having intact platelet and leukocyte precursors. Thus, PRCA has normal platelet and leukocyte numbers and morphology in the peripheral blood.

Kaznelson first described PRCA in 1922. The congenital or inherited form of PRCA, also called "Diamond-Blackfan syndrome," was first described by Joseph in 1936 and subsequently by Diamond and Blackfan in 1938. PRCA's thymoma association led to the discovery of the autoimmune mechanisms producing this rare disease. PRCA has also been the object of much laboratory research due to the condition's association with parvovirus B19 in patients with sickle cell disease. However, PRCA's rarity makes it difficult to conduct interventional trials. Thus, most PRCA treatment recommendations are based on retrospective studies or anecdotal case reports.

The Hematopoietic Process and Erythrocyte Formation

All cells in the peripheral blood and some solid tissues, eg, osteoclasts, arise from hematopoietic stem cells. Hundreds of billions of blood cells can form daily from a stem cell pool of only 100,000. Hematopoietic stem cells can undergo self-renewal and differentiation, allowing continuous blood cell regeneration and maintenance.

Blood cells appear in the 3rd week of embryonic development in the yolk sac. By the 3rd month, hematopoietic stem cells translocate from the yolk sac to the liver, the main site of blood cell production until the antenatal period. In the 4th month, hematopoietic stem cells start to populate various bone marrow sites. At birth, all skeletal marrow sites are hematopoietically active, replacing the liver and becoming the only blood cell source. The marrow remains red and hematopoietically active until puberty. By age 18, about half of the marrow spaces become fatty and inactive, and the only active sites remaining are found in the skull, vertebrae, sternum, ribs, pelvis, and proximal humeral and femoral epiphyses.

The hematopoietic cells arise from a pluripotent progenitor, which forms the common myeloid and lymphoid stem cell lines. Thrombopoietin and interleukin-11 (IL-11) commit some stem cells to become the common precursors for erythroid, megakaryocytic, and basophilic cells. Erythropoietin (EPO) promotes differentiation to proerythroblasts, which undergo several functional changes before becoming reticulocytes and mature erythrocytes. Red blood cells (RBCs) contain hemoglobin and are specialized to deliver oxygen from the alveoli to the peripheral tissues.