BFU: burst-forming units
CFU: colony-forming units
CFU-E: CFU erythrocyte
CFU-GM: CFU granulocyte and macrophage
CFU-Meg: CFU megakaryocyte
CKD: chronic kidney disease
CoA: coenzyme A
CSF: colony-stimulating factor
dTMP: deoxythymidine monophosphate
dUMP: deoxyuridine monophosphate
ESA: erythropoiesis-stimulating agent
FIGLU: formiminoglutamic acid
G-CSF: granulocyte colony-stimulating factor
GM-CSF: granulocyte-macrophage colony-stimulating factor
HFE: high Fe, hereditary hemochromatosis protein, hemeostatic iron regulator
HIF: hypoxia-inducible factor
HIV: human immunodeficiency virus
IRE: iron-regulating element
IRP: iron-regulating protein
ITP: immune thrombocytopenia
M-CSF: monocyte-/macrophage-stimulating factor
MDS: myelodysplastic syndromes
PBSC: peripheral blood stem cell
PteGlu: pteroylglutamic acid, folic acid
rHuMGDF: recombinant human megakaryocyte growth and development factor
TRA: thrombopoietin receptor agonist
TGFβ: transforming growth factor β
VHL: von Hippel-Lindau
The finite life span of most mature blood cells requires their continuous replacement, a process termed hematopoiesis. New cell production must respond to basal needs and states of increased demand. Erythrocyte production can increase more than 20-fold in response to anemia or hypoxemia, leukocyte production increases dramatically in response to systemic infections, and platelet production can increase 10- to 20-fold when platelet consumption results in thrombocytopenia.
The regulation of blood cell production is complex. Hematopoietic stem cells are rare marrow cells that manifest self-renewal and lineage commitment, resulting in cells destined to differentiate into the 10 or more distinct blood cell lineages. For the most part, this process occurs in the marrow cavities of the skull, vertebral bodies, pelvis, and proximal long bones; it involves interactions among hematopoietic stem and progenitor cells and the cells and complex macromolecules of the marrow stroma and is influenced by a number of soluble and membrane-bound hematopoietic growth factors. Several hormones and cytokines have been identified and cloned that affect hematopoiesis, permitting their production in quantities sufficient for research and, in some cases, therapeutic use. Clinical applications range from the treatment of primary hematological diseases (e.g., aplastic anemia, congenital neutropenia) to use as adjuncts in the treatment of severe infections and in the management of patients with kidney failure or those undergoing cancer chemotherapy or marrow transplantation.
Hematopoiesis also requires an adequate supply of minerals (e.g., iron, cobalt, and copper) and vitamins (e.g., folic acid, vitamin B12, pyridoxine, ascorbic acid, and riboflavin); deficiencies generally result in characteristic anemias or, less frequently, a general failure of hematopoiesis (Rojas-Hernandez and Oo, 2018). Therapeutic correction of a specific deficiency state depends on the accurate diagnosis of the basis for the anemia and on knowledge about the correct dose, formulation, and route of administration of the deficient mineral(s) or vitamin(s).
GROWTH FACTOR PHYSIOLOGY
Steady-state hematopoiesis encompasses the tightly regulated production of more than 400 billion blood cells each day. The hematopoietic organ also is unique in adult physiology in that several mature cell types are ...