Antibody-mediatedIsohemagglutinins:transfusionreactions,immunehydrops(Rhdiseaseofthenewborn)Autoantibodies:idiopathic(primary),drug-associated,systemiclupuserythematosusMechanicaltraumatoredcellsMicroangiopathichemolyticanemias:thromboticthrombocytopenicpurpura,disseminatedintravascularcoagulationDefectivecardiacvalvesInfections:malaria
Disturbedproliferationanddifferentiationofstemcells:aplasticanemia,pureredcellaplasia
DisturbedproliferationandmaturationoferythroblastsDefectiveDNAsynthesis:deficiencyorimpaireduseofvitaminB12andfolicacid(megaloblasticanemias)Anemiaofrenalfailure(erythropoietindeficiency)Anemiaofchronicdisease(ironsequestration,relativeerythropoietindeficiency)AnemiaofendocrinedisordersDefectivehemoglobinsynthesis
Deficienthemesynthesis:irondeficiency,sideroblasticanemiasDeficientglobinsynthesis:thalassemiasMarrowreplacement:primaryhematopoieticneoplasms(acuteleukemia,myelodysplasticsyndromes)Marrowinfiltration(myelophthisicanemia):metastaticneoplasms,granulomatousdisease later), the decrease in tissue oxygen tension that accompanies anemia triggers increased production of the growth factor erythropoietin from specialized cells in the kidney. This in turn drives a compensatory hyperplasia of erythroid precursors in the bone marrow and, in severe anemia, the appearance of extramedullary hematopoiesis within the secondary hematopoietic organs (the liver, spleen, and lymph nodes). In well-nourished persons who become anemic because of acute bleeding or increased red cell destruction (hemolysis), the compensatory response can increase the production of red cells fivefold to eightfold. The rise in marrow output is signaled by the appearance of increased numbers of newly formed red cells (reticulocytes) in the peripheral blood. By contrast, anemia caused by decreased red cell production (aregenerative anemia) is associated with subnormal reticulocyte counts (reticulocytopenia).
Anemia also can be classified on the basis of red cell morphology, which often points to particular causes. Features that provide etiologic clues include the size, color, and shape of the red cells. These are judged subjectively by visual inspection of peripheral smears and also are expressed quantitatively using the following indices:
Mean cell volume (MCV): the average volume per red cell, expressed in femtoliters (cubic microns)
Mean cell hemoglobin (MCH): the average mass of hemoglobin per red cell, expressed in picograms
Mean cell hemoglobin concentration (MCHC): the average concentration of hemoglobin in a given volume of packed red cells, expressed in grams per deciliter
Red cell distribution width (RDW): the coefficient of variation of red cell volume
Red cell indices are directly measured or automatically calculated by specialized instruments in clinical laboratories. The same instruments also determine the reticulocyte count, a simple measure that distinguishes between hemolytic and aregenerative anemia. Adult reference ranges for these tests are shown in