NOTES NOTES NORMOCYTIC ANEMIA (DECREASED PRODUCTION) GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Insufﬁcient production of erythrocytes AKA red blood cells (RBCs) CAUSES ▪ Chronic diseases most common cause (e.g. kidney disease, cancer, rheumatoid arthritis) SIGNS & SYMPTOMS ▪ Variable depending on degree of hypoxia, pallor; fatigue; dyspnea; activity intolerance; cardiorespiratory compromise DIAGNOSIS LAB RESULTS ▪ ▪ ▪ ▪ ▪ Complete blood count (CBC) Peripheral blood smear analysis Blood chemistry Iron studies Genetic testing (rarely) TREATMENT MEDICATIONS ▪ Dietary changes OTHER INTERVENTIONS ▪ Supplementation (address iron deﬁciency) ANEMIA OF CHRONIC DISEASE (ACD) osms.it/anemia-of-chronic-disease PATHOLOGY & CAUSES ▪ Deﬁcient RBC production due to chronic diseases (e.g. infection, inﬂammation, malignancy) ▪ AKA anemia of chronic inﬂammation CAUSES ▪ Inﬂammatory processes in iron homeostasis ▪ Systemic inﬂammation → ↑ circulation cytokines, interleukin 1 (IL1), interleukin 6 (IL6), tumor necrosis factor alpha (TNF alpha), interferon beta (IFN beta), interferon gamma (IFN gamma) ▫ ↑ hepcidin secretion by liver → ↓ iron absorption from gastrointestinal (GI) tract, ↓ iron sequestration in reticuloendothelial system → ↓ iron available for erythropoiesis ▫ ↓ secretion of erythropoietin ▫ Direct inhibition of erythropoiesis ▫ ↓ erythrocyte lifespan OSMOSIS.ORG 421
RISK FACTORS ▪ Advanced age, physical trauma SIGNS & SYMPTOMS ▪ Hypoxia, pallor; fatigue; dyspnea; activity intolerance; cardiorespiratory compromise ▪ Variable depending on degree of hypoxia DIAGNOSIS ▪ ▪ ▪ ▪ ▪ ▪ ▪ (ESR), C-reactive protein (CRP), IL6 Decreased serum iron levels High ferritin Decreased serum transferrin saturation Decreased total iron binding capacity Low serum erythropoietin concentration Decreased reticulocyte count Bone marrow examination ▫ Increased iron in macrophages (related to actions of hepcidin), erythroid precursors LAB RESULTS ▪ RBCs normochromic, normocytic ▪ Microcytic, hypochromic RBCs (rarely) ▪ Leukocytosis ▫ Underlying disorder ▪ Normal/low mean corpuscular hemoglobin (MHC), mean corpuscular volume (MCV) ▪ Normal mean corpuscular hemoglobin concentration (MCHC) ▪ Normal/increased red cell distribution width (RDW) normal/increased ▪ Erythrocyte hypoproliferation ▫ Decreased RBC count ▫ Mild to moderate decrease in hemoglobin ▪ Elevated erythrocyte sedimentation rate 422 OSMOSIS.ORG TREATMENT MEDICATIONS ▪ Supplemental iron ▫ IV more effective than oral iron for systemic inﬂammation ▪ Erythropoiesis-stimulating agents (e.g. epoetin alfa, darbepoetin alpha) ▫ For severe anemia OTHER INTERVENTIONS ▪ Transfusion of packed RBCs ▫ For severe anemia
Chapter 53 Normocytic Anemia (Decreased Production) APLASTIC ANEMIA osms.it/aplastic-anemia PATHOLOGY & CAUSES ▪ Pancytopenia due to bone marrow hypoplasia/aplasia ▪ Idiopathic/inherited/acquired CAUSES ▪ Inherited ▫ Fanconi anemia; Shwachman–Diamond syndrome; familial aplastic anemias; reticular dysgenesis ▪ Acquired ▫ Immune processes (e.g. systemic lupus erythematosus, graft-versushost disease, paroxysmal nocturnal hemoglobinuria) ▫ Drugs (e.g. cytotoxic cancer chemotherapy, carbamazepine, phenytoin, indomethacin, sulfonamides, chloramphenicol) ▫ Viruses (e.g. Epstein–Barr, HIV, hepatitis, herpes) ▫ Toxic chemicals (e.g., solvents, benzene, pesticides) ▫ Ionizing radiation ▪ Acquired or idiopathic ▫ Insidious onset of bone marrow hypoplasia/aplasia, hematopoietic cell loss → ↓ production of cell lineages (thrombocytes, leukocytes, erythrocytes) → peripheral pancytopenia COMPLICATIONS ▪ Impairment of blood’s immunity, hemostasis, oxygen-carrying capacities SIGNS & SYMPTOMS ▪ Deﬁcient thrombocytes, leukocytes ▫ Shorter lifespan ▪ Neutropenia ▫ Increased frequency/severity of infections ▫ Neutropenia-related sepsis common cause of death ▪ Thrombocytopenia ▫ Mucosal hemorrhage (e.g. gingival, nares, ecchymosis, petechiae, heavy menstrual ﬂow, occult blood in stool, intracranial hemorrhage) ▪ Anemia ▫ Pallor, fatigue, dyspnea, activity intolerance, cardiorespiratory compromise DIAGNOSIS LAB RESULTS Prolonged bleeding time Decreased hemoglobin, hematocrit Absolute neutrophil count decreased Platelet count decreased Reticulocyte count decreased ▫ Normal erythrocyte morphology ▪ Bone marrow biopsy ▫ Some lymphocytes, plasma cells, stromal elements (e.g. blastoid cells) ▫ No increase in blasts/dysplasia ▪ ▪ ▪ ▪ ▪ TREATMENT ▪ Treat underlying cause ▫ Discontinue offending drug treatment ▪ Varies by age, severity of symptoms, likelihood of ﬁnding donor match MEDICATIONS ▪ Manage cytopenias ▪ Antimicrobials for infections ▫ Medical emergency: fever + low absolute neutrophil count ▪ Growth factors ▫ Granulocyte colony-stimulating factor OSMOSIS.ORG 423
(G-CSF): frequent/severe infections ▫ Thrombopoietin (TPO) receptor agonists with immunosuppressive therapy ▫ Hematopoietic growth factors (rarely) ▪ Immunosuppressive therapy (IST) ▫ Consists of antithymocyte globulin (ATG) + cyclosporin A ▫ Administer glucocorticoid with ATG: steroid reduces risk of serum sickness; immunosuppressive properties ▫ Cyclosporin A: immunosuppressive ▫ Eltrombopag (thrombopoietic agent) to increase platelet count OTHER INTERVENTIONS ▪ Hematopoietic stem cell transplant ▫ Curative if effective ▪ Transfusions ▫ Platelets, packed red blood cells ▫ Increased risk of alloimmunization, graft rejection after bone marrow transplant 424 OSMOSIS.ORG Figure 53.1 A bone marrow biopsy from an individual with aplastic anemia. The bone marrow spaces contain large amounts of fat and minimal hematopoietic tissue is present.