Normocytic Normochromic Anemias

M H Qari, MD, FRCPAAssociate Professor of

Hematology

Aplastic anemia

Aplastic anemia is a severe, life threatening syndrome in which production of erythrocytes, WBCs, and platlets has failed.Aplastic anemia may occur in all age groups and both genders.The disease is characterized by peripheral pancytopenia and accompanied by a hypocellular bone marrow.

Hypocellular bone marrow in aplastic anemia

Aplastic anemia

Pathophysiology:The primary defect is a reduction in or depletion of hematopoietic precursor stem cells

This may be due to quantitative or qualitative damage to the pluripotential stem cell.In rare instances it is the result of abnormal hormonal stimulation of stem cell proliferation or the result of a defective bone marrow microenvironment or from cellular or humoral immunosuppression of hematopoiesis.

Aplastic anemia

EtiologyAcquired

Most cases of aplastic anemia are idiopathicExposure to ionizing radiation – hematopoietic cells are especially susceptible to ionizing radiation. Whole body radiation of 300-500 rads can completely wipe out the bone marrow. Chemical agents – include chemical agents with a benzene ring, chemotherapeutic agents, and certain insecticides.Idiosyncratic reactions to some commonly used drugs such as chloramphenicol or quinacrine.

Aplastic anemia

Infections – viral and bacterial infections such as infectious mononucleosis, infectious hepatitis, cytomegalovirus infections, and miliary tuberculosis ;Pregnancy (rare)Paroxysmal nocturnal hemoglobinuria – this is a stem cell disease in which the membranes of RBCs, WBCs and platlets have an abnormality making them susceptible to complement mediated lysis.Other diseases – preleukemia and carcinoma

Aplastic anemia

Congenital disordersFanconi’s anemia – the disorder usually becomes symptomatic ~ 5 years of age and is associated with progressive bone marrow hypoplasia. Congenital defects such as skin hyperpigmentation and small stature are also seen in affected individuals.Familial aplastic anemia – a subset of Fanconi’s anemia in which the congenital defects are absent.

Clinical manifestationsFatigueHeart palpitationsPallorInfectionsPetechiaeMucosal bleeding

Aplastic anemia

Lab findingsSevere pancytopenia with relative lymphocytosis (lymphocytes live a long time)Normochromic, normocytic RBCs (may be slightly macrocytic)Mild to moderate anisocytosis and poikilocytosisDecreased reticulocyte countHypocellular bone marrow with > 70% yellow marrow

Treatment – in untreated cases the prognosis is poorRemove causative agent, if knownMultiple transfusionsBone marrow transplant

Pure Red Cell Aplasia

Pure red cell aplasia s characterized by a selective decrease in erythroid precursor cells in the bone marrow. WBCs and platlets are unaffected.

AcquiredTransitory with viral or bacterial infectionsPatients with hemolytic anemias may suddenly halt erythropoiesisPatients with thymoma – T-cell mediated responses against bone marrow erythroblasts or erythropoietin are sometimes produced.

Pure Red Cell Aplasia

CongenitalDiamond-Blackfan syndrome – occurs in young children and is progressive. It is probably due to an intrinsic or regulatory defect in the committed erythroid stem cell.

Other causes of Normocytic Normochromic Anemia

Myelopthesic anemia – replacement of bone marrow by fibrotic, granulomatous, or neoplastic cellsHypersplenism – why can this lead to pancytopenia?

Severe Chronic infection or inflammation

Myelodysplastic syndromes – are primary, neoplastic stem cell disorders that tend to terminate in acute leukemia. The bone marrow is usually normocellular, or hypercellular with evidence of qualitative abnormalities in one or more cell lines resulting on ineffective erythropoiesis and/or granulopoiesis and/or megakaryopoiesis. The peripheral smear shows dysplastic (abnormality in development) cells including nucleated RBCs, oval macrocytes, pseudo-Pelger-Huet PMNs (hyposegmented neutrophils) with hyperchromatin clumping, hypogranulated neutrophils, and giant bizarre platlets.

Other hypoproliferative anemias

Renal disease – due to decreased erythropoietinEndocrine deficiencies – may lead to decreased erythropoietin production. For example: hypothyroidism leads to decreased demand for oxygen from tissues; decreased androgens in males; decreased pituitary function