Type Wintrobe's Morphology Classification Epidemiology Unique Features Pathophysio Cause Etiology/ Pathogenesis CBC & Retic results Add'l Dx tests to confirm

Megaloblastic Anemia (vit B12/ cobalamin deficient)


Pernicious anemia (atrophic gastritis with failure of production of Intrinsic Factor, caused by autoimmune attack on gastric mucosa -> atrophy of stomach-> malabsorption) most common cause in Western countries (esp N. Europeans, occurs in families, females>males, peak at 60 yrs); other causes: vegan diet, congenital lack of IF, gastrectomy, diverticulosis, Crohn's, etc.

low serum vit B12, normal or raised serum folate, normal or low red cell folate; Schilling test (B12 vit B12 is coenzyme for methionine absorption +/- IF, synthase (needed to convert methyl distinguishes insidious onset, may low retic count, malabsorption from THF to THF), also assists in be mildly jaundiced, inadequate diet, conversion of CoA to succinyl CoA; leukopenia with diminished DNA low vit B12-> defective DNA synthesis glossitis, angular hyperclassic pernicious stomatitis, weight loss, segmented anemia = positive synthesis -> asynchronous maturation of neural tube defects in granulocytes, test, < 8% urinary (diminished nucleus & cytoplasm-> developing fetus, CV disease, excretion if no IF erythropoiesis) erythroblasts in bone marrow appear mild/moderate sterility, melanin thrombocytogiven, becomes megaloblastic (large); vit B12 pigmentation penia normal when IF absorption occurs in ileum, requires IF added), also diet secreted by parietal cells of fundic history, endoscopy, mucosa IF/parietal cell Ab's, abnormal f.a. incorp into neuronal lipids > neuro s/s (not seen in folate def)

Megaloblastic Anemia (folate deficient)


Nutritional (esp old age, institutions, poverty, special diets), Malabsorption (gastrectomy, Crohn's), Excess utilization (pregnancy, lactation, prematurity, hematological diseases, CA, inflamm diseases), Excess urinary folate loss (liver Dx, CHF), Drugs (anticonvulsants, sulfa), Mixed (liver Dx, alcoholism, ICU)





folate deficiency inhibits thymidylate synthesis (a rate-limiting step in DNA synthesis in which thymidine monophosphate is synthesized); all body cells receive folate from plasma as methyl THF (vit B12 is then needed to convert methyl THF to THF), lack of folate is the proximate cause of anemia in Vit B12 deficiency



normal or borderline serum vit B12, low serum folate, low red cell folate, diet history, tests for intestinal malabsorption, duodenal biopsy, underlying Dx

low MCHC) may result from: 1) Dietary lack (esp elderly due to diet restrictions. microcytic (low MCV. other in US (esp toddlers. high serum ferritin. bacterial endocarditis. or stomatitis. high TIBC. poor absorption). Plummerto growth & expansion of blood Vinson syndrome low Hb. women of anemia. angular dietary contents i. esophageal webs. decline 3) Increased requirement (growing in psychomotor kids. countries. increased sTfR. often erythropoiesis). volume). steatorrhea. lung mildly dominant s/s are those inflamm/disease abscess). pregnant women). does NOT respond to iron therapy . TNF-a. gastrectomy. low serum ferritin. sprue. phosphates which inhibit childbearing age) raised platelet increased loss irritability. hypochromic of underlying Dx 2) Chronic immune (MCV rarely <75) & microcytic disorders (RA. most imp cause in Western world) increased sTfR level. IFN-g triggered by underlying chronic inflamm or neoplasm-> inadequate erythropoietin response to anemia low Hb (rarely <9) low serum iron. but also common relation to the synthesis painless glossitis). in kids get oxalates. test stools for occult blood most common cause of anemia among hospitalized pts in US. poor. low TIBC. abundant stored iron in mononuclear phagos. CA of lung & breast) diminished erythroid production assoc with reduced erythroid prolif. adolescents. Anemia of chronic progressive anemia. serum transferrin WNL (presence of increased storage iron in marrow macs. and reduced TIBC rules out irondeficiency as cause). assoc with 3 categories of illnesses: may be 1) Chronic microbial normocytic & usually mild/nonnormochromic. degree of (diminished dysphagia. low MCH. development 4) Chronic blood loss (from GI/GU tracts. adolescent girls. children due (koilonychia). count cognitive fxn. impaired iron utilization (due to block in the transfer of iron from storage pool to erythroid precursors) > may mimic iron deficiency. infants due to Pica.Anemias Type Wintrobe's Morphology Classification Epidemiology Unique Features Pathophsio Cause Etiology/Pathogenesis CBC & retic results Add'l Dx tests to confirm Iron Deficiency Anemia hypochromic. low Hct. regional enteritis). deficiency in adult men and postmenopausal women is probably GI bleed. 3) Neoplasms (Hodgkin's. (pharyngeal/ diminished Hb higher in developing low retic count in 2) Impaired absorption (diarrhea. secretion of cytokines IL-1. carbonates. spoon nails small amt of iron in milk. or infections (osteomyelitis.e. low serum iron.

need chelation tx). DNA analysis . cardiac Dx. pts. transfusion dependent anemia. Hb H disease. MCV. low MCH. b-Thalassemia Intermedia = hereditary. get excess of H disease. 1 gene deletion = silent carrier diminished synthesis of alpha globin chains (diminished erythropoiesis) caused by gene deletions on c'some 16. or translation of b-globin mRNA. hepatosplenomegaly. need DNA b-chains -> aggregate into insoluble normal Hb with analysis to diagnose. retic count kids suffer growth retardation & early elevated death unless supported by transfusions. hypochromic (low MCV. incidence in US is highest in low MCHC) b-Thalassemia Minor these immigrants = 1 normal gene in the heterozygotes. TIBC. most common type diminished synthesis of beta globin chains (diminished erythropoiesis) defects in transcription. microcytic (low but doesn't require parts of Africa & SE Asia. if survive -> face becomes overlarge/distorted (Thalassemic facies). serum ferritin to distinguish from irondef anemia. iron overload unless chelation tx. measure serum iron (high due to transfusions. Hb electrophoresis shows absence of HbA (all is HbF). lysis of mature RBC's in spleen (hemolysis). Hb ranges 3-6 in manifests at age 6-9 mos when Hb untransfused syntesis switches from HbF to HbA. inclusions in RBC precursors-> thalassemia normal a/b-synthesis premature destruction in marrow traits ratio is reduced (ineffective erythropoiesis). 2 gene deletions = a-thalassemia trait. severe Mediteranean countries. o/w normal. hydrops fetalis. get excess of a-chains-> aggretate into insoluble inclusions in RBC precursors -> premature destruction in marrow (ineffective erythropoiesis). severity classified acc to # of low Hb with Hb Hb electrophoresis is genes missing/inactive. processing. skull with "hair on end" on x-ray. normally 4 copies of a-globin gene. asymp with mild/absent anemia. severe.Anemias Type Wintrobe's Morphology Classification Epidemiology Unique Features Pathophsio Cause Etiology/Pathogenesis CBC & retic results Add'l Dx tests to confirm alphaThalassemia HbH disease = microcytic. lysis of mature RBC's in spleen (hemolysis) but less severe than in b-Thalassemia beta-Thalassemia b-Thalassemia Major = homozygous. usually die by age 30 NOT helped by iron therapy. heterozygous. regular transfusions. low MCH) hereditary 4 gene deletions = incompat with life. 3 gene deletions = anemia with splenomegaly. but see RBC abnormalities. esp hypochromic.

bone marrow sample cell lines. iron def. shift of Hb O2 dissoc curve to right (milder symptoms) low Hb. reticulocytosis presence of thrombocytopenia in pt with known CA is always suspicious of extensive marrow replacement Anemia due to leukemia nomochromic. burr cells. low platelets responds to Erythropoietin (EPO) tx Anemia due to marrow damage space-occupying lesions -> destroy/disturb bone marrow -> myelophthisic anemia. leukocytosis. anemia of chronic disorders.3-DPG in response to anemia -> decreased O2 affinity. spicules (spurs). lymphomas. TNF-a). chemicals. get increased 2. thrombomarrow hypercellular cytopenia. normocytic ALL (kids esp age 3-7). production/release of differentiated neutropenia. shortening of RBC lifespan in severe uremia. inherited thrombocytopenia = Fanconi anemia with defects in DNA repair diminished erythropoiesis failure/suppression of multipotent anemia. neutropenia. osteosclerosis. also multiple myeloma. aluminum excess. thrombocytopenia. most common cause is metastatic CA. LP shows normal. drugs. leukemia. and 3) irradiation. 2 major mechs: 1) thrombocytoimmuno mediated suppression by penia. immune by: 1) anemia. liver disease diminished erythropoiesis affects all formed elements of blood. WBC with >30% leukemic may be low. myeloid stem cells -> inadequate leukopenia. normocytic or macrocytic most cases idiopathic. or high. increased risk of venous thrombosis 2 g/dl fall in Hb for every 10 mmol/l rise in blood urea diminished erythropoiesis impaired RBC production due to defective erythropoietin secretion. low retic activated T cells (via IFN-g. CML (ages 40-60). infiltrative diseases destroy normal marrow envt -> reactive fibrosis -> inapprop release of erythroid & myeloid precursors into peripheral blood-> immature forms of RBC and WBC appear in peripheral blood (leukoerythroblastosis) low Hb. diminished erythropoiesis ALL/AML: low ALL/AML: bone Hb. blasts.Anemias Type Wintrobe's Morphology Classification Epidemiology Unique Features Pathophsio Cause Etiology/Pathogenesis CBC & retic results Add'l Dx tests to confirm Aplastic anemia normochromic. granulopoietic thrombocytopredominance penia . low platelets. abnormal platelet fxn. 2) count intrinsic abnormality of stem cells Anemia of Renal Failure normochromic see many hematological abnormalities in CRF: reduced erythropoietin production. AML (increases with age). viruses. accum of bone marrow blast cells -> CSF with leukemic CML: bone marrow failure -> anemia cells. but many causes: acquired = pancytopenia char stem cell defect. CML: bone marrow increased hypercellular with basophils. folate def. 2) mediated.

on pathology involved). protein). -> phagocytosis reticulocytosis DO NOT SEE hemoglobinemia. of mismatched blood). haptoglobins. reduced plasma haptoglobins. complement fixation (ex: transfusion 2) hemoglobinuria (brown urine). directly in the circulation 3) marked increase in erythropoiesis in bone marrow to compensate hemolytic normal RBC's damaged by mech Main lab features: injury (ex: mech heart valves). 2) accum of products RBC's broken down of Hb catabolism. free Hb enters haptoglobin. hyperbilirubinemia. excess free Hb is reticulocytosis 4)methemalbuminfiltered by the glomerulus.Anemias Type Wintrobe's Morphology Classification Epidemiology Unique Features Pathophsio Cause Etiology/Pathogenesis CBC & retic results Add'l Dx tests to confirm Intravascular immune hemolysis Char of hemolytic anemias: 1) shortened RBC life 1 of the 2 main mechs of span (premature hemolytic anemia (depends destruction). hemoglobinuria. excessive removal of RBC's by cells of the RE system " " hemolytic RBC's injured. splenomegaly . if rate of emia. DO SEE anemia. or less deformable (ex: Sickle Cell Anemia)-> sequestration in splenic cords. jaundice. renal tubules loaded with 7)hyperbilirubin-emia hemosiderin Extravascular immune hemolysis 1 of the 2 main mechs of hemolytic anemia (depends on pathology involved). 1)hemoglobinemia. 5) jaundice. or exogenous hemoglobin3) hemosiderinuria toxins (ex: malaria)-> free Hb emia (free Hb in (iron storage released -> saturates plasma blood). urine. rendered "foreign". hemolysis saturates renal tubular 6) decreased serum reabsorp capacity.

esp West Africa. reducing power to reduce glutathione nitrofurantions. fall in pH -> liver). pneumonia. SE Asia. point mutation-> substitution of Val for Glu at 6th position of b-globin chain -> HbS -> aggregation & polymerization when deoxygenated -> formation of HbS fibers -> distortion of RBC's -> 2 major consequences: 1) chronic hemolytic anemia (b/c low Hb.Anemias 4 categories of Sickle Cell first manifests at age 5Crises 6 mos. clinical course: severe anemia. Mediterranean. hepatitis. defective folding crises. maintaining 3)Sequestration intracellular volume (mostly by -> dehydrated/dense spleen. DNA analysis. protects against malaria manifests after exposure to oxidant stress (due to primaquine. 2) occlusion of small BV (due to increased expression of adhesion molecules on altered membranes or non-sickled cells. septicemia & meningitis due to pneumococci and H. low Hct. splenic atrophy Type Wintrobe's Morphology Classification Epidemiology Unique Features Pathophsio Cause Etiology/Pathogenesis CBC & retic results Add'l Dx tests to confirm G6PD deficiency X-linked genetic variant (defect expressed in all RBC's of affected male-> more vulnerable). HbS. fava low Hct with intravascular & glutathione metabolism -> beans)-> oxidation of oxidative stress. crises of vaso-occlusive Dx. chronic hyperbilirubinemia. Middle East. sickling is (may overlap): initially reversible with 1) Vaso-occlusion oxygenation. also cell. 4) decreased affinity HbS Aplastic/ for O2 -> increased hypoplastic sickling (result of Parvovirus infection) Sickle Cell Anemia 8% black Americans are heterozygous for HbS. 30% black Africans MCHC (due to in malaria-endemic areas dehydrated cells) are heterozygous (HbS in more severe affords slight protection cases against malaria). increased suscept to infections (impaired splenic fxn. sickled cells stuck in spleen. low Hb. deficient G6PD -> abnormalities in typoid fever. self-limiting after formation of Heinz only younger RBC's remain in circ bodies -> membrane damage. precipitation of HbS 2) Hyperfibers -> upsets RBC hemolysis membrane even in (hypersplenism non-sickled cells -> > autolose K+ and H2O. many variants. increased transit time back to heart) -> ischemic tissue damage. repeat (pain. decreased deformability-> splenic destruction . sulfas. reticulocytosis destroyed). 10% black Americans. viral normal b/t > protects against oxidant injury. organs). gain splenectomy. sickles only in severe hypoxia. electrophoresis shows HbS. heterozygous = 40% of Hb in RBC is HbS (rest is HbA). infarct of sickling-> irreversible. full-blown sickle cell may see high anemia. G6PD reduces NADP to NADPH-> chloroquine. extravascular sulfhydryl groups of decreased ability of RBC to protect reticulocytosis globin chains -> itself against oxidatve injuries -> hemolysis on recovery denaturation of Hb. of G6PD protein. or Ca2+-> probs splenomegaly). homozygous = almost all Hb in the RBC is normochromic. hemolytic disease. defects in complement) prototype hereditary hemoglobinopathy. influenza most common causes of death in kids with SSA hyperbilirubinemia.

thrombocytosis. low Hct.Anemias Acute hemorrhage polychromatophilic when recovering (at ~7days) if blood lost externally. leukocytosis immed after blood loss. reticylocytosis as marrow regenerates . adequacy of RBC recovery may be hampered by iron deficiency increased blood loss loss of blood volume -> shift of H2O from interstitial fluid compartment -> hemodilution-> lowered Hct low Hb.

Anemias Peripheral Blood Images oval macrocytes. bone marrow is hypercellular with large erythroblasts & giant/ abnormally shaped metamyelocytes " " .

microcytic cells with occasional target cells & pencil-shaped poikilocytes .Anemias Perpheral Blood Images hypochromic.

poikilocytosis. microcytic cells.Anemias Perpheral Blood Images marked hypochromic. "golf ball" cells caused by precipitation of bglobin chains (cresyl blue stain) severe abnormalities. target cells. marked anisocytosis. microcytic RBC's. target cells. poorly hemoglobinized normoblasts . hypochromic. basophilic stippling. inclusions not seen (b/c removed by spleen). fragments common.

nucleated RBC's. spurs thrombocytopenia.Anemias Perpheral Blood Images no abnormal cells. immature WBC's (presence of these distinguishes from multiple myeloma) blast cells. replacement of hemopoietic tissue with fat (75% of marrow) burr cells. myeloid cells . bone marrow shows hypoplasia.

Anemias Perpheral Blood Images increase in # of normoblasts in marrow " " .

Anemias sickled cells. target cells Perpheral Blood Images Heinz bodies. bite cells .

Anemias polychromatophilic macrocytes (reticulocytes) .

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