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Anemia OverviewAnemia Overview

Ruozhi XiaoRuozhi Xiao The Third Hospital of Sun Yat-sen UniversityThe Third Hospital of Sun Yat-sen University Ruozhi_xiao@yahoo.comRuozhi_xiao@yahoo.com

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Erythrocytes parametersErythrocytes parameters

– RBC = red blood cellsRBC = red blood cells– Hgb= hemoglobinHgb= hemoglobin– Mean corpuscular volume (MCV)Mean corpuscular volume (MCV)

– N: 80-100 flN: 80-100 fl

– RDW(Red cell DistrRDW(Red cell Distriibution Width) bution Width) – Mean corpuscular hemoglobin (MCH)Mean corpuscular hemoglobin (MCH)

– N: 27-34 pgN: 27-34 pg

– Mean corpuscular hemoglobin concentration Mean corpuscular hemoglobin concentration (MCHC)(MCHC)

– N: 310 – 370 g/lRBC (31-37 g/dl)N: 310 – 370 g/lRBC (31-37 g/dl)

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Survival and Production of Survival and Production of RBCRBC

Formed in bone marrow Formed in bone marrow Life span is 120 days (+/-20 days)Life span is 120 days (+/-20 days) Cleared in spleen Cleared in spleen Reticulocytes are newly formed RBC in cReticulocytes are newly formed RBC in c

irculation irculation If no new production, Hgb drops 1 gm/wIf no new production, Hgb drops 1 gm/w

eekeek

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ERYTHROPOIESIS

In developing from the stem cell, the RBC has to undergo the most changes, which can be categorized into several morphological/stainable stages

Proerythroblast

RBC

*

-blast is the common suffix for an immature form of a cell

Early erythroblast

Intermediate erythroblast

Late erythroblast

Reticulocyte

…

…

……

Stem cell

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HematocritHematocritss

Normal, Hemorrhage, IDA, Leukemia, Hemolysis, B12, P Vera

PlasmaWhite cellsRed cells

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DefinitinonDefinitinon

““Low blood”Low blood” Anemia is simply a hemoglobin level loAnemia is simply a hemoglobin level lo

wer than the normal range for a particuwer than the normal range for a particular age and sex of the patient. lar age and sex of the patient.

Most common hematologic disorder by Most common hematologic disorder by farfar

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The normal range for Hb and RBC

Hb Hb RBC RBC MalesMales ： ： 120120 －－ 160g/L (4.0-5.5)x 160g/L (4.0-5.5)x 10101212/L/LFemalesFemales ： ： 110110 －－ 150g/L (3.5-5.0)x 150g/L (3.5-5.0)x 10101212/L/LNeonatesNeonates ：： 170170 －－ 200g/L (6.0-7.0)x 200g/L (6.0-7.0)x 10101212//

LL

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Anemia classificationAnemia classification

Based on general mechanismsBased on general mechanisms morphological classificationmorphological classification

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AnemiaAnemiamorphological classificationmorphological classification

MicrocyticMicrocytic

NormocyticNormocytic

MacrocyticMacrocytic

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morphological morphological classificationclassification

Type MCV fl MCH pg MCHC%

Macrocytic anemia ＞ 100 ＞ 32 32-35

Normocytic anemia 80-100 27-32 32-35

Microcytic anemia ＜ 80 ＜ 27 ＜ 32

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Normal Red Blood Cells - Peripheral Blood SmearNormal Red Blood Cells - Peripheral Blood Smear

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Normal Red Blood Normal Red Blood CellsCells

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Microcytic anemia

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ThalassemiaThalassemia

ThalassaThalassa = the sea = the sea Defective globin synthesisDefective globin synthesis

– Normal Normal 11 thalassemiathalassemia

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b-Thalassemiab-Thalassemia

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Macrocytic anemia

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General mechanismsGeneral mechanisms of of anemiaanemia

1. RBC Loss without RBC destruction1. RBC Loss without RBC destruction 2. Deficient RBC production2. Deficient RBC production:: Marrow fMarrow f

ailureailure 3. Increased RBC destruction over 3. Increased RBC destruction over

productionproduction: Hemolysis: Hemolysis

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ANEMIAANEMIACauses - Cytoplasmic Protein Causes - Cytoplasmic Protein

ProductionProduction Decreased hemoglobin synthesisDecreased hemoglobin synthesis

– Disorders of globin synthesisDisorders of globin synthesis– Disorders of heme synthesisDisorders of heme synthesis

Heme synthesisHeme synthesis– Decreased IronDecreased Iron– Iron not in utilizable formIron not in utilizable form– Decreased heme synthesisDecreased heme synthesis

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PathophysiologyPathophysiology Decreased RBC productionDecreased RBC productiona.a. Iron deficiency Iron deficiency b.b. Folic acid deficiencyFolic acid deficiencyc.c. Aplastic anemiaAplastic anemia

Increased RBC loss or destruction Increased RBC loss or destruction a.a. sickle cell anemiasickle cell anemiab.b. blood lossblood lossc.c. infectioninfection

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:Leukemia

:trauma,surgery

:cancer and ulcer,menstrual periods

:Renal disease

: Malaria:Lead poisoning

:SLE

:PNH

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Bone Marrow DisordersBone Marrow Disorders

Aplastic anemiaAplastic anemia Myelodysplastic SyndromesMyelodysplastic Syndromes Acute LeukemiaAcute Leukemia

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Aplastic AnemiaAplastic Anemia

Blood Bone Marrow Biopsy

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Bone Marrow (BM) BiopsyBone Marrow (BM) Biopsy

Normal Aplastic

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DefinitionsDefinitions Aplastic Anemia (AA)Aplastic Anemia (AA)

– PancytopeniaPancytopenia– Hypocellular bone marrowHypocellular bone marrow

Myelodysplastic Syndrome (MDS)Myelodysplastic Syndrome (MDS)– Cytopenias with hypercellular bone Cytopenias with hypercellular bone

marrowmarrow Acute Leukemia (AL)Acute Leukemia (AL)

– Malignant proliferation of immature Malignant proliferation of immature cellscells

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Aplastic Anemia: Signs and Aplastic Anemia: Signs and SymptomsSymptoms

Anemia (low Hb, Hct)Anemia (low Hb, Hct)– fatigue, lassitude, dyspneafatigue, lassitude, dyspnea

Thrombocytopenia (low platelets)Thrombocytopenia (low platelets)– bruises, petechiaebruises, petechiae– serious bleedingserious bleeding

Neutropenia (low neutrophils, a type of wNeutropenia (low neutrophils, a type of white cell)hite cell)– infectionsinfections

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Acquired Aplastic AnemiaAcquired Aplastic Anemia DrugsDrugs ChemicalsChemicals VirusesViruses Immune diseasesImmune diseases Paroxysmal nocturnal hemoglobinuria Paroxysmal nocturnal hemoglobinuria

(PNH)(PNH) PregnancyPregnancy IDIOPATHICIDIOPATHIC

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Myelodysplastic Syndromes (MMyelodysplastic Syndromes (MDS)DS)

Clonal diseasesClonal diseases NeoplasticNeoplastic Refractory anemiasRefractory anemias Potential for acute myeloid leukemia (APotential for acute myeloid leukemia (A

ML)ML)

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Anemia

Check MCV

MCV < 80Microcytic

anemia

MCV 80 - 100Normocytic

anemia

MCV > 100Macrocytic

anemia

Defective synthesis of:

Heme

iron deficiency anemiaanemia of chronic disease

sideroblastic anemialead poisoning

Globin chains

thalassemiasHbE

Fe

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Clinical featuresClinical features

Mild:Mild dyspnea on exertion, palpitatiMild:Mild dyspnea on exertion, palpitationon

Moderate: As with MILD ANEMIA, may alModerate: As with MILD ANEMIA, may also have excessive dyspnea so have excessive dyspnea

Severe:Anemia:Dyspnea at rest, tachycaSevere:Anemia:Dyspnea at rest, tachycardia with pounding pulse, weakness, dizrdia with pounding pulse, weakness, dizziness, headache, insomnia ziness, headache, insomnia

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Diagnosis of AnemiaDiagnosis of Anemia

HistoryHistory

– –Diet Diet

– –Blood lossBlood loss

– –Family history Family history

– –Recent illness or immunization Recent illness or immunization

– –History of anemia and causeHistory of anemia and cause

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Diagnosis of AnemiaDiagnosis of Anemia

Physical ExaminationPhysical Examination – –Evaluate conjunctiva and mucous membEvaluate conjunctiva and mucous memb

ranes for palenessranes for paleness – –Cardiovascular system for murmur Cardiovascular system for murmur – –Liver Liver – –Spleen Spleen – –NodesNodes – –Look for jaundice or purpuraLook for jaundice or purpura

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Diagnosis of AnemiaDiagnosis of Anemia

LabsLabs – –Complete blood count with differential Complete blood count with differential

and platelets and platelets – –Evaluation of smear with red cell indicesEvaluation of smear with red cell indices – –Reticulocyte count Reticulocyte count

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Diagnosis of AnemiaDiagnosis of Anemia

Other testsOther tests – –Serum bilirubin, LDH, urinary hemosideSerum bilirubin, LDH, urinary hemoside

rin, hgb electrophoresis, quantitative hgrin, hgb electrophoresis, quantitative hgbA2 and FbA2 and F

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Common treatment to All “AnemiaCommon treatment to All “Anemias”s”

SupportSupport– Hematopoietic growth factorsHematopoietic growth factors– Blood transfusions, blood substitutesBlood transfusions, blood substitutes– Iron Iron

CureCure– Stem cell transplantStem cell transplant– Gene therapyGene therapy

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IRON DEFICIENCY IRON DEFICIENCY ANEMIAANEMIA

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TermsTerms

Fe = iron Fe = iron TIBC = total iron binding capacity TIBC = total iron binding capacity RDW = red cell distribution widthRDW = red cell distribution width

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CASE 1CASE 1

A A 5050 year old man comes to see you year old man comes to see you because of fatigue and a change in because of fatigue and a change in bowel habit. He is found to have a bowel habit. He is found to have a hemoglobin of 105 g/L (normal 120-hemoglobin of 105 g/L (normal 120-170) and MCV of 78 fL (80-100). 170) and MCV of 78 fL (80-100). Peripheral blood film shows microcytes Peripheral blood film shows microcytes and hypochromia. He previously had a and hypochromia. He previously had a hemoglobin of 165 g/L three years ago, hemoglobin of 165 g/L three years ago, with a normal MCV.with a normal MCV.

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Case 1 – Question 1Case 1 – Question 1

What is your approach to the history What is your approach to the history and physical examination?and physical examination?

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Case 1 - Question 1Case 1 - Question 1DiscussionDiscussion

iron deficiency most likelyiron deficiency most likely symptoms suspicious for lower GI symptoms suspicious for lower GI

tract malignancy.tract malignancy. still ask about chronic inflammatory still ask about chronic inflammatory

diseasesdiseases ask about melena, hematochezia, ask about melena, hematochezia,

weight loss, family history of colon caweight loss, family history of colon ca rectal exam indicatedrectal exam indicated

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CASE 1CASE 1 - - Question 2 Question 2

What other investigations are What other investigations are appropriate?appropriate?

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InvestigationsInvestigations

serum ferritin serum ferritin 12 ug/L 12 ug/L (30-400)(30-400) iron iron 8 umol/L 8 umol/L (10-(10-

28)28) TIBC TIBC 80 umol/L (38-76)80 umol/L (38-76) transferrin sat. transferrin sat. 10 % 10 % (20-55)(20-55)

Conclusion: Iron deficiency anemiaConclusion: Iron deficiency anemia

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IRON DEFICIENCY ANEMIAIRON DEFICIENCY ANEMIAPrevalencePrevalence

Country Men (%) Women (%)

Pregnant Women (%)

S. India 6 35 56 N. India 64 80 Latin America 4 17 38 Israel 14 29 47 Poland 22 Sweden 7 USA 1 13

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IRONIRON Functions as electron Functions as electron

transporter; vital for lifetransporter; vital for life Must be in ferrous (FeMust be in ferrous (Fe+2+2) state ) state

for activityfor activity Ferric (FeFerric (Fe+3+3) ions cannot ) ions cannot

transport electrons or Otransport electrons or O22

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IRON DEFICIENCY ANEMIAIRON DEFICIENCY ANEMIA

IRON METABOLISMIRON METABOLISM– ABSORPTION IN DUODENUMABSORPTION IN DUODENUM– TRANSFERRIN TRANSPORTS IRON TO TRANSFERRIN TRANSPORTS IRON TO

THE CELLSTHE CELLS– FERRITIN AND HEMOSFERRITIN AND HEMOSIIDERIN STORE DERIN STORE

IRON IRON 10% of daily iron is absorbed10% of daily iron is absorbed

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Iron MetabolismIron Metabolism

Heme IronHeme Iron– Hemoglobin and myoglobinHemoglobin and myoglobin

Non-heme IronNon-heme Iron– Breast milkBreast milk– Cow milkCow milk– All supplementsAll supplements

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Iron AbsorptionIron Absorption

Heme IronHeme Iron– Well absorbedWell absorbed– Not dependent on Not dependent on

Iron deficiency staIron deficiency statustus

– Not limited by dietNot limited by diet

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Iron AbsorptionIron Absorption

Non-heme IronNon-heme Iron– Absorption is sporadic, generally poorAbsorption is sporadic, generally poor– Improved absorptionImproved absorption

Iron deficient statusIron deficient status Heme iron (ie red meat, fish, chicken)Heme iron (ie red meat, fish, chicken) Vitamin CVitamin C

– Worsened absorptionWorsened absorption Cow’s milk, cheeseCow’s milk, cheese CerealCereal TeaTea

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IRONIRONBody Compartments - 75 kg manBody Compartments - 75 kg man

Stores1000mg

Tissue500 mg

Red Cells2300 mg

3 mgAbsorption < 1 mg/day

Excretion < 1 mg/day

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Iron deficiency anemiaIron deficiency anemia

Causes:Causes: inadequate dietary iron intakeinadequate dietary iron intake Malabsorption: gastrectomy, chronic diarrhea, Malabsorption: gastrectomy, chronic diarrhea,

increased iron needs: pregnancy and lactationincreased iron needs: pregnancy and lactation chronic occult blood loss: bleeding ulcers, GI ichronic occult blood loss: bleeding ulcers, GI i

nflammation, hemorrhoids, cancer, chronic henflammation, hemorrhoids, cancer, chronic hemoglobinuriamoglobinuria

Menstrual blood lossMenstrual blood loss

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Most body iron is present in hemoglobin Most body iron is present in hemoglobin in circulating red cellsin circulating red cells

The macrophages of the The macrophages of the reticuloendothelial system store iron reticuloendothelial system store iron released from hemoglobin as ferritin and released from hemoglobin as ferritin and hemosiderinhemosiderin

SSmall loss of iron each day in urine, mall loss of iron each day in urine, faecesfaeces,, skin and nails and in skin and nails and in menstruamenstruatingting females as blood (1-2 mg females as blood (1-2 mg daily)daily)

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IRON DEFICIENCY ANEMIAIRON DEFICIENCY ANEMIA

ETIOLOGY:ETIOLOGY: CHRONIC BLEEDING CHRONIC BLEEDING

MENORRHAGIA MENORRHAGIA PEPTIC ULCERPEPTIC ULCER STOMACH CANCERSTOMACH CANCER ULCERATIVE COLITISULCERATIVE COLITIS INTESTINAL CANCERINTESTINAL CANCER HAEMORRHOIDSHAEMORRHOIDS

DECREASED IRON INTAKEDECREASED IRON INTAKE INCREASED IRON REQUIRMENT (JUVENILE INCREASED IRON REQUIRMENT (JUVENILE

AGE, PREGNANCY, LACTATION)AGE, PREGNANCY, LACTATION)

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IRON DEFICENCY - STAGESIRON DEFICENCY - STAGES Prelatent Prelatent

– reduction in iron stores without reduced serum iron levelsreduction in iron stores without reduced serum iron levels Hb (N), MCV (N), iron absorption (Hb (N), MCV (N), iron absorption (), transferin ), transferin

saturation (N), serum ferritin (saturation (N), serum ferritin (), marrow iron (), marrow iron ()) LatentLatent

– iron stores are exhausted, but the blood hemoglobin level iron stores are exhausted, but the blood hemoglobin level remains normalremains normal Hb (N), MCV (N), TIBC (Hb (N), MCV (N), TIBC (), serum ferritin (), serum ferritin (), transfe), transferrrin rin

saturation (saturation (), marrow iron (absent)), marrow iron (absent) Iron deficiency anemiaIron deficiency anemia

– blood hemoglobin concentration falls below the lower limit blood hemoglobin concentration falls below the lower limit of normalof normal Hb (Hb (), MCV (), MCV (), TIBC (), TIBC (), serum ferritin (), serum ferritin (), transfer), transferrrin in

saturation (saturation (), marrow iron (absent)), marrow iron (absent)

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IRON DEFICIENCY ANEMIAIRON DEFICIENCY ANEMIA GENERAL ANEMIA’S GENERAL ANEMIA’S

SYMPTOMS:SYMPTOMS:– FATIGABILITYFATIGABILITY– DIZZENESDIZZENESSS– HEADACHEHEADACHE– IRRITABILITY IRRITABILITY – ROARINGROARING– PALPITATIONPALPITATION– CHD, CHFCHD, CHF

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CHARACTERISTICS CHARACTERISTICS SYMPTOMSSYMPTOMS

– GLOSSITIS, STOMATITISGLOSSITIS, STOMATITIS– DYSPHAGIA (DYSPHAGIA ( Plummer-Vinson syndrome Plummer-Vinson syndrome))– ATROPHIC GASTRITISATROPHIC GASTRITIS– DRY, PALE SKINDRY, PALE SKIN– SPOON SHAPED NAILS, KOILONYCHIA, SPOON SHAPED NAILS, KOILONYCHIA, – BLUE SCLERAEBLUE SCLERAE– HAIR LOSSHAIR LOSS– PICA (APETITE FOR NON FOOD SUBSTANCES PICA (APETITE FOR NON FOOD SUBSTANCES

SUCH AS AN ICE, CLAY)SUCH AS AN ICE, CLAY)– SPLENOMEGALY (10%)SPLENOMEGALY (10%)– INCREASED PLATELET COUNTINCREASED PLATELET COUNT

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KOILONYCHIAKOILONYCHIA

 

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Smooth tongue Smooth tongue

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IRON DEFICIENCY ANEMIAIRON DEFICIENCY ANEMIA MCVMCV

MCH MCH

MCHC MCHC NN

FeFe

TIBCTIBC TRANSFERIN SATURATIONTRANSFERIN SATURATION FERRITINFERRITIN

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BLOOD ROUTINE

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BLOOD AND BLOOD AND BONE MARROW SMEARBONE MARROW SMEAR

BLOOD:BLOOD:– microcytosis, hipochromia, microcytosis, hipochromia, anisocytosisanisocytosis

poikilocytosispoikilocytosis BONE MARROWBONE MARROW

– high cellularity high cellularity – mild to moderate erythroid hyperplasia (mild to moderate erythroid hyperplasia (25-35%; 25-35%;

N 16 – 18%N 16 – 18%) ) – polychromatic and pyknotic cytoplasm polychromatic and pyknotic cytoplasm of of

erythroblasts is vacuolated and irregular in erythroblasts is vacuolated and irregular in outlineoutline ( (micronormoblasticmicronormoblastic erythropoiesiserythropoiesis))

– absence of stainable ironabsence of stainable iron

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Anemia: Lab EvaluationAnemia: Lab Evaluation

Normal Periperhal SmeaNormal Periperhal Smearr

Iron Deficiency AnemiaIron Deficiency Anemia

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IDA blood smear

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IDA bone marrow

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Normal store iron(blue)

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IDA

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Reticulocytes up

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Using special stains such as methylene blue or brilliant cresyl blue, reticulocytes stain with

dark blue granules whereas mature erythrocytes evenly stain pale blue.

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ManagementManagement

History and physical examination History and physical examination is sufficient to exclude serious is sufficient to exclude serious disease (e.g pregnant or disease (e.g pregnant or lactating women, adolescents) lactating women, adolescents)

- CURE ANEMIA- CURE ANEMIA

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ManagementManagement

History and/or physical examination History and/or physical examination is insufficient (e.g old men, is insufficient (e.g old men, postmenopausal women) postmenopausal women)

- FIND ETIOLOGY OF ANEMIA AND - FIND ETIOLOGY OF ANEMIA AND CURE (CAUSAL TREATMENT)CURE (CAUSAL TREATMENT)

Benzidine test Benzidine test GastroscopyGastroscopy ColonoscopyColonoscopy Gynaecological examinationGynaecological examination

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IRON DEFICIENCY ANEMIAIRON DEFICIENCY ANEMIACURECURE

ORALORAL– 3300 mg of iron daily 00 mg of iron daily afterafter meal meal – How long?How long? 3-6 months 3-6 months to restore iron to restore iron

reservereserve– Absorption Absorption

is enhanced: vitis enhanced: vit C, meat, orange juice, fishC, meat, orange juice, fish is inhibited: tea, milkis inhibited: tea, milk

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IRON DEFICIENCY ANEMIAIRON DEFICIENCY ANEMIACURECURE

PARENTERAL IRON SUBSTITUTIONPARENTERAL IRON SUBSTITUTION– Bad oral iron tolerance (nausea, Bad oral iron tolerance (nausea,

diarrhoea)diarrhoea)– Negative oral iron absorption testNegative oral iron absorption test– Necessity of quick management (CHD, Necessity of quick management (CHD,

CHF)CHF)

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Remember:Remember:

Iron deficiency anemia is a Iron deficiency anemia is a manifestation of an underlying manifestation of an underlying

process.process.

Look for and treat the cause of the Look for and treat the cause of the iron deficiency.iron deficiency.

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Look for the causeLook for the cause

colonoscopy reveals colon carcinoma colonoscopy reveals colon carcinoma which is subsequently resected.which is subsequently resected.

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Iron Deficiency anemiaIron Deficiency anemia

Diagnostics:Diagnostics: Iron levelsIron levels Total iron-binding capacity (TIBC)Total iron-binding capacity (TIBC) Serum FerritinSerum Ferritin

Medications:Medications: Iron supplements, oral or parenteralIron supplements, oral or parenteral Vit. CVit. C

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