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Anemia Overview

Ruozhi Xiao

The Third Hospital of Sun Yat-sen University

[email protected]

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Erythrocytes parameters

RBC = red blood cells

Hgb= hemoglobin

Mean corpuscular volume (MCV)

N: 80-100 fl RDW(Red cell Distribution Width)

Mean corpuscular hemoglobin (MCH) N: 27-34 pg

Mean corpuscular hemoglobin concentration (MCHC) N: 310 370 g/lRBC (31-37 g/dl)

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Survival and Production of RBC

Formed in bone marrow

Life span is 120 days (+/-20 days)

Cleared in spleen Reticulocytes are newly formed RBC in

circulation

If no new production, Hgb drops 1gm/week

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ERYTHROPOIESIS

In developing from the stem cell, the RBC has to

undergo the most changes, which can becategorized into several morphological/stainable

stages

Proerythroblast RBC

*

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

Early

erythroblastIntermediate

erythroblast

Late

erythroblast

Reticulocyte

Stem cell

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Hematocrits

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

Plasma

White cells

Red cells

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Definitinon

Low blood

Anemia is simply a hemoglobin level

lower than the normal range for aparticular age and sex of the patient.

Most common hematologic disorder by

far

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The normal range for Hb and RBC

Hb RBC

Males 120160g/L (4.0-5.5)x 1012/L

Females 110150g/L (3.5-5.0)x 1012/L

Neonates170200g/L (6.0-7.0)x 1012/L

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Anemia classification

Based on general mechanisms

morphological classification

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Anemiamorphological classification

Microcytic

Normocytic

Macrocytic

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morphological classification

Type MCVfl MCHpg 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 Smear

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Normal Red Blood Cells

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Microcytic anemia

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Thalassemia

Thalassa= the sea

Defective globin synthesis

Normal a = b (a/b = 1)

a, b, db, gdb thalassemia

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b-Thalassemia

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Macrocytic anemia

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General mechanisms of anemia

1. RBC Loss without RBC destruction

2. Deficient RBC production: Marrowfailure

3. Increased RBC destruction overproduction: Hemolysis

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ANEMIACauses - Cytoplasmic Protein Production

Decreased hemoglobin synthesis

Disorders of globin synthesis

Disorders of heme synthesis

Heme synthesis

Decreased Iron

Iron not in utilizable form

Decreased heme synthesis

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Pathophysiology

Decreased RBC productiona. Iron deficiency

b. Folic acid deficiency

c. Aplastic anemia

Increased RBC loss or destruction

a. sickle cell anemia

b. blood lossc. infection

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The third hospital of Sun yat-sen university

:Leukemia

:trauma,surgery

:cancer and ulcer,menstrual periods

:Renal disease

: Malaria:Leadpoisoning

:SLE

:PNH

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Bone Marrow Disorders

Aplastic anemia

Myelodysplastic Syndromes

Acute Leukemia

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Aplastic Anemia

Blood Bone Marrow Biopsy

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Bone Marrow (BM) Biopsy

Normal Aplastic

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Definitions

Aplastic Anemia (AA)

Pancytopenia

Hypocellular bone marrow

Myelodysplastic Syndrome(MDS)

Cytopenias with hypercellular

bone marrow

Acute Leukemia (AL)

Malignant proliferation of

immature cells

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Aplastic Anemia: Signs andSymptoms

Anemia (low Hb, Hct)

fatigue, lassitude, dyspnea

Thrombocytopenia (low platelets) bruises, petechiae

serious bleeding

Neutropenia (low neutrophils, a type ofwhite cell)

infections

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Acquired Aplastic Anemia

Drugs

Chemicals

Viruses Immune diseases

Paroxysmal nocturnal hemoglobinuria

(PNH) Pregnancy

IDIOPATHIC

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Myelodysplastic Syndromes (MDS)

Clonal diseases

Neoplastic

Refractory anemias Potential for acute myeloid leukemia (AML)

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Anemia

Check MCV

MCV < 80

Microcytic

anemia

MCV 80 - 100

Normocytic

anemia

MCV > 100

Macrocytic

anemia

Defective synthesis of:

Heme

iron deficiency anemia

anemia of chronic diseasesideroblastic anemia

lead poisoning

Globin chains

thalassemiasHbE

Fe

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Clinical features

Mild:Mild dyspnea on exertion, palpitation

Moderate: As with MILD ANEMIA, mayalso have excessive dyspnea

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

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Diagnosis of Anemia

History

Diet

Blood loss

Family history

Recent illness or immunizationHistory of anemia and cause

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Diagnosis of Anemia

Physical ExaminationEvaluate conjunctiva and mucous

membranes for paleness

Cardiovascular system for murmur

Liver

Spleen

Nodes

Look for jaundice or purpura

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Diagnosis of Anemia

Labs

Complete blood count with differentialand platelets

Evaluation of smear with red cell indicesReticulocyte count

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Diagnosis of Anemia

Other tests

Serum bilirubin, LDH, urinaryhemosiderin, hgb electrophoresis,quantitative hgbA2 and F

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Common treatment to All Anemias

Support

Hematopoietic growth factors Blood transfusions, blood substitutes

Iron

Cure Stem cell transplant

Gene therapy

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IRON DEFICIENCY

ANEMIA

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Terms

Fe = iron

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

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CASE 1

A 50 year old man comes to see youbecause of fatigue and a change in bowelhabit. He is found to have a hemoglobin

of 105 g/L (normal 120-170) and MCV of78 fL (80-100). Peripheral blood filmshows microcytes and hypochromia. He

previously had a hemoglobin of 165 g/Lthree years ago, with a normal MCV.

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Case 1 Question 1

What is your approach to the history andphysical examination?

C 1 Q i 1

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Case 1 - Question 1Discussion

iron deficiency most likely

symptoms suspicious for lower GI tractmalignancy.

still ask about chronic inflammatorydiseases

ask about melena, hematochezia, weightloss, family history of colon ca

rectal exam indicated

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CASE 1 - Question 2

What other investigations are appropriate?

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Investigations

serum ferritin 12 ug/L (30-400)

iron 8 umol/L (10-28)

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

Conclusion: Iron deficiency anemia

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IRON DEFICIENCY ANEMIAPrevalence

Country Men (%) Women(%)

PregnantWomen (%)

S. India 6 35 56

N. India 64 80Latin America 4 17 38

Israel 14 29 47

Poland 22

Sweden 7

USA 1 13

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IRON

Functions as electron transporter;vital for life

Must be in ferrous (Fe+2) state foractivity

Ferric (Fe+3) ions cannot transportelectrons or O2

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IRON DEFICIENCY ANEMIA

IRON METABOLISM

ABSORPTION IN DUODENUM

TRANSFERRIN TRANSPORTS IRON TO THE

CELLS

FERRITIN AND HEMOSIDERIN STORE IRON

10% of daily iron is absorbed

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Iron Metabolism

Heme Iron

Hemoglobin and myoglobin

Non-heme Iron

Breast milk

Cow milk

All supplements

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Iron Absorption

Heme Iron

Well absorbed

Not dependent on

Iron deficiencystatus

Not limited by diet

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Iron Absorption

Non-heme Iron

Absorption is sporadic, generally poor

Improved absorption

Iron deficient status

Heme iron (ie red meat, fish, chicken)

Vitamin C

Worsened absorption Cows milk, cheese

Cereal

Tea

IRON

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IRONBody 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 anemia

Causes:

inadequate dietary iron intake

Malabsorption: gastrectomy, chronic diarrhea,

increased iron needs: pregnancy and lactation

chronic occult blood loss: bleeding ulcers, GIinflammation, hemorrhoids, cancer, chronic

hemoglobinuria Menstrual blood loss

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Most body iron is present in hemoglobin incirculating red cells

The macrophages of the

reticuloendothelial system store ironreleased from hemoglobin as ferritin andhemosiderin

Small loss of iron each day in urine, faeces,skin and nails and in menstruating femalesas blood (1-2 mg daily)

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ETIOLOGY: CHRONIC BLEEDING

MENORRHAGIA

PEPTIC ULCER

STOMACH CANCER

ULCERATIVE COLITIS

INTESTINAL CANCER

HAEMORRHOIDS

DECREASED IRON INTAKE

INCREASED IRON REQUIRMENT (JUVENILE AGE,PREGNANCY, LACTATION)

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IRON DEFICENCY - STAGES

Prelatent reduction in iron stores without reduced serum iron levels

Hb (N), MCV (N), iron absorption (), transferin saturation(N), serum ferritin (), marrow iron ()

Latent iron stores are exhausted, but the blood hemoglobin levelremains normal

Hb (N), MCV (N), TIBC (), serum ferritin (), transferrinsaturation (), marrow iron (absent)

Iron deficiency anemia blood hemoglobin concentration falls below the lower limit ofnormal

Hb (), MCV (), TIBC (), serum ferritin (), transferrinsaturation (), marrow iron (absent)

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GENERAL ANEMIAS SYMPTOMS: FATIGABILITY DIZZENESS

HEADACHE

IRRITABILITY

ROARING

PALPITATION

CHD, CHF

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CHARACTERISTICS SYMPTOMS

GLOSSITIS, STOMATITIS DYSPHAGIA ( Plummer-Vinson syndrome)

ATROPHIC GASTRITIS

DRY, PALE SKIN SPOON SHAPED NAILS, KOILONYCHIA,

BLUE SCLERAE

HAIR LOSS

PICA (APETITE FOR NON FOOD SUBSTANCES SUCH AS

AN ICE, CLAY) SPLENOMEGALY (10%)

INCREASED PLATELET COUNT

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KOILONYCHIA

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Smooth tongue

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MCV

MCH

MCHC N

Fe

TIBC

TRANSFERIN SATURATION

FERRITIN

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BLOOD ROUTINE

BLOOD AND

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BLOOD ANDBONE MARROW SMEAR

BLOOD: microcytosis, hipochromia, anisocytosis poikilocytosis

BONE MARROW high cellularity mild to moderate erythroid hyperplasia (25-35%; N

16 18%)

polychromatic and pyknotic cytoplasm oferythroblasts is vacuolated and irregular in outline(micronormoblastic erythropoiesis)

absence of stainable iron

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Anemia: Lab Evaluation

Normal Periperhal Smear Iron Deficiency Anemia

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IDA blood smear

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IDA bone marrow

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Normal store iron(blue)

IDA

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IDA

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Reticulocytes up

Using special stains such as methylene blue

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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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Management

History and physical examination issufficient to exclude serious disease(e.g pregnant or lactating women,

adolescents)- CURE ANEMIA

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Management

History and/or physical examination isinsufficient (e.g old men, postmenopausalwomen)

- FIND ETIOLOGY OF ANEMIA ANDCURE (CAUSAL TREATMENT)

Benzidine test

Gastroscopy Colonoscopy

Gynaecological examination


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IRON DEFICIENCY ANEMIACURE

ORAL 300 mg of iron daily after meal

How long? 3-6 months to restore iron reserve

Absorption is enhanced: vit C, meat, orange juice, fish

is inhibited: tea, milk


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IRON DEFICIENCY ANEMIACURE

PARENTERAL IRON SUBSTITUTION

Bad oral iron tolerance (nausea, diarrhoea)

Negative oral iron absorption test

Necessity of quick management (CHD, CHF)

R b

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Remember:

Iron deficiency anemia is a

manifestation of an underlying

process.

Look for and treat the cause of

the iron deficiency.

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Look for the cause

colonoscopy reveals colon carcinomawhich is subsequently resected.

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Iron Deficiency anemia

Diagnostics: Iron levels

Total iron-binding capacity (TIBC)

Serum Ferritin

Medications:

Iron supplements, oral or parenteralVit. C

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