Professor

Anwar SheikhaAnwar SheikhaMD, FRCP, FRCPath., FCAP, FRCPA, FRCPI, FACP

Senior Consultant Clinical & Lab. Hematologist

Clinical Professor of HematologyUniversity of Mississippi Medical Center, Jackson,

Mississippi

C.E.O., Raziana Company for Health Services, Hawler, IRAQ

Anemias

Reduction in the concentration of Hb below what is normal for age and sex

? ↓ RCCIs a Hb of 12 g/dL anemia?

Hb(g/dL)

Male Female Neonate 2-3 month13-17 12-15 13.5-19.5 9.5-13.5

Anemias

REDISTRIBUTION 2,3 DPG

C.O. PLASMA

Anemia

HYPOXIA

COMPENSATORYMECHANISMS

C.O.PATHOPHYSIOLOGY

OF ANEMAIS

Anemias TIREDNESS

LASSITUDE

EASYFATIGUABILITY

MUSCLE WEAKNESS

CLINICAL FEATURES

PALLORGI

GUS CVSCNS

Anemias

Etiological Morphological

Classification

AnemiasETIOLOGIC

Classification

BLOODLOSS

IMPAIREDRED CELL

FORMATION

INCREASEDRED CELL

DESTRUCTION

I

II III

AnemiasETIOLOGIC

Classification

BLOODLOSS

IMPAIREDRED CELL

FORMATIONHEMOLYTICANEMIAS

I

II III

CHRONICACUTE

DEFICIENCYNON

DEFICIENCY

RBCABNORMALITIES

RBC ENVIRONMENTABNORMALITIES

AnemiasDEFICIENCY ANEMIAS

ANEMIAS DUE TO DEFICIENCY OF SUBSTANCES ESSENTIAL FOR ERYTHROPOIESIS

IRONDEFICIENCYANEMAIS

MEGALOBLASTICANEMAIS

AnemiasNON

DEFICIENCY ANEMIAS

ANEMIAS NOT DUE TO DEFICIENCY OF SUBSTANCES ESSENTIAL FOR ERYTHROPOIESIS

APLASTICANEMIA

ACDANEMIA

OFCHRONIC

DISORDERS

ANEMIAOF

BONE MARROWINFILTRATION

AnemiasNON

DEFICIENCY ANEMIAS

ANEMIAS NOT DUE TO DEFICIENCY OF SUBSTANCES ESSENTIAL FOR ERYTHROPOIESIS

AAACDBM

INFILTRATION

INFECTION

COLLAGEN DISEASES

RENAL FAILURE

LIVER FAILURE

MALIGNANCY

LEUKEMIAS

LYMPHOMAS

MYELOMA

MYELOFIBROSIS

AnemiasOTHERNON

DEFICIENCY ANEMIAS

SIDEROBLASTIC ANEMIAS

CONGENITALDYSERYTHROPOIETIC

ANEMIAS

AnemiasMORPHOLOGIC

Classification

IIHYPOCHROMIC

MICROCYTIC

IIIMACROCYTIC

ANEMIAS

INORMOCYTIC

NORMOCHROMIC

Iron DeficiencyThalassemias

ACD

Megaloblastic

Macrocytosis

Megaloblastic AlcoholismLiver Diseases

“Alcoholic”

Reticulocytosis Hypothyroidism Chemotherapy

Sideroblastic Anemia LEA Paraproteinemias

Leukemias MDS 5q- Syndrome

MPDNewborn Pregnancy

Chronic Respiratory Failure

Iron Deficiency Anemias

IRON

4% of Earth’s Crust

3 to 5 grams in Adult Human

Hb1.5 to 3.0

gm

Storage1.2 to 2.0

gm

Essential Plasma

0.3gm

3 to 4mg

Hemosiderin

Ferritin

Iron Metabolism

Bone Marrow RES

Circulating RBC

PlasmaAbsorption Excretion1 mg 1 mg

30 mg

23 mg23 mg

30 mg

7 mg

AnemiasDAILY IRON LOSSES & REQUIREMTNS

Daily Loss

Menses

Growth

TotalLoss

INFANTS: 0- 4 INFANTS: 0- 4 mm

5-12 5-12 mm

0.50.5

0.50.5 0.50.50.50.5

1.01.0

CHILDCHILD 0.50.5 0.50.5 1.01.0

ADOLESCENT MALEADOLESCENT MALE 0.90.9 0.90.9 1.81.8ADOLESCENT ADOLESCENT FEMALEFEMALE

0.90.9 1.01.0 0.50.5 2.42.4MENSTRUATING MENSTRUATING

FEMALEFEMALE0.90.9 1.91.9 2.82.8

ADULT MALEADULT MALE 0.90.9 0.90.9POST-POST-MENAPAUSALMENAPAUSAL

0.90.9 0.90.9

AnemiasFACTORS AFFECTING IRON ABSORPTION

Favored By: Organ meat & Hem

iron Ferrous form Acid pH (e.g., Gastric

HCL) Vitamin C Low M.Wt. Chelate

(Sugar) Iron Deficiency Increased

Erythropoiesis Pregnancy

Reduced By:Reduced Animal FoodFerric formAlkalies (Pancreatic

secretion)

TeaIron overloadDecreased ErythrpoiesisAcute or Chronic

inflammation

Anemias

PALLOR

AnemiasGLOSSITIS

Anemias

DYSPHAGIA

AnemiasMARROW IRON STORES

AnemiasIRON DEFICIENT MARROW

Anemias

IRON DEFICIENT ERYTHROPOIESIS

Anemias

Ancylostoma

Anemias

Ca Colon

Causes of Iron deficiency Anemias

BLOODBLOODLOSSLOSS

MALABSORPTION

DIETARY

Causes of Iron deficiency Anemias

BLOODBLOODLOSSLOSS

MALABSORPTION DIETARY

UTERINE

Menorrhagia

Pregnancy

Post-Menopausal

Bleeding

GITEsophageal varices

Hiatus HerniaPU

AspirinHookworm

HHT

Cancer (Stomach; Colon)

Ulcerative Colitis

Meckle’s

Piles

RENAL

Hematuria

Hb-uria

LUNGS

BLEEDING

SELF-INDUCED

20 mg of iron is lost with each menstrual period

Iron loss per pregnancy ranges from 500 to 1000 mg

During vaginal delivery about 500 ml of blood is lost

In pregnancy, plasma volume is increased by 50%,while red cell mass is only increased by 10%-20%

in women not receiving iron and by 30% in those taking iron

This disproportionate expansion of plasma relative to red cell mass creates a state of dilutional anemiawhich is called physiological anemia of pregnancy.

Women with a hemoglobin level of < 9 gm/dl or > 13 gm/dL have an increased risk of poor fetal outcome

P R

E G

N A

N C

Y &

I R O

N

Anemias

Causes of Iron deficiency Anemias

BLOODLOSS

MAL-ABSORPTION

CeliacGastrectomy

Atrophic GastritisClay Eating

DIETARY

HEPCIDINIRONABSORPTION

SEQUENCE OF

EVENTS IN

IRON DEFICINCY

SEQUENCE OF EVENTS IN IRON DEFICINCY I

Hb 15 g/dL

RCC 5 million/ uL

MCH 30 pg Hct. 0.45

MCHC 35 g/dL

MCV 86 fL

Serum Iron UIBC

100 ug/dL 200 ug/dL

TIBC= 300 ug/dL

Saturation 33%

FERRITIN 150 ug/L

WBC7,500/uL

Platelet200,000/uL

SEQUENCE OF EVENTS IN IRON DEFICINCY II

BLEEDING

40 ml/ Day

20 mgIRON

Iron Absorption

up to5

mg/Day

Net Daily Loss= 20-5 = 15 mg

1500------ = 100 Days 15

Latent Iron

Deficiency

No Clinical FeaturesNormal Blood Values

Increased Iron Absorption↓Iron/ ↑TIBC/ ↓Ferritin

SEQUENCE OF EVENTS IN IRON DEFICINCY III

IRONDEFICIENCY

ANEMIA

↓ MCH

↓ MCHC

↓Iron ↑ TIBC

↓ Ferritin

APKHypochromiaMicrocytosisThrombocytosis

↓Hb ↓ MCV

↑ RDW

NAILPaleDryBrittleRidgesFlatKoilonychia

Glossitis

AngularStomatitis

DYSPHAGIAKelly

PatersonWhite

Syndrome

Pica

AtrophicGastritis

MANAGEMENT OF

IRON DEFICIECY ANEMIA

ORAL IRON THERAPY

Avoid giving iron blindly to all hypochromic microcytic anemias

Always evaluate iron status & look at blood smear

Thalassemia minor patients or sideroblastic anemia patients

do not need iron; they are already iron overloaded.

MANAGEMENT OF IRON DEFICIECY ANEMIA

Treatment of theUnderlying Cause

(e.g., Colon Cancer)

Correction of theDeficiency withInorganic Iron

Blood Loss is the usual cause of Iron Deficiency

Whenever possible the site of blood loss must beidentified and the lesion treated

Always give iron since the deficiency cannot be corrected from normal diet for many years

Even in most severe iron deficiency anemia states, the amount of dietary iron absorbed cannot increase above 5 mg/day.

Likewise, no matter how much is the extent of iron overload, obligatory iron loss cannot exceed 5 mg/day.

In severe iron deficiency anemia, up to 30 mg of iron can be absorbed if 180 mg of elemental iron is prescribed.

ORAL IRON THERAPY

IRON SALTIRON SALT TABLET TABLET STRENGTHSTRENGTH

((mgmg))

ElementalElemental

Iron ContentIron Content

((mgmg))

Ferrous SulphateFerrous Sulphate 200200 6363

Ferrous Ferrous GluconateGluconate

300300 3535

Ferrous Ferrous SuccinateSuccinate

100100 3535

Ferrous Ferrous FumarateFumarate

200200 6565Adult: 100 to 200 mg of Elemental Iron/dayChildren: 1 mg/kg tid as Liquid Iron (Teeth Staining)Space the doses as absorption is impaired for 4 hrs > dose

SIDE EFFECTS OF ORAL IRON THERAPY

GIT Irritation Nausea

Epigastric PainConstipation

Diarrhea

Reduce Iron Dose

Change to Low Iron Tab

Take Iron with Meal

Avoid Enteric-Coated & Sustained Release tabletsas iron is released past sites of optimal absorption

Give Iron for 6 months to correct anemia & replenish stores

Correction of Ferritin is a good guide for adequate treatment. Ferritin should be donea week after stopping iron

Reticulocytosis starts > 3 days & lasts 3 weeks

Ideally expect Hemoglobin rise of 1 gm/dL/weekor at least 2 gm/3 weeks

ORAL IRON THERAPY

FAILURE OF RESPONSETO ORAL IRON THERAPY

*Continued hemorrhage*Intolerance to Oral Iron*Lack of Compliance*Malabsorption*Incorrect Diagnosis*ACD “Anemia of Chronic Disorders”*H. pylori

PARENTERAL IRON THERAPY

Usually unnecessary & misused

Unfortunately Kurdish patients seem to enjoy the pain!

Oral Iron can provide marrow with more iron than its capacity to produce red cells

Parenteral Iron does not rise Hemoglobin faster than oral iron

IRON MUST BE GIVEN BY DEEP DEEP INTRAMUSCULAR INJECTIONS

INDICATIONS FOR

PARENTERAL IRON THERAPY

•Genuine Iron Intolerance

•GIT Disorders (Ulcerative Colitis; Crohn’s Disease)

•Celiac Disease “occasionally”

•Rapid repletion of iron stores (late preganacy; pre-operative; continued bleeding)

TOTALDOSE

INFUSIONOF

IRON

PARENTERAL IRON PREPARATIONS

“Iron Dextran”“Iron Sucrose”

IMFERONi.v. i.m.

JECTOFERi.m.

Facilities for CPR should be at hand

Avoid in Allergic Disorders (Asthma; Eczema; Anaphylaxis)

Only give oral iron > 5 days from last injection

Fefol

Vitamin C

MEGALOBLASTIC ANEMIAS

MEGALOBLASTIC ANEMIAS

Distinctive morphology of developing red cells in the bone marrow

B12↓ Folate↓

Others

Pernicious Anemia is rare in Kurdistan & ME

MEGALOBLASTIC ANEMIAS

BB1212 FolateFolate

Content in Content in

FoodFoodMeat: Meat: RichRich

Veg. PoorVeg. PoorMeat: Meat: ModerateModerate

Veg. Veg. RichRich

Cooking EffectCooking Effect 10-30% Loss10-30% Loss 70-100% Loss70-100% Loss

Daily Daily RequirementRequirement

1 ugm1 ugm 100 ugm100 ugm

Daily IntakeDaily Intake 5-30 ugm5-30 ugm 500-800 ugm500-800 ugm

AbsorptionAbsorption Terminal Terminal

ileumileumDuodenum & Duodenum & JejunumJejunum

StoresStores 2-5 mg2-5 mg 5-10 mg5-10 mg

Serum LevelSerum Level 160-925 160-925 ng/Lng/L

3-15 ugm/L3-15 ugm/L

MEGALOBLASTIC ANEMIAS

Causes of Vitamin B12 Deficiency

•Nutritional Vegans•Malabsorption

• Gastric:• Pernicious Anemia• Gastrectomy

• Intestinal:• Stagnant Loop• Tropical sprue• Ileal Resection & Crohn’s Disease• Fish Tapeworm

MEGALOBLASTIC ANEMIAS

Causes of Folate Deficiency

Dietary: Old Age; Infancy; Poverty; Alcoholics; Chronically invalids

Malabsorption: Celiac; Tropical Spru

Excess Use: Physiological (Pregnancy; Lactation; Prematurity)

Pathological (HA; MF; Cancer; Inflam. Diseases)

MEGALOBLASTIC ANEMIAS

Pernicious Anemia

Severe lack of Intrinsic Factor from Gastric Atrophy

Common in Europe & America; rare in ME

Macrocytosis; Low B12; Positive Schilling Test

Dramatic response to treatment

MEGALOBLASTIC ANEMIAS

MEGALOBLASTIC ANEMIAS

MEGALOBLASTIC ANEMIAS

Clinical Features

Anemia symptoms

Low Platelet & WBC

PallorWith a tinge

OfJaundice

Bruises from Thrombocytopenia

GLOSSITIS

ANGULARSTOMATITIS

SUBACUTE

COMBINEDDEGENRATION

OFTHE

SPINAL CORD

Premature GreyingBlue EyesVitiligo

BONEMARROW

ASPIRATION

HYPERCELLULARFRAGMENTS

&TRAILS

MEGALO-BALSTIC

ERYTHRO-POIESIS

Late

Intermediate

Early Megaloblasts

MANAGEMENTOF

MEGALOBLASTIC ANEMIAS

R/ B12 1000 ugm i.m. every other day

for 6 doses every 3 month

Folate 5 mg daily

In undiagnosed megaloblastic anemiaReplenish B12 before giving Folate

otherwise neuropathy is precipitated

Give prophylactic Folate in Pregnancy, Prematurity & HA

ىژهروپ رازیانه كومبانياىه نجه خانه ىپنه خوشخانه و شير

كاتەميديا دروست د

له بریتیه پزيشکان ۲۰۰پروژهكه مالى كلينيكو كومهلگاى و نهخوش ژورى

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