ANAEMIA: ANAEMIA: PreventablePreventable, ,

Yet a Problem!!Yet a Problem!!

DR. R. RAJKUMAR M.D., D.M.DR. R. RAJKUMAR M.D., D.M.

CONSULTANT MEDICAL ONCOLOGIST CONSULTANT MEDICAL ONCOLOGIST

MADURAI MEDICAL COLLEGEMADURAI MEDICAL COLLEGE

ANAEMIA: ANAEMIA: PreventablePreventable, ,

Yet a Problem!!Yet a Problem!!

DR. R. RAJKUMAR M.D., D.M.DR. R. RAJKUMAR M.D., D.M.

CONSULTANT MEDICAL ONCOLOGIST CONSULTANT MEDICAL ONCOLOGIST

MADURAI MEDICAL COLLEGEMADURAI MEDICAL COLLEGE

DefinitionDefinition

Anemia - insufficient Hb to carry out O2 requirement

by tissues.

WHO definition : Hb conc. 11 gm %

CDC definition : Hb conc. < 11gm % in 1st and 3rd trimesters and < 10.5 gm% in 2nd trimester

For developing countries : cut off level suggested is 10 gm %

- WHO technical report Series no. 405, Geneva 1968

Centre for disease control, MMWR 1989;38:400-4

Anemia - insufficient Hb to carry out O2 requirement

by tissues.

WHO definition : Hb conc. 11 gm %

CDC definition : Hb conc. < 11gm % in 1st and 3rd trimesters and < 10.5 gm% in 2nd trimester

For developing countries : cut off level suggested is 10 gm %

- WHO technical report Series no. 405, Geneva 1968

Centre for disease control, MMWR 1989;38:400-4

Degree Hb% Haematocrit (%)

Moderate 7-10.9 24-37%

Severe 4-6.9 13-23%

Very Severe <4 <13%

Degree Hb% Haematocrit (%)

Moderate 7-10.9 24-37%

Severe 4-6.9 13-23%

Very Severe <4 <13%

WHO Classification of Anaemia WHO Classification of Anaemia

Magnitude of ProblemMagnitude of ProblemMagnitude of ProblemMagnitude of Problem

Globally, is about 30 %Globally, is about 30 %

In developing countries & In developing countries & India, incidence is around India, incidence is around 40 – 90%.40 – 90%.

Responsible for 40% of Responsible for 40% of maternal deaths in third world maternal deaths in third world countries.countries.

Important cause of direct and Important cause of direct and indirect maternal deathsindirect maternal deaths

- Vitere FE Adv Exp Med Biol 1994;352:127- Vitere FE Adv Exp Med Biol 1994;352:127

Globally, is about 30 %Globally, is about 30 %

In developing countries & In developing countries & India, incidence is around India, incidence is around 40 – 90%.40 – 90%.

Responsible for 40% of Responsible for 40% of maternal deaths in third world maternal deaths in third world countries.countries.

Important cause of direct and Important cause of direct and indirect maternal deathsindirect maternal deaths

- Vitere FE Adv Exp Med Biol 1994;352:127- Vitere FE Adv Exp Med Biol 1994;352:127

Infection

Lack of Concentration

Weakness

Irritability

Palpitation

Fatigue

Dizziness

SymptomsSymptoms

Clinical FeaturesClinical FeaturesClinical FeaturesClinical Features

Pallor of skin And m/m

Edema

PlatynychiaKoilonychia PlatynychiaKoilonychia

Glossitis

Stomatitis

Tachycardi

a

Soft ejectionsystolic murmur

SignsSigns

Physiological

Pathological

Causes of Anaemia Causes of Anaemia Causes of Anaemia Causes of Anaemia

Nutritional

Haemorrhagic

Haemolytic

Nutritional

Haemorrhagic

Haemolytic

Iron RequirementIron Requirement

Iron Absorption Iron Absorption 11 Amount of iron in the

body Amount of iron in the

body

Iron Loss

Skin

Urine

Feces

Menstruation

1-2mg/d1-2mg/d

20-30mg/c20-30mg/c

Early Pregnancy

2.5 mg / day

32 to 40 weeks

6.8 mg / day

TOTAL800 – 1000

mg

20 to 32 weeks

5.5 mg / day

RBC =500mgFetus+Placenta =450mgThird stage blood loss=200mgTotal = 1150mg

Iron Requirement During PregnancyIron Requirement During Pregnancy

HbHb 13.5 – 14 gm %13.5 – 14 gm %

R.B.C.R.B.C. 4.5 – 4.7 million/cu mm4.5 – 4.7 million/cu mm

Serum IronSerum Iron 50 – 150 μg / dL50 – 150 μg / dL

TIBCTIBC 300 – 360 μg / dL300 – 360 μg / dL

Transferrin saturationTransferrin saturation 25 – 50 %25 – 50 %

S. Ferritin levelS. Ferritin level 30 μg / Lit30 μg / Lit

Red Cell protoporphyrinRed Cell protoporphyrin 30 μg / dL30 μg / dL

ErythropoietinErythropoietin 15.20 U / Lit15.20 U / Lit

MCVMCV 76 – 100 fL76 – 100 fL

MCHMCH 27 – 33 pg27 – 33 pg

MCHCMCHC 33.37 gm / dL33.37 gm / dL

PCVPCV 32 – 40 %32 – 40 %

Normal LevelsNormal Levels

Laboratory Diagnosis of AnaemiaLaboratory Diagnosis of Anaemia

IDAIDA ThalassemiaThalassemia Chronic DiseasesChronic Diseases

Serum IronSerum Iron Decreased Decreased Normal / Increased Normal / Increased DecreasedDecreased

TIBCTIBC IncreasedIncreased NormalNormal Decreased or NDecreased or N

TransferrinTransferrin

SaturationSaturation

DecreasedDecreased N or IncreasedN or Increased N or DecreasedN or Decreased

Serum FerritinSerum Ferritin DecreasedDecreased N or IncreasedN or Increased NN

Marrow IronMarrow Iron Decreased / Decreased / absentabsent

N or IncreasedN or Increased NN

Therapeutic test with Therapeutic test with oral ironoral iron

Rise in HbRise in Hb No rise in HbNo rise in Hb No riseNo rise

National Nutrition Anaemia Prophylaxis Programme (NNAPP 1971 - 72)

National Nutrition Anaemia Prophylaxis Programme (NNAPP 1971 - 72)

Anaemia continues – Major health problem

Nutritional Anaemia :Major Health ProblemsNutritional Anaemia :

Major Health Problems

FS + FA

Pregnancy

Lactating mothers

Family planning acceptors

Children – 1 to 11 years

Reason For Increased Reason For Increased Incidence Of AnemiaIncidence Of Anemia

Reason For Increased Reason For Increased Incidence Of AnemiaIncidence Of Anemia

Poor pre-pregnancy iron balance due to – Poor pre-pregnancy iron balance due to – untreated systemic diseases & menstrual untreated systemic diseases & menstrual disorders disorders

Improper supplementation of iron in pregnancy Improper supplementation of iron in pregnancy ( late registration and poor follow up)( late registration and poor follow up)

Repeated childbearingRepeated childbearing

Lack of awareness and illiteracyLack of awareness and illiteracy

Poor pre-pregnancy iron balance due to – Poor pre-pregnancy iron balance due to – untreated systemic diseases & menstrual untreated systemic diseases & menstrual disorders disorders

Improper supplementation of iron in pregnancy Improper supplementation of iron in pregnancy ( late registration and poor follow up)( late registration and poor follow up)

Repeated childbearingRepeated childbearing

Lack of awareness and illiteracyLack of awareness and illiteracy

Low socioeconomic status and poor hygieneLow socioeconomic status and poor hygiene

Chronic malnutritionChronic malnutrition

Poor availability of iron due to predominantly Poor availability of iron due to predominantly veg diet, diet low in calories but rich in phytates. veg diet, diet low in calories but rich in phytates. Food and religious taboosFood and religious taboos

GI infections and infestations GI infections and infestations (e.g. Kala azar, worm infestations)(e.g. Kala azar, worm infestations)

Low socioeconomic status and poor hygieneLow socioeconomic status and poor hygiene

Chronic malnutritionChronic malnutrition

Poor availability of iron due to predominantly Poor availability of iron due to predominantly veg diet, diet low in calories but rich in phytates. veg diet, diet low in calories but rich in phytates. Food and religious taboosFood and religious taboos

GI infections and infestations GI infections and infestations (e.g. Kala azar, worm infestations)(e.g. Kala azar, worm infestations)

Reason For Increased Reason For Increased Incidence Of AnemiaIncidence Of Anemia

Reason For Increased Reason For Increased Incidence Of AnemiaIncidence Of Anemia

IUGR

IUD IUH

CCFCCF

INFECTIONINFECTION

PRETERM LABOUR

PRETERM LABOUR

PIHPIH

Medical DisorderMedical Disorder

Complications - PregnancyComplications - PregnancyComplications - PregnancyComplications - Pregnancy

Instrumental delivery

PPH

FoetalDistressCCF

MATERNALPERINATAL

MorbidityMortality

Complications - LabourComplications - LabourComplications - LabourComplications - Labour

Management Options Management Options Management Options Management Options

Pre – pregnancy :

Treat the cause before conception

Pre-pregnancy balanced diet, education

and health support.

Build up iron stores during adolescent

phase

Pre – pregnancy :

Treat the cause before conception

Pre-pregnancy balanced diet, education

and health support.

Build up iron stores during adolescent

phase

Oral Iron

Blood transfusionParenteral

Injectable IronInjectable IronHuman Recombinant

Erythropoietin

Modalities of ManagementModalities of ManagementModalities of ManagementModalities of Management

100 mg elemental Iron ------- ↑ 0.18 gm % day100 mg elemental Iron ------- ↑ 0.18 gm % day

Iron stores poor

-ve-ve

Iron absorption

↓ Bioavailability

of Iron

-ve-ve-ve-ve

Phosphate phytate

Worm infestation

Oral IronOral IronOral IronOral Iron

Oral Iron Therapy Oral Iron Therapy Oral Iron Therapy Oral Iron Therapy

Ideal dose – 100mg per day (prophylactic)

Ferrous gluconate, ferrous fumarate, ferrous succinate, ferrous sulphate, ferrous ascorbate citrate

Rise in Hb – 0.8 gm / dl / week

Side effects -G I upset most common

Pt. compliance not guaranteed

Ineffective in pts with worm infestations

Inconclusive evidence on benefit of controlled release Iron preparation

Ideal dose – 100mg per day (prophylactic)

Ferrous gluconate, ferrous fumarate, ferrous succinate, ferrous sulphate, ferrous ascorbate citrate

Rise in Hb – 0.8 gm / dl / week

Side effects -G I upset most common

Pt. compliance not guaranteed

Ineffective in pts with worm infestations

Inconclusive evidence on benefit of controlled release Iron preparation

Iron salts are dissociated into bivalent or trivalent iron salts

Diffuses as free iron ions through the upper part of the gastrointestinal mucosa

Taken up by transferrin and incorporated into ferritin.

For binding to ferritin and transferrin ferrous iron has to be converted into ferric iron by oxidation

Highly reactive free radicals are produced during this process

All ionic iron including carbonyl iron are absorbed similarly

Iron salts are dissociated into bivalent or trivalent iron salts

Diffuses as free iron ions through the upper part of the gastrointestinal mucosa

Taken up by transferrin and incorporated into ferritin.

For binding to ferritin and transferrin ferrous iron has to be converted into ferric iron by oxidation

Highly reactive free radicals are produced during this process

All ionic iron including carbonyl iron are absorbed similarly

• Borbolla JR. Cicero RE, Dibilox MM, Sotres RD et al.. Rev Mex Pediatr 2000; 67(2): 63-67

• Heubers KA, Brittenham GM, Csiba E, Finch CA. J Lab Clin Med 1986 ; 108 ; 473-8.

• Borbolla JR. Cicero RE, Dibilox MM, Sotres RD et al.. Rev Mex Pediatr 2000; 67(2): 63-67

• Heubers KA, Brittenham GM, Csiba E, Finch CA. J Lab Clin Med 1986 ; 108 ; 473-8.

Absorption of Ferrous SaltsAbsorption of Ferrous SaltsUncontrolled Passive AbsorptionUncontrolled Passive Absorption

Fe+2Fe+2

Fe+2Fe+2

Dissociation

Passive diffusion

Fe+2

Fe+2

Fe+2

Fe+2

Fe+2 Fe+2

Gut Lumen Mucosal Cell Blood

Ferritin

Iron salts

Fe+3

Free Radical

Fe+2

Fe+2

Fe+2

Fe+2

Fe+2Fe+2

Fe+2

Fe+3

Free Radical

Transferrin

Incorporation into Hb

↑ Hb – 0.21 gm %

Fractionated Irondextran[Iron hydroxide dextran

complex]

Les s

Les s

Les

s Les

s

Parenteral TherapyParenteral Therapy

100 mg elemental Iron

Anaphylactic Anaphylactic reactionreaction

Anaphylactic Anaphylactic reactionreaction

I.M. I.V.

Parenteral Therapy : Parenteral Therapy : Traditional IndicationsTraditional IndicationsParenteral Therapy : Parenteral Therapy :

Traditional IndicationsTraditional Indications

Intolerance to oral iron Intolerance to oral iron

Poor compliance to oral iron Poor compliance to oral iron

Gastrointestinal disorders Gastrointestinal disorders

Malabsorption syndromesMalabsorption syndromes

Rapid blood loss Rapid blood loss

Intolerance to oral iron Intolerance to oral iron

Poor compliance to oral iron Poor compliance to oral iron

Gastrointestinal disorders Gastrointestinal disorders

Malabsorption syndromesMalabsorption syndromes

Rapid blood loss Rapid blood loss

Inability to maintain iron balance Inability to maintain iron balance (haemodialysis)(haemodialysis)

Patient donating large amount of blood Patient donating large amount of blood for auto-transfusion programmefor auto-transfusion programme

? Pregnant women with severe IDA, ? Pregnant women with severe IDA, presenting late in pregnancypresenting late in pregnancy

Inability to maintain iron balance Inability to maintain iron balance (haemodialysis)(haemodialysis)

Patient donating large amount of blood Patient donating large amount of blood for auto-transfusion programmefor auto-transfusion programme

? Pregnant women with severe IDA, ? Pregnant women with severe IDA, presenting late in pregnancypresenting late in pregnancy

Parenteral Therapy : Parenteral Therapy : Traditional IndicationsTraditional IndicationsParenteral Therapy : Parenteral Therapy :

Traditional IndicationsTraditional Indications

TheThe

World Health OrganisationWorld Health Organisation states…states…

‘‘transfusion should be transfusion should be

prescribed prescribed ONLYONLY for for

conditions for which there conditions for which there

is is NONO OTHER TREATMENT’ OTHER TREATMENT’

Diagnosis of Folate Deficiency Diagnosis of Folate Deficiency Anemia (FDA)Anemia (FDA)

Diagnosis of Folate Deficiency Diagnosis of Folate Deficiency Anemia (FDA)Anemia (FDA)

Special considerations in diagnosis

• FDA is suspected when the expected response

to adequate iron therapy is not achieved

• Macrocytosis can occur in pregnancy in absence

of FDA

• If FDA + IDA present, it will be masked by IDA

• Definitive diagnosis – Bone marrow aspirate

Special considerations in diagnosis

• FDA is suspected when the expected response

to adequate iron therapy is not achieved

• Macrocytosis can occur in pregnancy in absence

of FDA

• If FDA + IDA present, it will be masked by IDA

• Definitive diagnosis – Bone marrow aspirate

Megaloblastic AnemiaMegaloblastic Anemia- Diagnostic Problems- Diagnostic ProblemsMegaloblastic AnemiaMegaloblastic Anemia- Diagnostic Problems- Diagnostic Problems

HB estimationHB estimation

Peripheral smearPeripheral smear

MCV estimationMCV estimation

Serum folate Serum folate

Red cell folateRed cell folate

FIGLU estimationsFIGLU estimations

Marrow aspirateMarrow aspirate

HB estimationHB estimation

Peripheral smearPeripheral smear

MCV estimationMCV estimation

Serum folate Serum folate

Red cell folateRed cell folate

FIGLU estimationsFIGLU estimations

Marrow aspirateMarrow aspirate

Management of FDAManagement of FDAManagement of FDAManagement of FDA

Strong case for routine prophylaxis

Prophylaxis with anti convulsants

Continue routine oral therapy for

hemolytic anaemia

Parenteral therapy for severe deficiency

Strong case for routine prophylaxis

Prophylaxis with anti convulsants

Continue routine oral therapy for

hemolytic anaemia

Parenteral therapy for severe deficiency

Worm InfestationsWorm Infestations

Common cause of anaemia in developing countries

Most common – hookworm infestation, Round worm, whip worm, etc.

Oral iron therapy becomes ineffective

Treatment by antihelminthics is a must

Treatment

Mebendazole : 100mg twice daily for three days

Pyrantel pamoate : 10mg / kg in single dose.

Albendazole : 400mg once a day for three days

Common cause of anaemia in developing countries

Most common – hookworm infestation, Round worm, whip worm, etc.

Oral iron therapy becomes ineffective

Treatment by antihelminthics is a must

Treatment

Mebendazole : 100mg twice daily for three days

Pyrantel pamoate : 10mg / kg in single dose.

Albendazole : 400mg once a day for three days

HemoglobinopathiesHemoglobinopathies

A collective term for the inherited disorders A collective term for the inherited disorders of Hb synthesisof Hb synthesis

Disorders of globin synthesis e.g. Disorders of globin synthesis e.g. Thalassemia Thalassemia

Structural Hb variants e.g. Sickle cell Structural Hb variants e.g. Sickle cell anemia, HbCanemia, HbC

A collective term for the inherited disorders A collective term for the inherited disorders of Hb synthesisof Hb synthesis

Disorders of globin synthesis e.g. Disorders of globin synthesis e.g. Thalassemia Thalassemia

Structural Hb variants e.g. Sickle cell Structural Hb variants e.g. Sickle cell anemia, HbCanemia, HbC

ThalassemiaThalassemia

Genetic disorders; lack or Genetic disorders; lack or sed synthesis of globin sed synthesis of globin chainschains

Two types : Two types : & & thalassemia thalassemia

chains encoded by 2 pairs of genes on chains encoded by 2 pairs of genes on chromosome 16chromosome 16

chains encoded by single pair of genes on chains encoded by single pair of genes on chromosome 11chromosome 11

thalassemia more common and presents as eitherthalassemia more common and presents as either °(major) or °(major) or ++ (minor) (minor)

Genetic disorders; lack or Genetic disorders; lack or sed synthesis of globin sed synthesis of globin chainschains

Two types : Two types : & & thalassemia thalassemia

chains encoded by 2 pairs of genes on chains encoded by 2 pairs of genes on chromosome 16chromosome 16

chains encoded by single pair of genes on chains encoded by single pair of genes on chromosome 11chromosome 11

thalassemia more common and presents as eitherthalassemia more common and presents as either °(major) or °(major) or ++ (minor) (minor)

Diagnosis of ThalassemiaDiagnosis of Thalassemia

Hb estimationsHb estimations

Peripheral smearPeripheral smear

sed MCVsed MCV

sed MCHsed MCH

HbAHbA2 2 (( 2 222))

Hb estimationsHb estimations

Peripheral smearPeripheral smear

sed MCVsed MCV

sed MCHsed MCH

HbAHbA2 2 (( 2 222))

Diagnostic Strategy for Thalassemias

Hb Electrophoresis + CBC

Abnormal band

Normal No action

MCV MCH

Quantitative Hb electrophoresis

Raised Hb A2

B Thalassemia

Normal

sed Examine partners blood

? X Thalassemia

DNA analysis for x gene defects

Sickle Cell DiseaseSickle Cell Disease

Structural Hb variantStructural Hb variant

Exists in homo & heterozygous Exists in homo & heterozygous formsforms

Under hypoxic conditions, HbS Under hypoxic conditions, HbS polymerizes, gels or crystallizes.polymerizes, gels or crystallizes.

hemolysis of cells, & hemolysis of cells, & thrombosis of vessels in thrombosis of vessels in various organsvarious organs

In long standing cases, In long standing cases, multiple organ damage.multiple organ damage.

Structural Hb variantStructural Hb variant

Exists in homo & heterozygous Exists in homo & heterozygous formsforms

Under hypoxic conditions, HbS Under hypoxic conditions, HbS polymerizes, gels or crystallizes.polymerizes, gels or crystallizes.

hemolysis of cells, & hemolysis of cells, & thrombosis of vessels in thrombosis of vessels in various organsvarious organs

In long standing cases, In long standing cases, multiple organ damage.multiple organ damage.

Take Home MessageTake Home Message

Anaemia although preventable is a global problem

Anaemia still is the commonest cause of maternal mortality

and morbidity in spite of easy diagnosis and treatment

Anaemia can be due to a number of causes,

including certain diseases or a shortage of iron, folic

acid or Vitamin B12.

The most common cause of anemia in pregnancy is

iron deficiency.

Iron therapy is best given orally

Anaemia although preventable is a global problem

Anaemia still is the commonest cause of maternal mortality

and morbidity in spite of easy diagnosis and treatment

Anaemia can be due to a number of causes,

including certain diseases or a shortage of iron, folic

acid or Vitamin B12.

The most common cause of anemia in pregnancy is

iron deficiency.

Iron therapy is best given orally

The youth need to be educated about diet, The youth need to be educated about diet,

sanitation and personal hygienesanitation and personal hygiene

Hookworm infestation should be treatedHookworm infestation should be treated

Pregnant women should be given Iron and Pregnant women should be given Iron and

folate supplementsfolate supplements

The youth need to be educated about diet, The youth need to be educated about diet,

sanitation and personal hygienesanitation and personal hygiene

Hookworm infestation should be treatedHookworm infestation should be treated

Pregnant women should be given Iron and Pregnant women should be given Iron and

folate supplementsfolate supplements

Take Home MessageTake Home Message