vitb12, folat, thalassemia

7/28/2019 VitB12, Folat, Thalassemia

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Causes of megaloblastic anaemia

1. Folic acid deficiency

a. Inadequate diet

b. Alcoholism

c. Steatorrhea or sprue

d. Other causes of malabsorption, including partial gastrectomy

e. Pregnancy and lactation

f. Leukaemia, myelofibrosis, and chronic haemolytic anaemia

2. Vitamin B12 deficiencya. Pernicious anaemia

b. Gastrectomy

c. Sprue

d. Long-term dietary deficiency

e. Parasites (Diphyllobothrium latum

3. Drug induced megaloblastic anaemia

4. Congenital disorders (very rare)

5. Leukaemia

6. Di Guglielmos syndrome


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Source of folic acid

> Green vegetables, liver, yeast

> Destroyed by prolonged boiling & acid pH

Source of vitamin B12

> Synthesized by bacteria form large bowel

> Liver & kidney

> Dairy products, fish, shellfish


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LABORATORY DIAGNOSIS OF MACROCYTIC ANAEMIA

LABORATORY TEST INTERPRETATIONPeripheral smear

Bone marrowexamination

Reticulocyte count

Therapeutic response

Diagnosis

Macrocytic anaemia

Megaloblasticchanges No megaloblasticchanges

Low LowHigh

Possible

liver disease

Probable

haemolytic

anaemia

Responds tofolic acid

Respondsto vit B12

Vit. B12

deficiency

Folic acid

deficiency


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Terminal ileum Blood Tissue cells

Absorption of Vit. B12 Absorption of Vit. B12and folate

ABSORPTIONOFFOLIC ACID AND VIT. B12


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A Normal Healthy Individual

PGA

Vit.B12

Poly

glutamateis

stor

edinRBCs

Normal Red Blood Cell

Polyglutamate

(RBC folate)

DNA

5-m-THF(Serum Folate)

THF

LAB RESULTS FOR

NORMAL HEALTHY PERSON

Serum Folate Normal

RBC Folate Normal

Serum Vit. B12 Normal


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Folate Deficiency

Polyglu

tamateis

stored

inRBCs

islow

PGA

Normal

Vit.B12

Low THF

Low

Polyglutamate

(RBC folate)

Low DNA

Macrocytic Cells

Low 5-m-THF

(Serum Folate)

LAB RESULTS FOR FOLATE

DEFICIENCY

Serum Folate Low

RBC Folate Low

Serum B12 Normal


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Vit. B12 deficiency

PGA

Normal or High 5-m-THF

(Serum Folate)Low

Vit.B12

Low THF

Low or Normal

Polyglutamate

(RBC folate)

Low DNA

Macrocytic Cells

Polyglutamateis

storedinRBCs

islow

LAB RESULTS FOR Vit. B12DEFICIENCY

Serum Folate Normal or High

RBC Folate Low or Normal

Serum B12 Low


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Vit.B12 and Folate Deficiency

PGA

Low 5mTHF(Serum Folate)Low

Vit.B12

Low THF

Low

Polyglutamate

(RBC folate)

Low DNA

Macrocytic Cells

Polyglutamateis

stored

inRBCs

islow

As with folate or Vit.B12

deficiency,

the RBCs are macrocytic

With low Vit.B12 and low folate present,5-m-THF is not converted to THF

LAB RESULTS FOR

Vit.B12 and FOLATE DEFICIENCY

Serum Folate Low

RBC Folate Low

Serum Vit.B12 Low


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Deficiency Folic acid Serum

vit. B12

Serum RBC

Folic acid

Vit B12

Folic acid & B12

N /N


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THERAPEUTIC TRIALS

Usual diet

0,2 mg folic acid

oral

1 week

reticulocyte response

+ -

+ 1 - 2 mg Vit. B12reticulocyte response

Contraindications :

- patients on critical ill

- angina pectoris

- congestive heart disease

- thrombocytopenia with bleeding


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GENETIC DEFECTS OF HAEMOGLOBIN

(Haemoglobinopathy)

Reduced or abnormal synthesis of normal globin

Reduced Thalassaemia

Abnormal Hb - abnormalities

Hb varian

Fraction of normal haemoglobin in :

adult full-term infant

HbA2 < 3.5% < 1%

HbF < 1.0% 50 - 85%


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Occur in tropical = sub tropical area

Protection against Falciparum malaria

The geographycal distribution of thethlassaemia and haemoglobin abnormalities

Mediterania,

Afrika,

Timur Tengah,

India,

Burma,

Asia Tenggarameliputi :

China selatan,

Malaysia

Indonesia


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CLASSIFICATION

CLINICAL- Thalassaemia major

- Thalassaemia intermedia

- Thalassaemia minor

- Silent carrier

GENETIC


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The globin gene clusters on chromosom 16 and 11 in embrionic, foetal and adult

Prenatal age (weeks) Postnatal age (weeks)

Synthesis of individual globin chain in prenatal and postnatal life

PATHOPHYSIOLOGIC


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PATHOPHYSIOLOGIC a-THALASSAEMIAb chain2 genes

a chain4 genes

g chain2 genes

Child and adultFoetus and neonates

g4Hb Barts

a2 g2HbF

a2 b2HbA

b4HbH

Thalassaemia-aInclusion HbH

Hydrops foetalis HbH disease

Heinz bodiesprecipitation

DEATH

Bone marrow

IneffectiveErythropoiesis

Organ dysfunction

Peripheral blood

Iron overload

MICROCYTIC HYPOCHROMICANAEMIA

Iron

absorption

MultipleTransfusion

Increased erythropoiesis

Intramedullary ExtramedullaryBone changes Hepatosplenomegaly


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1. HYDROPS FETALIS

-- / --

4 gen deletion

Suppress a chain synthesis

Failure of HbF synthesis

Death in utero

(Hydrop fetalis)


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Laboratory

Hb 3 - 10 g/dL

MCV 110 - 119 fl,

MCH

Anisocytosis, poikilocytosis

Retikulocytosis, NRBC +++

Electrophoresis : Hb Barts (g4) 80-90%Hb Portland +

Hb A absent


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a thalassaemia : four a gene deletion(hydrops foetalis)


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2. HbH DISEASE

3 genes deletion

HbH (b4), unstable, termolabile Clinic :

Normal birth

Anaemia after one year

Hepatosplenomegaly & icterus

HbH diseaseHbH inclusion bodiesHaemoglobin electrophoresis

Normal

HbHb thal. HbENormal

b thal. traitb thal. trait

2 HbH DISEASE


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2. HbH DISEASE

Laboratory

1. Hb 8-10 g/dL

Microcytic hypochromic anaemia

Target cells ++, NRBC +, poikilocytosis andanisocytosis

2. Reticulocytosis, HbH inclusion bodies +++

3. Hb electrophoresis

adult neonates

Hb Barts 25%

HbH 2-40%

HbA2

HbF


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HbH maybe found in

1. a thalassaemia : HbH disease, a thal 1 trait2. Myeloproliferative disorders ALL, AML &

sideroblastic anaemia

Defect a gene transcription

Deficiency a RNA

Deficiency a chain

HbH (5-70%)


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3. a THALASSAEMIA 1 TRAIT (MINOR) 2 genes deletion

a- / a- homozygous a thal 2-- / aa heterozygous a thal 1

Clinic : none

Laboratory :

1. Hb 10 - 12 g/dL

Microcytic hypochromic anaemia

VER 60 - 70 fl

HER 20 - 25 pg

Anisocytosis


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3. a THALASSAEMIA 1 TRAIT (MINOR) Laboratory

2. Hb electrophoresis Cord blood : Hb Bart 5-6%

after 1-3 month

Hb Bart 0%

Adult :

Microcytic hypochromic without anaemia

Ferritin N /

Electrophoresis Hb : Hb Bart 0%

HbH inclusion bodies 1/1000 1/10.000

RBC


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4. a THALASSAEMIA 2 TRAIT (SILENT CARRIER) -a / aa Clinic : normal

Laboratory

Cord blood : HbH < 1%

PATHOPHYSIOLOGIC -THALASSAEMIA


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PATHOPHYSIOLOGIC b-THALASSAEMIA

d chain(2 genes)

g chain(2 genes)

b chain(2 genes)

a chain (4 genes)Child and adultFoetus and neonates

b Thalassaemia major

HbF

a2 g2HbA

a2 b2b Thalassaemia minor

HbA2a2 d2HbA

a2 b2HbF

a2 g2

Heinz bodies

Bone marrow

Ineffective Erythropoiesis

MICROCYTIC HYPOCHROMIC

MICROCYTIC HYPOCHROMIC

ANAEMIA

Iron absorption

Transfusion

Increased erythropoiesis

Intramedullary haematopoiesis Extramedullary haematopoiesis

Bone changes Haepatomegaly Splenomegaly

Hipersplenism

Iron overload

ORGAN DYSFUNCTION


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homozygote b thalassaemia(major) post splenectomy

homozygote b thalassaemia(major)

heterozygote b thalassaemia(minor)


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b Thlassaemia majorClinic :

Severe anaemia becomes apparent at 3 - 6month after birth

Hepatomegaly

Splenomegaly (increased RBC destruction inpooling), expansion the plasma volume

Expansion of bone (thalassaemic facies)

Iron overload (endocrine organs &myocardium)

Pneumococcal & meningococcal, hepatitis B,

hepatitis C, HIV infection


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b Thlassaemia majorLaboratory :

Microcytic hypochromic anaemia,reticulocyte (%), normoblasts, target cells &

basophilic stippling

Haemoglobin electrophoresis :HbA2 normal, or

HbF

HbA absence or almost complete absent Ferritin 1000 - 1500 mg/L

Ferritin is raised in viral hepatitis & inflamatory

disorders


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Mongoloid facies Hair on end appearance


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b thalassaemia trait (minor)Clinic :

Symptomless abnormality

Laboratory : Mild or no anaemia (Hb 10-15 g/dL)

RBC microcytic hypochromic

Haemoglobin electrophoresis :HbA2 > 3.5%

HbF N /


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vitb12, folat, thalassemia

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