Approach to anemia

1. R E F R E N C E : A V E R Y S O U T H A S I A E D I T I O N
( 7 T H )
P R E S E N T E D B Y : D R . M A H E S H Y A D A V
APPROACH TO ANEMIA

2. OBJECTIVES
 RBC DEVELOPMENT
 FETAL HAEMOGLOBIN AND ADULT HAEMOGLOBIN
 PATHOPHYSIOLOGY
 NORMAL HAEMOGLOBIN VALUES
 ANEMIA OF DIFFERENT TYPES AND PRESENTATION AND
MANAGEMENT
 BRIEF APPROACH TO ANEMIA

3. RBC DEVELOPMENT
 DIVIDED INTO 3 STAGES :
1. YOLK SAC LEVEL
2. LIVER LEVEL
3. BONE MARROW LEVEL
YOLK SAC LEVEL
 PRIMITIVE HEMATOPOIESIS
 OCCURS AT 16 – 18 DAYS OF GESTATION
 FORMS MACROPHAGES , NUCLEATED ERYTHROCYTES
AND SOME MEGAKARYOCYTES

4. LIVER LEVEL
 DEFINITVE HEMATOPOIESIS
8TH WEEK OF GESTATION
FORMATION OF HEMAPOIETIC STEM CELLS AND VARIOUS
TYPES OF LEUCOCYTES (GRANULOCYTES , BASOPHILS ,
EOSIONIPHILS), LYMPHOCYTES ,MEGAKARYOCYTES,
ANUCLEATED ERYTHROCYTES .
BONE MARROW LEVEL
AT 6TH MONTH OF GESTATION

5. FETAL AND ADULT HAEMOGLOBIN
 TETRAMER OF FOUR GLOBIN PROTEIN ENCODED BY GENES
ON CHROMOSOME 16 AND 11 .
 ON CHROMOSOME 16 –
EPSILON GAMMA
DELTA BETA
• ON CHROMOSOME 11 –
ZETA ALPHA
• SO FETAL HAEMOGLOBIN(HbF) HAVE 2 APLHA AND 2
GAMMA GLOBIN PROTEIN .

6. ADULT HAEMOGLOBIN
POST NATALLY FETAL HAEMOGLOBIN CHANGED INTO
ADULT HAEMOGLOBIN BY 6 - 10 MONTHS OF AGE ,SWITCH
TO LESS SENSITIVE HEPATIC TO MORE SENSITIVE RENAL
SITE FOR ERYTHROPOETIN.
ADULT HAEMOGLOBIN HAVE ALPHA AND BETA GLOBINS .

7. PATHO-PHYSIOLOGY
 ERYTHROID PRECURSORS ARE IDENTIFIED BY THEIR CELL
SURFACE ANTIGEN EXPRESSIONS AND GROWTH
CHARACTERISTICS IN CULTURE .
 NAMED AS BFU-E CFU-E .
 FETAL BLOOD HAVE 40 X MORE BFU-E ,AS COMPARED TO
ADULTS ,FROM EQUIVALENT VOLUME OF BLOOD .
KEEPS ON DECREASING ALONG THE SERIES OF FETAL
BLOOD ,CORD BLOOD , POST DELIEVERY BONE MARROW
AND BLOOD .

8.  EPO CONTROLS ERYTHROPOIESIS BY FEEDBACK LOOP
ACCORDING TO EYRTHROCYTE MASS AND VENOUS O2
TENSION,THAT’S WHY LEVELS OF EPO IN PREMATURE

9. NORMAL HAEMOGLOBIN
 TERM = Hb level 16.9 +/-1.6 gm%
 Pre term =Hb level 15.9 +/- 2.4 gm%
BASED ON HAEMOGLIBIN :
 Cord Hb <13gm% (TERM )
 Cord Hb < 12 gm/% (Pre – term )

10. ANEMIA CAUSES
 PHYSIOLOGIC ANEMIA AND ANEMIA OF PREMATURITY .
 ANEMIA CAUSED BY BLOOD LOSS .
 ANEMIA CAUSED BY HAEMOLYISIS .
 ANEMIA CAUSED BY ENZYMATIC DEFICIENCY AND
ERYTHROCYTE MEMBRANE .

11. PHYSIOLOGIC ANEMIA AND ANEMIA OF PREMATURITY
 BECAUSE OF TRANSIENT INCREASE IN Hb CONCENTRATION
AS PLASMA MOVES EXTRAVASCULARLY , therefore the Hb
concentration falls to reach .
 CAUSE :
1. Decrease in erythrocyte production ,evidenced by as increase in RETI-
COUNT .
2.Shortened survival of neonate erythrocyte and rapid body growth .

12. ANEMIA CAUSED BY BLOOD LOSS
 Before Birth – Occult Haemorrhage ,Faetomaternal haemorrhage , TTTB
 Obstetrics Accidents – Malformations of the Placenta and cord .
 Nuchal cord with placental blood trapping
 Internal haemorrhages – Excessive blood sampling .
 OTHERS :-
 Incision of the placentae during Cesarean section
 Placenta Previa
 Abruptio Placentae
 Internal Haemorrhage
 Sub galeal haemorrhage
 Laceration of the liver
 Ruptured Spleen
 Pulmonary Hemorrhage

13. FETO-MATERNAL HEMORRHAGE
 Sudden and unexpected decrease in fetal movement is sign of FMH .
 Manifest as Pallor after birth, sluggish and gasping respiration and signs of
circulatory shock .
 >20 % blood volume is sufficient to produce sign of shock and pallor after
birth within 3 hours of the event .
DIAGNOSIS:-
 Acute haemorrhage and Chronic Haemorrhage appear as Normochromic and
Normocytic and hypchromic , Macrocytic indicating fetal iron deficiency
anemia simultaneously .
 Coombs test – Negative
 No Jaundice
 Demonstration of fetal cells in the maternal blood .

14. TWIN- TO –TWIN TRANSFUSIONS
 CRITERIA:-
1. Monochorionic Twins
2. Polyhydramnios in one twin (Recipient ) and oligohyramnios in other.
3. Markedly Enlarged bladder in one twin (Recipient ) and enlarged
Small Bladder in the other .

15. OBSTETRICS ACCIDENTS
 May create a diagnostics confusion about the cause of shock in early hour of
life or presence of pallor and unexplained anemia and unexplained during the
2nd or 3rd .
Ex: Tight Nuchal cord
 INTERNAL HAEMORRHAGE :-
Traumatic deliveries ( vaccum assisted )
Breech delieveries result in rupture of ADRENALS , KIDNEY , SPLEEN or
RETRO-PERITONEAL AREA.
• DIAGNOSIS:- Appear in 24- 48 hrs of life and suddenly into shock
O/E = Abdomen Distended , Shifting Dullness , Elevation of the Rt.
Hemidiaphragm.
USG IS GOLD STANDARD .

16. ANEMIA CAUSED BY HAEMOLYSIS
 IMMUNE (ALLO-IMMUNE OR AUTO –IMMUNE ).
 NON –IMMUNE (MEMBRANOPATHIES ,ENZYMOPATHIES AND
HAEMOGLOBIN PATHIES ).

17. IMMUNE (ALLO-IMMUNE OR AUTO-IMMUNE)
 Rh. HAEMOLYTIC DISEASE :-
MBG – Rh -ve
BBG - Rh +ve
Rh Antigen is responsible .
Anti – D cause destruction .
• If first baby is Rh +ve , develop Anti-body of IgG in mother .
IgG is responsible for haemolysis .

18. DIAGNOSIS
 SIGNS :-
Jaundice , Pallor , Hepatosplenomegaly .
Petechiae and Purpura can be observed in severe anemia as result of
thrombocytopenia and a disturbance in the Intrinsic System of Coagulation
(vitamin k dependent factor )
• LABORATORY FINDINGS :-
Decrease in Haemoglobin , Hb < 13 in cord blood
Increase in Reti- count , Coombs test is –ve
Increase no of Nucleated Erythrocyte in PS
Polychromasia and Anisocytosis
Spherocytes are not abundant .

19. INTRA-UTERINE DIAGNOSIS AND TREATMENT
 Spectrophotometry .
 Indirect antibody test .
 Doppler USG.
 Fetal Rh (D) typing using DNA extracted from the amniotic fluid cells .
 Real time PCR .
TREATMENT :
Blood for intra- uterine transfusion should be o-ve , fresh and CMV safe .

20. ABO HAEMOLYTIC DISEASE
 MBG- O +ve ,BBG = A +ve or B+ve
 Maternal Anti –A and Anti – B antibodies on fetal erythrocytes of the corresponding
blood group .
 Anti - A and Anti- B antibodies are seen as IgG , IgM and IgM fractions of plasma .
 IgG is responsible for haemolysis.
 High level of IgG anti- A or anti- B titre +nt .
DIAGNOSIS:-
• Indirect hyperbilirubinemia .
• Jaundice appearing during the first 24 hours life .
• Increased no of spherocyte in the blood .
• Increase Reti-Count
• Presence of IgG , Anti- A , Anti - B in cord plasma or serum .

21. HAEMOLYTIC DISEASE RESULTING FROM MINOR
BLOOD
 Uncommon
 Anti- D , Anti –D or Anti – B not responsible .
 Anti – E , Anti – C and Anti – kell

22. HAEMOLYSIS DISEASE RESULTING FROM
MINOR BLOOD GROUP INCOMPATIBILTY
1. Enzymopathies – G6PD
2. Membrane function –
Herediatery Spherocytosis
Herediatery Elipocytosis
3. Haemoglobin Synthesis.

23. G6PD DEFICIENCY
 Major function of Erythrocyte is the delievery of O2 to the tissues .
CONCEPT :-
• X- linked recessive factor .
CONSTANTAL
LY EXPOSED
TO O2
CELL
ENZYME +nt (Prevent
oxidative damage )
ENZYME –nt (?)

24. DIAGNOSIS:-
1. Unexplained NNHB
2. Abnormal erythrocyte and HEINZ bodies in the P/S and intravascular
haemolysis.
3. Screening tests :
 Fluorescene .
 Spectrophotometric measurement .
TREATMENT :- Same as NNHB

25. HEREDITARY SPHEROCYTOSIS
 Defect in RED CELL CYTO-SKELETON.
 Occur in school going children .
 75% have +ve family history .
CLINICAL PICTURE:
• Anemia , Jaundice And SplenomegalyCLASSIFICA
TION
TRAIT MILD MODERATE SEVERE
Hb N 11-15 8-12 6-8
Retic-Count N 3-6 >6 >10
Bilirubin <17 17-34 >34 >51
Spectric per se 100 80-100 50-80 40-60
Splenectomy Not Required Not necessary Necessary Necessary

26.  DIAGNOSIS:-
1. Splenomegally clinically
2. Red Cell Indices :- Hb , MCV , MCHC , Hyper dense cells , RDW , R.C
3. Blood film :- Abnormal morphology , Microspherocytes
4. Direct Anti globulin test - -ve
5. Evidence of Haemolysis : Bilirubin . Reticulocytosis
OTHER TESTS :-
 Osmotic fragility
 Acidified Glycerol Lysis Test
 Osmotic Gradient Ektacytometry
 Hypertronic Cryohaemolysis test
 Eosin – 5- maleimide bindings