HEMATOLOGY
Hemolytic Anemia
Dr. Rafi Ahmed GhoriFCPS
Professor Medicine
"Pleasure in the job "Pleasure in the job puts puts
perfection in the perfection in the work."work."
-- Aristotle-- Aristotle
Blood Smear - Normal
C.B.C / FBC / Hemogram
Haemoglobin - 15±2.5, 14 ±2.5 - g/dl
PCV - 0.47 ±0.07, 0.42 ±0.05 - l/l (%) Haematocrit, Total RBC volume - better
RBC count - 5.5 ±1, 4.8 ± 1 x1012/l
MCHC - Hb/PCV - 30-36 - g/dl Hb synthesis within RBC
MCH - Hb/RBC - 29.5 ± 2.5 pg/l Average Hb in RBC
MCV - PCV/RBC 85 ± 8 – fl RBC Maturation
RBC disorders (Anemias) :
““Anemia is decreased red cell mass Anemia is decreased red cell mass affecting tissue oxygenation”affecting tissue oxygenation”
* Low Hb <13.5 (males), <11.5 (females)* Low Hb <13.5 (males), <11.5 (females)
Acquired / Congenital disorders:
Decreased production / Increased loss
Haemolytic An. Introduction
Anemia due to Increased RBC destruction
Decreased life span (<120d)
Breakdown ↑Bilirubin (Unconj) Jaundice
Increased RBC production - ↑ reticulocytes
Low Haptoglobins – Hb carrier proteins.
Ketabolism of Hb:
Polychromasia - Hemolytic An.
Blood Film Features:
Abnormal shape
Polychromasia
Nucleated RBC
Plt may be low.
Clinical Features:
Pallor mild – mucosal
Jaundice - Mild fluctuating
Splenomegaly
No bile in urine (dark on standing-UBG)
Pigment gall stones – in chronic forms
Crisis – aplastic, hemolytic, vascular
Ankle ulcers
Hemolytic Anemia - Types:
Immune lysis• Warm & Cold Ab, Auto & Allo immune
Mechanical Damage• Valve, Microangiopathy (DIC), prosthesis, march
Hereditary Defects• Membrane, Hb & Enzyme defect
Infection induced• Clostridia, malaria, septicemia
Clinical Features of Sickle
Cell Disease
Congenital RBC Disorders:
Membrane Disorders: Spherocytosis, Elliptocytosis
Hemoglobin Disorders: Hemoglobinopathies - Sickle cell, HbC etc.
Thalassemia Syndromes - , ,
Enzyme disorders: G6PD, PK deficiency
Laboratory Evaluation: Features of RBC breakdown:
Hyperbilirubinemia Increased Urine UBG & Faecal stercobilinogen. Low or absent Haptoglobins
Features of increased RBC Production: Reticulocytosis Marrow erythroid hyperplasia – bone changes
Damaged RBC Morphology, Osmotic Fragility Decreased RBC survival – 51Cr labelling. Hemoglobin electrophoresis, enzyme abnormality
Laboratory Evaluation:
Intravascular Haemolysis: Haemoglobinaemia, Haemoglobinuria Haemosiderinuria – Renal tubular cells Methhaemalbuminaemia – Schumm’s test.
Molecular genetics Hb Electrophoresis Globin synthesis studies.
CBC Analyzer Report
Blood Smear Interpretation:
A B C D
E F G H
I J
A. NormalB. Micro/hypoC. MacroD. TargetE. SpheroF. Heinz bodyG. SchistocyteH. nRBCI. PolychromJ. Teardrop
Hb Electrophoresis – New born
_
SFA
Barts
+
CSAF
pH 6.3pH 8.6
““Seeing much, suffering much Seeing much, suffering much and studying much are the and studying much are the three pillars of learning.”three pillars of learning.”
–Benjamin Disraeli
MOLECULAR PATHOLOGY :
Normal adult blood contain 3 types of Hb.
The major component is HbA - α 2ß2.
The minor component fetal Hb (α 2 γ 2) and Hb A2 (α 22)
Structure & Synthesis of Haemoglobin:
Hb in adult Hb A Hb F Hb A2Structure α2 ß 2 α2 γ2 α2δ2
Normal % 96-98 0.5-0.8 1.5-3.2
Introduction to Haemoglobins:Introduction to Haemoglobins:
GENE CLUSTER & HB SWITCH
EFFECTS OF EXCESS CHAINS
Thalassemia Syndromes:
Group of disorders with decreased production of or chains.
Features: Low Hb – depending on type. Microcytic Hypochromic RBC Unlike IDA, uniform - low RDW Target forms typical. No pencil forms. Heinz bodies – globin deposits HBH inclusions – Golf ball cells
Thalassemia Syndromes:
Etiologically , , thalassemia, HbH dis.
Clinically classified into
Hydrops fetalis() – IU death
Thalassemia major () – transfusion dep
Thalassemia intermedia () – spleenomegaly, Fe
Thalassemia minor () - symptomless.
-Thalassemia:
Decreased production of chains.
Classification 0 – (four gene deletion) - Hydrops fetalis
+ 2/3 gene deletion – Thal. Intermedia, HbH dis.
0 trait, + trait – Thal Minor, HPFH
No thalassemia major.
HbH inclusions can be demonstrated in some cases. (less in trait, more in intermedia)
Hydrops Fetalis:
-Thalassemia:
Blood Smear & HbH PreparationBlood Smear & HbH Preparation
Thalassemia Trait:
Thalassemia Major:
ß Thalassemia Major:
Sickle Cell Disease:
G6PD Def - Heinz bodies:
Her. Spherocytosis:
Hereditary Elliptocytosis:
G6PD Deficiency:
G6PD Deficiency Anemia:
If you don't If you don't stand for something, stand for something,
you will fall for anything…!you will fall for anything…!
Hb Barts levels in Cord blood in Hb Barts levels in Cord blood in thalassemia thalassemiaPhenotype Equivalent No
of FunctionalGenes
% Barts
Normal 4 0
thal trait(mild)
3 0-1
thal trait(severe)
2 2-8*
Hb H disease 1 10-40
Hb Barts Hydrops 0 ~80
Higgs DR et al Blood 73, 1081, 1989* Some references mention upto 15%