hemolytic anemia 1

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%