Haemolysis

Question 1

What is haemolysis?

Answer 1

Premature red cell destruction i.e. shortened red cell survival

Question 2

Why are red cells particularly susceptible to damage?

Answer 2

Need to have a biconcave shape ot transit the circulation successfully
Limited metabolic reserve and rely exclusively on glucose metabolism for energy (no mitochondria)
Can’t generate new proteins once in circulation (no nucleus)

Question 3

What is compensated haemolysis?

Answer 3

Increased red cell destruction compensated by increased red cell production
i.e. Hb maintained

Question 4

What is haemolytic anaemia (decompensated)?

Answer 4

Increased rate of red cell destruction exceeding bone marrow capacity for red cell production i.e. Hb falls

Question 5

What are the consequences of haemolysis?

Answer 5

Erythroid hyperplasia (increased bone marrow red cell production) 
Excess red cell breakdown products (bilirubin)

Question 6

What is the bone marrows response to haemolysis?

Answer 6

Reticulocytosis

Erythroid hyperplasia

Question 7

Are reticulocytes nucleated cells?

Answer 7

NO

Contain ribosomal RNA that results in polychromasia

Question 8

What is extravascular haemolysis?

Answer 8

Taken up by reticuloendothelial system (spleen and liver predominantly)

Question 9

What is intravascular haemolysis?

Answer 9

Red cells destroyed within the circulation

Question 10

What are the signs of extravascular haemolysis?

Answer 10

Hyperplasia at site of destruction - splenomegaly, hepatomegaly
Release of protoporphyrin ; jaundice, gall stones, urobilinogenuria
NORMAL products in excess

Question 11

What are the signs of intravascular haemolysis?

Answer 11

Haemoglobinaemia (free Hb in circulation)
Methaemalbuminaemia
Haemoglobinuria; pink urine that turns black on standing
Hemosiderinuria

Question 12

What causes intravascular haemolysis?

Answer 12

ABO incompatible blood transfusion 
G6PD deficiency
Severe falciparum malaria (blackwater fever) 
Paroxysmal Nocturnal Haemolysis 
Paroxysmal Cold Haemolysis

Question 13

How is haemolysis investigated?

Answer 13

Confirm haemolytic state

Identify cause

Question 14

Hw is haemolytic state confirmed?

Answer 14

FBC + blood film
Retic count
Serum unconjugated bilirubin
Serum haptoglobins
Urinary urobilinogen

Question 15

How can the cause for haemolysis be identified?

Answer 15

History and exam
Blood film
Direct and indirect coombs test

Question 16

What can be detected on a blood film in haemolysis that can point to a diagnosis?

Answer 16

Membrane damage = spherocytes
Mechanical damage = schistocytes 
Oxidative damage (G6PD) = heinz bodies 
HbS = sickle cells

Question 17

How can haemolysis be classified by the site of red cell defect?

Answer 17

Premature destruction of normal red cells (immune or mechanical)
Abnormal cell membrane
Abnormal red cell metabolism
Abnormal Hb

Question 18

What can cause acquired immune haemolysis?

Answer 18

Autoimmune

Alloimune

Question 19

What are the different types of autoimmune haemolysis?

Answer 19

Ward or cold
Warm = IgG
Cold = IgM

Question 20

What can cause warm autoimmune haemolysis?

Answer 20

IgG: 
Idiopathic
SLE
CLL 
Penicillin
Infection

Question 21

What can cause cold autoimmune haemolysis?

Answer 21

IgM:
Idiopathic
Infection - EBV, mycoplasma
Lymphoproliferative disorders - CLL

Question 22

What does a direct coombs test identify?

Answer 22

Antibody (and complement) bound to OWN red cells
Patients RBC + anti-human IgG
Look for agglutination

Question 23

What can cause an immune response alloimmune haemolysis?

Answer 23

Haemolytic transfusion reaction; immediate (IgM) = intravascular, delayed (IgG) = extravascular

Question 24

What can cause a passive alloimmune haemolysis?

Answer 24

Haemolytic disease of the newborn;
RhD
ABO incompatibility
Anti-Kell

Question 25

What can cause mechanical (microangiopathic) haemolysis?

Answer 25

DIC
HUS 
TTP 
Leaking heart valve
Malaria

Question 26

In what condition are microspherocytes seen?

Answer 26

Burns related haemolysis

Question 27

What can cause membrane defect mediated haemolysis?

Answer 27

Liver disease - Zieve’s Syndrome
Vit E deficiency
PNH

Question 28

What is Zieve’s syndrome?

Answer 28

Haemolysis
Alcoholic liver disease
Hyperlipidaemia
Blood film; anaemia, polychromatic macrocytes, irregularly contracted cells

Question 29

Why will red cell membrane abnormalities result in haemolysis?

Answer 29

Reduced membrane deformability
Increased transit time through spleen
Oxidant environment in spleen results in extravascular red cell destruction

Question 30

What is the commonest genetic cause of red cell membrane abnormality haemolysis?

Answer 30

Hereditary Spherocytosis

Question 31

What can result in abnormal red cell metabolism haemolysis?

Answer 31

Failure to cope with oxidant stress - G6PD deficiency
Failure to generate ATP - pyruvate kinase deficiency
EVEN the metabolic pathways of normal cells if sufficiently stressed can get oxidative damage e.g. dapsone

Question 32

What will dapsone therapy mediated haemolysis look like on a blood film?

Answer 32

Keratocyte

Irregularly contracted cell

Question 33

What can result in haemolysis from abnormal haemaglobin production?

Answer 33

HbS (point mutation in beta globin chain

Question 34

What will the blood film show in beta thal major?

Answer 34

Hypochromic 
Microcytic cells
Pappenheimer bodies 
Alpha chain precipitates 
Marrow = erythroid hyperplasia

Question 35

How is hereditary spherocytosis inherited?

Answer 35

AD

Question 36

What type of haemolysis will falciparum malaria cause?

Answer 36

Intravascular

Question 37

What can cause an acquired red cell membrane haemolysis?

Answer 37

Dapsone

Salazopyrin (rheum therapy)