Haemolysis Flashcards
What is haemolysis?
Premature red cell destruction i.e. shortened red cell survival
Why are red cells particularly susceptible to damage?
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)
What is compensated haemolysis?
Increased red cell destruction compensated by increased red cell production
i.e. Hb maintained
What is haemolytic anaemia (decompensated)?
Increased rate of red cell destruction exceeding bone marrow capacity for red cell production i.e. Hb falls
What are the consequences of haemolysis?
Erythroid hyperplasia (increased bone marrow red cell production) Excess red cell breakdown products (bilirubin)
What is the bone marrows response to haemolysis?
Reticulocytosis
Erythroid hyperplasia
Are reticulocytes nucleated cells?
NO
Contain ribosomal RNA that results in polychromasia
What is extravascular haemolysis?
Taken up by reticuloendothelial system (spleen and liver predominantly)
What is intravascular haemolysis?
Red cells destroyed within the circulation
What are the signs of extravascular haemolysis?
Hyperplasia at site of destruction - splenomegaly, hepatomegaly
Release of protoporphyrin ; jaundice, gall stones, urobilinogenuria
NORMAL products in excess
What are the signs of intravascular haemolysis?
Haemoglobinaemia (free Hb in circulation)
Methaemalbuminaemia
Haemoglobinuria; pink urine that turns black on standing
Hemosiderinuria
What causes intravascular haemolysis?
ABO incompatible blood transfusion G6PD deficiency Severe falciparum malaria (blackwater fever) Paroxysmal Nocturnal Haemolysis Paroxysmal Cold Haemolysis
How is haemolysis investigated?
Confirm haemolytic state
Identify cause
Hw is haemolytic state confirmed?
FBC + blood film Retic count Serum unconjugated bilirubin Serum haptoglobins Urinary urobilinogen
How can the cause for haemolysis be identified?
History and exam
Blood film
Direct and indirect coombs test
What can be detected on a blood film in haemolysis that can point to a diagnosis?
Membrane damage = spherocytes Mechanical damage = schistocytes Oxidative damage (G6PD) = heinz bodies HbS = sickle cells
How can haemolysis be classified by the site of red cell defect?
Premature destruction of normal red cells (immune or mechanical)
Abnormal cell membrane
Abnormal red cell metabolism
Abnormal Hb
What can cause acquired immune haemolysis?
Autoimmune
Alloimune
What are the different types of autoimmune haemolysis?
Ward or cold
Warm = IgG
Cold = IgM
What can cause warm autoimmune haemolysis?
IgG: Idiopathic SLE CLL Penicillin Infection
What can cause cold autoimmune haemolysis?
IgM:
Idiopathic
Infection - EBV, mycoplasma
Lymphoproliferative disorders - CLL
What does a direct coombs test identify?
Antibody (and complement) bound to OWN red cells
Patients RBC + anti-human IgG
Look for agglutination
What can cause an immune response alloimmune haemolysis?
Haemolytic transfusion reaction; immediate (IgM) = intravascular, delayed (IgG) = extravascular
What can cause a passive alloimmune haemolysis?
Haemolytic disease of the newborn;
RhD
ABO incompatibility
Anti-Kell
What can cause mechanical (microangiopathic) haemolysis?
DIC HUS TTP Leaking heart valve Malaria
In what condition are microspherocytes seen?
Burns related haemolysis
What can cause membrane defect mediated haemolysis?
Liver disease - Zieve’s Syndrome
Vit E deficiency
PNH
What is Zieve’s syndrome?
Haemolysis
Alcoholic liver disease
Hyperlipidaemia
Blood film; anaemia, polychromatic macrocytes, irregularly contracted cells
Why will red cell membrane abnormalities result in haemolysis?
Reduced membrane deformability
Increased transit time through spleen
Oxidant environment in spleen results in extravascular red cell destruction
What is the commonest genetic cause of red cell membrane abnormality haemolysis?
Hereditary Spherocytosis
What can result in abnormal red cell metabolism haemolysis?
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
What will dapsone therapy mediated haemolysis look like on a blood film?
Keratocyte
Irregularly contracted cell
What can result in haemolysis from abnormal haemaglobin production?
HbS (point mutation in beta globin chain
What will the blood film show in beta thal major?
Hypochromic Microcytic cells Pappenheimer bodies Alpha chain precipitates Marrow = erythroid hyperplasia
How is hereditary spherocytosis inherited?
AD
What type of haemolysis will falciparum malaria cause?
Intravascular
What can cause an acquired red cell membrane haemolysis?
Dapsone
Salazopyrin (rheum therapy)
