Haemolysis Flashcards
What is haemolysis?
Premature red cell destruction
Why are red cells susceptible to damage?
Biconcave shape to transmit the circulation successfully
Limited metabolic reserve and rely on glucose for energy
Can’t generate new proteins once in circulation
What is compensated haemolysis?
Increased red cell destruction compensated by increased red cell production i.e. Hb maintained
What is haemolytic anaemia?
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 eg billirubin (clinical features differ by aetiology and site of red cell breakdown)
What is the bone marrow response to haemoylsis?
Reticulocytosis
Erythroid hyperplasia
How is haemolysis classified?
Extravascular- Taken up by reticuloendothelial system (spleen and liver predominantly)
Intravascular- Red cells destroyed within the circulation
What is seen in extravascular red cell destruction?
Hyperplasia at site (spleen+-hepatomegaly)
Release of protoporphyrin: unconjugated bilirubinaemia (jaundice, gall stones), urobilinogenuria
Normal products in excess
What is see in intravascular red cell destruction?
Red cells are destroyed in the circulation spilling their contents. This explains the pathophysiology
Haemoglobinaemia (free Hb in circulation)
Methaemalbuminaemia
Haemoglobinuria: pink urine, turns black on standing
Haemosiderinuria
Abnormal products
May be life threatening
What are the causes of intra and extravascular haemolysis?
Intra: ABO incompatible blood transfusion G6PD deficiency Severe falciparum malaria (Blackwater Fever) Rarer still PNH,PCH Extra: all other causes
What Ix is required in haemolysis?
Confirm haemolytic state: FBC, film, reticulocyte count, serum unconjugated bilirubin, serum haptoglobins, urinary urobilinogen
Identify cause
What may be seen on the blood film in haemolysis?
Membrane damage (spherocytes) Mechanical damage (red cell fragments) Oxidative damage (Heinz bodies) Others e.g.. HbS (sickle cells)
What is another classification of haemolysis?
By site of defect: Premature destruction of normal red cells (immune or mechanical) Abnormal cell membrane Abnormal red cell metabolism Abnormal haemoglobin
What are the immune causes of acquired haemolysis?
AI haemolysis, alloimmune haemolysis
What are the causes of warm (IgG) autoantibody in AI haemolysis?
Idiopathic (commonest)
Autoimmune disorders (SLE)Lymphoproliferative disorders (CLL)
Drugs (penicillins, etc)Infections
What are the causes of cold(IgM) autoantibody in AI haemolysis?
Idiopathic
Infections (EBV, mycoplasma)
Lymphoproliferative disorders
What does the Direct Coombs’ Test do?
Identifies antibody and complement bound to own red cells
What are the causes of alloimmune haemolysis?
Immune response (Ab mediated)- haemolytic transfusion reaction: immediate (IgM) predominantly intra, delayed (IgG) extra Passive transfer of Ab: haemolytic disease of newborn: Rh D, ABO incompatibility, other
What are the mechanical causes of acquired haemolysis?
Disseminated intravascular coagulation Haemolytic uraemic syndrome (eg E. coli O157) TTP Leaking heart valve Infections e.g. Malaria Burns
What is seen on the film in burns related haemolysis?
Microspherocytes
Red cells are sheared as they pass through the damaged capillaries. Only seen therefore in severe burns
What are the membrane defect causes of acquired haemolysis (rare)?
Liver Disease (Zieve’s Syndrome) Vitamin E deficiency Paroxysmal Nocturnal Haemoglobinuria
What is Zieve’s syndrome?
Haemolysis
Alcoholic liver disease
Hyperlipidaemia
What is seen on the film in Zieve’s?
Anaemia
Polychromatic macrocytes
Irregularly contracted cells
What are the genetic red cell membrane abnormalities that cause haemolysis?
Reduced membrane deformability
Increased transit time through spleen
Oxidant environment in spleen causes extravascular red cell destruction
Hereditary Spherocytosis
What are the genetic abnormal red cell metabolism problems that cause haemolysis?
Failure to cope with oxidant stress (G6PD deficiency)
Failure to generate ATP: metabolic processes fail
Even the metabolic pathways of normal cells if sufficiently stressed e.g.by dapsone or salazopyrin can get oxidative damage
What are the genetic abnormal Hb problems that cause haemolysis?
Sickle cell disease (Hb S): affects physical properties of haemoglobin (abnormal polymerisation) resulting in shortened red cell survival
