Haemolysis Flashcards
Define haemloysis
This is premature destruction of red blood cells i.e. shortened red cell survivial
Define compensated haemolysis
Increased red cell destruction compensated by increased red cell production i.e. Hb Maintained
Define haemolytic anaemia (decompensated haemolysis)
Increased rate of red cell destruction exceeding bone marrow capacity for red cell production i.e. Hb Falls
What are the physiological consequences of haemolysis ?
- Erythroid hyperplasia (increased bone marrow red cell production) – would see an increase in recticulocytes in the peripheral blood
- Excess red cell breakdown products eg billirubin (clinical features differ by aetiology and site of red cell breakdown)
Can you measure haemolysis directly and if not what is done to try to measure haemolysis ?
No
Rely on detecting the consequences of haemolysis and then investigating the cause:
- Increased red cell production
- Detection of breakdown products - Specific products help determine cause
What is the bone marrow response to haemolysis ?
- Reticulocytosis - increased recticulocytes
- Erythroid hyperplasia - increased erythroid precursor cells i.e. immature red blood cells
The body will sense the fall in Hb and EPO will be produced in repsonse which will stimulate these effects
Is recticulocytosis diagnostic of haemolysis ?
No - it will be caused by other response to bleeding, iron therapy in iron deficiency anaemia, other anaemias etc
But it is a marker
What are the general clinical features of haemolytic anaemia (both extravascular and intravascular) ?
- Anaemia symptoms - e.g. weakness, pallor, pale conjunctiva, tachycardia, agnia etc
- Dark urine - more extravascular haemolysis
- Jaundice - can be both
- Enlarged liver and spleen - more in extravascular haemolysis
- Leg ulcers
- Gallstones - due to unconjugated bilirubin
- Signs of underlying disorder e.g. malar rash in SLE
- increased serum lactate dehydrogenase
What are the 2 main ways in which haemolysis can be classified as and describe their differences ?
Can be classified as extravascular or intravascular haemolysis
- In extravascular hemolysis RBCs are phagocytized by macrophages in the spleen and liver.
- In intravascular hemolysis RBCs lyse in the circulation releasing hemoglobin into the plasma
What classification of haemolysis is more common ?
Extravascular
Go over this pic of the normal break down of Hb
Note that on the pic it says heme, but the Fe2+ is recyclyed so its really prophyrin (protoporhyrin) which is being broken down
Describe extravascular haemolysis and its breakdown products and what does it result in excess of ?
In extravascular hemolysis spleen and liver macrophage Fc receptors bind immunoglobulin attached to RBCs and then either ingest small portions of the RBC membrane creating spherocytes or phagocytizing the RBCs.
This causes release of Hb which is broken down into porphyrin (protoporphyrin) and Fe2+, the Fe2+ is recycled
Essentially you get excess of uncongjugated bilirubin which can cause:
- jaundice
- gallstones
Also excess of Urobilinogenuria
This is essentially excess of normal products of Hb breakdown
In extravascular haemolysis what clinical feature may you also see in regards to the sites of breakdown?
Hyperplasia at site of destruction (splenomegaly +/- hepatomegaly)
What are the products of intravascular haemolysis and are these normal products ?
- Haemoglobinaemia (free Hb in circulation) - excess Hb in the plasma
- Methaemalbuminaemia - methemalbumin in the blood
- Haemoglobinuria: pink urine, turns black on standing – some patients might think their passing blood - excretion of free Hb in the urine
- Haemosiderinuria – iron containing compound, this is excreted in the urine
These are all abnormal products
Which classification of haemolysis is life-threatening ?
Intravascular
What are the main differentiating features of extravascular and intravascular jaundice ?
Mainly based on their different breakdown products
Extravascular:
- Hepatosplenomegaly
- High levels of uncongjugated bilirubin causing jaundice and potentially gallstones (may present as RUQ pain)
- Urobilinogenuria - dark urine
Intravascular:
- Haemoglobinaemia - free Hb in the plasma
- Methaemalbuminaemia - some haem combines with methaemalbumin to form this
- Decreased plasma haptoglobin - this mops up free Hb in the circulation and takes to liver for removal (i.e. its getting used up hence low)
- Haemoglobinuria - free Hb in the urine causing pink urine which turns black on standing
- Haemosiderinuria - when haptoglobin used up, Hb is filtered by renal glomeruli some is then excreted in the urine and some is stored in the renal tubules as an iron complex called haemosiderin, this complex is then excreted when tubular cells slough off and is ==> present in the urine
What are the causes of intravascular haemolysis ?
- ABO incompatible blood transfusion
- G6PD deficiency
- Severe falciparum malaria (Blackwater Fever)
- Rarer still PNH,PCH - dont really need to know this one
What investigations should you do for haemolysis ?
History and examination
- FBC - may not be anaemic as may be compensating, but if not compensating then see decreases Hb +/- increased MCV
- Blood Film - to look for features indicating specific conditions
- Reticulocyte count - this will often be increased and causes the increased MCV as their bigger than erythrocytes
- Serum unconjugated bilirubin
- Serum haptoglobins - Investigation for intravascular hemolytic anemia. In intravascular hemolysis, free hemoglobin will be released into circulation to bind the hemoglobin. This causes a decline in haptoglobin levels.
- Urinary urobilinogen
- Specialist investigations - Direct Coombs’ test, Hb electrophoresis for haemaglobinopathies
What are some of the different signs which you look for on blood film and what do they indicate ?
- Spherocytes - indicate hereditary spherocytosis or autoimmune haemolytic anaemia
- Schistocytes - indicating microangiopathic haemolytic anaemia
- Hypochromic microytic anaemia - thalassaemia
- Sickle cells - sickle cell anaemia
- Heinz bodies - G6PD
What are the causes of extravascular haemolysis ?
Essentially all other causes of haemolysis
How can haemolysis be classified/caused by different red cell defects what are the main 4 categories ?
- Premature destruction of normal red cells (destroyed through immune or mechanical)
- Abnormal cell membrane
- Abnormal red cell metabolism
- Abnormal haemoglobin
What 2 mechainsms can result in premature destruction of normal red cells ?
Immune or mechnical
What are the 2 different classes of immune haemolysis ?
- Autoimmune - patients own Ab’s destroying the red cells
- Alloimmune - foreign Ab’s destroying patinets red cells
What are the 2 main classes of autoimmune haemolytic anaemia and describe them
- Warm (IgG) - main antibody invovled is IgG
- Cold (IgM) - main antibody involved in IgM
These result in extravascular haemolysis so features of this type of haemolysis seen
A positive result of what test would make you think an autoimmune cause of haemolysis ?
Positive coombs test
What are the causes of warm and cold autoimmune haemolysis and what is the most common cause for both of them?
Warm:
- Idiopathic
- Autoimmune disorders e.g. SLE
- Lymphoproliferative disorders e.g. CLL - chronic lymphocytic leukaemia
- Drugs e.g. penicillins, etc
- Infections
Cold:
- Idiopathic
- Infections (EBV, mycoplasma)
- Lymphoproliferative disorders
Idiopathic (unknown) is the most common cause in both
What is the treatment of autoimmune causes of haemolysis ?
- Warm - give corticosteroids 1st line +/- transfusions if severe anaemia
- Cold - steroids etc usually ineffective, anti CD20 (rituxumab) shown to be effective sometimes
What are the 2 main types of alloimmune causes of haemolysis and there subtypes ?
Haemolytic transfusion reaction:
- Immediate (IgM) predominantly intravascular – destruction of an incompatiable red cell transfusion (ABO mismatch) – this can cause lifethreatening intravascular haemolysis
- Delayed (IgG) predominantly extravascular – IgG mediated, not lifethreatening, tends to occur 7-10 days following transfusion
Haemolytic disease of the newborn - due to passive transfer of antibodies in pregnancy:
- Most commonly when there is an ABO incompatability between mother and fetus
- Rh (D) incompatability - given anti-D to prevent this if needed
- Other irregular antibodies e.g. anti-Kell
What can the clinical features of haemolytic disease of the newborn vary from and how is it treated when a baby is born ?
Can vary from milk haemolytic anaemia to intrauterine death
Once born jaundice treatment followed
What type of cell seen on blood film might indicate autoimmune haemolytic anaemia ?
Spherocytes
