Haemolysis Flashcards
What is Haemolysis?
Premature destruction of circulating red cells - shortened red cell survival
Why are red cells susceptible to damage? (3)
- need to have biconcave shape to transit the circulation successfully
- limited metabolic reserve and rely exclusively on glucose metabolism for energy- no mito
- can’t generate new proteins once in the circulation if they get damaged- no nucleus
Compensated Haemolysis
Increased red cell destruction matched by increased red cell production- Hb maintained
Decompensated haemolysis - haemolytic anaemia
Increased rate of red cell destruction exceeds bone marrow capacity for red cell production- Hb falls
Consequences of haemolysis? (2)
Increase red cell production
AND
Increased red cell breakdown products
Bone marrow response to haemolysis (3)
increased red cell production
- Erythroid hyperplasia in the bone marrow- not specific to haemolysis
- Resultant reticulocytosis- not nucleated cells
Special stain to identify Reticulocytes (2)
Supravital stain that stains ribosomal RNA (new methylene blue) as black inclusions
Form a ‘net’ like pattern in the cell
What is needed to diagnose haemolysis (2)
Evidence of increase red cell production
AND
Evidence of increased red cell breakdown products
Products of red cell destruction (5)
Normally occurs in splenic macrophages
Bilirubin is produced and outstrips the ability of normal liver to conjugate it
Patient looks jaundiced, urine darker
Rest of LFTs ok, LDH raised
Work hypertrophy can result in splenomegaly
What happens if red cell destruction is outside the macrophage? (4)
If the red cells are destroyed in the circulation
then free Hb circulates and needs removed
It can ‘clog’ the kidneys and emerge in urine (haemoglobinuria)
Binds to albumin (metHaemalbuminaemia)
Binds to haptoglobin and removed
2 approaches to identifying haemolysis (4)
Pathophysiological approach – by site in the red cell where the problem is occurring
A practical approach by site in the body where the haemolysis is occurring=
-Extravascular (ie in the macrophage as normal)
-Intravascular (ie in the circulation – not normal so generates a short differential list)
Extravascular red cell destruction (8)
More common
Hyperplasia at site of destruction (splenomegaly +/- hepatomegaly as it is also part of the reticuloendothelial system)
This is the normal pathway for ‘aged red cell’ destruction
Release of protoporphyrin= unconjugated bilrubinaemia, jaundice, gall stones if a chronic process, urobilinogenuria
Normal products but in excess
Intravascular red cell destruction (7)
Red cells are destroyed in the circulation spilling their contents immediately. This explains the pathophysiology and is not normal.
- Haemoglobinaemia (free Hb in circulation)
- Methaemalbuminaemia (Hb mopped up by albumin)
- Haemoglobinuria: pink urine, turns black on standing
- Haemosiderinuria (iron taken up by tubular cells and converted to haemosiderin the cells are later shed into urine)
Abnormal products
May be life threatening
Intravascular vs extravascular
haemolysis - causes (6)
Intravascular
-ABO incompatible blood transfusion
-Mechanical RBC trauma (March haemoglobinuria, DIC, HUS/TTP, valve disease)
-G6PD deficiency if severe
-Rarer still PNH,PCH, severe malaria, toxins
eg clostridia, some snake venoms
Extravascular
-essentially all other causes of haemolysis.
In practice not always so clear cut - can be mixed.
Investigations to confirm haemolytic state (6)
- FBC (+ BLOOD FILM) identify causes
- Reticulocyte count (raised)
- Serum unconjugated bilirubin (raised)
- Serum haptoglobins (bind free Hb so will be low as consumed in haemolysis)
- Urinary urobilinogen (raised)
- Lactate dehydrogenase (raised) – non specific
Investigations to identify the cause (7)
History and examination : Family Hist, Organomegaly
Blood Film: Membrane damage (spherocytes)
Mechanical damage (red cell fragments)
Oxidative damage (Heinz bodies)
Others e.g.. HbS (sickle cells)
Specialist investigations (Direct Coombs’ test and others)
Pathophysiological approach to causes of haemolyic anaemia (3)
Consider the potential reasons for premature red cell destruction
Review the red cells structure and function
Remember it may one part of a wider spectrum of clinical problems based on the mechanism
Classification based on red cell structure and function (4)
- It could be normal! Premature destruction by extrinsic mechanism (immune or mechanical mechanisms)
- Abnormality of the cell membrane
- Abnormality of red cell metabolism
- Abnormality of haemoglobin structure
- Immune destruction (2)
Autoimmune haemolysis (make an antibody to self)
Alloimmune haemolysis (you make an antibody to someone else’s red cells that have been given to you, or an antibody is given to you that attacks your cells)
- Autoimmune haemolysis (2)
An autoantibody that binds to self proteins on red cells
Consequences depend on if an IgG or IgM autoantibody
IgG antibody (6)
Warm
-idiopathic- most common
-autoimmune- SLE
-lymphoproliferative - CLL
-drugs- penicillins
-infections
IgM antibody (4)
Cold
-idiopathic
-infections- EBV, mycoplasma
-ymphoproliferative
- Alloiummune haemolysis (6)
Immune response (antibody produced)=
-Make an antibody incoming cell
=Immediate (preformed abs to ABO mismatched blood) predominantly intravascular, IgM
=Delayed (immune response to another antigen RhD) predominantly extravascular, IgG
Passive transfer of antibody (antibody given)=
-Haemolytic disease of the newborn (mum’s antibody attached to baby’s cells)- Rh D, ABO incompatibility
- Mechanical Destruction (11)
Normal red cells being damaged by an abnormal circulation
March haemoglobinuria
Damaged heart valve
Damaged microcirculation=
-Severe burns
-Fibrin strands deposited in small vessels called
-Microangiopathic haemolysis (MAHA)
=DIC
=TTP
=HUS
=Preeclampsia/HELP
