Haemolysis Flashcards
what is haemolysis
Premature red cell destruction
i.e. shortened red cell survival
what is compensated haemolysis
increased red cell destruction compensated by increased rbc production = Hb MAINTAINED
what is haemolytic anaemia
DECOMPENSATED HAEMOLYSIS
increased rate of red cell destruction exceeding bone marrow capacity for production
= Hb FALLS
what are the physiological consequences of haemolysis
erythroid hyperplasia (increased marrow red cell production)
excess rbc breakdown products e.g. bilirubin
what is the bone marrow response to haemolysis
reticulocytosis
erythroid hyperplasia
do reticulocytes have nuclei
no
what colour are reticulocytes
polychromasia (due to ribosomal RNA)
what can reticulocytosis be a result of
haemolysis
bleeding
iron therapy in iron deficiency anaemia
what stain for RNA in reticulocytes
supravital new methyl blue
Automated reticulocyte counting:
Ribosomal RNA is labelled with a fluorochrome and fluorescent cells are counted
what is extravascular haemolysis
when rbcs are Taken up by reticuloendothelial system (spleen and liver predominantly)
what is intravasuclar haemolysis
when red cells are destroyed within the circulation
which is the more common type of haemolysis
extravascular
what happens at site of destruction in extravascualr haemolysis
hyperplasia= splenomegaly +/- hepatomegaly
what is released in extravascular haemolysis
protoporphyrin:
- unconjugated bilirubinaemia = jaundice + gallstones
- urobilinogenuria
(normal products but in excess)
what is released in intravascular haemolysis
Red cells are destroyed in the circulation spilling their contents. This explains the pathophysiology:
Haemoglobinaemia (free Hb in circulation)
Methaemalbuminaemia
(proteolytic breakdown of haemoglobin to form both haem and methaem. Methaem combines with blood plasma albumin to form methemalbumin)
Haemoglobinuria: pink urine, turns black on standing
Haemosiderinuria
(ABNORMAL products)
is intra or extra vascular haemolysis life threatening
intra (abnormal products in blood stream)
what can cause intravascular haemolysis
ABO incompatible blood transfusion G6PD deficiency Severe falciparum malaria (Blackwater Fever) HUS DIC TTP Rare: PNH,PCH
what can cause extravascular haemolysis
legit every other cause (autoimmune haemolytic anaemia, spherocytosis)
what Ix to confirm haemolysis
FBC (+ BLOOD FILM) Reticulocyte count Serum unconjugated bilirubin Serum haptoglobins Urinary urobilinogen
what Ix to identify the cause of haemolysis
Hx and exam: genetic/ acquired
blood film: spherocytes, mechanical damage, oxidative stress (heinz bodies), sickle cells
specialist tests: direct coombs etc
how can haemolysis be classified by red cell defect
- premature destruction of normal rbcs (immune/ mechanical)
- abnormal cell membrane
- abnormal cell metabolism
- abnormal haemoglobin
is premature destruction of normal red cells a congenital or acquired cause of haemolysis
acquired
what are the causes of premature destruction of normal red cells
immune: autoimmune haemolysis and alloimmune haemolysis
mechanical: DIC, HUS, TTP, leaking heart valve, infections (malaria), burns related
what are the types of autoimmune haemolysis
(these cause premature destruction of normal red cells)
warm IgG
cold IgM
what causes warm autoimmune haemolysis
idiopathic (most common) autoimmune disorders (SLE, lymphproliferative disorders, drugs (penicillin), infections
what causes cold autoimmune haemolysis
idiopathic
infections (EBV, mycoplasma)
lymphoproliferative disorders
what does direct coombs test do
identifies antibody and compliment bound to own red cells
uses patients RBCs + mouse anti -human IgG
+ve test = agglutination
what are the types of alloimmune haemolysis
immune response (antibody response)- haemolytic transfusion reaction
passive transfer of antibody- haemolytic disease of the newborn
what are types of haemolytic transfusion reactions
(both alloimmune, antibody produced)
immediate IgM- predominantly intravascular
delayed IgG- predominantly extravascular
what are the types of haemolytic disease of the new born
Rh D
ABO incombatability
anti-kell
what are the causes of mechanical premature destruction of normal red cells
(these all acquired) DIC HUS (ecoli 0157) TTP leaking heart valve infections (malaria) burns related (sheared as pass through damaged capillaries)
what are the acquired causes of abnormal red cell membrane (resulting in haemolysis)
liver disease (zieve syndrome) ( vit E def paroxysmal nocturnal haemoglobinuria
what are the features of zieves syndrome
haemolysis alcoholic liver disease hyperlipidaemia anaemia polychromatic macrocytes irregularly contracted cells
what are the congenital causes of abnormal red cell membranes (causing haemolysis)
hereditary spherocytosis (HS)
why does HS cause haemolysis
Reduced membrane deformability
Increased transit time through spleen
Oxidant environment in spleen causes extravascular red cell destruction
what are the congenital causes of abnormal red cell metabolism (causing haemolysis)
G6PD deficiency (failure to cope with oxidative stress) failure to generate ATP (metabolic processes fail)
what are the congenital causes of abnormal haemoglobin (causing haemolysis)
sickle cell diseases (point mutation in beta globin chain that causes abnormal polymerisation resulting in shortened cell survival)
what deformities happen in beta thalassaemia major
Bony deformities of chronic erythroid hyperplasia and marrow cavity expansion
what inheritance is HS
dominant
what type of haemolysis does HS causes
chronic extravascular (splenomegaly)
what type of haemolysis does malaria cause
intravascular
diagnose: Anaemic Hb80-100 supravital stain Thai girl Intermittant jaundice when has fever/unwell and oxidant drugs
HbH
A form of alpha thalassaemia. 3 of 4 alpha genes are not working so there is an excess of beta chains which can precipitate.
All cells contain some β4 and have a reduced survival as β4 is toxic and precipitates when ox stress.
Reduced red cell survival =haemolysis!!!
what are the acquired causes of altered red cell metabolism
Dapsone (antibiotic) or salazopyrin (rheumatology) therapy
what are the differences in ABO and RhD transfusion reactions
ABO= immediate intravascular haemolysis
RhD= delayed extravascular haemolysis
