Haematology - Haemolytic Anaemias Flashcards
Recall some causes of intravascular vs extravascular haemolytic anaemias
EXTRAvascular = hereditary spherocytosis INTRAvascualr = everything else (malaria, G6PDD, MAHA, PNH ETC)
Which infection are patients with haemolytic anaemias more susceptibile to?
Parvovirus B19
often develop gallstones
What is the expected LDH level in haemolytic anaemia?
High
What is the inheritance pattern of hereditary spherocytosis?
Autosomal dominant
How can hereditary spherocytosis be diagnosed (2)?
eosin-5 -maleimide (EMA) binding test
osmotic fragility test = increased susceptibility to lysis in hypotonic saline
In which parts of the world is G6PDD most common?
Where malaria is endemic
What is the inheritance pattern of G6PDD?
X linked recessive
What is the normal physiological role of G6PD?
NADPH generation
What is the main symptom of G6PDD in neonates?
Jaundice
Recall 4 triggers for a crisis in G6PDD
Moth balls
Fava beans
Anti-malarials
Antibiotics (sulphonamides, cipro
What is the typical appearance of erythrocytes in Pyruvate Kinase Deficiency?
echinocytes ‘hedgehog’ appearnce
What is the first investigation to do in haemolytic anaemia?
DAT/ Coombs test
Need to exclude autoimmune haemolysis
What does a positive urinary haemosiderin test show?
Intravascular haemolysis
What is homozygous hereditary elliptocytosis also known as?
Pyropoikilocytosis
Differentiate the class of immunoglobin involved in warm vs cold AIHA
Warm: IgG = EXTRAvascular haemolsysis - most common
Cold: IgM = INTRAvascular haemolysis
What abnormal shape of RBC may be seen on blood film in warm AIHA?
Spherocytes
Recall and compare the management of warm vs cold AIHA
Warm: steroids, splenectomy, immunosuppression
Cold: treat underlying condition (lymphoma/EBV), avoid the cold, chlorambucil
What is paroxysmal cold haemoglobinuria?
Hb in the urine, usually preceded by exposure to cold temperature and viral- infection
Which antibodies are the cause of paroxysmal cold haemoglobinuria?
Donath-Landsteiner antibodies
What is paroxysmal nocturnal haemoglobinuria?
Acquired loss of protective surface markers on RBCs leading to complement-mediated lysis and nocturnal intravascular haemolysis
Recall 2 symptoms of paroxysmal nocturnal haemoglobinuria
Morning haemoglobinuria
Throbosis
Recall 2 ways that paroxysmal nocturnal haemoglobinuria can be diagnosed?
- Altered GPI (surface proteins on RBC)
- Ham’s test
What is the pathophysiology of autoimmune Thrombotic thrombocytopenia purpura
mutation in ADAMST13 –> long strands of VWF (deficienct in VWF cleaving proteaste)
These VWF strands act like cheese wire in blood vessels
What is the classic pentad of symptoms in TTP?
MAHA
Fever
Renal impairment
Neurological abnormalities
Thrombocytopaenia
what’s a finding of extravascular HA
splenomegaly
state 2 inherited conditions w membrane defects
hereditary spherocytosis
hereditary eliptocytosis
state 2 inherited enzyme defects
G6PDD
pyruvate kinase def
state 2 inherited haemoglobiopathies
SCD
thalassemia
what is the membrane abnormality in hereditary spherocytosis
spectrin or ankyrin deficiency (membrane proteins)
2 histological findings of G6PDD
bite cells Heinz bodies (blue deposits, oxide Hb)
echinocytes and spherocytes seen in what condition
pyruvate kinase deficiency
echinocytes = hedgehog appearance
what stain for G6PDD
heinz body stains (methyl violet)
what causes HUS
e coli
what is the inheritance of hereditary eliptocytosis? what protein is affected
AD
spectrin
4 consequences of haemolysis broadly
anaemia
erythroid hyperplasia (increased RBC production and reticulocyte circulation)
increased folate demand
susceptibility to parvovirus B19, galstones etc
what does a positive DAT test indicate
autoimmune haemoytic anaemia
what cell do you see in MAHA
schistocytes
(fragmented RBC)
5 causes of MAHA
HUS
TTP
DIC
Pre-eclampsia
ADENOCARCINOMA
define MAHA
mechanical RBC destruction (as forced through fibrin/platelet mesh in damaged cels)
treatment of paroxsymal nocurnal heamoglobinuria
Eculizumab is a recombinant monoclonal antibody that inhibits terminal complement activation at the C5 protein and thereby reduces complement-mediated cell lysis
treatment of TTP
PLASMA EXCHANGE
triad of HUS
MAHA, thrombovytopaenia, AKI
5 bllod findings common to HUS and TTP
Hb down
Platelets down (bleeding, petechiae, haematemeis, melena)
DAT/Coombs -ve (not autoimmune)
schistocytes on blood smear
signs of haemlosys = bilirubin up, reticulocytes up, LDH up
thrombi are found where in HUS vs TTP
HUS - thrombi confined to kidney
TTP - cicrulation inclduing CNS
does HUS of TTP usually affect children
HUS - children mre (e coli from kids touchign animlas etc)
TTP - more adults (ADAMTS13 mutation)
does HUS typically have neuro sequelae
NO
HUS = renal failure
TTP= neuro (headache, sezire, redcued GCS, coma)
