Anaemias and Haemolytic Anaemias Flashcards
What is the life span of a RBC?
120 days
What is haemolysis?
Shortened RBC survival
What is haemolytic anaemia?
Anaemia (low RBC) due to shorter RBC survival
How do you classify haemolytic anaemias based on where they die?
Intravascular (within circulation)
Extravascular (removal/destruction by reticuloendothelial system)
Give examples of causes of intravascular anaemia
- Malaria (most common)
- G6PD deficiency
- Mismatched blood transfusion
- Cold antibody haemolytic syndromes
- Drugs (DAPSONE)
- Microangiopathic haemolytic anaemia (HUS, TTP)
- Paroxysmal nocturnal haemoglobinuria
Give examples of causes of extravascular anaemia
Autoimmune
Alloimmune
Hereditary spherocytosis
What type of intravascular anaemia offers protection against malaria?
G6PD deficiency
What is the aetiology of Paroxysmal nocturnal haemoglobinuria?
Acquired genetic defect in GPI anchor
How can you divide hereditary haemolytic anaemias?
- MEMBRANE (cytoskeletal proteins, cation permeability)
- Red cell metabolism (glycolysis)
- Haemoglobin (thalassaemia, sickle cell, unstable Hb variant)
What are consequences of haemolytic anaemia?
Anaemia
Erythroid hyperplasia (increased RBC production, increased reticulocytes)
Increased folate demand
Susceptibility to parvovirus (aplastic crisis)
Propensity to gallstones
Increased risk of iron overload
Increased risk of osteoporosis
What does parvovirus do to RBC?
It infects RBC precursors in the bone marrow, arresting their maturation (prevents iron uptake)
In someone with shortened RBC span, this causes dangerously low Hb > APLASTIC CRISIS
Which disease increases propensity for gallstones in haemolytic anaemia?
Gilbert’s
What is the mutation in Gilbert’s?
UGT1A1 TA7
What are clinical features of haemolytic anaemia?
Pallor
Jaundice
Splenomegaly
Pigmenturia (abnormal urine colour)
What are lab features of haemolytic anaemia?
- Anaemia (low RBC)
- High reticulocytes
- Polychromasia
- Increased LDH
- Reduces/absent haptoglobin
Which findings imply intravascular haemolysis?
haemoglobinuria
haemosiderinaemia
Hereditary spherocytosis occurs due to what kind of disorder?
VERTICAL interaction Band 3 Protein 4.2 Ankyrin Beta spectrin
Hereditary elliptocytosis occurs due to what kind of disorder?
HORIZONTAL interaction
alpha spectrin
beta spectrin
Protein 4.1
What tests can you do to detect hereditary spherocytosis?
OSMOTIC FRAGILITY TEST
RBC show increased sensitivity to lysis in hypotonic saline
DYE BINDING TEST
Shows reduced binding of the dye (eosin 5 maleiminde)
What does hereditary spherocytosis look like on blood film?
They lack the area of central pallor
This is because they have lost the biconcave shape
What does hereditary elliptocytosis look like on blood film?
Oddly shaped, but NO polychromasia
How is G6PD deficiency transmitted?
X linked recessive
What is the function of G6PD enzyme?
It reduces NADP+ to NADPH
This is to generate gluthianone, which protects RBC against oxidative stress ,
What occurs when G6PD is deficient?
RBC become vulnerable to oxidative stress > haemolysed
What are broad clinical effects of G6PD deficiency?
Neonatal jaundice
Acute haemolytic
Chronic haemolytic anaemia
What are most people with G6PD like?
Asymptomatic
Until exposed to trigger, causing intravascular haemolysis
What are triggers for G6PD ?
Drugs (antimalarials, antibiotics, analgesics, dapsone, VitK)
Infection
Fava beans, soy
Naphthalene
What shows up on blood film of G6PD deficiency ?
In acute haemolysis:
- Heinz bodies
- Bite cells
- Contracted cells. nucleated red cells, hemighosts
In steady state:
- NORMAL
What stain do you use to detect Heinz bodies?
methylviolet
What shows up on blood film with pyruvate kinase deficiency?
ECHINOCYTES (RBC with short projections) - spiky
What shows up on blood film with pyrimidine 5 nucleotidase deficiency?
Basophilic stippling
What are first line investigations for haemolytic anaemias?
Direct antiglobulin test > AI haemolysis
Urinary haemosiderin/Hb > IV haemolysis
Osmotic fragility test /dye binding > hereditary spherocytosis
G6PD/PK activity
Heinz Body stain
Ham’s test/Flow cytometry for GPI linked proteins >paroxysmal nocturnal haemoglobinuria
How do you manage haemolytic anaemias?
Folic acid supplement Avoid precipitating factors RBC transfusion/exchange Immunisation against blood borne viruses Monitor for chronic complications Cholecystectomy for gallstones Splenectomy if indicated
What are specific criteria for splenectomy
Transfusion dependence growth delay physical limitation hypersplenism age between 3.10
What stain shows Heinz bodies?
methylviolet
what are causes of microcytic anaemia
Iron deficiency
Anaemia chronic disease
Sideroblastic
THalassaemia
What are causes of normocytic anaemia
Acute blood loss ACD BM failure Renal failure haemolysis Pregnancy
WHat are causes of macrocytic anaemia
Megaloblastic: B12/folate
Non-megaloblastic: hypothyroidism, liver failure, myelodysplastic syndrome
What are signs of iron def anaemia
Koilonychia, atropgic glossigtis, angular cheilosis, post-cricoid webs (Plummer-Vinson)
What shows up on blood film of IDA?
Microcytic Hypochromic Anisocytosis Poikilocytosis Pencil cells
What does anisocytosis mean
varying in size
What does poikilocytosis mean
varying in shape
Explain causes of iron def anaemia
- Blood loss (menorrhagia in women, GI bleed in elderly)
- increased use (pregnancy, lactation, infants)
- decreased intake (prematurity, poor diet)
- decreased absorption (coeliac, post-gastric surgery)
How do you treat iron def anaemia
Treat the cause
+ oral ferrous sulphate
What must you be aware of when giving ferrous sulphate in sepsis
Do NOT give as in sepsis iron does not absorb well and it fuels infection
Blood transfusions are PREFERABLE
How does ACD occur
cytokines drive inhibition of RBC production
What are causeas of ACD
Chronic infection
Vasculitis
RA
malignancy
What are iron studies like in ACD and why
Low iron High ferritin (because of high stores, as the iron is all sequestered) Low TIBC (as all the transferrin is already used up=
What are iron studies like in IDA and wqhy
Low iron
Low ferritin
High TIBC (as no transferrin is used up yet)
What is sideroblastic anaemia
occurrence of ineffective erythropoesis > iron (instead of forming a proper RBC) deposits around the erythroid precursor forming a singed sideroblast
all this iron also causes haemosiderosis (iron deposition in endocrine, liver, cardiac tissue causing damage)
What are iron studies like in sideroblastic anaemia
High iron
Normal TIBC (as it is the body that is unable to merge iron properly)
High ferritin
What else can cause elevation of ferritin
Infectection / inflammation
Because ferritin is an acute phase proteinn
What food is B12 found in
meat and diary
What causes B12 deficiency
Insuff dietary uptake (vegans)
Malabsorption
- in stomach: lack of intrinsic factor to transpoort it to the terminal ileum > pernicious anaemia
- in terminal ileum : Chron’s, ileal resectio
Explain pernicious anaemia and the most common antibodies
Autoimmune atrophic gastritis > lack of intrinsic factor in the stomach
- Parietal cell antibodies 90%
- Intrinsic factor antibodies 50%
What other test other than antibodies can you do for pernicious anaemia
SCHILLING TEST
How do you manage B12 deficiency
Replenish B12 stores with IM HYDROXYCOBALAMIN
What are clinical fts of B12 def
glossitis, angular chhelosis
neuro: irritability, depression
PARASTHHESIA; PERIPHERAL NEUROPATHY
What kinds of food is folate found in
green venetables, nuts
What is needed to synthesise folate from the food
gut bacteria
what are causes of folate deficiency
poor diet
increased folate demand (pregnancy, high cell tunrover9
malabsorption
alcohol
How do you manage folate deficiency
oral folic acid
if a patient has both B12 and folate deficiency, which shoudl you correct first and wh
B12 first
If you correct folate first, B12 neuropathy will get wotse
What are lab features of ALL haemolytic anaemia
high bilirubin
high urobilinogen
high LDH
high reticulocytes
What is the clinical ft of extravasc haemolytic anameia
SPLENOMEGALY
as haemolysis occurs in the splee
What are the lab fts of intravasc haemolytic anaemia
high free plasba Hb
Low haptoglobin
haemoglobinuria
albumin + haem in urine
what are awquired causes of haemolytic anaemia
IMMUNE
- autoimmune (warm/cold)
- Alloimmune (haemolytic transfusion reaction()
NON-IMMUNE
- mechanical e.g. metal valves, trauma
- PNH, MAHA
- infections e.g. malaria
What are examples of autoimmune anaemias
warm/cold AIHA
Explain features of warm haemolytic anaemia
37 degrees
IgG (GHANA)
positive coombs
Spherocytes on blood film
explain features of cold haemolytic anaemia
<37 deegrees
IgM MOUNTAINS
Positive coombs
Raynauds
How fo you manage Warm AIHA
steroids
splenectomy
immunosuppression
How do you manage cold AIHA
treat underlying condition
avoid the cold
Chlorambucil (chemo)
Explain paroxysmal cold haemoglobiniurea
haemoglobin in urine caused by a viral infection
this leads to formation of DOnath-Landsteiner antibodies > stick to RBC in cold > complemented mediated haemolysis on rewarming
what are causes of Warm AIHA
IDIOPATHIC mainly
lymphoman
CLL
SLE
Methyldopa
What are causes of Cold AIHA
IDIOPATHIC mainly
lymphoma
infections e.g. EBV, mycoplasma
Explain cause of paroxysmal nocturla haemoglobinuri
AQUIRED loss of protective surface GPI markers on RBC
This causes complement mediated lysis > chronic IV haemolysis especially at night
What are features of PNH
morning haemoglobinuria n
thrombosis
How do you diagnose PNH (what tests)
HAM tests (in vitro acid induced lysis)
OR
IOmmunophenotype to show altered GO
GHow do you manage PNH
iron/folate supplements
prophylactic vaccines and antibiotis cs
