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September lectures yr 3 (2018) > Hemolytic anaemias > Flashcards

Hemolytic anaemias Flashcards

1
Q

What is the normal life span of RBC?

A

120 days
- if reduced to 15-120 days you rarely see anaemia = due to compensated hemolysis (bone marrow upregaulates RBC production)

<15 = Hemolytic anaemia - excessive destruction of RBCs in blood leading to increase output by the bone marrow

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2
Q

Where is the physiological sites for red cell destruction?

A

Extravascular - in reticulo-endoethelial system = bone marrow, liver and spleen

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3
Q

Where is the pathological sites for red cell destruction?

A

intravascular - in the bloodstream - releases free iron which is damaging to cells due to its toxicity
hemoglobin can damage the kidney W

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4
Q

What normally happens to be breakdown products of RBCs?

A

As it is normally extravascular the iron binds transferrin to prevent it causing toxicity and the bilirubin is conjugated in the liver and excreted in the bowel and kidneys

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5
Q

What are the features of haemolytic anaemia?

A

Increased red cell production

  • increased reticulocyte count = most mature form of RBCs
  • erythroid hyperplasia

Increased red cell break down

  • increased bilirubin, lactate dehydrogenase (LDH - very sensitive marker of hemolysis), urobilinogen
  • reduced haptoglobin level (reduced in intravascular hemolysis)
  • pigment gallstones - chronic hemolysis can lead to pigment gallstones due to byproducts such as bilirubin = can lead to cholecystitis
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6
Q

How can hemolysis be classified?

A

inherited - membrane, enzymes, hb (primarily related to RBCs)

acquired - immune (auto or alloimmune), non-immune
- allo-immune = mismatch RBC transfusion = can be fatal

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7
Q

What is hereditary spherocytosis?

A

inherited disorder of spectrin (RBC membrane protein - maintains integrity of cell)
Autosomal dominant
Cells lost membrane during circulation - lose a bit of membrane overtime the go through circulation - lose shape and don’t transport O2 well, therefore removed by macrophages before 120 days

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8
Q

What does hereditary spherocytosis look like clinically and histologically?

A

clinical - variable anaemia and jaundice (acholuric jaundice)
microspherocytes on blood film
increased osmotic fragility

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9
Q

How do you treat hereditary spherocyosis?

A

splenectomy if required - only required in small number of patients but can help to improve Hb as spleen is a key site of RBC destruction

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10
Q

What is hereditary elliptocytosis?

A

similar features to hereditary spherocytosis - another membrane defect
milder clinical features
variety of genetic disorders, autosomal recessive - may cause it to develop during childhood
Homozygotes produce severe disease = pyropoikilocytosis

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11
Q

What does NADPH do to RBCs?

A

protects them from oxidative damage

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12
Q

What is the source of NADPH in RBCs?

A

Glucose -6 - phosphate dehydrogenase (G6PD)

200 million people are deficient in this enzyme

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13
Q

What are the clinical features of G6PD deficiency?

A

anaemia after oxidative stress (drugs, fava beans, infection)
neonatal jaundice
non-spherocytic hemolytic anaemia

(blister cells)

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14
Q

Geographically, where is G6DP deficiency more commonly found?

A

often more common in tropical climates = africa, india, south and north america
Heterozygotes often found to be resistant to malaria - thought to be reason it is more common in tropical areas

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15
Q

How is G6DP deficiency inherited, diagnosed and treated?

A

inheritance is sex-linked
diagnosis is done by enzyme assay (not in an acute crisis)
treatment - treat symptoms

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16
Q

What type of inheritance is pyruvate kinase deficiency and what does it mean?

A

autosomal recessive and it means you have a failure to produce ATP

17
Q

What are the clinical features of pyruvate kinase deficiency?

A

variable anaemia - 4-10g.dl = well-tolerated

jaundice, gallstones (very pigmented in chronic hemolysis)

18
Q

How is pyruvate kinase deficiency diagnosed and treated?

A 
diagnosed = enzyme assay 
treatment= splenectomy if necessary
19
Q

What are congenital hemoglobin disorders

A

unstable hemoglobin disease - associated with heinz bodies, also knowns as congenital heinz-body hemolytic anaemia
hemolysis is a feature of many haemoglobinopathies such as sickle cell disease and thalassemia

20
Q

What are the different forms of acquired (immune) hemolytic anaemias?

A

1) auto-immune HA- warm or cold (most active at room temp) antibodies
2) allo-immune HA
3) drug induced HA

21
Q

What test can be done to check for autoimmune hemolytic anaemias?

A

Direct coombs test
- antibodies on the RBCs don’t do anything (do not clump and agglutinate - only cause them to be removed from circulation early) so you have to add anti-globing leads to clumping of RBCs with antibodies on them

22
Q

What are the causes of warm hemolytic anaemias?

A

idiopathic
secondary to: SLE, Lymphoma (CLL), drugs
due to IgG antibodies against red cells which lead to opsonization of red cells in RE system

occur at any age, hemolysis is variable in severity

23
Q

What investigations are carried out for warm AIHA and what are the treatments?

A

DCT+ and spherocytosis

treat: remove cause if present
- steroids
- splenectomy if failure
- blood transfusion

24
Q

What are the causes of cold AIHA?

A

Primary - cold hemagglutinin disease

Secondary - infection e.g. mycoplasma, EBV

25
Q

What is the antibody and antigen involved in cold AIHA?

A

Antibody is IgM = lower affinity and only binds at cooler temperatures e.g. extremities
Red cell antigen is nearly always I or i (specific antigen)

26
Q

What are the investigations and treatments for cold AIHA?

A

DCT+ for completment
Treatment = keep warm, occasional cytotoxic (chemo)
Tends to present in elderly with cold fingers and toes

27
Q

What is hemolytic disease of the newborn?

A

allo-immune haemolytic anaemia

  • maternal immune system recognizes a fetal antigen as foreign and AB crosses the placenta
  • usually antigen is RhD, also Kell, c
  • Sensitization usually occurs at delivery therefore most problems in the 2nd pregnancy
  • Anti-RhD Ab after delivery is effective at reducing sensitization
28
Q

What happens if the second baby is RhD+ve?

A

it can trigger an immune reaction - 2nd trimester onwards hemolysis can be fatal

29
Q

How many deaths are there per year from hemolytic disease of the newborn and what can be done to treat it?

A

50/year
in affected fetus in utero may need exchange transfusion and post delivery

ABO hemolytic disease of newborns is more common but less severe

30
Q

Other than hemolytic disease of the newborn what other aloo-immune hemolytic disease is there?

A

incompatible blood transfusion
- classic example of intravascular haemolysis - due to IgM antibodies
still causes fatalities

31
Q

What are the mechanisms of drug-induced immune hemolytic anaemia and what are some examples of drugs?

A

1) antibody to drug-red cell complex
2) complement fixation due to deposition of Ag-Ab complexes
3) Ab to red cell itself (role of the drug?)
- penicillins, quinidine, methyldopa

32
Q

What are the causes of non-immune acquired hemolytic anaemia?

A

red cell fragmentation syndrome = microangiopathic HA, march hemoglobinuria, cardiac valve hemolysis (blood going through mechanical heart valve can get damaged)

infection

toxins, drugs, chemical

PNH

33
Q

What happens in microangiopathic HA and what is it associated with?

A

due to mechanical intravascular hemolysis following pathological changes in small blood vessels
Associated with:
- hemolytic uraemic syndrome- caused by E.Coli 0157
- thrombotic thrombocytopenia purpura - medical emergency (lead to renal failure, requires emergency plasma exchange treatment)
- pre-eclampsia
- disseminated carcinoma
- collagen vascular diseases

34
Q

What is march haemoglobinuria caused by?

A

follows walking or running on hard surfaces

- treat by replacing footwear

35
Q

What is paroxysmal nocturnal hemoglobinuria?

A

acquired disorder of red cell membrane due to mutation within PIG-A gene which leads to inability to produce GPI anchor for membrane proteins
- leads to hemolysis due to lack of complement inhibitors on red cell surface

September lectures yr 3 (2018) (56 decks)

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