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Path - Haem > haemolytic anaemias > Flashcards

haemolytic anaemias Flashcards

1
Q

what is the reticuloendothelial system?

A

The Reticuloendothelial System (RES) consists of cells descending from the monocytes (macrophage, histiocytes) which are able to perform phagocytosis of foreign materials and particles. 90% of the RES are located in the liver.

other organs involved include; the spleen, connective tissue, BM, lungs

it is involved in extravascualr haemolysis

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2
Q

What are haemolytic anaemias and what are some of the classifications ?

A

RBC can be attacked in 3 locations:

  1. Membrane
    - Hereditary spherocytosis
    - Elliptocytosis
    - Autoimmune:
    • > A. associated with conditions eg RA
    • > B. Cold antiibody haemolytic syndromes- infections
  2. Haemoglobin
    - Sickle cell
    - Thalassaemia
    - Other unstable haemoglobin variants eg Hb Hammersmith
  3. Enzymes
    - G6PD deficiency
    - Pyruvate kinase dificiency

Can classify by intravascular and extra vascular.

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3
Q

List some intravascular causes of Haemolytic anaemia?

A

Haemolysis that occurs inside a BLOOD vessel

Malaria

G6PD deficiency

Mismatched blood transfusion

Drugs

MAHA - HUS+TTP !

DIC, HELLP !

Complement + IgM !

PNH

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4
Q

where does extravascular haemolysis occur?

A

spleen mainly - reticuloendothelial system

liver + lymph nodes can be implicated

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5
Q

what is the effect of parvovirus B19?

prognosis and ivx findings ?

A

infect erythroid cells in the bone marrow and arrest their maturation

in individuals with shortened red cell life span (e.g. 5-7 days) this can cause a dangerously low Hb (aplastic crisis)

prognosiis: self-limiting

ivx findings: low reticulocyte count

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6
Q

list some complications of Haemolytic anaemia and associations?

A
  1. Gallstones - due to high bilirubin
    • > Associated with gilberts syndrome - UGT1A1 7/7 genotype
  2. Iron overload
    - Due to increased intestinal absorption
    • Also due to transfusion
  3. Osteoporosis
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7
Q

what is the mechanism of gilberts syndrome?

A

UGT1A1 7/7 genotype:

there are 7/7 thymine-adenine repeats TA-TA repeats in the TATA promoter instead of 6/6

means there is LESS gene transcription and hence activity of the enzyme:

uridine diphosphate (UDP)-glycuronosyl transferase 1A1 (UGT1A1)

this means liver cant metabolise drugs or bilirubin so well.

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8
Q

how can iron overload be detected/ ivx?

A

Liver biopsy + Perls prussian blue stain:

may see haemosiderin deposits etc depending on condition

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9
Q

define polychromasia?

A

macrocytic red cells with bluish tinge - are immature red cells (retiiculocytes) found among normal cells.

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10
Q

list lab and clincial findings in Haemolytic anaemia?

A 
Clinical:
Large spleen - particularly extravascular h
Pallor
Jaundice
Pigmenturia
Family hx

Lab:
Anaemia
Reticulocytosis
Polychromasia

High bilirubin
High LDH - particularly intravascular (IH) + EH
Haemoglobin and haemosiderin in urine (red or brown urine) - IH
Low haptoglobin - IH + severe EH

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11
Q

what is the role of haptoglobin?

A

to bind to free circulating haemoglobin and form complexes that are excrreted

when there is too much Hb release, you get haemoglobin and hemosiderin in the urine

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12
Q

How can you tell from ivx results if something is Intravascular haemolyis?

A

involves molecules that were inside the ceell now coming out so;

haemoglubinuria,increased LDH etc

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13
Q

what is the mechanism responsible for PNH - paroxysmal nocturnal haemoglobinuria?

A

GPI - glycosylphosphatidylinositol on the red cell membrane is deficient.

this means molecules eg complement cant bind to red cell membrane = red cells prone to destruction

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14
Q

what is the mechanism responsible for hereditary spherocytosis?

A

defect in vertical interaction* at red cell membrane due to:

Band 3
Protein 4.2
Ankyrin
B Spectrin

  • between proteins that link the lipid bilayer to the cytoskeleton
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15
Q

what is the mechanism responsible for hereditary elliptocytosis?

A

defect in horizontal interaction at red cell membrane due to:

a Spectrin
B Spectrin
Protein 4.1

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16
Q

which is the MOST COMMON genetic defect of the red cell cytoskeleton ?

A

hereditary spherocytosis

17
Q

how is hereditary spherocytosis investigated and what would be the findings?

A

○ Osmotic Fragility Test - the hallmark of red cells in hereditary spherocytosis is that they show increased sensitivity to lysis in hypotonic saline

○ The cells also show reduced binding of the dye, eosin-5-maleimide -> deetermined using flow cytometry

○ Blood film:
§The cells lack the area of central pallor
because they have lost the biconcave shape
§ Microcytic and densely stained
§ FBC will probably show increased MCHC
§Polychromatic cells

18
Q

what are the genetic types of hereditary elliptocytosis?

A

Heterozygous - rbc less badly affected

Homozygous - Hereditary Pyropoikilocytosis - rbc very badly affected

19
Q

how is hereditary elliptocytosis investigated and what would be the findings?

A

Blood film:
NO polychromasia
Normal FBC
eliptical shaped rbc’s

Hereditary Pyropoikilocytosis:
Red cell fragments - schistocytes
Poikilocytosis

20
Q

which condition is endemic in west Africa and is thought to be protective against severe malaria - what are the genotypes associated?

A

G6PD Deficiency - is X linked. more common in males

the notable genotypes are:

Hemizygous males

Females: less affected as it is X-linked. In cases where there is ‘unfavourable Iyonisation’ ( random inactivation of an X-chromosome in certain cells), creates a population of G6PD-deficient red blood cells coexisting with unaffected red blood cells.

in rare cases, including double X-deficiency -> the condition in females can grow in severity similar to males.

21
Q

what is the role of G6PD enzyme ?

A

G6PD enzyme catalyses the first step in the pentose phosphate (hexose monophosphate) pathway

This reaction generates NADPH which is required to maintain intracellular glutathione (GSH)

Glutathione is needed to protect the red cell against oxidative stress

22
Q

what are the effects of haemolysis in G6PD deficiency ?

A

○ Neonatal jaundice -> kernicterus (brain damage)
○ Acute haemolysis (triggered by oxidants/infection)

○ Chronic haemolytic anaemia (rare)
• Most people with G6PD deficiency are asymptomatic

Can present as diabetic ketoacidosis
If very severe can present with AKI

•Certain triggers can cause acute haemolysis such as:
		○ Drugs 
			§ Antimalarials (primaquine)
	          § Antibiotics (sulphonamides, ciprofloxacin, nitrofurantoin)
			§ Dapsone - antibiotic
			§ Vitamin K
		○ Infections 
		○ Fava beans/broad beans
		○ Naphthalene mothballs
23
Q

what do Blood Film of G6PD Deficiency during Acute Haemolysis look like?

A

○ In the steady state, the blood film of someone with G6PD deficiency is usually NORMAL

○ Otherwise there are a lot of :
irregularly contracted cells,
nucleated red cells,
bite cells (cells that look like they’ve had part of their cytoplasm removed)
hemighosts (haemoglobin is retracted to one side of the cell)

Heinz bodies - with methylviolet stain

24
Q

What is a characteristic feature of oxidative haemolysis on blood film ?

A

Heinz bodies

25
Q

what are Heinz bodies?

A

denatured haemoglobin

26
Q

what is the MOST COMMON defect in the glycolytic pathway ?

A

Pyruvate Kinase Deficiency

27
Q

what do Blood Film of Pyruvate Kinase Deficiency look like?

A

Red cells will have short projections, these cells are known as echinocytes - number increased post-splenectomy

red cells may resemble spherocytes

Basophilic stippling, - numerous basophilic granules that are dispersed through the cytoplasm of erythrocytes

28
Q

How can haemolytic anaemia’s be ivx in general?

A 
• DAT 
		○ Check for autoimmune haemolysis
	• Urinary haemosiderin/haemoglobin
		○ Suggests intravascular haemolysis
		○ High LDH and low haptoglobin would also suggest intravascular haemolysis 
	• Osmotic fragility
		○ Suggests hereditary spherocytosis
		○ The dye binding test is being used more frequently now
  • G6PD +/- PK activity
  • Haemoglobin separation A and F%
  • Heinz body stain - Suggests oxidative haemolysis

• Ham’s test/Flow cytometry of GPI-linked proteins
○ Ham’s test looks at the sensitivity of red cells to lysis by acidified serum
- These are tests for paroxysmal nocturnal haemoglobinuria

• Thick and thin blood film
Check for malaria (important cause outside the UK)

29
Q

What is the main differences between G6PD and PK deficiency?

A

NOTE: G6PD tends to be characterised by EPISODIC haemolysis, where as PK deficiency causes chronic haemolytic anaemia

30
Q

how is haemolytic anaemia manged?

A

• Folic acid supplementation
• Avoidance of precipitating factors (e.g. oxidants in G6PD deficiency)
• Red cell transfusions/exchange
• Immunisations against blood-borne viruses (e.g. hepatitis B)
○ Because they are more likely to receive blood products
• Monitor for chronic complications (e.g. gallstones, iron overload, osteoporosis)

• Cholecystectomy for symptomatic gallstones 
	○ In patients who have co-inherited Gilbert's syndrome, an argument can be made for prophylactic cholecystectomy

Splenectomy if indicated

31
Q

List some indications for Splenectomy?

A

○ PK deficiency and some other enzymopathies
○ Hereditary spherocytosis
○ Severe eliptocytosis/pyropoikilocytosis
○ Thalassemia syndromes
○ Immune haemolytic anaemia
○ BUT
§ There is a risk of overwhelming SEPSIS
§ Susceptible to capsulated bacteria (e.g. pneumococcus)
§ This risk can be reduced by penicillin prophylaxis and appropriate immunisation

32
Q

what is the inheritance pattern for hereditary spherocytosis?

A

autosomal dominant

33
Q

list some mechanisms that can lead to extravascular haemolysis

A

IgM - opsonisation of RBC = macrophages phagocytose

G6PD

Path - Haem (13 decks)

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