1.2 Immune Haemolysis

Question 1

Causes
- Allo-immune haemolytic anaemia – immune reaction to foreign antigens in the blood, usually secondary to _______________
- Auto-immune haemolytic anaemia – can be part of an auto-immune disease such as SLE
o Drugs e.g. __________, ___________, even penicillins or cyclosporins
o Infections e.g. mycoplasma, EBV
o Malignancies – especially B cell lymphomas

Answer 1

blood product transfusions

methyldopa; hydralazine

Question 2

Pathogenesis
- Generation of immunoglobulins that coats red blood cells – commonly IgG or IgM
- IgM is more effective than IgG than fixing complements
o If significant, complement components binding to RBC membrane can lead to complement-mediated intravascular lysis
- Binding of IgG, IgM and complement system leads to ________ of the RBC, directing _____________ as it passes through the splenic sinusoids – extravascular haemolysis
o Splenic macrophages contain ___________ and complement receptors that can home in on coated RBCs

Answer 2

opsonisation;

splenic macrophages;

Fc receptors

Question 3

Laboratory features – immune haemolytic anaemia mirror many other features seen in other haemolytic anaemias
- Hyperbilirubinemia – due to increased breakdown of haem
- Increased lactate dehydrogenase (LDH) – leakage of LDH, found abundantly in RBCs
- Increased _________ – due to increased marrow response to decreasing haemoglobin levels
- Reduced haptoglobin – due to ________________
o In immune haemolysis, there is usually a mixture of both intravascular and extravascular haemolysis
- Laboratory tests more specific to immune haemolysis
o Peripheral blood film – microspherocytes or RBC agglutination
o Positive direct Coomb’s test
- Presence of microspherocytes implies a reduction in the _______________ – due to the removal of RBC membrane by splenic macrophages
- RBC agglutination – due to the presence of ____ on the surface of the RBC
o As IgM is pentameric in nature, they are able to cross link RBCs so that they agglutinate

Answer 3

reticulocytes;

binding of free haemoglobin in the circulation;

surface area to volume ratio;

IgM

Question 4

Direct Coomb’s test
- Detects the presence of IgG or complement components on RBC surface
- RBCs are incubated with antiglobulin against ____________________
o In the presence of IgG and complement components, RBCs will show agglutination

Answer 4

IgG or complement C3b and C3d