Complement and Adverse Affects of Transfusion Flashcards
What is complement
(6)
30+ soluble proteins and 10 cell surface receptors that function in response to a stimulus, interact to opsonise and clear or kill invading microorganisms or altered cells
Formation of MAC to punch holes in cells
Functionally inert until activated
Activation brings about proteolytic activity in some
3 pathways: classical, alternative and lectin
Classical pathway is initiated by antigen/antibody complex
What activates complement?
IgG binding to rbcs activated complement
What blood group systems do not bind complement
ABO, Kidd, Duffy
What are the functions of complement
Cell activation - chemotaxis
Cell lysis
Opsonisation where foreign organisms are coated with complement and are subsequently phagocytosed
Physiological side effects can be increased e.g. vascular permeability, blood vessel dilation, hypotension, fever and excessive activation of the coagulation cascade
How is the classical pathway initiated
Antibodies facilitate binding of C3 to rbc surface
Write about the importance of complement activation in blood transfusion
Some blood group antibodies activate large amounts of complement, resulting in gross red cell haemolysis, particularly in vivo - intravascular haemolysis - caused by ABO mismatch or Kidd antibodies
Many activate complement at a slower rate, resulting in accumulation of C3 molecules and subsequent phagocytosis and clearance by the liver in particular - extravascular haemolysis - Fy and Jk antibodies
What antibodies cause intravascular haemolysis
Kidd and ABO
What antibodies cause extravascular haemolysis
ABO and Kidd
What two things might happen when there is complement activation
(2)
Lysis of blood samples -> if complement pathway has gone to completion -> haemoglobinemia will be seen
Sensitisation of red cell - DAT will often be positive because many anti-human globulin reagents contain anti-C3b as well as Anti-IgG
What is haemoglobinaemia
The appearance of free haemoglobin in plasma
What does C3b coated cells mean
(3)
These cells will be removed by the liver - by Kuppfer cells and hence will result in a loss of red cells
This is seen in transfusion reactions or autoimmune haemolytic anaemia
igG coated cells removed by macrophages
Write about haemolytic transfusion reactions
(5)
In vivo destruction of donor cells caused by antibodies in recipients circulation
Most serious involve ABO errors
Many other antibodies are implicated
DIC and organ failure are the most profound events
Strict adherence to specimen collection, reception, record keeping, testing and labelling of blood can minimise such reactions
Describe the pathophysiology of a haemolytic transfusion reaction
(3)
Ag/Ab reaction triggers complement activation
Fragments C3a and C5a cause histamine release from mast cells - causing vasodilation and hypotension, bronchial and intestinal smooth muscle contraction
Red cell stroma can act as a ‘thromboplastin’ like agent to initiate the clotting cascade -> DIC
What is DIC?
Disseminated Intravascular Coagulopathy
What are the symptoms of ‘acute’ haemolytic transfusion reactions?
Fever or chills or both
Pain at infusion site
Flushing/rash
Hypotension
Nausea/vomiting
Dyspnoea
Dark urine/haemoglobinuria
Oozing/ bleeding under anaesthetic
Symptoms in less than 24 hours
