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
What are the symptoms of delayed haemolytic transfusion reactions?
Greater than 24 hours for symptoms
Under reported and under diagnosed
Usually due to secondary immunisation
Fever
Raised bilirubin
Drop in Hb/Hct
Rarely renal failure or DIC
Antibodies to many blood group antigens implicated
Some antibodies activate complement
RBC’s are removed extravscularly - splenic and liver macrophages
What are FNHTR
Febrile non haemolytic transfusion reactions
Reactions to white cells
Write about reactions to whire cells
Reactions involving pre-formed antibodies to white cell antigens e.g. HLA
Transfuse white cells bearing that antigen -> ingested by host monocytes
Causes release of pyrogens/cytokines
Causes an increase in temperature
Overcome by issuing leucodepleted blood
What is TRALI
Transfusion related acute lung injury
Write about TRALI
(4)
Severe, acute reaction characterised by respiratory distress and pulmonary infiltrates (oedema)
Leucocyte antigen/antibody complexes most likely cause -> antibodies in the donor plasma
Donor antibodies react with patient’s leucocytes, causing their activation and release of enzymes which damage pulmonary tissue/capillaries - oedema of the lung
FFP is a risk product here especially female multiparous donors
What is the mortality for TRALI and why is it so high
5% mortality
If you are getting a plasma transfusion you and generally really unwell
If not given high level of oxygen and lungs are cleared then the patient will die in a few hours
How long does it take someone to get over TRALI
Takes 24 hours to clear
Comes on quickly but disappears quickly
Write about reactions to platelets
(6)
Platelets express ABH, HLA and Platelet specific (HPA) antigens
All platelet donors are HLA typed
Usually go through a list of donors to find a match -> very expensive as donor has to be brought in especially
There are HLA or HPA antibodies in a recipient
Random donor transfusions may carry an antigen which recipient has antibodies against
Can cause post transfusion purpura
What is post transfusion purpura
(4)
Where by a recipient makes anti-HPA
Results in a significant drop in platelet count
Patient at very high risk of haemorrhage
Rare but serious
Write about anaphylactic reactions
Rare but life-threatening
Causes respiratory distress, nausea, flushing, hypotension and shock
e.g. IgA deficient person containing IgA antibodies transfused with plasma containing IgA antigens
Ag/Ab complexes generate C3a/C5a which are powerful vasodilators
What are some other adverse possibilities to transfusions
(6)
TACO -> volume overload
GVHD -> Graft versus host disease
Allergic reactions to plasma e.g. gluten allergy
Mishandled packs e.g. freezing or overheating causing haemolysis
Iron overload in mutli-tranfused
Immunisation in general -> begin to produce new antibodies
Giving an inappropriate product e.g. anti-D immunoglobulin to an RhD positive woman or forgetting to give CMV negative blood to immunocompromised
What bacteria are most likely to contaminate blood
Pseudomonas
Serratia
Yersinia
Staphylococci
Comment on bacterial risk of transfusion
(3)
Can be devastating with ‘endotoxic’ shock
Because of this quality of blood taking, processing and storage protocols are vital
More likely a problem with platelets stored at 22 degrees than with rbcs in the fridge
How do we prevent bacterial contamination
When taking a blood donation we section off the first 20 mls as this contains a skin plug from needle (source of staph = skin)
This first 20mls is put up in a blood culture bottle in the IBTS -> Back T Test
If any bacteria present this will show up positive
What viral contaminants are most commonly seen
(7)
Hepatitis A
Hepatitis B
Hepatitis C
Human Immunodeficiency virus
Nucleic acid testing for HBV/HCV/HIV
Human T Lymphotropic virus (causes leukaemia)
Cytomegalovirus
What percentage of patients are CMV positive
29%
Why is Hep A contamination not a major concern
Very common
Don’t carry it for life
Gone after 2 weeks
How do we test for viruses
Nucleic acid testing
What are 7 other infections we screen for
Screened in the IBTS
- HEV
- West Nile Virus (seasonally)
- Malaria (seasonally)
- Syphilis
Trypanosomiasis - sleeping sickness
Epstein-Barr virus
Parvovirus B19
