Blood Groups And Blood Transfusions Flashcards
ABO typing
ABO system so potently antigenic because the antibodies occur naturally
• ABO antigens inherited in mendelian pattern
• Gene on chromosome 9 codes for an enzyme rather than the sugar itself
• Another gene codes for the sugar base of the ABO antigen
• A: dominant- 40%, has anti-B antibodies
• B: dominant- 12%, has anti-A antibodies
• AB: universal acceptor- 3%, no antibodies
• O: universal donor, 45%, no antigens but has both anti-A and anti-B antibodies
• Immunoglobulin M (IgM) antibody is mainly produced by the spleen- cannot cross placenta
ABO antigens
Made from carbohydrates not proteins
H antigen- different sugars on end create different A, B, AB, O antigens
ABO antibodies
Theorised they develop against environmental antigens
• Infants <3 months produce few if any antibodies (maternal prior to this)
• First true ABO antibodies > 3 months
• Maximal titre 5-10 years
• Titre decreases with age
• Mix of IgG and IgM
• IgM mainly for group A and B
• Wide thermal range means they are reactive at 37°C
Blood group A antibodies and antigens
A antigen
Anti-B antibodies
Blood group B antibodies and antigens
B antigen
Anti-A antibodies
Blood group AB antibodies and antigens
A and B antigens
No antibodies
Blood group O antibodies and antigens
No antigens (H antigens)
Anti_A and anti-B anti bodies
Which chromosome codes for ABO blood typing
Chromosome 9
Rhesus antigens
> 45 different Rh antigens
• Series of C, D and E antigens (D is the most important)
• D is a null gene so no protein so anti-D is not possible
• D is dominant- 15% of population dd
• 2 genes, Chromosome 1
1. RHD – codes for Rh D
2. RHCE – codes for Rh C and Rh E
• Highly immunogenic
• Rhesus antibody (IgG) can cross placenta
• Can cause haemolytic transfusion reactions and haemolytic disease of the fetus and newborn (HDFN)
Which chromosome codes for rhesus antigens
Chromosome 1
Haemolytic disease of the fetus/newborn (HDFN):
mother’s antibodies attacks baby’s erythrocytes
• Rh D sensitization most common cause
• Develop anti-Rh antibodies
• Severe fetal anaemia
• Hydrops fetalis (oedema)
Prevention of HDFN
• Detect mothers at risk
• Maternal fetal free DNA
• Anti D prophylaxis
• In-utero blood transfusion
Result of HDFN
• in-utero death
• Still-birth
• Brain damage
• Deafness
• Blindness
How many different systems of erythrocyte antigens are there
Over 400
Universal acceptor
AB: universal acceptor- 3%, no antibodies
Universal donor
O: universal donor, 45%, no antigens but has both anti-A and anti-B antibodies
Forward typing - ABO and RhD grouping
Patient RBCs- antigens
Commercial antibodies
+ve agglutination: same blood type as antibodies
positive test is thin red line on top of gel as blood has agglutinated due to reacting against specific reagents
Reverse typing - ABO and RhD grouping
Patient plasma- antibodies
Commercial antigens
+ve agglutination opposite blood type to antigens
testing patient’s serum with known RBC antigens
Cross-matching blood
• Units of blood deemed suitable chosen from stocks available:
• Either exact match (e.g. A+ for A+) OR
• “Compatible” blood (e.g. O- for A+)
• Serological test
• Prevent transfusion reactions
Indirect Antiglobulin (Coombs) test:
• blood grouping for ABO and Rhesus D
• Detects antibodies in patients serum
Direct antiglobulin (Coombs) test:
• detect antibodies on patient’s erythrocytes
• Used for: autoimmune haemolysis, transfusion reaction, haemolysis due to foetal/maternal group incompatibility
Homologous transfusion
anonymous donor
Autologous transfusion
self-donor eg planned surgery
Blood donation:
can donate whole blood or apheresis (blood removed and externally separated to collect plasma and platelets)- blood is mixed with calcium oxalate to prevent coagulation
• 17-65 year olds can be 1st time donors
• Donors screened at donation centres
• Questionnaire
Highlight those at risk of infectious/transmissible disease
Health, lifestyle, travel, medical history, medications
• Body weight (50 – 158 kg)
What age do you have to be to donate blood
17-65
What weight do you have to be to donate blood
50-158 kg
Temporary Exclusion criteria for donating blood
• Travel
• Tattoos/Body piercings (3/4months)
• Lifestyle eg pregnant (6 months), anal sex with a new partner (3 months)
Permanent exclusion criteria for donating blood
• Certain diseases eg HIV, hep B/C
• Received blood products or organ/tissue transplant since 1980
• Notified at risk of vCJD
Tests done on donated blood
• Mandatory tests: Hep B, Hep C, Hep E, HIC, syphilis, HTLV, groups and antibodies
• Some: CMV, West Nile virus, malaria, trypanosoma
Separation and storage of donated blood
• Whole blood donated into closed system bags
• Blood centrifuged to packed red cells, Buffy coat (white blood cells and platelets) and plasma
• Plasma only kept from MALE donors
• Plasma frozen (FFP) or processed to cryoprecipitate
• Red cells passed through leucodepletion filter (to remove white cells, especially lymphocytes as could cause GVHD) and suspended in additive
• Buffy coats pooled with matching ABO and D type and then leucode
Why is plasma only kept from male donors
Female plasma is more antigenic
Blood products: erythrocytes
• Stored at 4°C, shelf life 35 days
• Some units irradiated to eliminate risk of transfusion-associated graft vs host disease- kill left over white cells
Indications and transfusion threshold for erythrocytes
Indications
• Severe anaemia (not purely iron deficiency)
Transfusion threshold
• Haemoglobin <70 g/L or <80 g/L + symptoms
• Transfuse 1 unit and recheck FBC (unless massive transfusion needed)
• Emergency stocks of O Rh D- available in certain hospital areas
Blood products: platelets
• Most units pooled from 4 donations
• Some single-donor apheresis units
• Stored at 22°C with constant agitation (prevent clotting), 7 day shelf life
Indications and transfusion thresholds for platelets
Indications
• Thrombocytopaenia (low platelet count) and bleeding
• Severe thrombocytopaenia < 10 due to marrow failure (150-450)
Transfusion threshold (NICE)
• <10 x 109 if asymptomatic and not bleeding
• <30 x 109 if minor bleeding
• <50 x 109 if significant bleeding
• <100 x 109 if critical site bleeding (brain, eye)
• Part of massive transfusion protocol
• ABO type still important (units contain ABO antibodies)
Blood products: fresh frozen plasma
• From whole donations or apheresis
• Patients born > 1996 can only receive plasma from low vCJD risk
• Single donor packs have variable amounts of clotting factors. Pooled donations can be more standardised
Indications for using fresh frozen plasma
Indications
• Multiple clotting factor deficiencies and bleeding (DIC)
• Some single clotting factor deficiencies where no concentrate available
Blood products: cryoprecipitate
• Made by thawing FFP to 4°C and skimming off fibrinogen rich layer
• Used in DIC with bleeding, and in massive transfusion
• Therapeutic dose: 2 packs (each pooled from 5 plasma donations)
Blood products: immunoglobulin
• Made from large pools of donor plasma
• Normal IVIg: Contains Ab to viruses common in population- Used to treat immune conditions e.g. ITP
• Specific IVIg: From selected patients- Known high AB levels to particular infections/conditions eg Anti D immunoglobulin used in pregnancy and VZV immunoglobulin in severe infection
Blood products: Granulocytes
• Used very rarely
• Effectiveness controversial
• indication: Severely neutropaenic patients with life threatening bacterial infections
• Must be irradiated (to kill T cells)
Blood products: factor concentrates
Single factor concentrates
• Factor VIII for severe haemophilia A (recombinant version – no risk of viral or prion transmission)
• Fibrinogen concentrate (Factor I)
Prothrombin complex concentrate (Beriplex/Octaplex)
• Multiple factors
• Rapid reversal of warfarin
Safe delivery of blood
• Patient identification
• 2 sample rule
• Hand-written patient details
• Blood selected and serologically cross matched
Indications for transfusions
• hypovolaemia due to blood loss
• Severe anaemia with inadequate oxygenation of tissues
• Anaemia- check B12 deficiency before considering, not indicated for iron or B12 deficiency
Avoiding transfusions
• Optimise patients with planned surgical procedures pre-op
• Use of EPO-stimulating drugs in renal failure and in patients with cancers
• Intraoperative cell salvage
• IV iron for severe iron deficiency
• Some patients may tolerate lower haemoglobin concentrations and not require transfusion at all
Early hazards of blood transfusions
• ABO incompatibility reaction
• Fluid overload- pulmonary oedema
• Febrile reaction- antigens target donor antigens, can cause life-threatening respiratory failure
• Bacterial and malarial infection
Late hazards of blood transfusions
• rhesus D and other antibody sensitisation
• Delayed transfusion reaction
• Viral infection, hep B/C or HIV
• Prion infection
• Iron overload resulting in cardiac, hepatic and endocrine damage
Haemolytic reactions
• ABO incompatibility
Rapid intravascular haemolysis
Cytokine release
Acute renal failure and shock
DIC
Can be rapidly fatal
• Treatment
STOP transfusion immediately
Fluid resuscitate
• Can be acute or delayed (>24 hrs)
• Must be reported to SHOT (serious hazards of transfusion)
Bacterial contamination of blood
• Most commonly with platelets (still v. rare)
• Symptoms very soon after transfusion starts
Fever and rigors
Hypotension
Shock
• Inspection of unit may show abnormal colouration/cloudiness
Transfusion-related lung injury
• antibody in donor blood reacts with recipient’s pulmonary epithelium/neutrophils
• Inflammation causes plasma to leak into alveoli
• Symptoms:
Shortness of breath
Cough with frothy sputum
Hypotension
Fevers
• Supportive treatment
Transfusion-associated circulatory overload (TACO)
• Acute/worsening pulmonary oedema within 6 hours of transfusion
• Older patients more at risk
• Symptoms:
Respiratory distress
Evidence of positive fluid balance
Raised blood pressure
• Careful assessment of transfusion need and limiting amount can help avoid.
Alternatives to transfusion
Treat anaemia pre-op
Stop anti-platelet and anti-coagulant drugs
Operative erythropoietin to stimulate RBC production
When are first true ABO antibodies produced
> 3 months
Age of maximal titre of ABO antibodies
5-10 years
What causes the titre of ABO antibodies to decrease
Aging
Haemolytic disease of the foetus and newborn (HDFN) process
- RhD -ve mum and RhD +ve dad: RhD is dominant
- RhD +ve baby no.1 ——-> sensitisation (primary immune response)——-> mum makes IgM anti-D antibodies (can’t cross placenta) then IgG anti-D antibodies
- RhD +ve baby no.2 ——-> secondary immune response——> mum makes lots of IgG anti-D antibodies which cross placenta. Attack RhD antigens on fetal RBCs ——> haemolysis——-> anaemia
How to prevent sensitisation for HDFN
Anti-D injections
Universal blood donor
O-
Group and save
Determine blood group and check plasma for antibodies from previous transfusions
Separate and save plasma
