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Haematology > Blood Groups and Transfusions > Flashcards

Blood Groups and Transfusions Flashcards

1
Q

Blood Groups and Blood Transfusions

A

Blood Groups:
-Antigens (Ags) are found on the surface of RBCs
-Function of blood groups is not always clear, but it is
important in transfusion medicine
-Over 400 different blood groups have been describe,of these ABO and Rh systems are important

Blood transfusion:

  • Infusion of a blood product
  • Important form of treatment
  • Compatibility of blood groups between the donor and the patient (recipient) is NB to avoid haemolytic transfusion reactions
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2
Q

ABO Blood Groups

A

Discovered in 1901 by Karl Landsteiner

The ABO antigens are carbohydrates

The basic substance is the H antigen (Ag)
-A, B and H antigens on red cells are predominantly glycoproteins

Majority are present on the N-glycans of the anion
exchanger (band 3) and the glucose transporter

The A, B and O genes are alleles of each other on
chromosome 9

80% of the population also have secretor genes which
secrete ABO Ags into saliva, etc.

The ABO gene is located on the long arm of chromosome 9

Encodes for glycosyltransferase enzymes

A allele codes for a GalNActransferase enzyme:
-Adds N-acetyl-galactosamine to the H substance

B allele codes for a Gal-transferase enzyme:
– Adds galactose to the H substance

O allele: similar to A allele but has a single base deletion in exon 6, so that no glycosyltransferase enzyme is produced

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3
Q

Blood Group A

A

The A allele codes for an enzyme that adds N-acetylgalactosamine to the H substance to form the A Ag

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4
Q

Blood Group B

A

The B allele codes for an enzyme that adds galactose to

the H substance to form the B Ag

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5
Q

Blood Group O

A

The O allele does not code for an enzyme. Nothing is
added to the H substance, therefore the O antigen consists of only the H substance

ABO BLOOD GROUPS
• Definitions of Genotype and Phenotype
– Genotype:
• Genetic constitution of an individual person
– Phenotype:
• The physical or biochemical characteristics of a
person reflecting genetic constitution, posttranscriptional and post-translational modifications
and environmental influence
• ABO blood groups are inherited in a co-dominant fashion

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6
Q

ABO Blood Groups:

Genotype vs Phenotype

A

Genotype:
-Genetic constitution of an individual person

Phenotype:
-The physical or biochemical characteristics of a person reflecting genetic constitution, posttranscriptional and post-translational modifications
and environmental influence

ABO blood groups are inherited in a co-dominant fashion

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7
Q

ABO Blood Groups

A

Clinical importance of a blood group system in blood
transfusion lies in frequency of its antibodies and in
possibility that such antibodies will destroy incompatible
cells in vivo

ABO system was the first to be recognized and remains the most NB

Reason: almost everybody over age of +/- 6 months has clinically significant anti-A and/or anti-B in their serum if they lack the corresponding antigens on their red cells

ABO antibodies arise in response to A- and B-like antigens present on bacterial, viral or animal molecules

Due to this cross-reaction between the Ags of e.g. gut
bacteria and blood groups, IgM Abs are produced against those blood group Ags that are foreign to that person:

  • Blood group O: anti-A & anti-B
  • Blood group A: anti-B
  • Blood group B: anti-A
  • Blood group AB: no anti-A or anti-B

These IgM Abs may cause intravascular, complement
mediated, haemolysis when incompatible blood is
transfused

Unique in that it is the only blood group system where
reciprocal or antithetical Abs are present with no prior
exposure to Ag

“Naturally occurring” antibodies

Reason why ABO compatibility is so important in
transfusion testing

Provide the tools for ABO testing

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8
Q

ABO Compatibility

A

IgM is a pentamer

IgM ABO antibodies cause agglutination of RBCs carrying the corresponding ABO blood group antigen

Donors Recipients:
O neg = “universal donor”
AB pos = “universal recipient”

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9
Q

RH Blood Group System

A

In 1940, Karl Landsteiner and Alexander S. Wiener reported a serum that reacted with +/- 85% of different human RBCs

Serum was produced by immunizing rabbits with
RBCs from Rhesus macaque monkeys

Antigen that induced this immunization was designated by them as Rh factor “to indicate
that rhesus blood had been used for the
production of the serum.”

Second most important system

Major antigen: D-Antigen
– Rh positive ( D+) 85%
– Rh negative ( D-) 15%

D Ag is highly immunogenic

Antibodies are “unexpected” and are immune - they result from previous transfusion or pregnancy

Three closely linked gene loci:
– Define the 5 major Ags: D, C, E, c, e.
– D or “no D” is inherited at one locus
– C or c is inherited at a second locus
– E or e is inherited at a third locus

D is the most important Ag
• – presence of D Rh positive
• – absence of D Rh negative (No D

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10
Q

Inheritance

A

ABO & RH genes are not linked

ABO & Rh(D) type are inherited independently

For example:
An A Rh(D) pos mother and a B Rh(D) pos father
could have an O Rh(D) neg child

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11
Q

RH Inheritance

A

The 5 major Ags are inherited as haplotypes(one gene complex) from each parent.
-Cde from the mother and the cde from the father>Cde/cde

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12
Q

RH Antibodies

A

Anti-Rh antibodies only occur in Rh-negative people after exposure to Rh-positive blood through:
– Blood transfusion
– Pregnancy

Anti-Rh antibodies are IgG (small Abs)
– It crosses the placenta
– It cannot agglutinate RBCs

Importance of this blood group is that it can cause
Haemolytic disease of the foetus & newborn (HDFN)

Can also cause delayed haemolytic transfusion reactions

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13
Q

Unexpected/Immune Allo-Antibodies

A

Need understanding

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14
Q

How is ABO and Rhesus Grouping Done

A

Patient’s red cells with anti-A and anti-B Antisera (forward grouping)

and

Patient’s plasma for the presence of anti-A and anti-B
against reagent A and B cells (reverse grouping)

This test is done at room temperature and a positive reaction is determined by agglutination of the red cells.

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15
Q

Haemolytic Disease of the Foetus and Newborn(HDFN):

Definition

A

Shortened life span of foetal/neonatal RBC due to destruction by maternal antibodies

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16
Q

Haemolytic Disease of the Foetus and Newborn(HDFN):

Pathophysiology

A

When:
– Mother: Rh negative
– Foetus: Rh positive

First pregnancy:
– Foetal cells enter mother’s circulation
– Mother produces anti-D antibodies
– Clinically no problems

Second pregnancy:
– Prompt anamnestic response
– IgG anti-D cross placenta and coat foetal red cells
– Red cells removed by foetal RE system
– Haemolytic disease of the foetus & newborn
– HDFN may also be caused by ABO incompatibility with IgG Abs

Common blood group mismatches:

Antigen-antibody reaction leads to haemolysis in foetus/newborn:
– Anaemia
– Hyperbilirubinaemia

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17
Q

Haemolytic Disease of the Foetus and Newborn(HDFN):

Clinical Picture

A

Mild:
Jaundice-Acummulation of unconjugated bilirubin

Severe:
Anaemia-Destruction of red blood cells
Kernicterus-Bilirubin deposition in the basal ganglia and as a result brain damage is caused by the hyperbilirubinemia as the bilirubin moves form the blood to the brain tissue.

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18
Q

Haemolytic Disease of the Foetus and Newborn(HDFN):

Laboratory Diagnosis

A
  1. Haematology
  2. Immunology
  3. Chemistry
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19
Q

Haemolytic Disease of the Foetus and Newborn(HDFN):

Laboratory Diagnosis-Haematology

A

FBC:

  • Anaemia (Hb low for age!)
  • Differential count: many NRBCs
  • Erythroblastosis foetalis
  • Instrument unable to generate DIFF
  • NRBC’s counted as lymphos

Peripheral smear:
-NRBCs, polychromasia, spherocytes
-Difficulty: normal neonates can have NRBCs &
polychromasia!!

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20
Q

Haemolytic Disease of the Foetus and Newborn(HDFN):

Laboratory Diagnosis-Immunology

A

Local Lab:
1. Is there an antibody present?
– Coombs test: direct & indirect

  1. Against what antigen is it directed?
    – Blood group testing (ABO, Rh for mother & baby)
    Reference Lab:

Specificity
3. How strong is the antibody?
– Titre

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21
Q

Haemolytic Disease of the Foetus and Newborn(HDFN):

Laboratory Diagnosis-Chemistry

A

Hyperbilirubinaemia

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22
Q

Haemolytic Disease of the Foetus and Newborn(HDFN):

Treatment

A

Depends on severity of haemolysis & jaundice:

– Phototherapy (UV lights) to solubilise the bilirubin

– Exchange transfusion with Rh-neg RBCs

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23
Q

Haemolytic Disease of the Foetus and Newborn(HDFN):

Prevention

A

All pregnant women:
– Blood group (ABO & Rh)
– Screening for preformed antibodies (indirect Coombs)

All Rh- women:
– Anti-D prophylaxis after birth of Rh+ baby - destroys the Rh-pos baby cells before an immune response is
launched

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24
Q

Other Blood Groups

A

These are not as immunogenic or NB as Rh & ABO blood groups

Most NB: Kell, Lewis, MN, P, Ii, Duffy

Cause problems in patients with multiple transfusions

May also be involved in HDN

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25
Q

Blood Transfusions

A

All blood in South Africa is collected from non-remunerated
voluntary donors
• Screened via comprehensive donor questionnaire so that
only those at lowest risk for transfusion transmissible
infections (TTIs) are allowed to donate
• Transfusion transmissible pathogens of concern in SA:
– Human Immunodeficiency virus (HIV)
– Hepatitis B virus
– Hepatitis C virus
– Treponema Pallidum (syphilis)
– Other bacteria
– Malaria parasites
SAFETY OF THE BLOOD SUPPLY
• Every single unit collected in SA is TESTED for the
presence of
– Hepatitis B & C
– Syphilis
– HIV 1 & 2, (window period NB)
• Donors are ABO, Rh typed
• Blood is crossmatched for ABO & Rh
• Patient tested for other Abs that may cause haemolysis
• Check that the right patient gets the right blood
product for the right indication at the time
SAFETY OF THE BLOOD SUPPLY
• Specific tests:
– Hepatitis B surface antigen
– Hepatitis C antibody
– HIV 1 and 2 antibodies
– Syphilis
– Nucleic Acid Amplification testing for HIV 1, HBV and
HCV
• All reactive units are removed from quarantine and carefully
disposed of
• Further confirmatory tests are performed; donors
subsequently notified and deferred
• The addition of NAT-testing has significantly reduced
the window period for HIV, HBV and HCV
SAFETY OF THE BLOOD SUPPLY
• Look back programme
• Initiated in 1985 by blood transfusion services to assess the
incidence of transfusion-transmitted infection
• Programme traces any patient who received HIV and
Hepatitis negative blood from a donor whose subsequent
donation is found positive for either infection
• Patients are contacted through the hospital or their private
physician and are offered counselling and testing
ADDITIONAL SAFETY MEASURES
• Where the applicable technology exists, blood product is
further treated to inactivate any latent infection
• Currently the following products undergo viral inactivation
procedures or include steps as part of the manufacturing
process that have been documented as viral reduction
steps:
– Albumin
– Stabilised Serum
– Factor VIII and IX concentrates
– Immunoglobulins
– Fresh Dried Plasma (FDP)

26
Q

Components

A 
Leucocytes, platelets & clotting factors do not survive for
long in donated blood
• Thus donated blood is centrifuged and components
separated:
• Packed red cells:
– To increase oxygenation when this is critically reduced
by anaemia or haemorrhage
• Platelets:
– To replace deficient or dysfunctional platelets resulting in
significant haemostatic problems
• Fresh frozen plasma:
– Scoline apnoea
– To correct haemostatic disorders associated with:
• Clotting factor deficiencies (e.g. DIC)
• Reversal of life threatening Warfarin effects
• TTP (Cryosupernatant)
• Collected into a top and bottom
bag
• Primary collection bag contains
anticoagulant (CPD) and has
an empty transfer bag
connected to top
• Another transfer bag
containing optimal additive
solution (SAGM) is connected
to bottom
• After centrifugation plasma is
expressed out of top and red
cells out of bottom leaving
buffy coat in primary collection
bag
• Components obtained:
– Red cell concentrate in
bottom bag
– Buffy coat layer of white
cells and platelets in
primary bag
– Plasma in top transfer bag
27
Q

Components: Red Cell Concentration

A

Keep at 4-10°C

Shelf life: 35-42 days

28
Q

Compoents: Platelets

A

Keep at room temperature

Shelf life: 5 days

29
Q

Components: Fresh Frozen Plasma

A

Keep at at least -18°C (Shelf life: 3 months)

If stored at -25 °C: Shelf-life = 3 years

30
Q

Alternative Procedures to Allogeneic Blood Donation

A
  1. Aphaeresis
  2. Autologous donation
  3. Directed/designated donation
31
Q

Alternative Procedures to Allogeneic Blood Donation:

Apheresis

A

Only the necessary
components are collected.
Rest is returned to donor.

32
Q

Alternative Procedures to Allogeneic Blood Donation:

Autologous donation

A

Collection of blood from a person and its subsequent

re–infusion into the same person.

33
Q

Alternative Procedures to Allogeneic Blood Donation:

Directed/Designated Donation

A

These are compatible blood donations made by

family and/or friends of a particular patient

34
Q

Transfusion: General Guidelines

A

Blood products are living human tissues – should actually be viewed as a blood “transplantation” not transfusion

Only prescribe when benefit is likely to outweigh risk

Prescribe according to accepted transfusion guidelines: www.sanbs.org.za

Minimise blood loss

Use non-blood fluids for resuscitation

Transfuse to meet the clinical needs of a patient and not according to laboratory results

Obtain informed consent

35
Q

General Indications for Red Cell Transfusion

A

Acute Blood Loss

General Surgery

Anaemia in Acute Coronary Syndromes(ACS)

Anaemia

Cardiac Surgery

Obstetric Haemorrhage

36
Q

General Indications for Red Cell Transfusion:

Acute Blood loss

A

An acute blood loss of ≥ 20% of blood volume (about 1000-
1200 ml of blood in an adult) will often result in the need for
a red cell transfusion

37
Q

General Indications for Red Cell Transfusion:

General Surgery

A

Consider transfusion if:
• Pre-operative Hb is < 8 g/dl and the surgery is associated
with major blood loss (> 500 ml)
• Intra- or post-operative haemoglobin falls below 7 g/dl
• Higher Hb may be indicated in patients at risk for
myocardial ischaemia or who are > 60 yrs old
• Pre-operative anaemia must be investigated in every case:
medical management to raise Hb may be more appropriate
than transfusion

38
Q

General Indications for Red Cell Transfusion:

Anaemia in Acute Coronary Syndrome(ACS)

A

In patients with ACS there is evidence that a haemoglobin
level below 8g/dl may be deleterious

• T

39
Q

General Indications for Red Cell Transfusion:

Anaemia

A

he aetiology of anaemia should be investigated and, as
far as possible, a definitive diagnosis should be made in
every case
• Medical management will be determined by cause
• Appropriate alternatives to blood transfusion must be
considered
• Consider transfusion in normovolaemic patients only if they
are severely symptomatic e.g. shortness of breath at rest,
angina, incipient cardiac failure
• Patients with Hb < 7g/dl often require a transfusion

40
Q

General Indications for Red Cell Transfusion:

Obstetric Haemorrhage

A

During an obstetric haemorrhage, red cells should be
administered to maintain the patient free of signs and
symptoms of inadequate tissue oxygen delivery
• Hb should be maintained between 6 and 10g/dl during the
resuscitation phase

41
Q

Other Measures

A
  1. Investigate all anaemias
  2. Minimise surgical bleeding
  3. Good antenatal care
  4. Correct anaemia with conservative measures
42
Q

Minimise Surgical Bleeding

A
  1. Pre-op
    - Early pre-operative evaluation for elective surgery

-Address abnormal coagulation profiles, thrombocytopenia, liver/renal impairment

-Stop/bridge anticoagulants prior to surgery (aspirin,
clopidogrel, warfarin, NSAIDS)

  1. Intra-Op
    -Cell saver technology: autotransfusion of
    recovered blood
  • Pre-operative autologous donations
  • Acute normovolaemic haemodilution
  • Haemostatic drugs
  • Local haemostatic agents (Thrombin glue, Microfibrillar collagen etc.)

-Meticulous haemostasis, laparoscopic
techniques etc.

  1. Post-OpP

-Cell saver technology: autotransfusion of
recovered blood

  • Meticulous wound care and monitoring
  • Early intervention if bleeding
43
Q

Good Antenatal Care

A

Early booking

Haematinics

Early referral

Family planning

44
Q

Correct Anaemia with Conservative Measures

A

Oral haematinics

Erythropoietin

Parenteral iron

Address underlying condition!

45
Q

Transfusion Reactions:

Types

A
  1. Haemolytic Reactions
  2. Allergic Reactions
  3. Fluid Overload
46
Q

Transfusion Reactions:

Haemolytic Reactions

A

Caused by patient Abs to transfused RBCs

47
Q

Transfusion Reactions:

Allergic Reactions

A

Mainly caused by platelet & leukocyte remnants;
cytokines NB.

These can be removed by special filters in the blood

48
Q

Transfusion Reactions:

Fluid Overload

A

To much product

To quickly transfused

49
Q

Risk of Transfusion in SA

A

Higher risk for non-infectious than infectious
complications after a blood transfusion
• In South Africa:
• SANBS 2014 Haemovigilance report:
• Since the implementation of ID-NAT in 2005 (approximately
7,5 million donations screened), there has been only one
case of HIV transmission via blood transfusion (2014)
• 2014 haemovigilance report:
– No Hep B, Hep C or malaria, but one case of HIV and
one case of HTLV
– Compare this to a total of 961 non-infectious
complications in the same year
SANBS. Haemovigilance report 2014.
Just how dangerous is a transfusion?
Carson JL et al. Red blood cell transfusion: A Clinical Practice Guideline From the AABB. Ann Intern Med. 26 March 2012

50
Q

Haemolytic Transfusion Reactions:

Types

A

Ensue when transfused red cells are destroyed by the
immune system

Typically occurs when antigen-positive donor red cells are transfused to patient with clinically significant alloantibody to the corresponding antigen

  1. Severe Acute HTRs (AHTRs)
  2. Delayed HTRs (DHTRs)NP > 1,5
51
Q

Haemolytic Transfusion Reactions:

Severe Acute HTR(AHTRs)

A

Occur within 24 hours of the incompatible transfusion

Due to intravascular haemolysis caused by
complement fixing IgM antibodies. (E.g. ABO A/bodies)

Less severe AHTRs may also be caused by
extravascular haemolysis due to IgG antibodies, (e.g.
anti-D/anti-K) in recipients sensitized by previous
transfusions or pregnancy

52
Q

Haemolytic Transfusion Reactions:

Delayed HTRs (DHTRs):

A

Occur 5–8 days after transfusion

Due to an anamnestic (secondary, IgG) immune
response leading to extravascular haemolysis, in a
previously sensitized recipient in whom no alloantibody can be detected in the pre-transfusion specimen

Reported to be 1 in 2500 transfused units

Amount of incompatible blood needed for HTR:
– some people react after a few millilitres
– others will tolerate a whole unit with minimal effects

53
Q

Haemolytic Transfusion Reactions:

Clinical Presentation

A

Fever & chills: usually the 1st signs of an HTR
– Not usually possible to distinguish from febrile non-HTR
(FNHTR)
– Due to release of anaphylatoxins
• Back or loin pain: very common but cause is unknown
• Sensations of unrest, dyspnoea: caused by lung
perivascular and peribronchial oedema
• Hypotension, shock: in 10% of patients with intravascular
HTR but rarely seen in extravascular haemolysis
– Complement activation probably a significant factor
• Renal failure: may occur in either type of HTR but is more
common in AHTR
• DIC: seen in intravascular AHTRs but is very rare in
extravascular HTRs
HTR: INVESTIGATION

54
Q

Haemolytic Transfusion Reactions:

Investigations

A

• STOP transfusion immediately!
• Check all labelling: If wrong blood has been transfused,
trace units of blood intended for that patient, so as to avoid
incompatible transfusion to another patient
• Obtain properly labelled specimen from patient and send
to blood bank with the original transfusion bag and
administration set
• DAT,Peripheral blood film, Retic. count, Haptoglobin, LDH,
Unconj. Bilirubin, etc. to confirm haemolysis
• Blood bank: Repeat ABO and Rh testing, allo-antibody
screening, crossmatches
• If above tests fail to confirm an HTR, consider an
alternative transfusion complication such as bacterial
contamination

55
Q

Haemolytic Transfusion Reactions:

Management

A

Guided by clinical picture: minimally symptomatic
patients may be observed only, but severe reactions
require early aggressive intervention
• FIRST: Assess immediately for life threatening ABC
compromise. Maintain venous access. Check patient
identity.
• ABO incompatibility and severe haemolysis: exchange
transfusion may be needed
• Prevent renal failure by maintaining urine output with IV
fluids and diuretics. Consider vasopressor support.
• Treat DIC
• IVIG has been successfully used on occasion, as pretreatment when incompatible blood is given to an alloimmunised patient.
• REPORT!

56
Q

Allergic Reactions:

Types

A

Febrile Non-Haemolytic Transfusion Reaction

Allergic Reaction

Anaphylaxis

57
Q

Allergic Reactions:

Febrile Non-Haemolytic Transfusion Reaction

A

Only a mild fever: Temp rises < 1.5°C, stable observations
and patient is otherwise well. No resp. distress!

Rx: paracetamol. Restart infusion at a slower rate,Observe closely

58
Q

Allergic Reactions:

Allergic Reaction

A

Mild urticarial rash only. No resp. distress!

Give chlorpheniramine 10 mg slowly IV. Restart transfusion at a slower rate. Observe more frequently.

59
Q

Allergic Reactions:

Anaphylaxis

A

Resp Distress, Bronchospasm, angio-oedema,laryngeal oedema and stridor, abdominal pain, hypotension, etc

Chlopheniramine 10 mg slow IV, O2 salbutamol
nebulisation, adrenaline etc. Saline wash future
components

60
Q

TRALI

A

• Transfusion Related Acute Lung Injury
• Acute non-cardiogenic pulmonary oedema in the setting of
transfusion
• All blood products have been implicated, but more common
in FFP, Platelets, Whole Blood, RBCs
• Complex, partially understood pathogenesis:
– Anti-granulocyte a/bodies or other bioactive
substances in donor product, binding to or priming
recipient granulocytes
– Inflammation in pulmonary capillaries, granulocytes
release proteolytic enzymes, O2 radicals
– Pulmonary oedema ensues
– TRALI

61
Q

TACO

A

Transfusion Associated Circulatory Overload

Fluids given too fast or too much

Inc JVP

Inc CVP

Inc Pulm Wedge Pressure

BNP > 100pg/dl

Post-transfusion BNP/Pre-transfusion BNP > 1,5

Haematology (10 decks)

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