Special blood requirements
An overview
Dr. Syed Naqvi, SpR Clinical Haematology
Dr. Kate Pendry, Consultant haematologist
Commonly encountered special
requirements
Irradiated blood products
CMV negative blood products
Phenotyped blood products.
Kell negative blood for women of child
bearing age
All events in haematology
Special Requirements Not Met
Irradiated blood products
Rationale
Indications according to BCSH guidelines.
Incidents, SHOT reports
Transfusion associated Graft versus host
disease.
Rationale
The major technology for preventing TA-GvHD is irradiation of blood
components to inactivate residual lymphocytes.
Either Gamma or X ray radiations are used at specific doses for a
certain length of time.
Indications For Irradiated Blood Products
According to BCSH Guidelines,
published in 2010 and updated in
2012.
All cases of transfusion-associated graft-versus-host
disease (TA-GvHD) should be reported to the national
haemovigilance system, as should all ‘near misses’
Red cells may be irradiated at any time up to 14
d after collection,
and thereafter may be stored for a further 14
d. Where the patient
is at particular risk from hyperkalaemia, e.g. intrauterine or
neonatal exchange transfusion, it is recommended that red cells be
transfused within 24
h of irradiation or that the cells are washed
.
Platelets can be irradiated at any stage during storage and can
thereafter be stored up to their normal shelf life after collection (1A).
All granulocyte components should be irradiated before
issue and transfused with minimum delay.
All human leucocyte antigen (HLA)-selected
components should be irradiated, even if the patient is
immunocompetent.
All blood and platelets for intrauterine transfusion (IUT) should be
irradiated.
It is essential to irradiate blood for neonatal exchange transfusion
(ET), and platelets if there has been a previous IUT or if the
donation comes from a first- or second-degree relative.
All severe T lymphocyte immunodeficiency syndromes should be
considered as indications for irradiation of cellular blood
components. Once a diagnosis of immunodeficiency has been
suspected, irradiated components should be given while further
diagnostic tests are being undertaken.
There is no need to irradiate red cells or platelets for infants
undergoing cardiac surgery unless clinical or laboratory features
suggest a coexisting T lymphocyte immunodeficiency syndrome
All recipients of allogeneic haemopoietic stem cell transplantation
(SCT) must receive irradiated blood components from the time of
initiation of conditioning chemoradiotherapy. This should be
continued while the patient continues to receive graft-versus-host
disease (GvHD) prophylaxis, i.e. usually for 6
months post-
transplant, or until lymphocytes are >1
× 109/l.
If chronic GvHD is present or if continued immunosuppressive
treatment is required, irradiated blood components should be given
indefinitely.
Patients undergoing bone marrow or peripheral blood stem cell
‘harvesting’ for future autologous re-infusion should receive
irradiated cellular blood components during and for 7
d before the
bone marrow/stem cell harvest to prevent the collection of viable
allogeneic T lymphocytes which can potentially withstand
cryopreservation.
All patients undergoing autologous bone marrow transplant or
peripheral blood stem cell transplant should receive irradiated
cellular blood components from initiation of conditioning
chemo/radiotherapy until 3
months post-transplant (6 months if total
body irradiation was used in conditioning).
All adults and children with Hodgkin lymphoma at any stage of the
disease should have irradiated red cells and platelets for life
Patients treated with purine analogue drugs (fludarabine, cladribine
and deoxycoformicin) should receive irradiated blood components
indefinitely.
The situation with other purine antagonists and new and related
agents, such as bendamustine and clofarabine, is unclear, but use
of irradiated blood components is recommended as these agents
have a similar mode of action. Irradiated blood components should
be used after alemtuzumab (anti-CD52) therapy
In view of the recent switch from horse anti-thymocyte globulin (ATG)
to the more immunosuppressive rabbit ATG, we now recommend use
of irradiated blood components for aplastic anaemia patients
receiving immunosuppressive therapy with ATG (and/or
alemtuzumab).
It is not necessary to irradiate blood components for patients
undergoing routine surgery, those with solid tumours HIV infection,
autoimmune diseases or after solid organ transplantation (unless
alemtuzumab (anti-CD52) has been used in the conditioning
regimen).
As new potent immunosuppressive drugs and biological agents are
introduced into practice there is a need for regular review of these
recommendations.
TRANSFUSION ASSOCIATED GVHD
In TA-GvHD, donor T lymphocytes are derived from blood
components containing viable lymphocytes.
Typically, in immunocompetent hosts, viable T lymphocytes are
destroyed by the recipient's immune system.
In susceptible patients, with immune deficiency, transfused T cells
are not destroyed; they proliferate and can induce an immune
response ‘rejecting’ the host tissues.
Signs and symptoms of TA-GvHD usually begin 2–30
days after
transfusion.
Skin, gastrointestinal, and liver signs and symptoms similar to BMT-
related GvHD also occur in patients with TA-GvHD
With TA-GvHD, the marrow is uniformly affected and is the source
of greatest morbidity and mortality. Bone marrow failure with
pancytopenia, especially neutropenia, progressively develops with
death often occurring due to infection and/or bleeding complications.
TRANSFUSION ASSOCIATED GVHD
Fresh blood (<
3 days) has been shown to have caused
TA-GvHD more commonly than blood that has been
stored for longer time (>
7 days), presumably due to
decreased viability of lymphocytes on refrigerator
storage.
Granulocyte transfusions (which contain many
lymphocytes) given fresh to immunocompromised
patients have an increased propensity for causing TA-
GvHD.
No documented cases of TA-GvHD have been attributed
to fresh-frozen plasma (FFP). So no need for irradiation.
Any blood component from relatives is considered to be
at higher risk for causing TA-GvHD due to shared HLAs
between donor and recipient.
Emergency intrauterine transfusion (IUT) for fetal anaemia
Fetus of 21 weeks gestation
Maternal parvovirus infection during pregnancy
Required an urgent IUT following signs of severe anaemia on ultrasound.
Transfused 15 mL maternal blood to the fetus (non-leucodepleted, non-irradiated and related).
Hb rose from 44 g/L to 100 g/L
The fetus subsequently developed bradycardia with poor cardiac output so an emergency
transfusion with a further 18 mL maternal blood was given.
The baby was delivered by emergency C/S at 32 weeks gestation due to reduced fetal
movements.
Hydropic at birth with pleural and pericardial effusions requiring chest drains and ventilation.
Pancytopenic, required multiple blood and platelet transfusions.
Parvovirus negative
Later also developed conjugated hyperbilirubinaemia and a fungal chest infection.
A bone marrow aspirate at 2 months of age confirmed aplasia.
Chimerism studies confirmed maternal engraftment.
The mother was found to be (HLA) homozygous.
A diagnosis of TA-GvHD was made, and the baby underwent a stem cell transplant (maternal
donor) but died of pneumonitis a week later.
Summary of Main Findings and Cumulative Results
Number of cases of TA-GvHD reported to SHOT each
year
Background
Herpes virus
Gives rise to chronic, persistent and, for the most part, asymptomatic
infection.
More severe disease may occur in certain groups, such as foetuses,
neonates and immunocompromised adults. .
In the UK 50-60% of adults are CMV seropositive
CMV may be transmitted horizontally in saliva and other body fluids, blood,
haemopoietic stem cells and organ transplants.
The risk of transmission in multiply-transfused CMV negative recipients was
greatly reduced by the provision of leucodepleted and/or CMV seronegative
blood products. Although this significantly reduces the risk of CMV
transmission it is not 100% effective.
Transmission of CMV present in blood components can give rise to primary
infection in CMV naïve recipients (transfusion-transmitted CMV) or to
reinfection in previously infected individuals.
CMV infection in neonates or pregnancy
CMV is the commonest cause of congenital infection in the developed
world.
Up to 20% of babies who acquire congenital CMV die
Also a leading cause of cerebral palsy, deafness, chorioretinitis and
cataracts.
Primary infection may increase the risk of abortion, stillbirth and foetal
hydrops.
Much higher incidence if the baby is premature, who are already most likely
to be given blood components.
Given the potential severity of the consequences of CMV infection in this
patient group, and the difficulty in monitoring neonates for infection
(preventing pre-emptive therapy), it was considered to be important that
leucodepleted and CMV seronegative blood components should continue to
be provided.
As there is a high risk of congenital CMV infection following primary
maternal infection, Therefore it is recommended to continue to minimise this
risk by the use of CMV seronegative leucodepleted blood components in
pregnant women receiving elective transfusions.
Indications
(Recommended by SABTO)
1. CMV seronegative red cell and platelet components should be provided for intra-
uterine transfusions and for neonates..
2. Granulocyte components should continue to be provided as CMV seronegative for
CMV seronegative patients.
3. CMV seronegative blood components should be provided where possible for pregnant
women, regardless of their CMV serostatus, who require repeat elective transfusions
during the course of pregnancy (not labour and delivery). This mainly applies to
patients with haemoglobinopathies who are managed in specialist centres.
4. All blood components in the UK now undergo leucodepletion, which provides a
significant degree of CMV risk reduction. This measure is considered adequate risk
reduction for all other patients requiring transfusion (haemopoietic stem cell
transplant patients, organ transplant patients, and immune deficient patients,
including those with HIV) without the requirement for CMV seronegative components
in addition.
5. CMV PCR monitoring should be considered for all haemopoietic stem cell and solid
organ transplant patients (even CMV negative donor/negative recipients) to allow
early detection of any possible CMV infection.
6. Transfusion-transmitted CMV infections should be reported via the SHOT (Serious
Hazards of Transfusion) and SABRE (Serious Adverse Blood Reactions & Events)
systems.
Appropriately phenotyped blood
products for patients with
haemoglobinopathies requiring
blood transfusion
Appropriately Phenotyped blood products
Extended phenotype (or genotype) & compatibility testing
Phenotype/genotype prior to transfusion
Serological usually; molecular if recently transfused
C c E e K k Jka Jkb Fya Fyb S s
U typing if S-s-
Fully automated systems for ABO grouping
Antibody screening as standard
Antibody identification if screen positive
Antibody card if alloantibodies detected
Choice of blood product:
Match for Rh (D C c E e) and K as a minimum
Select R0 blood for R0 individuals; use rr in emergency if R0 unavailable
If antibodies, select blood that is negative for corresponding antigens
HbS negative
<14 days old; <7 days old for automated exchange if possible
Risk of Alloimmunisation
The serious problem of alloimmunisation
Reported frequency 18-36% in sickle cell disease
30% sickle v 5% non-sickle
Likely an underestimate 37% of antibodies undetectable.
K C E account for 66% of antibodies.
Higher rate of multiple alloantibodies.
Increased rate of autoantibodies
Factors implicated in alloimmunisation
Phenotype differences between donors and recipients
Greater number of transfusions
Later start to transfusions
Minimizing Alloimmunisation
Reduced use of transfusions
Avoid transfusion unless absolutely necessary
Hydroxycarbamide.
Give phenotype-matched blood
Matching for K, C, E reduced alloimmunisation
rate from 3% to 0.5%
10x reduction if fully Phenotyped (17
alloantigens)
Kell negative blood products for
women of child bearing age
Kell negative blood products for women of
child bearing age
One of the three most common red cell alloantibodies which cause significant HDN. (anti D,
anti c and anti Kell.
In HDN due to anti K, the antibody also causes reduced foetal red cell production. This is
due to anti K binding to red cell progenitor cells; in such cases the anaemia is often very
severe while jaundice may be minimal.
Reports of affected pregnancies are associated with antibody titres of at least 32.
The majority of cases of anti-K in pregnant women are the consequence of previous K
positive transfusions.
The transfusion history of women with anti-K should be established and a sample from the
father of the foetus should be K typed. If the woman has not been transfused and the father
is K positive, the patient should be referred to a specialist unit and titration of samples
should be performed at monthly intervals to 28 weeks, and at fortnightly intervals thereafter.
If the father is K negative ,no further samples are required until 28 weeks when the antibody
should be titrated and further antibodies excluded.
The foetus can be K typed from an amniocentesis or by extracting ffDNA from maternal
blood.
The incidence of anti-K could be reduced by selecting K negative units for
transfusion to females with potential for childbearing.