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1. Transfusion Support for
Haematological Patients
Dr Dora Foukaneli
Consultant in Haematology and Transfusion Medicine
Cambridge University Hospitals and NHSBT Cambridge

2. Appropriate use of blood
in Haematology
• Indications
– Consider transfusion alternatives
• Blood ordering
– Validity of samples
• Patient information
– Valid consent
– Information regarding blood transfusion at the discharge summary
• Prescription
– Special requirements (for example irradiated)
– Adequate volume and rate
– Appropriate time
• Observation
• Chelation

3. • Rationale for ↓ exposure to allogeneic blood
– Are they any exceptions?
• Methods for minimizing transfusion
• Blood-sparing agents

4. Reasons to Reduce Blood Exposure:
• Limited resources
– Increasing demands
– New donor selection criteria: ↓ donor panels
– Rare blood group
– Multiple red cell and HLA antibodies
• To reduce risks
– Errors
– Transfusion-transmitted infections (TTIs)
– Immunological complications

5. • Transfusion related morbidity and mortality
– Haemovigilance system
– SHOT
Reasons to Reduce Blood Exposure:

6. • TTI:
– Viral: Hep E
– Bacteria
– Other pathogens
• vCJD, Sen-V, TT, HHV 6-8,
• Emerging agents
Reasons to Reduce Blood Exposure:

7. Reasons to Reduce Blood Exposure
• Immunological complications
– Red cell alloantibodies
– TRALI
– Refractoriness due to HLA sensitisation
– Post transfusion purpura
• Immunomodulation
– Post surgical infection
– Tumour reoccurrence

8. 31287, 68%
12250, 26%
2663, 6%
136, 0%
Medicine Surgery O and G Not recorded
Usage by broad category
National Survey Red Cell Use 2014 (NCA-NHS BT)

9. Highest use by diagnosis in medicine
Sub Category Number Percentage of total
usage
Haematological Malignancies 7876 17
•MDS 2923 6.31.
•AML 1987 4.29
•Lymphoma/CLL 1881 4.06
•Myeloma 1085 2.34
Non-Haematological cancer 4541 9.8
GI Bleeding 4538 9.79
•Upper GI Bleed 2192 4.73
•Lower GI Bleed 1255 2.71
•GI blood loss site unknown 1091 2.35
Renal Failure 2242 4.84
Critical care 1649 3.56
Non Haem Anaemia NOS 1338 2.89
Iron deficiency 1255 2.71
Total 24789 53.5

10. Section 4: Diagnosis of patients receiving RBC
transfusions
National
(N=4641)
Acute leukaemia (tick one of the options below) 22.0% 1023
Acute myeloid leukaemia excluding APML 18.6% 864
Acute promyelocytic leukaemia (APML) 0.6% 27
Acute lymphocytic leukaemia 2.5% 115
Other acute leukaemia 0.3% 17
Aplastic anaemia 4.3% 198
Chronic leukaemia (tick one of the options below) 6.8% 314
Chronic lymphocytic leukaemia (CLL) 4.8% 224
Chronic myeloid leukaemia (CML) 1.1% 52
Other chronic leukaemia 0.8% 38
Lymphoma (tick one of the options below) 14.8% 687
Burkitt’s lymphoma 0.3% 16
Diffuse large B cell lymphoma (DLBCL) 5.3% 238
Follicular lymphoma 1.6% 71
Hodgkin’s lymphoma (HL) 1.8% 83
Other lymphoma 5.9% 279
Myelodysplasia 28.5% 1323
Myelodysplastic/myeloproliferative neoplasms (includes CMML, JMML) 6.8% 314

11. Section 4: Indication for RBC
transfusion
National
(N=4328)
A. Symptomatic anaemia 47% 2048
 Mild (Chronic fatigue, loss of energy) 20% 844
 Moderate (Palpitations; Shortness of breath on exertion etc.) 22% 948
 Severe (Shortness of breath at rest; symptoms of ischaemic heart
disease, such as chest pain; hypotension or tachycardia unresponsive
to fluid resuscitation; cardiac failure)
4% 178
 Unspecified 2% 78
B. Hb level less than the local threshold 23% 1005
C. Chronic transfusion programme 26% 1114
D. Cannot determine reason for transfusion 3% 117
Not stated 1% 44
Please note: each participant had to tick one indication therefore it is
possible that were patients that had more than one reason to be transfused.
i. e a patient in a chronic transfusion programme that also had symptoms

12. Diagnosis of patients transfused as part of chronic transfusion
programme n=1114
National
(N=1114)
Acute leukaemia 10.1% 113
Aplastic anaemia 7.2% 80
Chronic leukaemia 4.5% 50
Lymphoma 5.5% 61
Myelodysplasia 50.3% 560
Myelodysplastic/myeloproliferative neoplasms (includes CMML, JMML) 10.5% 117
Myeloproliferative neoplasms including myelofibrosis 9.9% 110
Myeloma/Plasma cell dyscrasia 5.9% 66
Other 0.5% 6

13. NG24
• Consider alternatives for blood transfusion as follows:
• Do not offer erythropoietin to reduce the need for blood
transfusion in patients having surgery, unless:
– - the patient has anaemia and meets the criteria for blood
transfusion, but declines it because of religious beliefs or
other reasons or -the appropriate blood type is not available
because of the patient’s red cell antibodies.
• Offer oral iron before and after surgery to patients with iron-
deficiency anaemia.
• Consider intravenous iron before or after surgery for patients
who:
– have iron-deficiency anaemia and cannot tolerate or
absorb oral iron, or are unable to adhere to oral iron
treatment
– are diagnosed with functional iron deficiency
– are diagnosed with iron-deficiency anaemia, and the
interval between the diagnosis of anaemia and surgery is
predicted to be too short for oral iron to be effective
• For guidance on managing anaemia in patients with
chronic kidney disease, see the NICE guideline on anaemia
management in chronic kidney disease.
Does this apply to
haematology patietns?

14. NG 24
• Identify appropriate blood component /
product to be transfused

15. Give appropriate verbal and written information
to the patient and/or carer
• Provide verbal and written information to patients who may have or who have had
a transfusion, and their family members or carers (as appropriate), explaining:
– the reason for the transfusion
– the risks and benefits
– the transfusion process
– any transfusion needs specific to them
– any alternatives that are available,
– and how they might reduce their need for a transfusion
– that they are no longer eligible to donate blood - that they are encouraged to ask questions.
• Document discussions in the patient's notes.
• Provide the patient and their GP with copies of the discharge summary or other
written communication that explains:
– the details of any transfusions they had
– the reasons for the transfusion
– any adverse events
– that they are no longer eligible to donate blood.

16. Alternatives
• Epo
– Renal failure
– Chemotherapy induced anaemia
– MDS
• Treatment of underline condition
• Use of lenalidomide for 5q-
• Use of azacytidine
– Oral aza trial

17. Clinical indications for
red cell transfusion
• There are no universal triggers for red cell
transfusion
• Need for transfusion should be based on:
– Concentration of haemoglobin
– Symptoms
– Chronic anaemia
– Bleeding patients

18. Multicentre, Randomised, Controlled Clinical Trial
of Transfusion Requirement in Critical Care
Herbert et al (1999)
838 patients
Restrictive Strategy : Hb 7 - 9 g/dl
Liberal Strategy : Hb 10 - 12
g/dl
30 day mortality was similar in both
groups

19. A restrictive strategy of red cell
transfusion is at least as effective as,
and possibly superior to, a liberal
transfusion strategy in critically ill
patients.
Possible exceptions:
• Recent myocardial infarction
• Unstable angina

20. Red Blood cell transfusion: A clinical
Practice Guideline from AABB
• JAMA, 2016
• Lack of evidence for haematology patients
• Co-existing thrombocytopenia
– Contribution of anaemia to bleeding

21. NG 24:Red blood cells
recommendations
• Use restrictive red blood cell transfusion
thresholds for patients who need red blood
cell transfusions and who do not: -
– have major haemorrhage
– or have acute coronary syndrome
– or need regular blood transfusions for chronic
anaemia.

22. When using a restrictive red blood cell
transfusion threshold
• consider a threshold of 70 g/litre
• and a Hb target of 70-90 g/litre after transfusion.
• Consider a red blood cell transfusion threshold of
80 g/ litre and an Hb target of 80-100 g/litre after
transfusion for patients with acute coronary
syndrome.
• Consider setting individual thresholds and haemoglobin
concentration targets for each patient who needs regular
blood transfusions for chronic anaemia.

23. • Hb threshold 80 g/ litre is often used by
haematology units(Oxford, Cambridge)
• Individual assessment
• Symptoms of anaemia and bleeding

24. Guidelines on the management of anaemia and red
cell transfusion in adult critically ill patients
BJH 2013
• Recommendations
• The introduction of blood conservation sampling devices should
be considered to reduce phlebotomy-associated blood loss
• Paediatric blood sampling tubes should be considered for
reducing iatrogenic blood loss
• In the early resuscitation phase in patients with severe sepsis, if
there is clear evidence of inadequate DO 2 , transfusion of RBCs to
a target Hb of 90–100 g/l should be considered
• During the later stages of severe sepsis, a conservative approach
to transfusion should be followed with a target Hb of 70–90 g/l

25. Red cell trasnfusion: Doses
• Consider single-unit red blood cell transfusions
for adults (or equivalent volumes calculated
based on body weight for children or adults with
low body weight) who do not have active
bleeding.
• After each single-unit red blood cell transfusion
(or equivalent volumes, calculated based on body
weight, for children or adults with low body
weight), clinically reassess and check
haemoglobin levels, and give further transfusions
if needed

26. • Stable patients receiving intensive
chemotherapy for haematological
malignancies should be transfused with:
– One single RBC unit for pre-transfusion Hb
75<Hb<80g/L.
– Two RBC units for pre-transfusion Hb≤75g/L.
Practical recommendation
(CUH current recommendations)

27. • Monitor the patient's condition and vital signs
before, during and after blood transfusions, to
detect acute transfusion reactions that may need
immediate investigation and treatment.
• Observe patients who are having or have had a
blood transfusion in a suitable environment with
staff who are able to monitor and manage acute
reactions.

28. Optimal use of blood
Ann Intern Med. 2012 Jul 3;157(1):49-58..Red blood cell transfusion: a clinical practice
guideline from the AABB
Appropriate transfusion practice
Individual approach
• Massive blood loss
• One off transfusion
• Regular transfusions
– Congenital disorders
– Post chemotherapy
– Bone marrow failure
– Anaemia of chronic disease

29. Myelodysplastic syndromes
(MDS)
MDS
group of closely related clonal
hematopoietic disorders.
characterized by ineffective
haematopoiesis
manifested with peripheral blood
cytopenias.

30. Incidence
The American Journal of Medicine 2012 125, S2-S5DOI:
(10.1016/j.amjmed.2012.04.014)
Per 100.000 population
United States: 3.6
United Kingdom: 3.6
Germany: 4.1
Sweden: 3.6
France: 3.2
Japan: 1.0.
•36.3/100,000 in 80 and above age group
10,000 new cases of MDS each year
Median age at diagnosis= 76.5 years

31. Clinical presentation
Low and intermediate risk MDS (70%)
65%
anaemia
±mild thrombocytpenia
±mild neutropenia
57% Hb <100g/L
27% Hb <80g/L
Thrombocytopenia: <100.000x10^9L
Neutropenia: <1.500x10^9L
Symptoms
Chronic fatigue
Shortness of breath
Rarely bruising and bleeding, recurrent
infections
<5% present with
Isolated thrombocytopenia or
Isolated neutropenia

32. Alternatives to blood transfusion
for MDS patients
• EPO +/-GCSF
• Lenalidomide
• Azacitidine
– SC or Oral Aza trial
• Definitive treatment
– Transplantation
– Curative chemotherapy for selected patietns

33. EPO +G+CSF
?
Erythropoietin plus granulocyte colony-stimulating factor is
better than erythropoietin alone to treat anemia in
low-risk myelodysplastic syndromes: results from a
randomized single-centre study.
Balleari E, Rossi E, Clavio M et al
Ann Hematol. 2006 Mar;85(3):174-80.
rHuEPO vs rHuEPO+G-CSF
rHEPO 10,000 IU s.c. three times a week)
vs
rHEPO same dose + G-CSF 300 μcg s.c. twice a
week)
Duration: 8 weeks
Results
6/15 (40%) vs 11/15 (73.3%)
Addition of G-CSF produced responses to
50% of patients in the rHuEPO that did not
respond to erythropoietin alone

34. Duration of response in responding patients

35. Use of RBC units in MDS patients in UK
150.000-200.000 units RBC per year.

36. Triggers for transfusion
Most Centres in Europe use a threshold of
80-85g/L for patients with no cardiac or pulmonary comorbities
100g/L for patients with cardiac or pulmonary comorbities
Evidence
????
There are scarce studies on transfusion triggers in MDS
transfusion dependent patients.
Criteria from other chronic disorders with transfusion dependent
anaemia, particularly thalassaemia, have been adapted as
translated evidence

37. BCSH guidelines
• Br J Haematol. 2014 Feb;164(4):503-25.
• Guidelines for the diagnosis and management of adult
myelodysplastic syndromes. Killick S at AL.
– No specific transfusion trigger can be
recommended
• Br J Haematol. 2001, April;113(1):24-31
• Guidelines for the clinical use of red cell transfusions. Working
Party: M. F. Murphy T. B. Wallington
– Keep haemoglobin just above the lowest concentration that is not
associated with symptoms of anaemia (8g/dl)

38. • No single concentration of Hb can be recommended as
an optimal level below which transfusion should be given.
• The decision should be based on patient’s symptoms and
co-morbitities
Transfusion triggers should be determined in studies that will use
outcomes relevant to the objectives for transfusion in MDS

39. Health Related Quality of Life instruments
(HRQoL)

40. QoL assessment
How?
Evaluation of QoL in patients with MDS is
complex
• QoL instruments
simple or anemia specific?
sensitivity?
• Single vs multiple assessments
• Frequency of assessments
• Time points of assessment related to specific
treatments
• Recall period

41. EQ-5D
EQ-5D is primarily designed for self-completion by respondents
It is cognitively simple, taking only a few minutes to complete.
Instructions to respondents are included in the questionnaire
Does not include questions related to anaemia
Sensitivity?

43. REDDS study funded by NHSBT
A pilot, feasibility study comparison of two transfusion thresholds
• restrictive arm : threshold Hb <80g/L, target 85-100g/L
• liberal arm: threshold Hb <105g/L, target 100-120g/L
Secondary outcome measures
• QoL
• Rate of transfusion reactions
• Rate of alloimmunization
• Iron overlaod (ferritin)
• Amount of RBC transfused
HRQoL instruments
EQ-5D, outcome difference of 0.08 points
EORTC-QLQ-30 , outcome difference of 10 points
Enrolment started

44. NG24
• Offer tranexamic acid to adults undergoing surgery who are
expected to have at least moderate blood loss (greater than
500 ml)
• Consider tranexamic acid for children undergoing surgery
who are expected to have at least moderate blood loss
(greater than 10% blood volume).
• Do not routinely use cell salvage without tranexamic acid.
• Consider intra-operative cell salvage with tranexamic acid for
patients who are expected to lose a very high volume of blood
(for example in cardiac and complex vascular surgery, major
obstetric procedures, and pelvic reconstruction and scoliosis
surgery).

45. Chronically transfused patients
• Individual transfusion plan
– Documented in the notes
• Trigger
• Target
– Symptoms
– Quality of life-Activities
– Co-morbidities

47. A No-Prophylaxis Platelet-Transfusion Strategy for Hematologic Cancers
Simon J. Stanworth et al,2013

48. NG 24
Reducing risk for bleeding
• Offer tranexamic acid to adults undergoing surgery who are
expected to have at least moderate blood loss (greater than
500 ml)
• Consider tranexamic acid for children undergoing surgery
who are expected to have at least moderate blood loss
(greater than 10% blood volume).
• Do not routinely use cell salvage without tranexamic acid.
• Consider intra-operative cell salvage with tranexamic acid for
patients who are expected to lose a very high volume of blood
(for example in cardiac and complex vascular surgery, major
obstetric procedures, and pelvic reconstruction and scoliosis
surgery).

49. Tranexamic acid
• ITP
• Congenital bleeding disorders

50. TREATT
• Randomised control clinical trial of tranexamic
acid(oral or IV) versus placebo for AML
patients

51. Patients with thrombocytopenia who are
bleeding
• Offer platelet transfusions to patients with
thrombocytopenia who have clinically significant
bleeding (World Health Organization [WHO]
grade 2) and a platelet count below 30×109 per
litre.
• Use higher platelet thresholds (up to a maximum
of 100×109 per litre) for patients with
thrombocytopenia and either of the following:
• severe bleeding (WHO grades 3 and 4)
• bleeding in critical sites, such as the central
nervous system (including eyes).

52. Patients who are not bleeding or having
invasive procedures or surgery
• Offer prophylactic platelet transfusions to
patients with a platelet count below 10×109/L
who are not bleeding or having invasive
procedures or surgery, and who do not have any
of the following conditions:
• chronic bone marrow failure
• autoimmune thrombocytopenia
• heparin-induced thrombocytopenia
• thrombotic thrombocytopenic purpura.

53. Patients who are having invasive
procedures or surgery
• Consider prophylactic platelet transfusions to raise the platelet
count above 50×109 per litre in patients who are having invasive
procedures or surgery.
• Consider a higher threshold (for example 50–75×109 per litre) for
patients with a high risk of bleeding who are having invasive
procedures or surgery, after taking into account:
• the specific procedure the patient is having
• the cause of the thrombocytopenia
• whether the patient's platelet count is falling
• any coexisting causes of abnormal haemostasis.
• Consider prophylactic platelet transfusions to raise the platelet
count above 100×109 per litre in patients having surgery in critical
sites, such as the central nervous system (including the posterior
segment of the eyes).

54. When prophylactic platelet
transfusions are not indicated
• Do not routinely offer prophylactic platelet
transfusions to patients with any of the following:
• chronic bone marrow failure
• autoimmune thrombocytopenia
• heparin-induced thrombocytopenia
• thrombotic thrombocytopenic purpura.
• Do not offer prophylactic platelet transfusions to
patients having procedures with a low risk of bleeding,
such as adults having central venous cannulation or
any patients having bone marrow aspiration and
trephine biopsy.

55. • PICC line insertion, traction removal of all CVC’s, Bone marrow aspirate + Trephine, DIC if not
bleeding
– Not required
• Acquired platelet function disorder secondary to anti-platelet medications
– Not required
• Bone marrow failure due to disease, chemotherapy or irradiation keep
– PLT >10 x109 /L
• If additional risk factors(sepsis, treatment with ATG)
– PLT>20 x109 /L
• Insertion of CVC PLT>20 x109 /L
• Lumbar puncture, spinal anaesthesia PLT >40 x109 /L
• OGD, transbronchial biopsy, liver biopsy, laparotomy or other major surgery >50 x109 /L
Guidelines for the Use of Platelet Transfusions A British
Society for Haematology Guideline. 2016.

56.  OGD, transbronchial biopsy, liver biopsy, laparotomy or other major surgery
◦ PLT>50 x109 /L
 Inserting/removal epidural catheter PLT>80 x109 /L
 Neuro- or ophthalmic surgery PLT>100 x109 /L
 Adult Bleeding
 Non-severe PLT >30 x109 /L
 Severe or life-threatening PLT >50 x109 /L
 DIC PLT>75 x109 /L
 Multi-trauma,
 traumatic brain injury, spontaneous intracerebral haemorrhage
◦ PLT>100 x109 /L

57. Doses
Do not routinely transfuse more than a single dose
of platelets.
• Only consider giving more than a single dose of
platelets in a transfusion for patients with severe
thrombocytopenia and bleeding in a critical site,
such as the central nervous system (including
eyes).
• Reassess the patient's clinical condition and
check their platelet count after each platelet
transfusion, and give further doses if needed.

58. Fresh frozen plasma
• Thresholds and targets
• Only consider fresh frozen plasma transfusion for patients with
clinically significant bleeding but without major haemorrhage if
they have abnormal coagulation test results (for example,
prothrombin time ratio or activated partial thromboplastin time
ratio above 1.5).
• Do not offer fresh frozen plasma transfusions to correct abnormal
coagulation in patients who:
• are not bleeding (unless they are having invasive procedures or
surgery with a risk of clinically significant bleeding)
• need reversal of a vitamin K antagonist.
• Consider prophylactic fresh frozen plasma transfusions for patients
with abnormal coagulation who are having invasive procedures or
surgery with a risk of clinically significant bleeding.

59. Doses-FFP
Reassess the patient's clinical condition and repeat the
coagulation tests after fresh frozen plasma transfusion to
ensure that they are getting an adequate dose, and give
further doses if needed.

60. Cryprecipitate
• Dose:2 adult pools
• Source of fibrinogen

61. • Mobilised donors
– or
• October 2012 a pooled whole blood derived
component became available. “Granulocytes,
Pooled, Buffy Coat Derived, in Platelet
Additive Solution and Plasma, Irradiated”
Granulocytes

62. Therapeutic granulocyte transfusions may be indicated for patients
with severe neutropenia who fulfill all of the following criteria:
 Severe neutropenia, defined as ANC <0.5 x 109/L [WHO 1999] due
to congenital or acquired bone marrow failure syndromes.
 Receiving active treatment in an attempt to achieve disease
remission.
 Proven or highly probable fungal or bacterial infection that is
unresponsive to appropriate antimicrobial therapy as demonstrated
by visible spreading lesions on skin, mucosa or radiological
examination
 In whom neutrophil recovery is expected (ANC>0.5x109/l) in the
near future and / or in whom definitive therapy of curative
potential is planned.
CLINICAL INDICATIONS FOR GRANULOCYTE
TRANSFUSIONS

63. • Granulocytes are stored at 22+2ºC ideally
without agitation
• Granulocytes MUST be irradiated
• In view of the residual red cell and plasma
content, granulocyte preparations should
fulfill the compatibility requirements
• The product has a 24 hour expiry shelf-life
• Granulocytes should be transfused through a
standard red cell giving set. The whole dose
should be infused over 1-2 hours.

64. Special requirements
• 1. Irradiated cellular components
• 2. HEV negative: Updated SaBTO recommendation: universal
screening
– Transplant patients
– AML
CMV negative: no longer a requirement
– Please check CMV status at diagnosis for
appropriate donor selection
• 3. HLA matched components(PLT)
• 4. Washed

65. Current indication for usage of irradiated
blood components
• • Patients receiving transfusions from a first
degree relative (parent, child or sibling) or
second degree relative
• Patients receiving a granulocyte transfusion
• Patients receiving Human Leucocyte Antigen
(HLA) – selected components

66. • Patients receiving purine analogues (e.g.
fludarabine, cladrabine, deoxycoformicin:
probably safer to use them indefinitely.
• For newer purine analogues and related
drugs, such as bendamustine, irradiated
component must be offered until further data
become available
• Patients with Hodgkin Lymphoma, at any stage
of the disease (for life)

67. • Patients receiving allogeneic haemopoietic
stem cell (HSC) grafts, from the start of
conditioning therapy and while the patient
remains on Graft-versus-Host Disease (GvHD)
prophylaxis (usually six months post
transplant).
• If chronic GvHD is present or the patient is
taking immuno-suppressants, continue
irradiated blood components indefinitely

68. • Allogeneic HSC donors being transfused seven
days prior to or during he harvest of their HSC
• Patients who will have autologous HSC graft:
• – Any transfusion seven days prior to and
during the bone marrow/stem cell harvest
• – Any transfusion from the start of
conditioning chemo-radiotherapy until three
months post-transplant (six months in total
post TBI)

69. • Patients with aplastic anaemia receiving
immunosuppressive therapy with anti-
thymocyte globulin (ATG) and/or
alemtuzumab (anti-CD52