Bone marrow failure due to disease, cytotoxic therapy or irradiation
This section covers the use of platelet (Table 12) and red cell transfusion in situations where thrombocytopenia and anaemia commonly occur due both to the underlying disease and the effects of treatments including chemotherapy, radiation and antibiotics and antifungal drugs.
Table 12 Platelet transfusion in patients with bone marrow failure
Threshold or target platelet count
Clinical trials suggest that the threshold for prophylactic platelet transfusion in stable, uninfected patients can safely be lowered from 20 x 109/l.
Prophylactic platelet transfusion threshold 10 x 109/l.
Acute promyelocytic leukaemia
Coagulopathy may increase the risk of haemorrhage at any given platelet count.
Platelet count should be kept above 20 x 109/l if patient haemorrhagic.
Haemopoietic stem cell transplantationin acute leukaemia
Mucosal injury is more likely with transplantation than with chemotherapy alone, but studies indicate that the threshold for platelet transfusion can be lowered to 10 x 109/l.
Duration of thrombocytopenia shorter with PBSC transplant than with BMT.
Prophylactic platelet transfusion threshold 10 x 109/l.
Chronic stable thrombocytopenia
Patients with chronic and sustained failure of platelet production (for example, some patients with myelodysplasia or aplastic anaemia) may remain free of serious haemorrhage, with platelet counts consistently below 10 x 109/l or even below 5 x 109/l.
Long-term prophylactic platelet transfusions increase the risk of alloimmunisation with platelet refractoriness and other complications of transfusion.
In a patient who is otherwise stable, platelet transfusions should be restricted to treating haemorrhage.
During unstable periods associated with infection or active treatment, prophylactic platelet transfusions may be needed to prevent recurrent bleeding.
Note on thresholds for platelet transfusion:
As a general guide, for this group of patients, a threshold platelet count of 10 x 109/l appears to be as safe as a higher level, for patients without additional risk factors. A threshold of 20 x 109/l should be observed in patients with risk factors such as sepsis, concurrent use of antibiotics or other abnormalities of haemostasis.
Patients with chronic stable thrombocytopenia are best managed on an individual basis depending on the degree of haemorrhage.
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Patients with chronic stable thrombocytopenia are best managed on an individual basis depending on the degree of haemorrhage.(PMID16351634)(PMID15495093)
ABO and RhD compatibility of platelet transfusions
ABO incompatibility can reduce the expected platelet count increment (CI) by 10−30%.
If it is necessary to give RhD positive cellular blood components to a female with childbearing potential, anti RhD immunoglobulin should be given to avoid the risk of the patient developing RhD antibodies (see Potentially sensitising events). The dose of anti RhD immunoglobulin is 125 iμ per ml of red cells transfused.
Refractoriness is defined as a repeated failure to achieve a satisfactory increment after two or more platelet transfusions. The platelet count the morning after transfusion should be raised by at least 20 x 109/l. If the increase is persistently less than 20 x 109/l this suggests refractoriness. Non-immune causes include infection, fever, splenomegaly, DIC and treatment with antifungals such as amphotericin or antibiotics such as ciprofloxacin. Immune causes are anti-HLA or anti-platelet antibodies, e.g. anti-HPA1a.
Management of refractoriness
It is important to identify refractoriness due to HLA or anti-platelet antibodies as compatible platelet transfusions may be more effective. Poor responses to HLA-matched platelets could also be due to ABO antibodies or to unrecognised non-immune causes. Further guidance on diagnosis and management is available in British Committee for Standards in Haematology (BCSH) guidelines.
Red cell transfusion
The local clinical management protocol should define the range within which a patient's haemoglobin should be maintained. A suggested arbitrary guide is to maintain Hb at not less than 9.00 g/l.
Prevention of transfusion-associated graft-versus-host disease (TA-GvHD)
Transfused donor lymphocytes which are compatible with the recipient, but which recognise the recipient as foreign, can engraft and initiate TA-GvHD. Patients develop skin rash, diarrhoea and abnormal liver function, and deteriorate, with bone marrow failure and death from infection usually within two to three weeks of transfusion. TA-GvHD can be prevented by gamma irradiating (25 Gy dose) the blood components to be transfused. This inactivates the donor lymphocytes. Leucocyte depletion cannot be considered to remove risk of TA-GvHD. Patients requiring irradiated blood should be given an information leaflet and card available from blood centres, informing them about their need for irradiated blood and the fact that they should make clinical staff aware of this (see Table 14).
Table 13 Transfusion support in stem cell transplant patients with donor/recipient ABO incompatibility
In a patient who has received an ABO-incompatible stem cell transplant, the transplant may express a new A and/or B antigen from the donor (major mismatch) or a new A and/or B antibody from the donor (minor mismatch)
Blood components for transfusion should be according to the following guidance
Plasma and platelets
Major ABO mismatch
Use red cells of the recipient’s ABO type until recipient ABO antibodies are undetectable and the DAT is negative
Use plasma (and platelets) of the recipient’s ABO type
Minor ABO mismatch
Use red cells of the donor ABO type throughout
Use plasma and platelets of the recipient type until recipient-type red cells are no longer detectable
Major plus minor ABO mismatch
Use group O red cells until recipient ABO antibodies are undetectable and then change to red cells of the donor’s type
Use group AB plasma and platelets until recipient-type red cells are undetectable
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Prevention of cytomegalovirus transmission
Cytomegalovirus (CMV) infection can cause serious morbidity in immunocompromised CMV-negative patients. The risk can be minimised by the use of CMV-antibody-negative (seronegative) blood components. Leucocyte depletion also confers some protection since the virus is associated with white blood cells. A consensus conference in 2001 concluded that components that are both CMV-seronegative and leucodepleted should be used for CMV-seronegative pregnant women, intrauterine transfusions, and CMV-seronegative-allogeneic stem cell transplant recipients. Some studies, however, suggest that effective leucodepletion may confer as much protection as the use of CMV-negative components.
Indications for the use of CMV-antibody-negative and gamma-irradiated cellular blood components
CMV-antibody-negative pregnant women
CMV-antibody-negative recipients of allogeneic stem cell grafts
Intrauterine transfusions (IUT)
Patients with HIV disease
Transfusions from first- or second-degree relatives
Any granulocyte transfusion for any recipient
HLA-selected platelet units
Patients receiving purine analogues (fludarabine, cladribine, deoxycoformycin): probably safer to use indefinitely
Intrauterine transfusion (IUT)
Exchange transfusion (provided that irradiation does not unduly delay transfusion)
Red cell or platelet transfusion in neonates − only if there has been a previous IUT or if blood is from first− or second−degree relative
All recipients of allogeneic haemopoietic stem cell (HSC) grafts, from start of conditioning therapy and while patient remains on GvHD prophylaxis
Blood transfused to allogeneic HSC donors before or during the harvest of their HSC
Patients who will have autologous HSC graft:
- any transfusion within 7 days of the collection of their HSC
- any transfusion from the start of conditioning therapy until:
- 3 months post transplant
- 6 months post transplant if conditioning TBI has been given
Hodgkin’s disease, at all stages of the disease
Congenital immunodeficiency with defective cell-mediated immunity (e.g. SCID, Di George syndrome, Wiskott Aldrich syndrome, purine nucleoside deficiency, reticular dysgenesis, ADA, Ataxia telangectasia, chronic mucosal candidiasis, MHC class 1 or 2 deficiency)
¹ Red cells, platelets and granulocyte components must be irradiated for all at-risk patients. It is not necessary to irradiate fresh frozen plasma, cryoprecipitate, cryosupernatant or plasma derivatives.
² It is not necessary to irradiate components for patients with solid tumours, organ transplants, HIV or aplastic anaemia.
³ As new cytotoxic and immunosuppressive agents, including monoclonal antibodies, are introduced, these guidelines will be updated.
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