Issues With Transfusion-Dependent Conditions Flashcards
Who are transfusion-dependent patients?
Patients who require frequent and long-term transfusion support to sustain life
Examples:
– A condition of severe anemia typically arising when erythropoiesis
is reduced
– Person continuously requiring RBC-transfusions over a specified
interval
Defining a person as RBC-transfusion-dependent has important implications in diverse hematological disorders especially because it is strongly-correlated with decreased survival
What is alloimmunisation?
Allogeneic blood transfusion is a form of temporary transplantation
Introduces a multitude of foreign antigens into the recipient that persist for variable times
Immuno-competent recipient often mounts an immune response to the donor antigens
Various clinical consequences, depending on the blood cells and specific antigens involved
The more donors a patient is exposed to during the course of treatment, the greater the risk of alloimmunisation:
– More likely they are to produce antibodies to other red cell
antigens (or HLAs, HPAs etc.)
– Production of antibodies against red cell antigens such as Kell,
Kidd, Duffy etc. can have detrimental effects at the next
transfusion
– This makes the provision of blood units for these patients hard
What are problems with Alloimmunisation to RBCs?
Recognition of foreign donor antigen by recipient antibodies
Binding of recipient antibodies to donor RBCs
Full immune response targeted towards donor RBCs - lysis
Severity of the reaction depends on the antigen/antibodies involved
Outcome: pointless transfusion as Hb levels have not been increased – in some cases, the anaemia may have been exacerbated – in some cases extreme reaction
What are problems with Alloimmunisation to platelets?
Antibody production to HLAs or HPAs can result in refractoriness to platelet transfusion (immediately produce antibodies to destroy them)
Seen as a significantly lower increase in platelet count after transfusion than was expected
Post-transfusion purpura
- thrombocytopenia after platelet transfusion, associated with
presence of platelet alloantibodies
What are problems with Alloimmunisation to granulocytes?
People whose BM is suppressed by chemotherapy are at risk of infection. They can be given prophylactic antibodies, but in severe disease e.g. severe leukaemia, the patient will need repeated granulocyte transfusions to build up WBC count.
Antibody production against granulocytes
– granulocyte-specific (HNAs)
– HLA antigens
Can result in refractoriness to granulocyte transfusion
– Febrile non-haemolytic transfusion reactions
– Transfusion-related acute lung injury (i.e. a transfusion reaction in
which donor HLA antibodies react against recipient antigens)
What is the pathophysiology of alloimmunisation?
Prior to Leukodepletion, alloimmunisation caused:
- Presentation of donor antigens by donor APCs to recipient T cells
- Recognition of the MHC class II alloantigens by CD4+ recipient T cells (T helper cells)
- Subsequent activation of the Th cells via co-stimulatory signals
from donor APCs - Studies show that since leukodepletion, and hence removal of donor
APCs, there has been a dramatic reduction in incidence of
alloimmunisation, 20% of patients still develop alloimmunisation
- as this isn’t the only mechanism
What is the pathophysiology of platelet refractoriness?
Presence of HLA antigens on the platelet surface is the most common cause of platelet refractoriness
Other non-HLA antigens present on the platelet surface (e.g. platelet-specific antigens, HPA) are also involved in a number of cases (≈ 20%)
Patients not previously sensitised develop anti-platelet antibodies approximately 3-4 weeks after the transfusion
Patients previously immunised by previous transfusion, produce high levels of the specific antibody as early as 4 days after transfusion
Macrophages in the liver, spleen, and other tissues destroy antibody-coated platelets
Risk factors for developing anti-platelet antibodies include:
– Presence of more than 1 million donor leukocytes in transfused
products (leukodepletion overcomes this)
– transfusing ABO-mismatched platelets
– Presence of an intact immune system (ie, absence of cytotoxic or
immunosuppressive therapy)
– Female sex (approximately 75% of cases)
- Pregnancy increases likelihood of mother being allocompromised
due to fetal haemorrhage
– History of multiple transfusions (>20)
How is RBC alloimmunisation minimised?
Multi-transfused patients are likely to be exposed to many allogeneic RBC antigens (due to diversity of RBC antigenic make-up among different individuals)
Exposure to foreign RBC antigens is more likely when there are racial differences between the blood donor population and the recipients
This is particularly important in the treatment of Thalassaemia and SCD as patients are receiving blood from European Caucasian donors
- diagnosed early in life and require regular transfusions
Approx. 30% of transfusion dependant patients are reported to develop RBC antibodies
Most antibodies that develop post-transfusion are within the Rh and Kell systems
It has been observed that patients who do not develop Rh and Kell antibodies are less likely to develop other antibodies
Once Rh/K antibodies develop, they are more likely to form other RBC antibodies resulting in multiple antibodies
It is therefore recommended to provide phenotyped RBC units that are K compatible and also matched for the Rh antigens D, C, E, c and e, to prevent primary immunisation to these antigens
- All transfusion-dependent patients should have RBC
phenotyping prior to initiating the transfusion regime
- Matching for antigens other than D, C, E, c, e and K, provides
no added benefit
What other problems are associated with repeat transfusions?
Iron Overload:
– May be due to the disease itself (Thalassaemias) or due to
regular RBC transfusions
- Each unit of RBCs contains approx. 250mg of iron
- Iron excretion very limited – once iron stored become fully
saturated, free iron builds up and becomes toxic
- This is usually seen after 10-50 units of RBCs have been
transfused
Build-up of iron deposits:
– Potentially fatal without iron chelation
– Can lead to diabetes mellitus, hypothyroidism, cardiac complications
and can be fatal
Infection - immunosupression
Bone deformities – due to expansion of the marrow
Enlarged spleen - due to task of removing abnormal RBCs – may reduce life-span of transfused RBCs
When should RBCs be transfused?
Patient symptoms (fatigue, activity level) are the most important factor determining the need for transfusion
Some people can tolerate anaemia well, tolerance is affected particularly by respiratory function
In these cases transfusion may not be required and the risks of alloimmunisation and TTIs can be avoided
The Hb level is monitored closely
Why are regular blood transfusions essential for people with thalassaemia, and what are the risks?
Transfusion-dependent Thalassaemics receive blood transfusions from a very early age
Regular blood transfusions are administered every 2-5 weeks
Maintain pre-transfusion Hb levels at 90-105g/L
– Promote normal growth
– Allow normal activity
– Adequately suppress BM activity (trying to overcompensate)
Iron toxicity can become a problem at a very early age
Life-long chelation treatment from 2-3yrs age – 5 x per week subcutaneously
If patients respond well to iron chelation therapy, they have 90% chance of suriving to 4th decade
If response is poor, high mortality rates at 30-40 years of age
What are component requirements for RBCs?
For all transfusion-dependent patients, the red cell units selected should be less than 2 weeks old to ensure maximum possible survival in the patient’s circulation
– if not possible freshest, available suitable units may be transfused
Minimise necessary transfusions by transferring units with the greatest volume of red cells
- higher haematocrit levels
What are component requirements for platelets?
Alloimmunisation is best managed by use of platelet crossmatching – detects significant HLAs/HPAs
Directed donations from blood relatives is another strategy that helps find compatible products
Severe refractoriness that is unresponsive to HLA-matched or crossmatch-compatible platelets is often an insurmountable clinical problem
High-dose intravenous immunoglobulins (IV IG), plasma exchange, splenectomy (antibody binding to RBCs without lysis as complement must be fixed, instead the spleen and it removes them - removing spleen prevents this break down), and continuous platelet infusions have occasionally been tried but their effectiveness has not been proven in controlled clinical trials
