None listed
Conditions
Brief summary
Chronically transfused patients receive multiple units of blood products over the course of their treatment. Multiple red blood cell (RBC) unit transfusions may lead to adverse transfusion related outcomes including the production of antibodies directed against RBC surface markers (antigens), haemolytic diseases and potential long-term donor cell survival, which is termed ‘microchimerism’. Patients requiring transfusion are routinely typed for ABO and Rh (D) blood group antigens via serological methods since these antigens are immunogenic and its incompatibility with donor RBCs can lead to severe and fatal transfusion outcomes. Patients are also screened for the presence of clinically significant RBC antibodies that are either immunoglobulin (Ig) G or IgM isotypes. Antibodies against RBC antigens are either alloantibodies that are formed in response to foreign RBC antigens acquired during transfusion and pregnancy, or autoantibodies that are directed against an individual’s own RBC antigens observed in patients with haemolytic anaemias and autoimmune disorders. Haemolytic anaemia is a condition where circulating immunoglobulins and/or complement bind to the surface of RBCs leading to their destruction. Direct antiglobulin testing (DAT) is used in clinical investigations to confirm and diagnose the cause of haemolytic anaemia. It detects the presence of IgG or various activated complement components attached to RBC surface membrane when haemolysis or haemolytic anaemia is present. In patients diagnosed with haemolytic anaemia, a ‘pan-reactive’ autoantibody (antibodies indiscriminately reacting with all RBCs) coupled with a positive DAT result can cause difficulty in pre-transfusion testing, since the patient’s serum reacts to multiple donor RBC units. Furthermore, a strongly positive auto agglutinin may mask the presence of concurrent alloantibodies if present. The detection of patient alloantibodies via the auto- and allo- adsorption procedures are prolonged, labour intensive, complex and can often have no clear result. In these situations, a least incompatible but best matched donor RBC unit against the patient’s known phenotype becomes the only option available for transfusion. This project will determine whether the use of RBC genotyping can be a useful integration into routine laboratory transfusion practice in Australia. Information on the patient’s blood group genotype can be used to predict the patient’s blood group phenotype and allow clinical staff managing chronically transfused patients to provide more appropriately matched donor RBC units. The ability to closely match a donor RBC unit to the patient could also prevent several rounds of manual serological laboratory investigations and reduce the risk of alloimmunisation in patients requiring long-term chronic transfusion regimes.
Interventions
The Australian Red Cross Blood Service is supporting the study to evaluate the benefits of blood group genotyping in chronically transfused patient as a part of a routine transfusion laboratory protocol since this patient group is at greater risk of RBC antigen alloimmunisation. Since these patients form antibodies to red blood cell antigens this can cause laboratory staff to perform laborious and time consuming serological investigations. Performing red blood cell genotyping on these patients will enable better matching of donor units to patients which will potentially reduce the number of transfusions needed by the patient overall and should reduce the number of antibodies they form. To test this theory transfusion data and allo -antibody rates patients who are not receiving closely matched red blood cells units will used. To perform the genotyping, a single research blood sample will be obtained from a newly diagnosed haematology patient who is transfusion naive (or before their next transfusion if they are not transfusion naive but have only had up to 3 transfusions in the last 12 months). This blood sample will be taken at the same time as baseline samples are taken for standard of care requirements and will be 3mL in volume (1 teaspoon). Genomic DNA will be purified and blood group genotyping will be performed on the Australian Red Cross Blood Service HEA bead chip platform. No other blood samples will be used for the genotyping platform. Genotyping results will be provided to the researchers who can advise transfusion staff of which donor unit will be most suitable to transfuse into each patient. Hospital based transfusion laboratory staff will use this information to choose the most suitable unit prior to every transfusion received by that patient during the study period. The most suitable donor unit will be chosen on the closest available phenotype predicted by the genotype results. Donor units are phenotyped to at least 5 of the 39 red blood cell group systems. The decision to choose a unit will depend on how many blood systems each unit has had phenotyped and issued to that particular hospital. In some cases hospital transfusion laboratories can request certain phenotype units to be issued to them for a particular patient. This may be the case if patients are found to require more rare blood types. All other information for this project on the rate of allo-antibody formation rates will be determined from the serum samples collected under routine hospital sample collections before each blood transfusion. The hospital laboratories will perform their own investigations on the serum from the patient to determine if antibodies have formed. This information will be provided to researchers via medical record data and will be used to compare with patients who had no genotyping performed prior to their blood transfusion. The data collection will be performed for each patient for up to 24 months and will vary depending on their individual treatment regimes.
Sponsors
Study design
Eligibility
Inclusion criteria
Male and female patients over 18-80 years of age. Patients with a haematological condition who require chronic RBC transfusions - it is hoped that as many patients as possible are transfusion naive for this study. where this is not possible patients who have had up to 3 blood transfusions within the last 12 months may also be recruited for analysis.
Exclusion criteria
Minors under the age of 18 years patients over 80 years of age Mentally impaired or individuals in dependent relationships who are not sound of mind to consent to participate in this study