Regional
How Canadian Blood Services provide specialized blood products to highly refractory platelet transfusion patients
Akash Gupta
Medical Director of the CBS National Platelet Immunohematology Reference Lab and a Transfusion Medicine Specialist at Sunnybrook Health Sciences, Canada
Platelet Refractoriness
Platelet refractoriness is a challenging complication in transfusion dependent patients. Refractoriness is a concern as there is a risk of life-threatening bleeding when the platelet count drops below 10x109/L.
The effectiveness of platelet transfusions are typically evaluated by the post-transfusion increment. This can be measured via:
· Corrected Count Increment (CCI)
· Percentage of platelet recovery
· Post-transfusion platelet count
The CCI utilizes a formula (Figure 1) which takes into account the platelets within the transfused unit and the body surface area of the recipient. The percentage of platelet recovery is calculated based on the platelet count increment, the recipient’s total blood volume, and the number of platelets transfused. The post-transfusion platelet count is the simplest and most commonly used technique, where the recipient’s platelet count after transfusion is compared to the pre-transfusion value.
Figure 1: CCI formula
The majority of patients have non-immune causes for refractoriness, which include bleeding, thrombosis, infection, and certain medications. Immune causes for platelet refractoriness include anti-HLA class 1 antibodies and anti-HPA antibodies.
Platelets express class 1 Human Leukocyte Antigens (HLA). Class 1 HLA includes HLA-A, HLA-B, and HLA-C. HLA-C are not well expressed on the platelet surface and therefore are not regarded as a significant contributing factor for HLA-mediated refractoriness. HLA antibodies are typically formed due to exposure to foreign antigens, such as previous pregnancy, transfusion, or transplant. The implementation of universal leukoreduction of blood products in Canada has led to a 50% reduction in HLA alloimmunization.
Platelets also express Human Platelet Antigens (HPA). Similar to HLA, exposure for foreign HPA antigens can lead to sensitization and alloantibody formation.
Testing
The detection of HLA antibodies is performed with a Luminex based assay that tests the recipient’s plasma against a series of beads with pre-defined HLA antigens on them. Using the positive reactions, the specificity of the HLA antibodies present can be determined and used to get the calculated panel reactive antibody percentage (cPRA).
HPA antibodies are detected using either the PakPlus kit, which is an ELISA based method, or the PakLx kit, which is a Luminex based assay. Antibodies detected by either of these two methods are then confirmed by MAIPA (Monoclonal antibody specific immobilization of platelet antigen).
Donor Selection
In Canada, all apheresis platelet donors are typed for HLA class 1 and HPA-1. A subset of donors will also get a full HPA genotypes. Patients who have a cPRA of >20% are eligible to be enrolled in the matched platelet program. Based on the patient’s HLA type and HLA class 1 antibodies detected, the platelet donor database is queried for possible matches. The top choice includes donors who have the same HLA type as the patient, however with the increasing diversity in our country, this is not always possible. The second round of options is looking donors who express antigens that the patient has not made antibodies against (partially matched or HLA-permissive).
This process begins with a request for special products from the hospital. This request must be accompanied by test results that demonstrate the elevated cPRA. Canadian Blood Services will then enter those results into a donor search tool named the Platelet Donor Selection (PDS). The donor list that is produced lists all of the apheresis platelet donors who have donated in the past 5 years who would be suitable for this patient and their date and type of last donation. In our experience, donors who last donated more than 2 years ago are unlikely to be re-recruited. The donor list is screened to look for any donations that have been collected in the last 2 days, as those products are likely still held at our production facility and can be tagged and re-directed to the hospital within the next day.
The list is then filtered by location to look for donors within the same jurisdiction as the requesting hospital. Local collections can be transported to the hospital in a timelier manner. Finally, depending on the cPRA, the list is expanded to include all possible donor matches. Depending on where the donor is located, these products can take 3-4 days to reach the requesting hospital after the donation has been made.
The vast majority of patients who develop transfusion depending thrombocytopenia and subsequent immune-refractoriness are being treated for a hematologic malignancy. The expected duration of thrombocytopenia is well defined based on the type of treatment that the patient is receiving. The request for special products form asks the hospital to outline their anticipated needs (eg. 3 platelets per week for 4 weeks), which allows CBS to recruit donors in advance and provide patients with selected platelets throughout their period of thrombocytopenia.
References
- For further information, please refer to Chapter 18 of the CBS Clinical Guide to Transfusion: https://professionaleducation.blood.ca/en/transfusion/clinical-guide/platelet-transfusion-alloimmunization-and-management-platelet
