Evaluation of the provision of fresh compatible platelets for haematology patients who have become refractory to random platelet transfusions

The demand for platelet donations has increased due to a rise in the incidence and intensity of treatment for haematological malignancies and an aging population (Estcourt et al., 2016). Although platelet transfusions are vital to the ongoing management of patients with haematological malignancies, many patients become refractory to platelet transfusion. Refractoriness is defined as having a poor response (immediate or 24 hour increment post platelet transfusion of <10 x 109/L) to random donor platelets on two or more occasions. Refractoriness can occur due to immune (antibody-mediated) and non-immune mechanisms, yet when samples are tested for the presence of platelet antibodies, only a small proportion are positive, indicating that other mechanisms are responsible for the platelet destruction. Platelet crossmatching can be used to select compatible units for refractory patients, but un-like for red cell transfusions, platelet cross-matching is not performed routinely. The proposed research aims to determine whether use of platelet crossmatching for haematology patients who have become refractory to random platelet transfusions would improve outcome. Haematology patients with confirmed platelet refractoriness will be recruited into the study. Up to 35% of haematology patients who depend on platelet transfusion support become refractory to platelets during their treatment (Millar, 2018), yet, alloimmunisation only accounts for 3-5% of these patients (Slichter, 1998). The term non-immune has been used to include other causes of refractoriness, which can be mis-leading as complement could play a major role in platelet destruction. This study will look at measuring complement as a marker of platelet destruction in the absence of detectable platelet antibodies. If antibodies are suspected to be the cause, these patient samples will be sent to Bristol NHSBT for HLA/HPA antibody testing and provision of matched platelets if antibodies are detected. If HLA/HPA antibodies are not detected, random donor platelets will continue to be given as per protocol. In these cases retrospective crossmatch of platelet concentrates will be done to determine whether the random donor units issued to these patients were compatible or incompatible, and what the effects of the transfusion were on the following biological parameters: PLT count, complement protein levels (C1 and C3) and IgG sensitization of platelets. These parameters will be analyzed in blood samples taken from patients at 1 hour and 24 hours post platelet transfusion using flow cytometry. The platelet donations will also be tested daily for PLT count, complement protein levels (C1 and C3) and IgG sensitization of platelets to see if the length of platelet storage could affect subsequent platelet destruction in the patient and to see what happens to these markers as the platelets are stored up to their expiry date. Taken together the results will provide an indication of whether immune platelet destruction is occurring in the absence of detectable antibodies due to complement activation in the pre-transfusion platelet donation or in the patient. This study could provide a true prospective assessment of the ability of providing crossmatched platelet units to reduce the incidence of platelet refractoriness in the haematological setting. It could also determine whether giving crossmatched fresh platelets enables a better recovery due to a possible contributory factor involved in giving platelets that are already expressing markers of complement destruction. This research will be conducted for approximately 18 months which would equate to at least 50 patients with multiple transfusion events.

Outputs

Still doing the research so abstract is not complete – only the introduction included