A registered clinical study investigating the effect of platelet activation status on transfusion outcomes was conducted at Vancouver General Hospital (VGH) from 2011 to 2014 under the guidance of Dr. Kate Chipperfield. This study enrolled 200 hematology-oncology patients with informed consent.
Recently, a retrospective analysis was conducted investigating the patients in that study who became refractory to platelets. An abstract describing the analysis, written by Dr. Elisabeth Maurer and reviewed by Dr. Chipperfield, has been accepted by the International Society of Hematology (ISH) for oral presentation. The post below gives an overview of the content in the abstract and provides supporting commentary. The abstract will be presented at the 2018 ISH meeting to be held in Vancouver, British Columbia, September 13th-16th.
Platelet refractoriness is defined as two consecutive platelet transfusions with 24-hr corrected count increments below 5x109/L. Up to 35% of hematology-oncology patients who depend on platelet transfusion support become refractory to platelets during their treatment. One possible cause of platelet refractoriness is alloimmunization, however, literature suggests this only accounts for 3-5% of patients. The term “non-immune” refractory is commonly used to describe cases where alloimmunization is not the cause of refractoriness. However, this term may be misleading as complement and other immunomodulatory factors likely play a major role in the removal of platelets. As this map depicts, there are many immunomodulatory factors associated with activated platelets.
The figure below is adapted from this guide on platelet refractoriness by the University of Michigan and shows platelet transfusion responses measured as Corrected Count Increments (CCIs) in the recipient over time. The intended response of a platelet transfusion is a substantial increase in CCI within 1 hour of transfusion and good survival of platelets for about two days, but this is only observed in 65-85% of patients (green curve). If the transfused platelets lead to a sufficient 1-hour CCI but do not survive until the next day patients are said to be “non-immune refractory”. This is observed in 10-30% of transfusion recipients (yellow curve). When there is insufficient recovery of transfused platelets this leads to inadequate 1-hr CCIs in 3-5% of transfusion recipients and they are said to be immune refractory due to alloimmunization (red curve). There are serious patient care and cost consequences to platelet refractoriness making it important to understand the causes of the largely untreated “non-immune” refractoriness segment.
Refractoriness in the Vancouver General Hospital Study
Of the 200 patients enrolled in the VGH study, 52 became refractory. Of the 52 refractory patients, only 3 received HLA matched platelets during the study implying a low alloimmunization rate. This means the remaining 49 were “non-immune” refractory patients. Although refractory patients represented only 26% of the study population, they were the driving force in platelet consumption receiving over 58% of the platelet transfusions. Refractory patients also received over 3 times the number of activated platelets compared to non-refractory patients.
The distribution of underlying diagnoses was consistent between the refractory and non-refractory patient populations. The sex distribution of refractory patients was nearly even, with 56% male patients and 46% female patients.
Incidents of WHO bleeding scores of 2 or higher were rare in this study, however, bleeding was more common for refractory patients with 5.3% of refractory patients recording a WHO bleeding score above 2 compared to only 2.2% of non-refractory patients. Furthermore, refractory patients’ average body temperature was 0.5°C higher, their average length of stay was 42% longer and the end of study survival rate was 10% lower than non-refractory patients.
Conclusions from the Retrospective Analysis
Based on this retrospective analysis alloimmunization, bleeding, gender and underlying diagnosis were not major factors associated with platelet refractoriness. However, elevated body temperature and the activation status of the platelets received were associated with platelet refractoriness. It has long been thought that fever can cause poor platelet response, perhaps it is possible that activated platelets contribute to a febrile response and subsequent transfusion failures due to the immunomodulatory factors associated with activated platelets. Further investigation is needed to determine the precise relationship between these factors.