Improving platelet transfusion safety: biomedical and technical considerations

Abstract

Platelet concentrates account for near 10% of all labile blood components but are responsible for more than 25% of the reported adverse events. Besides factors related to patients themselves, who may be particularly at risk of side effects because of their underlying illness, there are aspects of platelet collection and storage that predispose to adverse events. Platelets for transfusion are strongly activated by collection through disposal equipment, which can stress the cells, and by preservation at 22 °C with rotation or rocking, which likewise leads to platelet activation, perhaps more so than storage at 4 °C. Lastly, platelets constitutively possess a very large number of bioactive components that may elicit pro-inflammatory reactions when infused into a patient. This review aims to describe approaches that may be crucial to minimising side effects while optimising safety and quality. We suggest that platelet transfusion is complex, in part because of the complexity of the "material" itself: platelets are highly versatile cells and the transfusion process adds a myriad of variables that present many challenges for preserving basal platelet function and preventing dysfunctional activation of the platelets. The review also presents information showing--after years of exhaustive haemovigilance--that whole blood buffy coat pooled platelet components are extremely safe compared to the gold standard (i.e. apheresis platelet components), both in terms of acquired infections and of immunological/inflammatory hazards.

Figure 1

Platelet components are far from being standardised, manufactured medicines, as there are several million distinct products throughout the world. Shown in cartoon form here are some of the major possibilities for obtaining PC by two major processes: WB-derived-PC and SDA-PC (platelet-rich plasma is not featured here). Numbers in parentheses indicate the major choices: for example, we considered here that, with regards to WB-derived-PC (buffy-coat pools), there are three main brands of bags, three main brands of agitation devices for whole blood collection, etc. (these are probably largely underestimated but deduced from the French market). Here some more details. * It is considered that there are three external temperatures that may influence the quality of blood: extreme heat, extreme cold, and standard medium. ** Time for transportation from the collection site to the processing site has been limited to three scenarios: short distance, medium distance and long distance. *** Leucoreduction has been considered to require any of three major commercially available kits (∘ same for centrifugation with 3 main centrifuge types, and extraction with 3 main extraction machines, while there are basically 2 systems for pooling buffy-coats automatically). ∘∘∘ Regarding inventory, we estimated that each day from 1 to 5 (thus excluding day 0) represents a factor of variability of the final PC). # Not precisely defined factors, probably related to the Blood Establishment, which may, at some point, affect the quality and characteristics of the final component (this multiplication by a factor of 2 is largely speculative, but likely). ⋄Estimated number of commercially available PAS. ⋄⋄As the male policy only (or female testing for anti-HLA antibodies of significant titres and clinical relevance) is applied or not, this has been attributed 2 (Yes or No). ⋄⋄⋄The numbers for PRT are as follows: 1) no PRT; 2) amotosalen-treatment; 3) riboflavin-treatment; 4) future or possible UVC-treatment. Of note, the steps applying to both WB-derived PC and SDA-PC are shown within the box. PC: platelet concentrate; WB: whole blood; SDA-PC: single donor apheresis PC; PRT: pathogen reduction technology.

Figure 2

The various steps that contribute to the containment and/or the reduction of infectious risk associated with blood donation to make a safe platelet concentrate. The process begins with donor recruitment and education to self-deferral. It continues with the compilation of a donor questionnaire, which is reviewed by a medical health worker (a physician in several countries) and completed by a medical interview, in which the donor should be able to ask all relevant questions and receive adequate explanations on the reason for his/her eventual deferral. Importantly, this step can be used to sensitise candidate donors to report post-donation hazardous events, allowing blood/blood components to be discarded or quarantined if necessary. The establishment of a computer-assisted, extensive post-donation information system strengthens global donor and recipient safety in transfusion medicine. At the end of this interview, the health worker makes a decision on:

1. Eligibility, temporary or permanent deferral;

2. Type of donation (WB or apheresis), type and volume of components to be collected;

3. Eventual volume of compensation fluids;

4. Need for additional tests [for both immunological [immunisation to blood cell Ags] and infectious risks].

In this sequence, steps 1) and 4) are particularly relevant to prevent transmission of any infectious pathogens from donor to recipient. Avoidance of blood component-related infection continues with the strict application of procedures during the collection process: hand-washing, skin disinfection, no-touch procedure for the puncture, protection of the needle, etc. The use of a satellite pouch, allowing the diversion of the first 30–40 mL of blood in a side bag used for testing purposes, washes out donor skin bacteria that have escaped disinfection. The efficacy of this measure in terms of bacterial contamination has been proven; as the bacterial risk is greater in PC transfusion, this step appears crucial for SDA-PC in particular, but is also valuable for WB donations from which platelets are separated to make pools, though some phagocytosis can occur before the leucocytes that eliminate bacteria are removed,. Finally, platelet donations undergo biological testing according to the rules applied to all other blood components. Tests performed on donors have been standardised among countries, and global polices have been proposed, for example by the Council of Europe. Most tests are standard and universally applied; some remain optional, such as nucleic acid testing for conventional or emerging viruses, or are linked to potential donor exposure, such as testing for transfusion-transmissible protozoa (Plasmodium spp., Babesia spp., Trypanosoma cruzi–121). Interestingly, although the former two protozoa are barely considered issues in PC transfusion, Trypanosoma transmission has rarely if ever been associated with RBC transfusions, but has been well-documented in the case of PC transfusion. In countries in which no effective PRT is applied to PC, a policy to detectTrypanosoma infection in exposed donors should be considered. Given that quarantine is not feasible for PC, in the case of virus outbreak and epidemics, Blood Establishments in affected regions may be forced to set up additional testing, usually based on nucleic acid amplification testing, to detect carriers (for example, dengue virus, West Nile virus or Chikungunya virus), if no effective PRT has been introduced. WB: whole blood; Ags: antigens; PC: platelet concentrate; SDA-PC: single donor apheresis PC; RBC: red blood cell; PRT: pathogen reduction technology