The impact of bilirubin ditaurate on platelet quality during storage

Abstract

Bilirubin ditaurate (BRT), a conjugated bilirubin analogue, has demonstrated anti-platelet characteristics following acute ex vivo exposure. Scavenging of mitochondrial superoxide and attenuation of granule exocytosis suggested a potential benefit for including BRT for storage. With no reports of cytotoxicity following acute exposure, the impact of 35µM BRT on platelet function was investigated, in clinically suppled units, for up to seven days. Exposure to 35µM BRT significantly reduced mitochondrial membrane potential and increased glucose consumption until exhaustion after 72 hours. Platelet aggregation and activation was significantly impaired by BRT. Mitochondrial superoxide production and phosphatidylserine expression were significantly elevated following glucose exhaustion, with decreased viability observed from day five onwards. Lactate accumulation and loss of bicarbonate, support a metabolic disturbance, leading to a decline of quality following BRT inclusion. Although acute ex vivo BRT exposure reported potentially beneficial effects, translation from acute to chronic exposure failed to combat declining platelet function during storage. BRT exposure resulted in perturbations of platelet quality, with the utility of BRT during storage therefore limited. However, these are the first data of prolonged platelet exposure to analogues of conjugated bilirubin and may improve our understanding of platelet function in the context of conjugated hyperbilirubinemia.

Keywords:

• Antioxidants
• blood platelets
• conjugated bilirubin
• platelet storage lesion
• reactive oxygen species

Acknowledgments

The authors thank Dr Jelena Vider MD for her assistance. The authors would also like to thank the Australian Red Cross Blood Service for kindly providing the platelet products. The Australian governments fund the Australian Red Cross Blood Service to provide blood, blood products, and services to the Australian community. This work was supported by internal funding provided from the Health Group, Griffith University. The Australian Red Cross Blood Service did not provide any fiscal or other incentive for this research to be undertaken.

Declaration of Interests

All authors declare no conflicts of interest.

Supplementary material

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Additional information

Funding

This work was supported by the Griffith University [School of Medical Science - Internal Funding].