Human platelet concentrates (PCs) stored in plasma in blood banks are life-saving transfusion products to manage bleeding in various clinical settings [1]. Platelet aggregation along with activated coagulation factors (CFs) and a few other proteins present in plasma participate in a cascade of events that ultimately facilitate hemostasis and eventual clotting of blood, coagulation at the site of vascular injury [2]. This sequential activation of CFs (Fig. 1), coupled with positive feedback loops is a highly regulated process, where upon dysfunction can result in suboptimal performance of both platelets and plasma CFs [3].

In order to protect the critical hemostasis functions of PCs and CFs, it is imperative that any treatments performed during PC manufacturing, prior to storage for transfusion, should be gentle to both platelets and plasma. While treatment of blood components with existing chemical and UV light-based pathogen reduction technologies (PRTs) effectively inactivate pathogens, these PRTs are also known to cause measurable, but somewhat tolerable, impediments to both platelets and plasma CFs [4]. Consequently, while the transfusion medicine field recognizes the benefits of PRTs, it acknowledges a measurable reduction in quality of cellular and protein components following PRT treatment [5]. Thus, there is a need for improving PRTs by identification and evaluation of better approaches while being cognizant of the fact that there will be a measurable reduction in the quality of cell and protein components following a PRT treatment [5]. Therefore, improvements to PRT refer to identifying and choosing a technology that demonstrates the least effect on the product by maintaining product quality.

Within this context, there has been a surge of research initiated by our group and others in evaluating alternatives to UV light-based technologies, such as 405 nm violet-blue light of the visible spectrum that does not require use of chemicals or photosensitizers [6,7]. We have previously demonstrated that a 405 nm light dose of up to 270 J/cm2 is effective in reducing (by inactivation) several bacteria, HIV-1, and parasites in plasma alone or in platelets suspended in plasma [8,9]. Further, we have shown that microbicidal 405 nm light does not affect the recovery and survival of the light-treated platelets in a SCID mouse model [10], demonstrating the safety of the treatment for ex vivo platelets. In another study, we evaluated the effect of 405 nm light on the integrity of plasma proteins, higher doses of 405 nm light up to <720 J/cm2 did not impart any visible changes to plasma protein integrity based on SDS-PAGE analysis [11]. This report implies that the 405 nm light dose of 270 J/cm2 that has been used for pathogen inactivation in our studies is well below the threshold light dose (720 J/cm2) at which plasma protein integrity is affected. However, to date, experimental verification of the impact of 270 J/cm2 dose of 405 nm light on functions of individual CFs and global hemostasis potential of PCs is lacking.

In this report, we evaluated the impact of 405 nm light on global hemostasis potential of PCs and the coagulation profile of several individual CFs of platelet poor plasma obtained from PC treated with 405 nm light (denoted as PPP-1) and platelet poor plasma treated directly with 405 nm light (denoted as PPP-2), by using three well established in vitro standard assays (i) activated partial thromboplastin time (aPTT) -based potency assay and (ii) prothrombin time (PT) -based potency assay, as well as (iii) thromboelastography (TEG) for global hemostasis potential of PCs. The results demonstrated that global hemostasis potential of PCs was retained and has a milder effect on coagulation protein activity following treatment with 270 J/cm2 dose of 405 nm violet-blue light.