Photochemical Treatment Platelet Research Articles

Prevention of Transfusion-Associated Graft Versus Host Disease (TA-GVHD) by Photochemical Treatment of Platelet Components: Clinical Experience in Routine Use.

Background: In 2003 the Blood Transfusion Center, Cliniques Universitaires Mont Godinne, Yvoir, Belgium implemented routine use of pathogen inactivation photochemical treatment (PCT) of platelet (PLT) components (INTERCEPT™ Blood System, Cerus Europe, Leusden, The Netherlands) for transfusion support of thrombocytopenia. Based on in vitro clonal T cell proliferation assays (> 5 log T cell inactivation), biochemical assays (1 adduct every 83 base pairs), animal studies (prevention of GVHD in a parent to F-1 model), and clinical trial experience (Bone Marrow Transplantation 2004; 33: 1–7), PCT of PLT was used in place of gamma irradiation to inactivate residual donor T cells for prevention of TA-GVHD. Other blood components continued to be treated with gamma irradiation according to standard operating procedures. Surveillance of all patients at risk for TA-GVHD transfused with PCT PLT was conducted for 3 years (11/2003 – 11/2006) after adoption of PCT, and the incidence of TA-GVHD determined.Methods: PLT were collected on the Amicus Cell Separator (Fenwal Blood Technologies, Nivelles, Belgium) with process leuko-reduction. PLT were suspended in Intersol (Fenwal) with a ratio to plasma of ∼ 65:35%. PLT containing 2.5 to 6.0 × 1011 plts in ∼ 300 mL were prepared with an integrated processing set using amotosalen (150 uM) and UVA (3 J/cm2) to inactivate pathogens and leukocytes. PCT PLT units were issued the day after collection and stored for up to 7 d. Hematopoietic stem cell transplant (HSCT) patients were selected as a high risk population for TA-GVHD, and monitored for evidence of TA-GVHD with an active hemovigilance program. TA-GVHD was diagnosed using established criteria (N Engl J Med 1990; 323:315–21).Results: During 3 years, 756 patients received 7,538 PCT PLT transfusions and 76 patients with a spectrum of hematologic diseases (Table) were treated with HSCT (n = 93: 75 auto- and 18 allo-grafts) and were supported with PCT PLT. 15 patients received 2 auto grafts, and one received 3. All HSCT patients were deemed at risk for TA-GVHD due to immune suppressive and/or myelo-ablative therapy including TBI (n = 19). Auto graft patients (n = 59) received a median of 7 PCT PLT (range 2–94). Allo graft patients (n = 17) received a median of 11 PCT PLT (range 3 – 127). No patient developed evidence of TA-GVHD during the 3-year period.Conclusions: PCT of PLT prevented TA-GVHD in a population of HSCT patients at risk for TA-GVHD exposed to multiple platelet transfusions. Use of PCT to treat all PLT components avoided the need to identify at risk patients and permitted the use of a single PLT inventory. These clinical data support the use of PCT for replacement of gamma irradiation to prevent TA-GVHD.Diagnoses of HSCT Patients At Risk For TA-GVHDDiagnosis/Year2003200420052006Total%Myeloma27972532.9NH Lymphoma26872330.2Acute Leukemia22441215.8Hodgkins031045.3Myelofibrosis030145.3Myelodysplasia010125.3Solid Tumor011022.6CLL011022.6CML010011.3Waldenstrom's010011.3

Effect of extending the platelet storage time on platelet utilization: predictions from a mathematical model of prophylactic platelet support

Bacterial culturing (BCU) or photochemical treatment (PCT) of platelet (PLT) concentrates may permit extending the storage time to 7 days at the cost of decreased viability of transfused PLTs. This study was aimed at predicting the impact this may have on the routine management of patients on prophylactic PLT support. The method included a mathematical model that represents the dynamics of prophylactic PLT support with standard, BCU or PCT PLTs. Data on posttransfusion PLT kinetics and the effect of PCT or storage time on PLT recovery and survival were obtained from published studies. Variables that influenced the level of PLT usage were the proportion of transfusions supplied with PLT on the last day of shelf-life, the use of PCT and the assumed degree of synergy between clinical factors of PLT consumption and either PCT or storage time. In the reference-case scenario, extending the PLT shelf-life to 7 days by BCU or PCT increased by 9 and 19%, respectively, the number of PLT transfusions per patient-year. In the worst-case scenario, these figures rose to 27 and 38%, respectively. Despite more intensive PLT usage, in most scenarios, the time that patients spent at PLT counts <10 x 10(9) L(-1) increased. Extending the shelf-life of PLT products will increase PLT usage. Such increase may be disproportionately larger for patients with complex conditions if there is a synergic interaction between storage time or PCT and clinical factors of PLT consumption, an issue that is worth further clinical research.

Leukoreduced buffy coat–derived platelet concentrates photochemically treated with amotosalen HCl and ultraviolet A light stored up to 7 days: assessment of hemostatic function under flow conditions

Amotosalen plus ultraviolet A light photochemical treatment (PCT) inactivates high titers of bacteria, and other pathogens, in platelet concentrates (PCs) potentially allowing the storage of platelets (PLTs) for up to 7 days. Adhesion and aggregation of PLTs to injured vascular surfaces are critical aspects of PLT hemostatic function. Two ABO-identical leukoreduced buffy coat-derived PCs in additive solution were mixed and divided: one-half underwent PCT (PCT-PCs) and the other was kept as a control (C-PCs); both were stored under standard conditions. The total number of paired PCs studied was nine. Samples were taken on Day 1 (before PCT) and after 5 and 7 days of storage. The adhesion and aggregation capacities were evaluated under flow conditions in a ex vivo perfusion model. Compared to control, PCT resulted in a decrease in PLT count of 6.5 percent (p = 0.004) and 10.2 percent (p = 0.008) after 5 and 7 days' storage, respectively (n = 9). PLT interaction with subendothelium was mainly in form of adhesion. The surface covered by PCT PLTs on Day 1 was 26.0 +/- 4.2 percent (mean +/- SEM). On Day 5, PCT-PCs showed a covered surface of 20.9 +/- 2.2 percent, and the C-PCs, 20.6 +/- 1.6 percent. After 7 days, PCT-PCs produced a nonsignificant higher PLT deposition compared to control (27.1 +/- 2.9% vs. 21.2 +/- 2.8%, p = 0.06). PCT of PCs and storage up to 7 days was associated with a 10.2 percent decrease in PLT count due to processing losses compared to C-PC. PLT adhesive and aggregating capacities under flow conditions of PCT-PCs were similar to C-PCs and remained well preserved for up to 7 days of storage.

In vitro evaluation of metabolic changes and residual platelet responsiveness in photochemical treated and gamma‐irradiated single‐donor platelet concentrates during long‐term storage

Photochemical treatment (PCT) prevents replication of pathogens in platelet concentrates (PCs) by cross-linking nucleic acids and thus affects all cells containing DNA or RNA. Fourteen double-dose single-donor PCs were divided into two study arms. The double-dose PCs were split in two identical units, PCT and conventional control PCs. Study Arm A consisted of seven PCT PCs with corresponding untreated controls, whereas Study Arm B consisted of seven PCT PCs with corresponding gamma-irradiated control. Metabolic changes and agonist-induced platelet (PLT) response were evaluated during storage for up to 12 days. Higher rate of PLT destruction, illustrated by reduced PLT content, increased lactate dehydrogenase levels, and higher CD61+ microparticle formation rate, were observed after PCT. Generally PCT accelerated metabolic changes in PCs and reduced agonist-induced (collagen or thrombin receptor activator peptide [TRAP]) aggregation responses. Flow cytometric analysis of CD62P and CD42b (GPIbalpha) expression showed higher spontaneous PLT activation in PCT PCs from 5 days of storage. Correspondingly, a reduced capacity for up regulation of CD62P expression and down regulation of CD42b was observed in PCT PLTs after stimulation by the agonists ADP or TRAP. Generally reduced in vitro PLT quality was observed after PCT during storage for up to 12 days, with marked reduction from 5 days of storage. Compared to conventional PCs, reduced agonist-induced aggregation and glycoprotein expression were observed after PCT during storage, corresponding to significantly higher level of spontaneous PLT activation in PCT PCs. Clinical studies of efficacy and safety of PCT PCs stored for more than 5 days are recommended.

Release of Immune Modulation Factors from Platelet Concentrates during Storage after Photochemical Pathogen Inactivation.

Background. Platelets (plt) prepared for transfusion contain multiple molecules that modulate immune function, mediate acute transfusion reactions, induce immune responses, and affect hemostasis. These cytokines/chemokines are secreted differentially from plt during storage (Transfusion 2006; 46:1184), and may be affected by processing, including pathogen inactivation.Aims. The INTERCEPT Blood System (IBS) for platelets utilizes amotosalen-HCl (S-59) with ultraviolet A (UVA) light to inactivate a broad spectrum of pathogens and leukocytes. This study was designed to evaluate the effects of photochemical treatment on in vitro release of immune modulation molecules after processing during 7 days (d) of storage.Methods. Platelet concentrates (n = 10) collected by aphaeresis (CPA) with process leuko-reduction (< 106) containing 8.15x1011 ± 0.8 platelets were suspended in 35% donor plasma and 65% platelet additive solution (Intersol, Baxter, France) and divided into two equal components. One served as an untreated control (C) and the other was prepared with 150 uM amotosalen and a 3 J/cm2 UVA photochemical treatment (PCT) and stored at 22°C with shaking for 7 days. Platelet concentration (106/uL), pH and levels of immune modulation factors were measured: CD62p(ng/mL), PDGF-AB(ng/mL), IL8(pg/mL), sCD40L(pg/mL), IL1β(pg/mL) and TNFα(pg/mL). The concentration of each factor was determined by specific enzyme linked immunosorbent assays in plt and supernatant (s) fractions isolated from stored PCT and C plt components. Mean values ± SD were calculated and compared by paired t-test.Results. Platelet content, pH and cytokine/chemokine content and release from CPA prepared with photochemical treatment were not statistically different (p > 0.05) from C during 7 d of storage (Table). From d1 to d7, the pH of PCT and C units decreased similarly, but remained within acceptable ranges. No detectable IL1β and TNFα were observed in PCT or C CPA. During platelet storage CD62p, PDGF-AB, IL8, and sCD40L increased similarly in supernatants of PCT and C units. The increase in supernatant levels correlated with a decrease of these cytokines in plt. Platelets in PCT and C retained measurable levels of CD62, IL8, sCD40L and PDGF-AB though 7 d. Levels of sCD40L demonstrated marked variation.Conclusions. Cytokines increased moderately in the supernatants of CPA and decreased in platelets during storage. After 7 d C and PCT platelets in CPA retained detectable levels of cytokines. PCT had no differential influence on release of immune modulation molecules in vitro over 7 d of storage.DayOO5577ProductCPCTCPCTCPCTpH7.1 ±.17.1 ±.16.9 ±.16.8 ±.16.9 ±.16.8 ±.1Plt ct1.29 ±.31.30 ±.21.30 ±.31.19 ±.21.27 ±.21.18 ±.2CD62p-s89 ± 2187 ± 17110 ± 23115 ± 27117 ± 22119 ± 25CD62p-plt149 ± 33151 ± 33141 ± 23141 ± 25139 ± 25139 ± 26PDGF-s14.5 ± 3.513.6 ± 3.517.7 ± 2.415.8 ± 1.518.0 ± 2.117.5 ± 1.8PDGF-plt28.3 ± 3.530.3 ± 3.125.2 ± 3.624.9 ± 2.523.2 ± 4.023.3 ± 3.3IL8-s107 ± 17108 ± 14136 ± 42116 ± 9123 ± 20120 ± 22IL8-plt135 ± 29134 ± 28110 ± 11117 ± 12103 ± 17119 ± 32CD40L-s51 ± 8666 ± 94172 ± 157237 ± 214188 ± 198201 ± 167CD40L-plt990 ± 8051098 ± 747485 ± 373474 ± 331346 ± 293314 ± 282

Platelets photochemically treated with amotosalen HCl and ultraviolet A light correct prolonged bleeding times in patients with thrombocytopenia

Photochemical treatment (PCT) with amotosalen HCl with ultraviolet A illumination inactivates pathogens and white blood cells in platelet (PLT) concentrates. In a Phase II crossover study, 32 patients with thrombocytopenia received one transfusion of PCT and/or one transfusion of untreated (reference) apheresis PLTs. Hemostatic efficacy was assessed with the cutaneous template bleeding time and clinical observations. Paired bleeding time data for PCT and reference transfusions were available for 10 patients. Mean pretransfusion bleeding times were 29.2 +/- 1.6 minutes in the PCT group and 28.7 +/- 2.5 minutes in the reference group. After transfusion of a dose of PLTs of at least 6.0 x 10(11), mean 1-hour posttransfusion template bleeding times corrected to 19.3 +/- 9.5 minutes in the PCT group and 14.3 +/- 6.5 minutes in the reference group (p = 0.25). In 29 patients receiving paired PCT and reference transfusions, mean 1-hour posttransfusion PLT count increments were 41.9 x 10(9) +/- 20.8 x 10(9) and 52.3 x 10(9) +/- 18.3 x 10(9) per L for PCT and reference, respectively (p = 0.007), and mean 1-hour posttransfusion PLT corrected count increments (CCIs) were 10.4 x 10(3) +/- 4.9 x 10(3) and 13.6 x 10(3) +/- 4.3 x 10(3) for PCT and reference, respectively (p < 0.001). The time to next PLT transfusion was 2.9 +/- 1.2 days after PCT transfusions versus 3.4 +/- 1.3 days after reference transfusions (p = 0.18). Clinical hemostasis was not significantly different after PCT and reference transfusions. PCT PLTs provided correction of prolonged bleeding times and transfusion intervals not significantly different than reference PLTs despite significantly lower PLT count increments and CCIs.

Pathogen inactivation of platelets with a photochemical treatment with amotosalen HCl and ultraviolet light: process used in the SPRINT trial

A photochemical treatment (PCT) system has been developed to inactivate a broad spectrum of pathogens and white blood cells in platelet (PLT) products. The system comprises PLT additive solution (PAS III), amotosalen HCl, a compound adsorption device (CAD), a microprocessor-controlled ultraviolet A light source, and a commercially assembled system of interconnected plastic containers. A clinical prototype of the PCT system was used in a large, randomized, controlled, double-blind, Phase III clinical trial (SPRINT) that compared the efficacy and safety of PCT apheresis PLTs to untreated apheresis PLTs. The ability of multiple users was assessed in a blood center setting to perform the PCT and meet target process specifications. Each parameter was evaluated for 2237 to 2855 PCT PLT products. PCT requirements with respect to mean PLT dose, volume, and plasma content were met. Transfused PCT PLT products contained a mean of 3.6 x 10(11) +/- 0.7 x 10(11) PLTs. The clinical process, which included trial-specific samples, resulted in a mean PLT loss of 0.8 x 10(11) +/- 0.6 x 10(11) PLTs per product. CAD treatment effectively reduced the amotosalen concentration from a mean of 31.9 +/- 5.3 micromol per L after illumination to a mean of 0.41 +/- 0.56 micromol per L after CAD. In general, there was little variation between sites for any parameter. The PCT process was successfully implemented by 12 blood centers in the United States to produce PCT PLTs used in a prospective, randomized trial where therapeutic efficacy of PCT PLTs was demonstrated. Process control was achieved under blood bank operating conditions.

Transfusion of 7‐day‐old amotosalen photochemically treated buffy‐coat platelets to patients with thrombocytopenia: a pilot study

Photochemical treatment (PCT) of platelets (PLTs) with amotosalen and ultraviolet A light to inactivate bacteria may facilitate extension of storage from 5 to 7 days. A randomized, double-blinded, crossover, noninferiority, single-site pilot study utilizing pooled buffy-coat PLTs was conducted. The primary endpoint was the 1-hour corrected count increment (CCI) after one transfusion each of 7-day-old PCT and reference (R) PLT components. Secondary endpoints included 1-hour count increment, time to next transfusion, hemostasis, transfusion reactions, and serious adverse events. Twenty patients with thrombocytopenia were randomly assigned: 9 to the PCT-R sequence and 11 to the R-PCT sequence. A significant treatment-by-period interaction was observed. Therefore, the first period only was also analyzed for the primary endpoint. Including both treatment periods, mean 1-hour CCI was 6587 +/- 4531 for PCT versus 8935 +/- 5478 for R-PLTs. For the first period only, mean 1-hour CCI was 8739 +/- 3785 for PCT versus 7433 +/- 5408 for R-PLTs. The upper bound of the one-sided 95 percent confidence interval of 2400 for the mean difference was higher than the specified noninferiority margin of 2200 for both analyses. Overall median time to next transfusion was 22 hours for PCT versus 27 hours for R-PLTs. Hemostasis was adequate and no transfusion reactions or serious adverse events were reported. Although this pilot study of a limited number of patients failed to show noninferiority within the specified noninferiority margin, 7-day-old PCT PLTs showed acceptable efficacy and safety for support of thrombocytopenia. The results, however, warrant evaluation in a larger trial of 7-day-old PCT PLTs.

Clinical safety of platelets photochemically treated with amotosalen HCl and ultraviolet A light for pathogen inactivation: the SPRINT trial

A photochemical treatment (PCT) method utilizing a novel psoralen, amotosalen HCl, with ultraviolet A illumination has been developed to inactivate viruses, bacteria, protozoa, and white blood cells in platelet (PLT) concentrates. A randomized, controlled, double-blind, Phase III trial (SPRINT) evaluated hemostatic efficacy and safety of PCT apheresis PLTs compared to untreated conventional (control) apheresis PLTs in 645 thrombocytopenic oncology patients requiring PLT transfusion support. Hemostatic equivalency was demonstrated. The proportion of patients with Grade 2 bleeding was not inferior for PCT PLTs. To further assess the safety of PCT PLTs, the adverse event (AE) profile of PCT PLTs transfused in the SPRINT trial is reported. Safety assessments included transfusion reactions, AEs, and deaths in patients treated with PCT or control PLTs in the SPRINT trial. A total of 4719 study PLT transfusions were given (2678 PCT and 2041 control). Transfusion reactions were significantly fewer following transfusion of PCT than control PLTs (3.0% vs. 4.1%; p = 0.02). Overall AEs (99.7% PCT vs. 98.2% control), Grade 3 or 4 AEs (79% PCT vs. 79% control), thrombotic AEs (3.8% PCT vs. 3.7% control), and deaths (3.5% PCT vs. 5.2% control) were comparable between treatment groups. Minor hemorrhagic AEs (petechiae [39% PCT vs. 29% control; p < 0.01] and fecal occult blood [33% PCT vs. 25% control; p = 0.03]) and skin rashes (56% PCT vs. 42% control; p < 0.001) were significantly more frequent in the PCT group. The overall safety profile of PCT PLTs was comparable to untreated PLTs.

Amotosalen interactions with platelet and plasma components: absence of neoantigen formation after photochemical treatment

The INTERCEPT Blood System (Baxter Healthcare Corp., and Cerus Corp.) is a photochemical treatment (PCT) process that uses amotosalen (S-59) and ultraviolet A (UVA) illumination to inactivate a broad spectrum of pathogens. To evaluate the potential of the process to create neoantigens, the amounts of residual amotosalen and photoproducts present in PCT platelets (PLTs) and PCT plasma were quantified. The initial amount of amotosalen was 150 micromol per L. After illumination with 3 J per cm2 UVA and before transfusion, a compound adsorption device was used to substantially reduce the amounts of free amotosalen and unreactive photodegradation products. Patient serum samples from Phase III clinical trials were assayed by enzyme-linked immunosorbent assay (ELISA) for antibodies to potential amotosalen neoantigens. After PCT, 15 percent of the starting amount of amotosalen remains bound to PLTs, and 15 to 22 percent remains bound to plasma components. The majority of bound amotosalen is associated with lipid. Less than 1 percent of PLT-bound amotosalen and approximately 2 percent of plasma-bound amotosalen can be extracted into the water-soluble protein fraction. In seven Phase III clinical trials, 523 patients received more than 8000 units of PCT PLTs or PCT plasma. None of the patients exhibited clinical or laboratory manifestations of neoantigenicity. Furthermore, no other alteration of PLT membrane proteins was identified based on testing for lymphocytotoxic antibodies and PLT-specific alloantibodies. These results indicate that no neoantigens were detected by ELISA after PCT, suggesting that transfusion of PCT PLTs or PCT plasma does not induce adverse immunologic responses.

Recovery and life span of 111indium‐radiolabeled platelets treated with pathogen inactivation with amotosalen HCl (S‐59) and ultraviolet A light

A photochemical treatment (PCT) method to inactivate pathogens in platelet concentrates has been developed. The system uses a psoralen, amotosalen HCl, coupled with ultraviolet A (UVA) illumination. Three sequential clinical trials evaluated viability of PCT platelets prepared with a prototype device. Posttransfusion recovery and lifespan of (111)Indium-labeled autologous 5 day-old platelets in healthy subjects was assessed. In the first study, 23 subjects received transfusions of autologous PCT and/or control platelets. In a second study, 16 of these subjects received PCT platelets processed with a Compound Adsorption Device (CAD) (PCT-CAD) to reduce patient exposure to residual amotosalen. In the third study, the effect of gamma-irradiation on PCT platelets was studied. Data from control transfusions from Study A were used for paired comparisons in the latter 2 studies. Mean PCT-CAD platelet recovery for the 16 subjects with paired data was 42.5 +/- 8.7% versus 50.3 +/- 7.7% for control platelets, mean difference of 7.8% (p < 0.01). Mean lifespan for PCT-CAD platelets was 4.8 days (+/-1.3) versus 6.0 days (+/-1.2) for control platelets, mean difference of 1.3 days (p < 0.01). Platelet recovery and lifespan were similar to PCT-CAD for PCT without CAD treatment and PCT-CAD with gamma-irradiation. Viability of 5 day-old PCT platelets was less than for control platelets. However, both were within ranges reported for 5 day-old platelets.

Transfusion of pooled buffy coat platelet components prepared with photochemical pathogen inactivation treatment: the euroSPRITE trial

A nucleic acid-targeted photochemical treatment (PCT) using amotosalen HCl (S-59) and ultraviolet A (UVA) light was developed to inactivate viruses, bacteria, protozoa, and leukocytes in platelet components. We conducted a controlled, randomized, double-blinded trial in thrombocytopenic patients requiring repeated platelet transfusions for up to 56 days of support to evaluate the therapeutic efficacy and safety of platelet components prepared with the buffy coat method using this pathogen inactivation process. A total of 103 patients received one or more transfusions of either PCT test (311 transfusions) or conventional reference (256 transfusions) pooled, leukoreduced platelet components stored for up to 5 days before transfusion. More than 50% of the PCT platelet components were stored for 4 to 5 days prior to transfusion. The mean 1-hour corrected count increment for up to the first 8 test and reference transfusions was not statistically significantly different between treatment groups (13,100 +/- 5400 vs 14,900 +/- 6200, P =.11). By longitudinal regression analysis for all transfusions, equal doses of test and reference components did not differ significantly with respect to the 1-hour (95% confidence interval [CI], -3.1 to 6.1 x 10(9)/L, P =.53) and 24-hour (95% CI, -1.3 to 6.5 x 10(9)/L, P =.19) posttransfusion platelet count. Platelet transfusion dose, pretransfusion storage duration, and patient size were significant covariates (P <.001) for posttransfusion platelet counts. Clinical hemostasis, hemorrhagic adverse events, and overall adverse events were not different between the treatment groups. Platelet components prepared with PCT offer the potential to further improve the safety of platelet transfusion using technology compatible with current methods to prepare buffy coat platelet components.

Functional Characteristics of S-59 Photochemically Treated Platelet Concentrates Derived from Buffy Coats

Background: A photochemical treatment (PCT) process for inactivation of infectious pathogens and leukocytes has been developed and evaluated using single-donor platelet concentrates. This study assessed the application of PCT to platelets prepared from pooled buffy coats. In this study, in vitro functional characteristics of PCT platelets were compared to control platelets prepared from pooled buffy coats using the approved platelet-additive solution T-Sol^®. Platelets in platelet PAS III additive solution without PCT were evaluated as well. PCT also included the use of a psoralen (S-59) reduction device (SRD). Materials and Methods: Four types of platelet concentrates were compared: (1) platelet concentrate in plasma/T-Sol; (2) platelet concentrate in plasma/PAS III; (3) platelet concentrate in plasma/PAS III, PCT, 9 h SRD and (4) platelet concentrate in plasma/PAS III, PCT, 16 h SRD. PCT occurred on the day after whole-blood collection. In vitro assay parameters included: pH, pO₂, pCO₂, HCO^–₃, platelet count, mean platelet volume, plasma glucose, plasma lactate, total ATP, expression of p-selectin, hypotonic shock response and electron microscopy. Results: The results indicate that PCT is compatible with platelet concentrates prepared from pooled buffy coats for up to 7 days of storage. Conclusion: The PCT process resulted in acceptable in vitro platelet functional characteristics and is currently in clinical trials to evaluate the haemostatic efficacy of PCT platelets in thrombocytopenic patients requiring multiple platelet transfusions.