Clinical impact of Amotosalen and UV-A treatment (INTERCEPT™ Blood System) for platelet concentrate preparation in cardiac surgery

Abstract

Background

Ensuring transfusion safety remains a major challenge. Pathogen-reduction technologies (PRT), such as the INTERCEPT™ Blood System (IBS), use amotosalen (a psoralen) as intercalating agent in nucleic acids and ultraviolet A (UV-A) light to block pathogen replication, reducing the risk of transfusion-transmitted infections. While IBS is approved for platelet concentrate (PC) treatment, its clinical impact on platelet function remains debated. In November 2017, IBS was implemented across all French blood banks (Établissement Français du Sang, EFS) for PCs.

Materials and methods

We conducted a retrospective “before-after” study to evaluate the impact of PRT on platelet transfusion and clinical bleeding in cardiac surgery. The pre-PRT period was from January 2016 to June 2017, and the post-PRT period from January 2018 to June 2019. The study included adult patients who received PCs during or within two days after cardiac surgery in two teaching hospitals (Nancy and Reims). Patients with heart transplantation or requiring mechanical circulatory support were excluded.

Results

A total of 357 (Nancy) and 314 (Reims) patients were included, with no changes in anticoagulation, antiplatelet therapy, or surgical procedures. Platelet transfusion amount significantly decreased post-PRT (from 0.64 [0.54–0.81] to 0.57 [0.49–0.75] ×10¹¹/10 kg; p<0.01), while transfusion of other blood products remained unchanged. Postoperative outcomes, including mediastinal drainage, reoperation for bleeding, ICU stay, and overall hospital stay, were also unchanged.

Discussion

The implementation of PRT using IBS did not impair the hemostatic properties of transfused platelets during cardiac surgery. Platelet and other blood product use, as well as clinical outcomes, were similar before and after PRT introduction. IBS-treated PCs are thus comparable to standard PCs in managing bleeding in cardiac surgery.

INTRODUCTION

The safety of blood transfusion was greatly improved since the 1990s with blood donor selection and biological testing. Nevertheless, all infectious agents cannot be detected (lack of tests for emerging pathogens like Chikungunya, Tick-borne encephalitis, Zika or more recently SARS-CoV-2). In epidemic context, safety of blood products is unknown, and blood products inventories might be destroyed to prevent transmission. A solution is to “inactivate” pathogens to “reduce” the load of pathogens by preventing their proliferation and inducing apoptosis. Pathogen reduction technology (PRT) can be achieved by a combination of an intercalating agent, amotosalen (a psoralen), and ultraviolet light A (UV-A) lighting to create irreversible covalent linking between amotosalen and nucleic acids, thus preventing DNA/RNA replication by polymerases, including residual nucleated cells after leukocyte reduction. This PRT (INTERCEPT™ Blood System [IBS], Cerus Corporation, Concord, CA, USA) is licensed for platelet concentrates (PCs) and fresh frozen plasmas (FFPs) and is available for clinical use in many countries, including the U.S. Innocuity and microbiological efficacy of this technology have been proven to reduce transfusion-transmitted disease^1–6 but also to prevent hypersensitivity reactions or the need for irradiation of blood products for transplanted patients, especially stem cells and bone marrow grafts for hematologic malignancies. IBS was efficient to prevent T cell activation and prevent transfusion-associated graft versus host disease^6–9. Moreover, platelet functions seemed to be preserved in some fundamental in vitro studies^10–14 when others evidenced a modification of intracellular proteins and signalling pathways¹⁵ or membrane proteins expression (lower CD42b, no effect on CD62P and higher αIIbβ3), with little impact on platelet aggregation¹⁶. Platelet apoptosis, p38 activation and GPIb shedding, with decreased aggregation and survival, were observed in one study^17,18. Nevertheless, these in vitro effects seemed to be moderate, and their clinical impact greatly unknown.

For the Cochrane database, Escourts et al. in 2017 conclude that pathogen-reduced platelet transfusions for the prevention of bleeding increase the risk of platelet refractoriness and the platelet transfusion requirement in hematology and oncology patients without any impact on all-cause mortality, the risk of clinically significant or severe bleeding, or the risk of a serious adverse event. However, they cannot conclude for patients with other diagnoses¹⁹. Two clinical studies have been published regarding treatment of acute bleeding and challenged this conclusion. Amato et al. did not observe any difference in the count of PCs transfused in a large number of patients (including patients in cardiac surgery) as well as for red blood cell packs or fresh frozen plasmas transfusion²⁰ in a before/after clinical study. In massive transfusion, PRT-PCs were as efficient as conventional PCs regarding transfusion of other products, length of stay or survival²¹. Transfusion is frequent in cardiac surgery, with about one-fifth of patients receiving PCs in a large cohort study in Australia²². Cardiac surgery requires the use of cardiopulmonary bypass (CPB) in a lot of procedures to allow to stop the heart and to perfuse and oxygenate the organs. CPB is responsible of acquired coagulopathy including hemodilution (CPB priming and fluid challenge), anticoagulation (heparin), platelet destruction (rotative pump) and blood loss. Moreover, a growing number of patients are treated with antiplatelet drugs (salicylic acid and/or P2Y¹² inhibitors) for coronary or peripheral vascular disease and/or anticoagulated for atrial fibrillation. Most of these treatments are mandatory. Dual antiplatelet therapy can be changed for aspirin alone, but withdrawal of all drugs is rare before surgery. Bleeding and platelet consumption/loss is very frequent in the perioperative period and platelet transfusion is frequently used during cardiac surgery and in the early period in critical care units.

The aim of this study was to evaluate the clinical impact of PRT implementation for all PCs in France in November 2017. All PCs are in platelet additive solution (55–60%) and plasma (40–45%). We designed and performed a retrospective “before/after” study to assess the amount of platelets transfused in cardiac surgery in two university hospitals but also the transfusion of other blood products (red blood cells [RBCs], FFPs, lyophilized fibrinogen [Lyo-FIB] and 4F-PCC) and the clinical consequences on drainage, surgical reprises and Intensive Care Unit (ICU) course.

MATERIALS AND METHODS

Study design

This is a French “before/after” bicentric retrospective study evaluating, in the field of cardiac surgery, the impact of the implementation of PRT by IBS technology for 100% of PCs production, which occurred in November 2017. PCs, either buffy-coat or from apheresis, are prepared with platelet additive solution (55–60% PAS-E/SSP⁺ or PAS-C/Intersol and 40–45% plasma) to reduce platelet storage lesions since 2005. All clinicians were informed of this change by the French National Blood Bank (Établissement Français du Sang [EFS]). To minimise the impact of time modification in medical and surgical practices, we chose two 18-month periods close to the change in November 2017, one before implementation (01/01/2016 to 30/06/2017) and one just after (01/01/2018 to 30/06/2019). The study was approved by the Strasbourg University School of Medicine Ethics Committee (CE-2020-158) and registered at Strasbourg University Hospital (HUS) Research Department (RNI 2020 - HUS #7994).

Study patients

All adult patients undergoing a cardiac surgical procedure with cardiopulmonary bypass during the two periods were screened in Nancy and Reims university hospitals. Patients were included if they received PCs in the operating theatre (OT) or during the first 48 hours while in ICU. Patients requiring heart transplantation, ventricular assist devices or extracorporeal life support were excluded. The flow chart is depicted in Figure 1. All patients were informed of the study and gave consent.

Figure 1.

Flow-chart

Data collection

All data including demographics, etiology, past medical history and current treatments were recorded in the medical sheet of each patient. Surgical procedure, including anesthesia, and critical care were obtained from hospital discharge forms, labs and medical sheets with emphasis on RBCs transfusion and hemostatic treatments including prothrombin complex concentrate (FII, FVII, FIX, FX, PC, PS [4F-PCC]), Lyo-FIB and fresh frozen plasma (FFPs). Transfusion data were provided by the EFS, including platelet content and storage duration at delivery for each PC. Side effects were collected from hemovigilance ward in each hospital and from EFS for safety.

Perioperative guidelines

Transfusion was guided by bleeding assessment, laboratory values and hemodynamic evaluation by attending physicians in the OT as well as in ICU. According to current practice, biological triggers were severe anemia (with a threshold around 7.0 g/dL or a hematocrit of 25%, especially during CPB), thrombocytopenia (less than 50×10⁹/L, for chest tube ablation) and fibrinogen less than 1.5 g/L. PCs could be prescribed either in number of PC units, or in whished-for platelet dose. PCs delivery was adapted to body weight, according to the 2015 Health Authority (Haute Autorité de Santé [HAS])/National Agency for Drug and Medical Devices Safety (Agence Nationale de Sécurité du Médicament et des Produits de Santé [ANSM]) guidelines (0.5–0.7×10¹¹/10 kg body weight, supposed to increase platelet count by about 30×10⁹/L) and was dependent of available PCs.

Platelet concentrates preparation

Two types of PCs were routinely available: apheresis PCs (single donors-mean content 5.1±0.6×10¹¹/PC) or buffy-coat PCs (BC-PCs). Until July 2018, BC-PCs were obtained from pooling five buffy-coats after centrifugation of whole blood units and PCs contained 4.2±0.4×10¹¹ platelets. From August 2018 on, BC-PCs were pooled from eight buffy-coats and subsequently divided in 2 twin sub-units containing 3.3±0.3×10¹¹/PC each. All PCs were pathogen reduced with IBS for the second study period. All PCs (both periods) were filtered for leukoreduction and were stored at 20–24°C with agitation up to 5 days, except for IBS treated apheresis PCs that could be stored up to 7 days from July 2018 on. Platelet content was unitary measured for all PCs and printed on the PC label. For IBS-treated PCs, measurement was performed after treatment.

Statistical analysis

Quantitative data were expressed as mean ± SD or median [IQR], depending on the normality of the distribution. Comparisons of quantitative variables between groups were fulfilled using Student t test, Mann-Whitney test depending on the normality of the distribution. The normality of the distribution was assessed graphically and using Shapiro-Wilk test. Categorical variables were described as frequency, and comparisons were performed using χ² test or Fisher’s exact test according to the effective sample size.

A p<0.05 was considered statistically significant. All statistics and graphs were performed with Systat 11, Systat Software Inc. (Cranes Software, Chicago, IL, USA) and GraphPad Prism version 9.0.2 for Mac OS (GraphPad Software, San Diego, CA, USA).

RESULTS

Patients and surgical procedures

Baseline characteristics of patients receiving CPs are provided in Online Supplementary Content, Table SI. There were very few differences regarding both periods: patients were slightly younger in the second period (−4 years), but most of them were older than 60 years old, and hypertension was less frequent. Interestingly, anticoagulation and antiplatelet therapies were not different, as the distribution of dual antiplatelet therapy (DAPT).

Surgical procedures were not different between the 2 periods except for less aortic valve replacement or repair in the second period due to improved availability of alternative technique with transcatheter aortic valve implantation (TAVI) for elderly or at high surgical risk patients (Online Supplementary Content, Table SII). About 65% of patients were on antiplatelet therapy on surgery day. DAPT was withdrawn 5 days before surgery as recommended, except for non-elective surgery and aspirin was continued. Cardiopulmonary bypass (CPB) lasted more than 1 hour (with a median time at 105–110 minutes) and about one-third of patients underwent multiple procedures. Most of patients remained in normothermia during the CBP (90%). Heparin was injected as a bolus before the beginning of the CPB after cannulation of the aorta and the right atrium or the venae cavae then adjusted for an activated clotting time (ACT) above 450 s for a total dose infused of 206 [200–302] and 327 [288–415] U/kg respectively (p<0.01). At the end of CBP, heparin was antagonised by the same dose of protamine sulphate. Moreover, tranexamic acid is perfused during the surgery in almost all patients (data not shown).

Platelet transfusion

Platelet transfusion rate was slightly but significantly reduced during the second period (24.0 and 20.4% of screened patients respectively; p=0.02). Most patients (about 85%) were transfused in the OT (Table I). The number of PCs transfused was not different between the two periods in the OT. The total amount of platelet transfused was significantly reduced in the OT as well as during the first 48 hours of surgery (including OT and ICU days 1 and 2) from 0.64 (0.54–0.81) to 0.57 (0.49–0.75) × 10¹¹/10 kg in the second period (p<0.01). Antiplatelet therapy had no impact on the amount of platelet transfused (data not shown). Only 70 (19.6%) and 54 (17.2%) of patients received more than 0.90×10¹¹/10 kg platelets for significant bleeding (p=0.43).

Table I.

Quantity of platelets transfused (×10¹¹/10 kg)

		No. (%)	Med.	[IQR]	Mean ± SD	p1
Operating theatre	Before	311 (87.1)	0.61	[0.52–0.71]	0.69±0.33	<0.01
	After	266 (84.7)	0.56	[0.48–0.68]	0.63±0.25
ICU day 1	Before	82 (23.0)	0.67	[0.53–0.77]	0.80±0.51	0.28
	After	59 (18.8)	0.58	[0.52–0.75]	0.68±0.28
ICU day 2	Before	17 (4.8)	0.62	[0.55–0.90]	0.72±0.26	0.36
	After	31 (9.9)	0.63	[0.53–0.81]	0.74±0.31
Global	Before	357 (100.0)	0.64	[0.54–0.81]	0.81±0.57	<0.01
	After	314 (100.0)	0.57	[0.49–0.75]	0.73±0.49

¹Kolmogorov-Smirnov test for cumulative distribution of transfused blood products.

ICU: Intensive Care Unit

The number of patients transfused in the OT and later in ICU during day 1 and/or day 2 was not different between the 2 periods, excluding impaired function of IBS-treated transfused platelets in the OT requiring further transfusion (13.2 vs 11.1%; p=0.48). These patients presented obvious bleeding with more transfusions of other products and more readmissions to the OT for surgical hemostasis. Only a few patients were transfused during day 2, about half of them were previously transfused for clinical bleeding. There were significantly more patients transfused only during day 2 in the second period (17 vs 7), especially for nude thrombocytopenia without concomitant RBCs or other blood products.

The duration of storage of PCs at delivery was not different during the two periods (4 [4–5] days both) and only 19 patients received apheresis PCs of more than 5 days after IBS implementation. No adverse reaction or transfusion incident have been reported to local hemovigilance services or to the EFS during both periods.

Platelet count was not different before and after implementation during ICU course (Online Supplementary Content, Table SIII).

Impact on other blood products transfusion and biology

Beside the number of platelets transfused, we analyzed the clinical impact regarding blood loss (including returning to the OT), transfusion of other blood products and biology.

In this study, most patients were transfused with RBC packs (>85%) without any difference regarding the number of patients or the number of RBCPs (Table II). Hemoglobin level was not different on admission in ICU (Online Supplementary Content, Table SIII).

Table II.

Transfusion of other blood products

		No. (%)	Med.	[IQR]	Mean ± SD	Sum	p1	p2
Red blood cells (unit)
Operating theatre	Before	273 (76.5)	3.0	[2.0–4.0]	3.14±1.99	841	0.79	0.89
	After	237 (75.5)	3.0	[2.0–3.0]	3.15±2.57	719
ICU day 1	Before	89 (24.9)	2.0	[1.0–3.0]	2.65±2.44	233	0.72	>0.99
	After	74 (23.6)	2.0	[1.0–3.0]	2.62±2.31	194
Global	Before	308 (86.3)	3.0	[2.0–4.0]	3.79±3.07	1,152	0.91	0.61
	After	272 (86.6)	3.0	[2.0–3.0]	3.79±3.51	1,007
Fresh frozen plasma (units)
Operating theatre	Before	240 (66.5)	2.0	[2.0–3.0]	2.36±1.18	566	0.62	0.42
	After	202 (64.1)	2.0	[2.0–3.0]	2.50±1.58	504
ICU day 1	Before	66 (18.3)	2.0	[1.0–3.0]	2.61±2.44	172	0.36	0.99
	After	46 (15.6)	2.0	[1.0–2.5]	2.18±1.65	107
Global	Before	276 (77.3)	2.0	[2.0–3.0]	2.67±2.07	738	0.03	0.66
	After	220 (70.1)	2.0	[2.0–3.0]	2.77±2.08	494.9
4F-PCC (mL)
Operating theatre	Before	49 (13.6)	80	[60–80]	79±42	3,860	0.33	0.74
	After	53 (16.5)	60	[40–80]	76±44	4,070
ICU day 1	Before	9 (2.5)	60	[45–80]	66±21	590	0.28	0.82
	After	12 (3.8)	50	[40–60]	52±23	620
Global	Before	54 (15.1)	80	[60–80]	82±47	4,450	0.18	0.58
	After	60 (19.1)	60	[40–100]	78±48	4,690
Lyo-FIB (g)
Operating theatre	Before	65 (18.0)	3.0	[3.0–4.5]	3.8±2.5	249.5	0.92	0.95
	After	60 (17.5)	3.0	[3.0–3.0]	2.7±1.1	200.0
ICU day 1	Before	28 (7.8)	3.0	[2.0–3.0]	3.2±1.7	89.0	0.45	0.93
	After	19 (4.8)	3.0	[1.5–3.0]	2.7±1.1	50.5
Global	Before	85 (23.8)	3.0	[3.0–4.5]	4.0±3.1	338.5	0.93	0.81
	After	73 (23.2)	3.0	[3.0–3.0]	3.4±2.1	250.5

¹Fischer exact test for number of patients;

²Kolmogorov-Smirnov test for cumulative distribution of transfused blood products.

Transfusion routine practice remained unchanged between the two periods regarding fresh frozen plasmas (FFPs) Lyo-FIB and/or prothrombin complex concentrates (4F-PCCs). Interestingly, 62.9 and 64.4% received more than 1 g of fibrinogen respectively (Table II and Online Supplementary Content, Table SIV). Among patients receiving more than 0.9×10¹¹ platelets for 10 kg, transfusion of RBCPs (4.0 [3.0–6.0] vs 5.0 [2.0–7.0] units, p=0.92), FFPs (2.5 [2.0–5.0] vs 3.0 [2.0–4.0] units, p=0.12), Lyo-FIB (3.0 [3.0–7.5] vs 3.0 [ 2.0–2.0] g, p =0.35) and 4 F-PCC ( 80 [80–140] vs 70 [40–100] mL, p=0.28) were not different.

Prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen concentration were not different on admission in ICU (Online Supplementary Content, Table SIII).

Clinical impact

Clinical impact was evaluated regarding blood loss and surgical reprises, ICU stay and 28-day mortality.

Blood losses were not different at day 1 or at tube ablation as was the length of drainage. Moreover, no more patients returned to the theatre for bleeding or clot removal at day 1 or day 2 (Table III). Mechanical ventilation, norepinephrine infusion and renal replacement therapies were not different, as well as the length of stay in ICU or in hospital. Mortality was not different.

Table III.

Postoperative care (excluding transfusion)

	Before (No.=357)	After (No.=314)	p
Simplified acute physiology score 2 - median [IQR]	31 [25–41]	29 [23–40]	0.07
Drain tube loss (mL)
Day 1 - median [IQR]	430 [240–740]	475 [300–740]	0.10
At tube ablation - median [IQR]	1,110 [780–1,674]	1,020 [720–1,940]	0.74
Length of drainage (days) - median [IQR]	4 [3–5]	4 [3–5]	0.27
Returning to the theatre for bleeding
Day 1	22 (6.2)	14 (4.5)	0.39
Day 2	3 (0.9)	7 (2.3)	0.20
Mechanical ventilation
2nd postoperative day - No. (%)	96 (27.4)	71 (23.1)	0.21
Length (days) - median [IQR]	1 [1–2]	1 [1–1]	0.73
Norepinephrine infusion
2nd postoperative day - No. (%)	166 (47.8)	144 (46.8)	0.81
Length (days) - median [IQR]	2 [1–4]	2 [1–3]	0.16
Renal replacement therapy - No. (%)	20 (5.8)	18 (6.0)	>0.99
Length of stay (days)
In ICU - median [IQR]	5 [3–8]	4 [3–8]	0.12
In hospital - median [IQR]	11 [8–18]	11 [8–18]	0.97
Mortality at day 28 - No. (%)	10 (2.8)	17 (5.4)	0.11

DISCUSSION

We designed a retrospective “before/after” study in cardiac surgery assessing blood loss, blood transfusion requirement and critical care outcome to evaluate the impact of pathogen reduction technique for platelet concentrates by IBS. Overall platelet transfusion rate (about 22%) was close to a recent multiple centre study in Australia (21.5%)²². The total amount of platelets transfused was significantly decreased after IBS implementation. No impact on other blood products transfusion (RBCs, FFPs, 4F-PCC and Lyo-FIB) was evidenced. ICU course, including surgical reprise for bleeding or clot removal and for drainage volume losses remained unchanged. Pathogen reduction by IBS does not induce a lack of efficiency.

Pathogen reduction by amotosalen and UV-A illumination in PCs has proven its ability to reduce the risk of transfusion-transmitted bacterial infections (TTBIs)²³. One impact was the ability to extend the shelf life from 5 to 7 days, ensuring a better coverage of the week for PCs supply and reducing the risk of destruction. In a French national survey, the incidence of TTBIs was decreased by a 17.75 factor, from 15 (1/92,687 PCs) between 2013 and 2016 to 4 (1/1,645,787 PCs) between 2018 and 2022²⁴. No fatality linked to PC-TTBI was ever reported in France since pathogen reduction was implemented. Moreover, this technology was efficient to prevent SARS-CoV and MERS-CoV transmission^25,26, allowing to collect and transfuse safe blood products during SARS-CoV-2 outbreak in 2020^26,27. Only non-enveloped viruses (Parvoviridæ and Caliciviridæ) are less sensitive to inactivation.

The recommended dose of platelets is 0.5 to 0.7×10¹¹ for 10 kg body weight to increase platelet count by about 30×10⁹/L and platelet count over 50×10⁹/L is considered effective to treat bleeding (in the absence of antiplatelet therapy)²⁸. Amount of platelets for transfusion are delivered regarding platelet count (if available), body weight and clinical bleeding. Beside PRT implementation, BC-PCs preparation was modified with a lower platelet content to allow a better concordance between body weight and platelet delivery (see PCs preparation). This change may be the reason why there is a slight but significant decrease in the amount of platelets transfused between the 2 periods. Interestingly, only 19.6% and 17.2% of patients received more than 0.9×10¹¹ for 10 kg excluding “over transfusion” and even in those patients, other transfusion of blood products were not different.

Most of our patients were transfused with platelets for clinical bleeding in the OT (85%), after CPB withdrawal and protamine sulphate administration. Despite a lower quantity of platelets delivered and IBS treatment, other blood products consumptions were unchanged during the second period, excluding a lack of efficiency of platelets. Among them, only few patients required additional transfusion while admitted in ICU for persistent bleeding. We observed no difference in the prevalence of patients returning to the OT for bleeding or clot removal between the 2 periods.

In the Cochrane meta-analysis, platelet count restoration 1 and 24 hours after IBS-treated PCs transfusion was described to be lower than with untreated PCs, with a reduced delay between two transfusions¹⁹. The impact on bleeding is uncertain. In patients with blood diseases or post-chemotherapy severe thrombocytopenia, when platelet transfusion is meant to be prophylactic, i.e., to prevent bleeding or to allow an invasive procedure, the clinical impact could be relevant. Interestingly, such thrombocytopenic patients who experience minor bleedings and transfused with IBS-treated PCs do not require more RBCPs, supporting an effective hemostatic power of transfused platelets²⁹. In the case of bleeding, as in our study, the main goal of platelet transfusion is to maintain a sufficient number of efficient platelets to stop bleeding regardless platelet count itself (including exhausted platelets after CPB and inhibited platelets by antiplatelet therapies) without a specific threshold. After transfusion, platelet count was not different during the first 2 days in ICU course (Online Supplementary Content, Table SIII) not supporting a reduced recovery. Moreover, no more patients required a new transfusion for bleeding (assessed by concomitant administration of other blood products).

PCs shelf life has been reported to affect platelet recovery^30,31. PRT allowed an extension of shelf life from 5 to 7 days. From July 2018 on, only for apheresis PCs were concerned as it has been generalized since to all buffy coat PCs only in July 2019. Only 19 patients were transfused with apheresis platelet concentrates older than 5 days and it was not possible to evaluate a specific impact.

Pathogen reduction technologies may not be equivalent, and our results cannot be translated to others. The literature supports some differences between IBS and Mirasol^® PRT System (Terumo, Tokyo, Japan). Mirasol^® associates a treatment by riboflavin (vitamin B2) and exposure to UV and is efficient to decrease TTBI²². In one study, Riboflavin-treated PCs as well as IBS-PCs seemed to be non-inferior to untreated PCs in a prospective, multicentre, controlled, randomized non-inferiority study in patients with hypoproliferative thrombocytopenia (MiPLATE trial)³². Nevertheless, in a recent meta-analysis of randomized clinical trials, Riboflavin-PCs were significantly less efficient than untreated-PCs to prevent bleeding grade ≥2 (OR 1.34 [1.03–1.75], p=0.03) while IBS-PCs were not (OR 1.12 [0.89–1.41], p=0.33). All-cause mortality was not significantly different for pathogen inactivation (OR 0.82 [0.45–1.52], p=0.24) but was, between the two techniques, favouring IBS (OR 0.61 [0.36–1.04] vs 3.04 [0.81–11.47], p=0.03)³³. This result, in opposition with previous studies and meta-analysis might be confirmed in large-randomized studies^28,32.

This study had some limits. This is a retrospective study as a “gold standard” randomized clinical trial was not designed and initiated before PRT implementation for all PCs in France in late 2017. In this context, only retrospective trials can be done. To avoid practice discrepancies, we chose two periods just before and after implementation with very few differences regarding patients and surgery. Transfusion was based on physician judgment and expertise. Nevertheless, we cannot evidence a modification of practice between the two periods.

CONCLUSIONS

Emerging pathogens result in unknown safety for blood products during outbreaks. A “universal” technology to reduce significantly the risk of transmission is of great interest to avoid destruction of stocks, to prevent secondary disease in the transfused patient and to cure patients requiring transfusion. In this real-life study, transfusion of pathogen-inactivated IBS-PCs was as efficient as untreated-PCs to treat surgical or postoperative bleeding in cardiac surgery. No side effect to IBS technology was reported. The total amount of platelets transfused was significantly lower after implementation of IBS technology, without any clinical impact on RBCs transfusion, fibrinogen and clotting factors administration (Lyo-FIB, 4F-PCC and/or FFPs) or chest tube drainage and ICU course were unchanged in this “before/after” clinical trial. The benefit seemed to overpass a hypothetical reduced activity.