Influence of short-term refrigeration on collagen-dependent signalling mechanisms in stored platelets.

Platelet concentrates (PC) are used to treat patients with thrombocytopenia and hemorrhage, but there is still the demand to find the optimal strategy for temperature-dependent storage of PC. Recently, we could show that cold storage for 1 h (short-term refrigeration) is sufficient to induce enhanced platelet responsiveness. The aim of this study was to investigate effects of cold storage on collagen-dependent activating signalling pathways in platelets from apheresis-derived PC (APC). APC on day 1 or day 2 of storage, were either continuously kept at room temperature (RT, 22 °C), or for comparison, additionally kept at cold temperature (CT, 4 °C) for 1 h. CD62P expression was determined by flow cytometry. Western Blot technique was used to analyze collagen-induced phosphorylation of p38, ERK1/2 or Akt/PKB and its inhibition by prostaglandin E1 (PGE1) or nitric monoxide donor. Adhesion of platelets on collagen-coated surfaces and intracellular phosphorylation of vasodilator-stimulated phosphoprotein (VASP) was visualized by immune fluorescence microscopy. CD62P expression was increased after short-term refrigeration. CT exposition for 1 h induced an elevation of basal ERK1/2 phosphorylation and an alleviation of PGE1- or DEA/NO-suppressed ERK1/2 phosphorylation in APC on day 1 and 2 of storage. Similar, but more moderate effects were observable for p38 phosphorylation. Akt/PKB phosphorylation was increased only in APC on day 2. Refrigeration for 1 h promoted platelet adhesion and reduced basal VASP phosphorylation in adherent platelets. The attenuation of inhibitory signalling in short-term refrigerated stored platelets is associated with enhanced reactivity of activating signalling pathways, especially ERK1/2. Functionally, these processes correlate with increased adhesion of refrigerated platelets on collagen-coated surfaces. The results help to further optimize temperature-dependent strategies for platelet storage.

Evaluation of activation characteristics of a canine platelet concentrate produced by a commercial double centrifugation system.

Introduction: In veterinary medicine there are few readily available products for platelet transfusion to patients with thrombocytopenia. Commercial tabletop platelet concentrating systems have recently become available to veterinarians, primarily directed towards uses associated with regenerative medicine. These systems could potentially be used to produce fresh concentrated platelets for use in transfusion medicine. This study evaluated the concentration, activation, and sterility of a double centrifugation platelet concentrate (PC) produced by a commercial benchtop system. Methods: Ten healthy dogs were studied. Whole blood was collected and mixed with ACD-A in a 1:7.6 ratio of ACD-A to whole blood. 12 mL of this mixture was processed into PC via single centrifugation, while 60 mL of the anticoagulated whole blood was processed via a commercial double centrifugation system. Both types of PC were evaluated for platelet concentration, CD62P expression with and without thrombin stimulation, and for sterility. Results: Mean platelet count in the double centrifuged PC was 863 ± 352 × 103/µL, with very low white blood cell contamination (median of 0.47 × 103 leukocyte/µL (range 0.15-2.18 × 103/µL)). The double-centrifuged PC had similar baseline activation characteristics (as determined by P-selectin expression) as the single centrifuge PC (0.76% vs. 0.72% unstimulated, 30.5% vs. 34.9% stimulated, p = 0.432). Discussion: The benchtop PC system studied here did not cause activation of platelets during production and produced a sterile product that can be further investigated as a source of fresh platelet concentrates for transfusion purposes.

Indocyanine Green-Labeled Platelets for Survival and Recovery Studies.

Introduction: Before being implemented in daily clinical routine, new production strategies for platelet concentrates (PCs) must be validated for their efficacy. Besides in vitro testing, the establishment of new methods requires the labeling of platelets for in vivo studies of platelets' survival and recovery. Indocyanine green (ICG) is a Food and Drug Administration-approved near-infrared (NIR) fluorescent dye for diagnostic use in vivo, suitable for non-radioactive direct cell labeling of platelets. Methods: Platelets from PCs in storage solutions with different plasma concentrations were labeled with ICG up to concentrations of 200 µm. Whole blood (WB) was used as an ex vivo matrix to monitor the labeling stability of ICG-labeled platelets. The impact of labeling processes was assessed by the quantification of CD62P expression and PAC-1 binding as platelet function markers. Platelet aggregation was analyzed by light transmission aggregometry. ICG-labeling efficiency and stability of platelets were determined by flow cytometry. Results: Platelets from PCs could be successfully labeled with 10 µm ICG after 1 and 4 days of storage. The best labeling efficiency of 99.8% ± 0.1% (immediately after labeling) and 81% ± 6.2% (after 24 h incubation with WB) was achieved by plasma replacement by 100% platelet additive solution for the labeling process. Since the washing process slightly impaired platelet function, ICG labeling itself did not affect platelets. Immediately after the ICG-labeling process, plasma was re-added, resulting in a recovered platelet function. Conclusion: We developed a Good Manufacturing Practice compatible protocol for ICG fluorescent platelet labeling suitable for survival and recovery studies in vivo as a non-radioactive labeling alternative.

We developed a simple, reproducible method according to Good Manufacturing Practice guidelines for labeling of platelets from platelet concentrates (PCs) with indocyanine green (ICG) as a non-radioactive alternative. PCs are medicinal drugs that are transfused to prevent or treat bleeding. They consist of the blood cells' platelets which are responsible for clotting processes in the body. Manufacturing procedures of PCs are continuously refined, and for in vivo testing, these platelets have to be labeled to track and to distinguish them from proband's or patient's own cells. Radioactive labeling, for a long time the gold standard for cell labeling, is no longer accepted. ICG is a fluorescent dye approved by the drug authorities and already used for diagnostic purposes in humans. We used ICG to label platelets from PCs. With our method, we achieved a labeling efficiency of 99.8%. We used whole blood (WB) as an ex vivo matrix to monitor the labeling stability of ICG-labeled platelets. After the addition of ICG-labeled platelets to WB, the labeling efficiency decreased to 81% after 24 h. However, we were still able to distinguish the ICG-labeled platelets from the WB platelets. We could also show that platelet function was not impaired by the labeling processes. The good tolerance of ICG indicates a short path to clinical application in healthy volunteers and investigations of novel PC-manufacturing procedures. As a read-out system, flow cytometry systems equipped with NIR lasers and filters could offer the possibility of rapid visualization, cell tracking, re-isolation, and ex vivo studies.

Autologous platelet concentrate in epiretinal membrane surgery: A single-centre prospective comparative non-inferiority study.

PURPOSE: The purpose of the study was to compare the anatomical and functional results including reading ability after epiretinal membrane (ERM) surgery in patients with and without the use of autologous platelet concentrate (APC). METHODS: Design: Prospective, comparative non-inferiority series. SETTING: Institutional. PATIENTS: 51 eyes of 51 patients, who underwent pars-plana vitrectomy (PPV) for ERM surgery. 29 eyes additionally received intraoperative APC, 22 eyes underwent standard procedure without APC use. OBSERVATIONS: anatomical and functional outcome parameters (central retinal thickness (CRT), best corrected visual acuity (BCVA) and reading ability (RA)) were compared between the two groups at 6 weeks and 6 months postoperatively. Subjective assessment of visual acuity and reading ability was also analysed. MAIN OUTCOME MEASURES: BCVA, RA and CRT. RESULTS: Both groups showed significant CRT reduction and RA improvement, while BCVA improvement was significant only in eyes with intraoperative APC use during the follow-up time of 6 months. There was no statistically significant difference between CRT reduction, BCVA and RA improvement between the groups. CONCLUSION: Intraoperative APC use for ERM surgery results in similar anatomical and functional outcomes compared with standard ERM surgery without APC use.

Routine results of an algorithm for managing the production of blood components.

BACKGROUND AND OBJECTIVES: The variability in the number of donations together with a growing demand for platelet concentrates and plasma-derived medicines make us seek solutions aimed at optimizing the processing of blood. Some mathematical models to improve efficiencies in blood banking have been published. The goal of this work is to validate and evaluate an algorithm's impact in the production of blood components in the Blood and Tissues Bank of Aragon (BTBA). MATERIALS AND METHODS: A mathematical algorithm was designed, implemented and validated through simulations with real data. It was incorporated into the fractionation area, which uses the Reveos® fractionation system (Terumo BCT) to split blood into its components. After 9 months of daily routine validation, retrospective activity data from the Blood Bank and Transfusion Services before and during the use of the algorithm were compared. RESULTS: Using the algorithm, the outdating rate of platelet concentrates (PC) decreased by 87.8% in the blood bank. The average shelf life remaining of PC supplied to Transfusion Services increased by almost 1 day. As a consequence, the outdating rate in the Aragon Transfusion Network decreased by 33%. In addition, extra 100 litres of plasma were obtained in 9 months. CONCLUSIONS: The algorithm improves the blood establishment's workflow and facilitates the decision-making process in whole blood processing. It resulted in a decrease in PC outdating rate, increase in PC shelf life and finally an increase in the volume of recovered plasma, leading to significant cost savings.

Impact of production methods and storage conditions on extracellular vesicles in packed red blood cells and platelet concentrates.

The use of blood and blood products can be life-saving, but there are also certain risks associated with their administration and use. Packed red blood cells (pRBCs) and platelet concentrates are the most commonly used blood products in transfusion medicine to treat anemia or acute and chronic bleeding disorders, respectively. During the production and storage of blood products, red blood cells and platelets release extracellular vesicles (EVs) as a result of the storage lesion, which may affect product quality. EVs are subcellular structures enclosed by a lipid bilayer and originate from the endosomal system or from the plasma membrane. They play a pivotal role in intercellular communication and are emerging as important regulators of inflammation and coagulation. Their cargo and their functional characteristics depend on the cell type from which they originate, as well as on their microenvironment, influencing their capacity to promote coagulation and inflammatory responses. Hence, the potential involvement of EVs in transfusion-related adverse events is increasingly recognized and studied. Here, we review the knowledge regarding the effect of production and storage conditions of pRBCs and platelet concentrates on the release of EVs. In this context, the mode of processing and anticoagulation, the influence of additive solutions and leukoreduction, as well as the storage duration will be addressed, and we discuss potential implications of EVs for the clinical outcome of transfusion.

A tight interplay between platelet activation and mitochondrial DNA release promotes platelet storage lesion in platelet concentrates.

BACKGROUND AND OBJECTIVES: Platelet storage lesion (PSL) adversely affects the quality of platelet concentrates (PCs). Platelets are prone to activation during storage. Moreover, elevated free mitochondrial DNA (mtDNA) levels in PCs are associated with a higher risk of adverse transfusion reactions. Therefore, we aimed to evaluate the correlation between platelet activation markers and mtDNA release during PC storage. MATERIALS AND METHODS: Six PCs prepared by the platelet-rich plasma method were assessed for free mtDNA copy number using quantitative real-time PCR and CD62P (P-selectin) expression by flow cytometry on days 0 (PC collection day), 3, 5 and 7 of storage. Lactate dehydrogenase (LDH) activity, pH, platelet count, mean platelet volume (MPV) and platelet distribution width (PDW) were measured as well. The correlation between free mtDNA and other PSL parameters, and the correlation between all parameters, was determined. RESULTS: Significant increases in free mtDNA, MPV and PDW, and a significant decrease in platelet count and pH were observed. CD62P expression and LDH activity elevated significantly, particularly on storage days 5-7 and 0-3, respectively. Moreover, a moderate positive correlation (r = 0.61) was observed between free mtDNA and CD62P expression. The r values between free mtDNA and LDH, pH, platelet count, MPV and PDW were 0.81, -0.72, -0.49, 0.81 and 0.77, respectively. CONCLUSION: The interplay between platelet activation and mtDNA release in promoting PSL in PCs may serve as a promising target for future research on applying additive solutions and evaluating the quality of PCs to improve transfusion and clinical outcomes.

Efficacy of autologous platelet concentrate products for alveolar preservation: A meta-analysis.

PURPOSE: The purpose of the study was to systematically evaluate the efficacy of autologous platelet concentrate products in the preservation of the alveolar ridge after tooth extraction through meta-analysis and provide a theoretical basis for the clinical application of autologous platelet concentrates to reduce alveolar bone resorption. METHODS: This study conducted a meta-analysis of clinical trials between 2013 and 2023, focusing on autologous platelet concentrate products (e.g., PRP, PRF, CGF, and PRCF) used for alveolar ridge preservation after tooth extraction. The analysis included 122 articles and 371 extraction sockets. All statistical analyses were performed using Review Manager version 5.4. RESULTS: Results indicate that these platelet concentrates effectively reduced changes in horizontal width 1 mm below the alveolar crest and vertical socket height. They also promoted a higher percentage of new bone formation in extraction sockets compared with control groups. However, they did not significantly prevent horizontal bone resorption at 3 and 5 mm below the alveolar crest. CONCLUSION: In conclusion, autologous platelet concentrates are useful for alveolar ridge preservation, but larger clinical studies are needed to confirm these findings due to the relatively small sample size in this study.

L-carnitine contributes to enhancement of viability and quality of platelet concentrates through changing the apoptotic and anti-apoptotic associated microRNAs.

BACKGROUND: Micro RNAs are known as the main regulator of messenger RNA translation in platelets and have a vital role in process of apoptosis during platelet storage. Our pervious study revealed that the expression of miR-145 and miR-326 changed significantly in platelets under maintenance conditions. This study aimed to evaluate the effect of L-carnitine (LC) as an additive to augment platelet quality by changing the microRNA expression. METHODS: We used ten platelet concentrate (PC) bags and divided each into two equal parts, LC- treated, and LC free PC. The expression of miR-145 and miR-326 were determined using real-time PCR. Moreover, we measured platelet count, platelet aggregation, platelet viability, and lactate dehydrogenase activity in all samples. RESULTS: The miR-326 expression significantly increased during platelet storage with mean fold changes of 3.2 for the control and 2.5 for LC- treated PC. The mean fold changes in miR-145 expression was less in the control PC (0.52) compared to the LC- treated PC (0.79). Increased levels of platelet count, platelet aggregation, and platelet viability were found in the LC-treated compared to the untreated PC. CONCLUSION: LC has a protective effect on platelet apoptosis, reduces the expression of apoptotic microRNA, and prevents the reduction of anti-apoptotic microRNA.

Clinical impacts of severe thrombocytopenia in the first cycle of azacitidine monotherapy and cytogenetics in patients with myelodysplastic syndrome: The Kyoto Conditional Survival Scoring System.

Azacitidine (AZA) has been one of the standard treatments for transplantation-ineligible patients with myelodysplastic syndrome (MDS); however, hematological toxicities frequently cause treatment interruption in the early phase of the therapy. The present study conducted a multicenter retrospective study to investigate the prognostic impacts of various factors, including factors included in the Revised International Prognostic Scoring System (IPSS-R) and severe cytopenia in the early phase of AZA monotherapy in 212 patients with MDS. Severe cytopenia was evaluated after the initiation of therapy by absolute neutrophil counts on the 29th day after AZA (ANC29) initiation, and red cell concentrates (RCC) and platelet concentrate (PC) transfusion units required within 28 days from the start of AZA, designated in the present study as RCC28 and PC28, respectively. The survival period was determined from the 29th day of AZA treatment to death from any cause as the conditional survival period after the first cycle of AZA (CS-AZA1). Multivariate analysis demonstrated that severe thrombocytopenia defined by >30 units of PC28 and very poor risk cytogenetics according to IPSS-R were independent prognostic factors for CS-AZA1. The Kyoto Conditional Survival Scoring System was subsequently developed by incorporating severe thrombocytopenia defined by PC28 and very poor risk cytogenetics, which successfully stratified the risks of the patients in CS-AZA1. In conclusion, extreme PC transfusion dependency during the first cycle of AZA and very poor risk cytogenetics are important prognostic factors in AZA monotherapy for MDS.

Effect of adjuvant autologous platelet concentrates on secondary repair of alveolar clefts: A systematic review and meta-analysis.

OBJECTIVE: To review the existing evidence on the adjuvant use of autologous platelet concentrates (APCs) with iliac crest bone graft (ICBG) in the reconstruction of the secondary alveolar cleft. METHODS: Electronic databases were searched systematically until November 2022. Clinical trials comparing the three-dimensional radiological outcomes of patients who underwent secondary alveolar bone grafting (SABG) with ICBG and APCs to those with ICBG alone and the radiological outcomes assessed 6 months after surgery were included. Two authors performed the study selection and the assessment of the risk of bias. Meta-analysis was performed using the random-effects model to determine the risk ratio (RR) for developing wound dehiscence and the mean difference (MD) with a 95% confidence interval (CI) for the percentage of newly formed bone. RESULTS: Nine studies (seven RCT and two CCT) were included with a low to high risk of bias. At the 6-month follow-up, the study group revealed insignificant results regarding the percentage of newly formed bone (MD = 6.49; 95% CI: -0.97, 13.94; p = .09; χ2  = 0.01; I2  = 71%). In addition, the overall risk of developing wound dehiscence was lower in the study group (RR = 0.34; 95% CI: 0.15, 0.78; p = .01; χ2  = 0.67; I2  = 0%). CONCLUSION: Currently, there is insufficient evidence to support the adjuvant use of APCs with ICBG on enhanced bone regeneration following secondary alveolar bone grafting. However, combining ICBG and APCs might be beneficial in reducing the risk of developing wound dehiscence.

Implementation of amotosalen plus ultraviolet A-mediated pathogen reduction for all platelet concentrates in France: Impact on the risk of transfusion-transmitted infections.

BACKGROUND AND OBJECTIVES: Pathogen reduction (PR) technology may reduce the risk of transfusion-transmitted infections (TTIs), notably transfusion-transmitted bacterial infection (TTBI) associated with platelet concentrates (PCs). PR (amotosalen/UVA treatment) was implemented for all PCs transfused in France in November 2017. No bacterial detection was in place beforehand. The study aimed to assess the impact of PR PC on TTI and TTBI near-miss occurrences. MATERIALS AND METHODS: TTI and TTBI near-miss occurrences were compared before and after 100% PR implementation. The study period ran from 2013 to 2022. Over 300,000 PCs were transfused yearly. RESULTS: No PC-related transmission of human immunodeficiency virus, hepatitis C virus, hepatitis B virus and human T-cell lymphotropic virus was reported throughout the study period. PC-mediated hepatitis E virus and hepatitis A virus infections occurred irrespective of PR implementation. Mean PC-mediated TTBI occurrence before PR-PC implementation was 3/year (SD: 1; n = 15; 1/92,687 PC between 2013 and 2016) with a fatal outcome in two patients. Since PR implementation, one TTBI has been reported (day 4 PC, Bacillus cereus) (1/1,645,295 PC between 2018 and 2022; p < 0.001). Two PR PC quarantined because of a negative swirling test harboured bacteria: a day 6 PC in 2021 (B. cereus and Staphylococcus epidermidis) and a day 7 PC in 2022 (Staphylococcus aureus). Five similar occurrences with untreated PC were reported between 2013 and 2020. CONCLUSION: Transfusion of 100% PR PC resulted in a steep reduction in TTBI occurrence. TTBI may, however, still occur. Pathogen-reduced PC-related TTI involving non-enveloped viruses occurs as well.

Expired Platelet Concentrate Up-Cycling: Growth Factor-Rich Bioproduct Preparation for FBS Substitute.

Due to the short storage period, large quantities of platelet concentrate (PC) are expiring. The expired PC cannot be injected into a blood vessel, but the activity of bioactive molecules, especially growth factors, is still preserved. In this paper, we organized a process to obtain a growth factor-rich bioproduct for use as a supplement in human cell culture by optimizing freezing, thawing, and sterilization conditions. Each unit of PC displayed visual differences, diverse biochemical values, and growth factor concentrations. To minimize lot-to-lot variation, we pooled a minimum of 10 PC units. The concentrations of growth factors were maximized through five freeze-thaw cycles for 12 h at -80 °C for freezing and for 5 min at 36 °C for thawing. We used a cell strainer with 40 µm pores, followed by a 0.45 µm filter and a 0.22 µm filter sequentially to sterilize the bioproduct with minimizing loss. The obtained growth factors remained stable for 4-6 h at room temperature (23 °C), 24 h at 4 °C, and 12 months at -80 °C. Cellular responses to the growth factor-rich bioproduct were tested with primary human renal proximal tubule epithelial cells. The cells exhibited a significantly increased growth rate, compared to the fetal bovine serum (FBS)-treated control group. The cells maintained their characteristic cuboidal shape, and stem cells and renal progenitor cells also preserved their genetic characteristics during culture. Therefore, the growth factor-rich bioproduct isolated from expired PC through our process can be used as a medium supplement to replace FBS in human cell culture for clinical application.

Efficacy and safety of platelet additive solution-E stored platelet concentrates.

INTRODUCTION: In 2018, platelet (PLT) additive solution-E (PAS-E) was introduced. The implementation of PAS-E was expected to diminish the number of allergic reactions in recipients following a PLT transfusion. Here, we evaluated the efficacy and safety of transfusions with PLTs stored in PAS-E. STUDY DESIGN AND METHODS: After implementation of PAS-E, data were collected from 2 cohorts of patients with hematological disorders as well as oncology patients, receiving PLTs in PAS-E. A similar patient group in a recent RCT, receiving PLTs in plasma, was used as a historical control group for both cohorts. Endpoints were corrected count increments (CCIs), bleeding scores (only reported in cohort 1), and the incidence of adverse reactions. RESULTS: In cohort 1, the mean 1-h CCI was 14.3 ± 6.9, and the 24-h CCI was 8.7 ± 5.6. In cohort 2, the 1-h CCI was 11.6 ± 7.8 and the 24-h CCI was 7.0 ± 6.1. In the control group, the 1-h CCI was 15.4 ± 5.5 and 24-h CCI 8.7 ± 4.8. Bleeding complications of WHO grade ≥2 occurred in 40% of patients in cohort 1 compared to 44% in plasma PCs. The incidence of adverse reactions was 1.2% in the two PAS-E cohorts, compared to 3.0% in plasma PCs. National hemovigilance data showed a significant reduction in allergic reactions with PAS-E PC transfusions as compared to plasma PCs with an odds ratio of 0.46 (CI 95% 0.37-0.58). CONCLUSION: The CCIs of PLTs in PAS-E were decreased compared to plasma PCs, but clinically acceptable. Allergic transfusion reactions were decreased in PAS-E PCs compared to plasma PCs.

Are Buffy-coat Pooled Platelet Concentrates an Effective Alternative to Apheresis Platelet Concentrates? An In vitro Analysis at a Tertiary Care Center in Northern India.

Background: There is a need for platelet products to have the best quality. Apheresis platelet concentrates (PCs) obtained from single-donors PCs (SD-PCs) are considered best but have issues such as feasibility and cost. Buffy-coat pooled PCs (BCP-PCs) are considered an alternative to SD-PCs. This study compares BCP-PCs and SD-PCs for in vitro quality parameters and their changes during storage. Materials and Methods: Fifteen units of BCP-PCs and 15 units of SD-PCs were prepared. In this study, a pool of five buffy coats was prepared. Fifteen units of BCP-PCs were analyzed on day 1 and day 5 of storage, while 15 SD-PCs were analyzed on day 1 while ten units on day 5. The parameters analyzed were volume, hematological parameters, pH, swirling, and sterility. Results: The mean platelets count of SD-PCs was found to be significantly higher as compared to BCP-PCs. White blood cells (WBCs) contamination was significantly lower in BCP-PCs as compared to SD-PCs. The mean pH and mean platelet volume of SD-PCs were significantly lower than BCP-PCs. During storage, the mean platelets count of BCP-PCs was decreased significantly while that of SD-PCs nonsignificantly. The mean WBCs count and pH decreased in both BCP-PCs and SD-PCs significantly. All units in both types of PCs were sterile. Conclusion: Platelet yield was significantly better in SD-PCs, while mean WBCs contamination was significantly lower in BCP-PCs. BCP-PCs may be preferred in place of SD-PCs in case of nonavailability of apheresis, difficulty in finding a willing donor, or when the cost is of consideration.

Alveolar Ridge Preservation with Autologous Platelet-Rich Fibrin (PRF): Case Reports and the Rationale.

In dental implantology, alveolar ridge preservation (ARP) has emerged as a standard technique to address dimensional changes that affect alveolar ridge morphology following tooth loss. Various alternative graft materials, including xenografts, alloplasts, and allografts, have been effectively employed in fresh extraction sites for ARP. Current evidence suggests that these materials primarily serve as bio-scaffolds, which are slowly incorporated, thus necessitating a waiting period of at least 4-6 months before implant placement. Consequently, the ARP technique extends the overall duration of implant treatment by several months. Recently, the incorporation of a form of autologous platelet concentrate, known as platelet-rich fibrin (PRF), has been advocated in conjunction with ARP as a method of bioenhancement of soft- and hard-tissue healing and regeneration. PRF contains platelet-derived growth factors, hormones, and bioactive components like cytokines that have demonstrated the ability to stimulate angiogenesis and tissue regeneration throughout all phases of wound healing. Additionally, the concentration of leukocytes present in the PRF matrix plays a vital role in tissue healing and regeneration as part of the osteoimmune response. The reported advantages of incorporating autogenous PRF platelet concentrates during ARP encompass reduced healing time, improved angiogenesis and bone regeneration, socket sealing through the fibrin matrix, antibacterial properties, and decreased post-extraction pain and infection risk. Therefore, the objective of this paper is to review the existing evidence regarding the application of PRF in alveolar ridge preservation (ARP) following tooth extraction. Two clinical case studies are presented, wherein ARP was enhanced with PRF, followed by implant placement within a relatively short period of 8 weeks. These cases serve as further proof of concept for supporting the adjuvant use of PRF to enhance healing and accelerate implant placement after ARP.

Expanding applications of allogeneic platelets, platelet lysates, and platelet extracellular vesicles in cell therapy, regenerative medicine, and targeted drug delivery.

Platelets are small anucleated blood cells primarily known for their vital hemostatic role. Allogeneic platelet concentrates (PCs) collected from healthy donors are an essential cellular product transfused by hospitals to control or prevent bleeding in patients affected by thrombocytopenia or platelet dysfunctions. Platelets fulfill additional essential functions in innate and adaptive immunity and inflammation, as well as in wound-healing and tissue-repair mechanisms. Platelets contain mitochondria, lysosomes, dense granules, and alpha-granules, which collectively are a remarkable reservoir of multiple trophic factors, enzymes, and signaling molecules. In addition, platelets are prone to release in the blood circulation a unique set of extracellular vesicles (p-EVs), which carry a rich biomolecular cargo influential in cell-cell communications. The exceptional functional roles played by platelets and p-EVs explain the recent interest in exploring the use of allogeneic PCs as source material to develop new biotherapies that could address needs in cell therapy, regenerative medicine, and targeted drug delivery. Pooled human platelet lysates (HPLs) can be produced from allogeneic PCs that have reached their expiration date and are no longer suitable for transfusion but remain valuable source materials for other applications. These HPLs can substitute for fetal bovine serum as a clinical grade xeno-free supplement of growth media used in the in vitro expansion of human cells for transplantation purposes. The use of expired allogeneic platelet concentrates has opened the way for small-pool or large-pool allogeneic HPLs and HPL-derived p-EVs as biotherapy for ocular surface disorders, wound care and, potentially, neurodegenerative diseases, osteoarthritis, and others. Additionally, allogeneic platelets are now seen as a readily available source of cells and EVs that can be exploited for targeted drug delivery vehicles. This article aims to offer an in-depth update on emerging translational applications of allogeneic platelet biotherapies while also highlighting their advantages and limitations as a clinical modality in regenerative medicine and cell therapies.

Combined Biologic Augmentation Strategies with Collagen Patch Graft, Microfractures, and Platelet Concentrate Injections Improve Functional and Structural Outcomes of Arthroscopic Revision Rotator Cuff Repair.

BACKGROUND: Arthroscopic revision rotator cuff repair (ARRCR) is challenging. Biologic strategies seem to be promising. The aim was to evaluate the effectiveness of the combination of microfractures of the greater tuberosity, augmentation with collagen patch graft, and platelet concentrate injections in ARRCR. METHODS: A retrospective comparative study was conducted on patients that underwent ARRCR with a minimum follow-up of two years. Patients in the augmentation group underwent ARRCR combined with microfractures, collagen patch graft, and postoperative subacromial injections of platelet concentrate. A standard rotator cuff repair was performed in the control group. PRIMARY OUTCOME: Constant-Murley score (CMS). SECONDARY OUTCOMES: disease-specific, health-related quality of life using the Disabilities of the Arm, Shoulder, and Hand (DASH) score; assessment of tendon integrity with magnetic resonance at least six months after surgery. Significance was set at p < 0.05. RESULTS: Forty patients were included. Mean follow-up was 36.2 ± 8.7 months. The mean CMS was greater in the augmentation group (p = 0.022). No differences could be found for DASH score. Healing failure rate was higher in the control group (p = 0.002). CONCLUSION: Biologic augmentation of ARRCR using a combination of microfractures, collagen patch graft, and subacromial injections of platelet concentrate is an effective strategy in improving tendon healing rate. LEVEL OF EVIDENCE: retrospective cohort study, level III.

Let Us Know Transfusion Triggers for Prophylactic Use of Platelet Concentrate-Analysis of Compliance with Recent Transfusion Guidelines in a Large Academic Medical Center.

Platelet concentrate (PC) is a blood component that is used to prevent or manage bleeding associated with thrombocytopenia or impaired platelet function. The aim of our study was to assess the compliance of ordering physicians with the most recent PC transfusion guidelines in our academic medical center. All PC transfusions performed between January 2019 and December 2022 were analyzed. The appropriateness of PC transfusions was assessed based on the most recent PC transfusion guidelines. During 2019-2022, there were 362 (0.2%) PC recipients out of 161,762 hospitalized patients. There were 971 PCs transfused during the analyzed period. Inappropriate transfusions accounted for 53.3% of cases, and most of them were given prophylactically (80.2%). Compliance with platelet transfusion guidelines varied among departments. The overall percentage of inappropriately transfused PC ranged from 50.7% to 60.8% in successive years. Educational activities should target clinicians performing procedures associated with high rates of inappropriate PC transfusions. Implementing clinical decision support systems can help reduce unnecessary PC transfusions and associated costs. The majority of inappropriate PC transfusions in our medical center were given as prophylaxis against bleeding. Prescribers should be educated about evidence-based transfusion triggers for the prophylactic use of PC in various clinical scenarios.

Prevention and management of drug-induced osteonecrosis of the jaws using platelet-rich fibrin: A clinical feasibility study.

OBJECTIVE: Although a standard treatment guideline has not been established to date, various treatment modalities have been described in the literature based on the staging of medication-related osteonecrosis of the jaw (MRONJ). The aim of this case series was to describe the outcomes of surgical intervention of MRONJ cases with the adjunctive use of platelet-rich fibrin (PRF). MATERIALS AND METHODS: Thirteen patients under therapy with zoledronic acid, seven of them underwent surgical removal of necrotic bone with debridement, followed by placement of three to four PRF membranes and achieving primary closure. In six patients, PRF was used preventively to avoid MRONJ. RESULTS: The surgical treatment outcomes were successful in all patients, with a follow-up range of 12-48 months. In the presented cases, the intraoral evaluation showed excellent soft tissue healing except for one patient secondary wound healing was reported. Additionally, there was no recurrence of bone exposure in all cases. PRF membranes were comparatively effective in postsurgical pain control. CONCLUSION: The use of PRF could represent a valuable adjunct in the surgical management for advanced stages of MRONJ cases. CLINICAL RELEVANCE: This clinical case series describes the use of PRF membranes as a valuable adjunct in the surgical management of MRONJ patients, especially when treating advanced MRONJ cases. Moreover, PRF demonstrates usefulness in preventing such difficult complications from occurring.