Neutrophil extracellular traps (NETs) are increasingly recognised for their role in primary antiphospholipid syndrome (PAPS) pathogenesis. Herein, we examined underlying mechanisms driving NET formation and the thrombogenic effects of NETs in patients with PAPS, along with potential inhibitors. We examined NET release in PAPS, asymptomatic antiphospholipid autoantibodies (aPLs) carriers, and healthy controls (HCs) as well as NET-bound proteins by immunofluorescence, immunoblotting, quantitative polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA). We assessed platelet-neutrophil aggregates by flow cytometry (CD61/CD66b staining) and autophagy using LC3B immunofluorescence and immunoblotting. Immunofluorescence was performed in paraffin-embedded kidney, skin ulcer, and endoarterial thrombus tissues from patients with PAPS. Suppression of NET release via CD40-CD40L inhibition was tested in in vitro and venous thrombosis mouse models. Neutrophils from patients with PAPS exhibited increased NET release compared with asymptomatic aPL carriers and HCs. NETs from patients with PAPS expressed tissue factor (TF) that induced thrombin generation in platelet-poor plasma from HCs. aPL induced in vitro intracellular TF expression in HC neutrophils. TF-expressing NETs were abundant in the kidney, skin ulcer, and endoarterial thrombus tissues from patients with PAPS, and colocalised with fibrinogen. NET release in PAPS neutrophils was driven by aPL-mediated platelet activation, subsequent platelet-neutrophil interaction, and autophagy induction. CD40-CD40L blockade reduced platelet activation, autophagy, and NET formation in patients with PAPS. In a mouse model, inhibition of CD40-CD40L reduced neutrophil-platelet aggregates and myeloperoxidase (MPO)-DNA complexes in mouse peripheral blood, and the presence of NETs in the formed thrombi. Targeting the platelet-neutrophil/autophagy/TF-expressing NETs axis by CD40-CD40L inhibition attenuates thromboinflammation in PAPS and should be explored as a potential therapeutic target.

Background: Periodontitis is a multifactorial, chronic inflammatory disease that leads to progressive destruction of the periodontal apparatus. Despite the effectiveness of scaling and root planing (SRP), residual inflammation and limited regenerative potential justify the search for adjunctive biologic therapies. Platelet-derived concentrates, including platelet-rich plasma (PRP), platelet-rich fibrin (PRF), concentrated growth factors (CGF), and platelet-poor plasma (PPP), have gained attention as autologous sources of growth factors enhancing periodontal regeneration. Aim: This narrative review provides a comparative analysis of the biological mechanisms, preparation protocols, and clinical outcomes associated with the adjunctive use of platelet-derived concentrates in non-surgical periodontal therapy. Methods: A narrative literature review was conducted using English-language publications retrieved from PubMed and Google Scholar, covering studies published from 2012 onward. The search strategy was based on combinations of keywords related to platelet-derived concentrates and non-surgical periodontal therapy. In vitro, in vivo, and clinical studies, as well as relevant narrative, systematic, and umbrella reviews evaluating the adjunctive use of platelet-derived concentrates (PRP, PRF, CGF, and PPP) were considered. Studies focusing on biological mechanisms, preparation protocols, and clinical periodontal outcomes were included, whereas case reports, studies unrelated to periodontal therapy, and publications lacking relevant clinical or biological outcome data were excluded. Results: Most clinical studies reported improvements in probing depth reduction, clinical attachment level gain, and bleeding indices following adjunctive use of platelet-derived concentrates with SRP. PRF tended to demonstrate more consistent clinical outcomes compared to PRP, potentially related to its simplified preparation and sustained release of bioactive molecules. CGF showed promising osteogenic and angiogenic properties in preclinical and early clinical studies. PPP, although less extensively investigated, exhibited regenerative and antimicrobial potential in preliminary reports. Conclusions: Platelet-derived concentrates may serve as valuable adjuncts in non-surgical periodontal therapy; however, the current evidence is characterized by methodological heterogeneity and variable study quality. While PRF appears to yield more consistent clinical results, definitive conclusions regarding superiority among different platelet concentrates cannot be drawn. Further well-designed randomized controlled trials are required, particularly for CGF and PPP.

This study assessed the effect of low-dose aspirin (81 mg) on thrombin generation in healthy volunteers using the calibrated automated thrombogram (CAT). This single-center prospective crossover study involved healthy volunteers, each serving as their own control. After Institutional Review Board approval and informed consent, healthy participants were administered aspirin (81 mg daily) for 7 days. Blood samples were collected at baseline, after the 7-day aspirin regimen, and 2 weeks postaspirin discontinuation. Platelet-poor plasma (PPP) samples were analyzed using CAT to measure endogenous thrombin potential (ETP) and other CAT parameters. The primary endpoint was change in ETP from baseline to after 7 days of aspirin. Data were analyzed with paired t tests. Data from 18 participants (ages 27-54) showed no significant change in ETP after aspirin administration (primary endpoint). Specifically, mean (standard deviation) ETP at baseline and on-aspirin were 1750 (237) vs. 1832 (301) nmol/l min, respectively. Secondary CAT parameters (lag time, peak thrombin generation, time to peak, and velocity index) also showed no significant differences. We did not observe a significant effect of low-dose aspirin (81 mg) for 7 days on any measure of thrombin generation in healthy volunteers. This study's controlled design in healthy subjects contrasts with previous studies that focused on patients where confounding effects of comorbidities and concomitant medications may have influenced the results.

Modulation of coagulation activity by thymoquinone (TQ), a 1,4-benzoquinone derivative of Nigella sativa, prompted the identification and validation of a molecular mechanism for hemostasis. Consequently, this research utilizes network pharmacology, molecular docking, and dynamics approaches to investigate the role of TQ for improved hemostasis. Initially, protein targets related to hemostasis and TQ were extracted, where the common targets were subjected to KEGG pathway enrichment and gene ontology analysis to determine the top pathways responsible for inducing hemostasis. The key protein targets from the identified pathways were selected for molecular docking and MM-GBSA calculations, where the targets with the highest absolute Glide docking and ΔGbind scores were further considered for molecular dynamics simulation. The results indicated that TQ exerts potential effects on hemostasis by modulating cMet, PDGFR, and PI3KA proteins involved in the EGFR-TKIR pathway. The nontoxic concentration of TQ was determined using the MTT assay, which revealed a safe concentration (<2.5µM) of TQ for biological applications. In practice, TQ was found to induce the formation of stable fibrin clots in platelet-poor plasma, confirming its hemostatic potential. Finally, in vivo studies in a rat tail hemorrhage model confirmed its clotting activity, where modulation of cMet and PDGFR indicates the potential of TQ in inducing rapid hemostasis. Thus, this study integrated in silico, in vitro, and in vivo approaches to investigate the role of TQ in hemostasis through the EGFR-TKIR pathway, a mechanism that remains largely unexplored in blood clotting.

The effects of pseudoserum on thrombin-induced fibrin networks: Potential for clinical insight into coagulation independent of traditional parameters.

Epigenetic regulation of thrombo-inflammation in Behçet and antiphospholipid syndrome.

Platelet-related biomarkers and catheter-associated thrombosis in critically ill children: An exploratory study.

Prosthechea karwinskii is an orchid endemic to Mexico used for medicinal purposes. The objective of this study was to determine the anticoagulant potential ex vivo of the extract isolated using green solvents. Coagulometric assays were performed to evaluate the anticoagulant activity: activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). For each assay, different concentrations of the extract were evaluated (0.5, 1.0, 1.5, 2.5, 3.5, 4.5, 5.5, 7.5, and 8.5 mg/mL) using platelet-poor plasma from healthy donors. The P. karwinskii leaves extract showed an anticoagulant effect by significantly prolonging (p &lt; 0.05) the APTT and TT from a concentration of 3.5 and 2.5 mg/mL, respectively, compared to basal. The anticoagulant activity was concentration dependent. In addition, the hydroethanolic extract of P. karwinskii leaves inhibited factor XI activity by 86.10 ± 2.3%. The compounds in the extract were identified by ultra-high-performance liquid chromatography coupled with electrospray ionization and quadrupole time-of-flight mass spectrometry (UPLC-ESI-qTOF-MS/MS). The compounds identified were quinic acid, malic acid, succinic acid, L (-)-phenylalanine, guanosine, neochlorogenic acid, chlorogenic acid, rutin, kaempferol-3-O-rutinoside, azelaic acid, sebacic acid, pinellic acid, and embelin.

IntroductionPlatelet-rich plasma (PRP) is widely used for pain relief, wound healing, and so on. However, recent reports have documented cases of infections occurring after PRP therapy. In this study, we aimed to examine potential microbial contamination risks associated with PRP therapy and evaluate rapid microbial detection methods suitable for clinical use.MethodsWe assessed the risk of microbial contamination during blood collection, PRP preparation, and sterility testing. To evaluate suitable detection methods, we compared the microbial detection sensitivities of flow cytometry (FCM) and polymerase chain reaction (PCR) for identifying microbial contamination in PRP. For this purpose, PRP samples were inoculated with Staphylococcus aureus, Streptococcus spp., Cutibacterium acnes, Micrococcus spp., Bacillus subtilis, and Candida albicans.ResultsFollowing skin disinfection, microbial colonies were detected at the venipuncture site in six out of ten patients. Environmental monitoring identified airborne microbial colonies in two out of three anonymous PRP preparation facilities. Sterility tests revealed negative results for all 85 residual PRP and 15 platelet-poor plasma (PPP) cases. FCM sensitivity for microbial detection in PRP was effective at a concentration of 102–103 colony forming units (cfu)/mL or higher. While C. albicans could not be detected separately from non-specific PRP signals using FCM, it was detectable in PPP at ≥102 cfu/mL. PCR sensitivity for microbial detection was excellent when analyzing pure microbial suspensions, however, it yielded a high rate of false-negative and false-positive results when PRP samples contained certain microbial strains.ConclusionThe risks of microbial contamination were identified during both venipuncture and PRP production. To reduce these risks, it may be necessary to improve disinfection protocols for venipuncture sites and blood collection methods, implementing appropriate facility-specific measures. Although requiring further detection sensitivity improvements, FCM is a promising method for detecting viable bacteria in PRP. Given that microbial contamination cannot be completely eliminated, clinicians providing PRP therapy should remain alert to the potential for postoperative infections and ensure appropriate follow-up protocols are established.

Background: Small extracellular vesicles (sEVs) circulate throughout the body via blood. They contain various cargoes, including microRNA (miRNA), and have known roles in modulating inflammation and disease. Plasma-based orthobiologics such as platelet-rich plasma (PRP) are commonly used to treat osteoarthritis and synovitis. The role of extracellular vesicle–derived miRNA in PRP therapy is unknown. Purpose: To characterize sEVs from PRP and platelet-poor plasma (PPP) by using known sEV markers, quantify sEV miRNA content, and evaluate sEV bioactivity via an in vitro IL-1β–induced synovitis model. Study Design: Controlled laboratory study. Methods: sEVs were isolated from leukocyte-rich PRP, leukocyte-poor PRP, and PPP by precipitation or tangential flow methods. The size and concentration of sEVs were quantified, and their cellular origin was determined. The total miRNA content of sEVs was analyzed, and the cellular pathways affected by the sEV miRNA cargo were determined. The effect of plasma-derived sEVs on synoviocyte proliferation and response to inflammation was determined in an IL-1β–induced synovitis model. sEVs were also fluorescently stained, and incorporation was visualized through fluorescent imaging. Results: sEVs isolated from plasma were predominantly derived from platelets, with a small subset derived from monocytes and macrophages. miRNA contained within sEVs targeted various cellular pathways, including metabolism, PI3K-AKT, and calcium signaling. IL-1β–treated synoviocytes treated with native PRP, PPP, or their isolated sEVs were protected from the catabolic effects of IL-1β as compared with the same treatments depleted of sEVs. Conclusion: sEVs were present in all tested fluids. Most sEVs were derived from platelets, with a small subset from white blood cells. miRNA within the sEV affected various cell signaling pathways associated with inflammation, and plasma sEVs were crucial in protecting synoviocytes from inflammation. Clinical Relevance: sEVs in PRP are one mechanism of action by which PRP can protect synoviocytes from inflammation.

Chronic kidney disease is a progressive condition characterized by a decline in kidney function that is the impetus for an increased retention of uremic metabolites (UMs) in the blood compartment which is correlated with adverse patient outcomes. The inefficient clearance of some UMs using membrane hemodialysis is a significant problem, and adsorptive materials are actively being researched to overcome this issue. Albumin is an abundant serum protein known to bind UMs and minimize non-specific protein adsorption at albumin-modified surfaces: two important aspects for designing modified surfaces for clearing UMs from blood. Herein, we anchored albumin to nanoparticles to understand if UM effects on protein-driven host responses to nanoparticles could be minimized. UM doped platelet-poor plasma was used to characterize protein-initiated clotting kinetics and immunoblot analysis of important protein mediators of the immune, fibrinolytic, and coagulation cascades. The amount of particles and density of adsorbed BSA could return clot formation to that seen for uremic plasma controls, but were unable to return these conditions to that seen for normal plasma. These surfaces significantly lower amounts of adsorbed C3, α1-antrypsin, Protein S, cleavage fragments of fibrinogen, prothrombin, factors XI and XII, and antithrombin compared to bare controls with UMs. However, in almost all cases the effect of UMs still led to dramatic increases in adsorbed proteins, and BSA films only reduced adsorption of IgG, vitronectin, prothrombin and antithrombin compared to normal plasma results. BSA films did ameliorate the effect of nanoparticles in uremic plasma. At these concentrations, these films were unable to adsorb enough UMs to negate their effects. This is an important milestone in the design of hemocompatible surfaces for clearing UMs from the blood.

Reduced plasma thrombin generation potential and increased thrombomodulin resistance in β-thalassemia/hemoglobin e

Impact of treatment with fostamatinib on coagulation profile of patients with immune thrombocytopenia

Platelets enhance factor VIII activity through protection from activated Protein C

Cell-free DNA is associated with central venous catheter-associated deep venous thrombosis in critically ill children

Abstract Background: In recent years, orthobiologics have gained a substantial interest for the treatment of various sports related musculoskeletal injuries. However, their use and effectiveness remain controversial. Objectives: In this review, the current literature on the use of orthobiolgoics for sports related injury among kicking athletes was reviewed. The primary goal of the paper is to provide an evidence-based resource for clinicians on the orthobiologics treatment in kicking athletes. Data Sources: Eligible studies were identified through searches of PubMed, ScienceDirect, and Embase up to May 22, 2024. The search terms included “orthobiologics”, “platelet-rich plasma”, “platelet-poor plasma”, “PRP”, “PPP”, bone-marrow aspirate concentrate”, “mesenchymal stem cell”, “BMAC”, “MSC”, “ultrasound guided hydrodissection”, “ultrasound guided hydrodilatation”, “ultrasound guided percutaneous tenotomy”, “barbotage”, “ultrasound guided ablation”, “kicking sport athletes”, “soccer player”, “placekicker”, “futsal”, “football”, and “soccer”. Main results: The initial literature search yielded 2264 articles after duplicates were excluded. After screening titles and abstracts, 138 articles were assessed for eligibility. Following the full-text evaluation, a total of 20 articles were included in the final analysis. Of the 20 studies, 2 were randomized control trials, 1 was a retrospective cohort study, 4 were case series, and 13 were case reports. The average Coleman Methodology Score modified for conservative therapy for all included studies is 30.30 (range 18-74) and overall the quality is in the poor range. Conclusions: While platelet-rich plasma and prolotherapy appear to be a safe adjunctive treatment, comparison and outcome interpretation are limited due to the nature of heterogeneity of the PRP protocols and pathologies reported among reviewed studies. Future studies are warranted to evaluate orthobiologics treatment, focusing on protocols including the timing, dosing/concentration, and number of injections, to allow clinicians to understand utility of orthobiologics treatment when treating kicking athletes.

Background and Aims: Transthyretin amyloidosis (ATTRwt) is a progressive and life-threatening disorder caused by misfolding and extracellular deposition of transthyretin. Thromboembolic events are common in ATTRwt, with a reported prevalence of 6-28%. Recent evidence suggests that extracellular vesicles (EVs) may play a role in the pathogenesis of amyloidosis related complications. The analysis of EVs in ATTRwt may unveil disease-specific alterations in intercellular communication, contributing to understand amyloidogenic mechanisms and to discover novel biomarkers for diagnosis and prognosis. The study aims: i) to compare plasma-derived EVs in ATTRwt patients vs. healthy controls by new generation flow cytometry (CytoFLEX S); ii) to evaluate their potential involvement in disease progression. Methods: Twenty-four ATTRwt patients (median age 78 yrs; 17 males, 7 females) were included and compared with 9 (4 males and 5 females) aged matched (±3 yrs) healthy controls. Large extracellular vesicles (L-EVs) were isolated from platelet-poor plasma by centrifugation at 14,000 g for 30 min at 4°C, immunolabeled with calcein-am/-red, annexin V, CD41, CD62P, CD45, CD14, CD62E, anti-human-tissue factor and CD105, and resuspended in 120 μl of sterile filtered Annexin V buffer. For EV size calibration, fluorescent polystyrene beads Gigamix were used to set a rectangular gate between 0.2 and 0.9 μm bead populations, defined as L-EVs gate. The side scatter from the 405 nm violet laser was used as a trigger signal to discriminate the noise with a size detection limit of 80 nm. Parallel incubation was performed with isotype-matched control and with the secondary antibodies alone to exclude non-specific staining. Unstained samples were used as negative control and flow cytometer acquisition settings were maintained for all samples. EVs were expressed as events/μl (absolute count) with the volume measurement of the CytoFLEX S. This research was funded by the PRINN 2022 grant-PROT. 2022ZSA2JP. Results: Angiogenesis-related L-EVs expressing Annexin V and CD105 were significantly higher in cases vs. controls (p&lt;0.001), reflecting endothelial activation and ongoing vascular remodeling (Table 1). According to the inflammation panel, AnnexinV+CD45+ and AnnexinV+CD14+ L-EVs were significantly higher in cases vs. controls (p&lt;0.001), consistent with a heightened inflammatory state (Table 1). No significant differences according to platelet- and endothelial-derived L-EVs were observed between cases and controls (Table 1). Conclusions: In conclusion, ATTRwt patients display a L-EV profile characterized by endothelial activation and inflammation. Platelet- and endothelial-derived L-EVs were similar between cases and controls. Our findings support EVs as potential biomarkers of vascular and immune dysfunction in the studied population though their clinical role remains to be elucidated.

Background and Aims: Porto-sinusoidal vascular disorder (PSVD) has recently been proposed to delineate a group of hepatic vascular diseases characterized by lesions involving the portal venules and sinusoids, irrespective of the presence/absence of portal hypertension. Although data is still limited, several hypotheses and emerging evidence suggest that extracellular vesicles (EVs) might exert a functional role in the pathogenesis of PSVD. The analysis of EVs in PSVD may unveil disease-specific alterations in intercellular communication, contributing to understand the prothrombotic mechanisms and to discover novel biomarkers for diagnosis and prognosis. The study aims: i) to compare plasma-derived EVs in PSVD patients vs. healthy controls by flow cytometry; ii) to evaluate their potential involvement in disease progression. Methods: Twenty-nine PSVD patients (median age 58 yrs; 20 males, 9 females) were included and compared with 9 (4 males and 5 females) aged matched (±3 yrs) healthy controls. Large extracellular vesicles (L-EVs) were isolated from platelet-poor plasma by centrifugation at 14,000 g for 30 min at 4°C, immunolabeled with calcein-AM, annexin V, CD41, CD62P, CD45, CD14, CD62E, anti-human-tissue factor (TF), CD105 and CD147. For EV size calibration, fluorescent polystyrene beads Gigamix were used to set a gate between 0.2 and 0.9 μm bead populations, defined as L-EVs gate. EVs were expressed as events/μl (absolute count) with the volume measurement of the CytoFLEX S. Results: All enrolled patients had histologically confirmed PSVD. Among them, 12 had unprovoked PSVD, 4 were drug-related, 3 were associated with gastrointestinal diseases, 3 with immune-mediated conditions, and 7 cases were linked to myeloproliferative disorders. Endothelium-derived L-EVs co-expressing calcein-AM, annexin V, CD62E, and TF were significantly increased in PSVD patients compared to healthy controls (p&lt;0.0001), reflecting endothelial activation and prothrombotic predisposition (Table 1). Patients also exhibited a marked increase in platelet-derived L-EVs, particularly calcein-AM+/annexin V+/CD41+/CD62P+ L-EVs (p=0.004), indicating enhanced platelet activation and a contribution to vascular and coagulative responses (Table 1). Notably, endothelial and platelet L-EV significantly correlated with PSVD etiology (r=0.38, p=0.04), with patients affected by myeloproliferative disease–related PSVD showing significantly higher levels than those with other etiologies (p=0.046 and 0.032, respectively). Angiogenesis-related calcein-AM+/annexin V+/CD105+/CD147+ L-EVs were significantly elevated in patients compared to controls (p&lt;0.0001), suggesting active vascular remodeling. Regarding the inflammatory panel, patients showed significantly lower levels of calcein-AM+/annexin V+/CD45+/CD14+ L-EVs compared to controls (p=0.0002), indicating reduced monocyte/leukocyte-driven inflammatory activation (Table 1). Conclusions: In conclusion, patients with PSVD display a L-EV profile characterized by vascular remodeling, endothelial and platelet activation. On the other hand, patients exhibited significantly lower levels of inflammatory L-EVs, suggesting limited systemic immune activation. Our preliminary findings support the hypothesis that PSVD is primarily driven by endothelial dysfunction and platelet activation, rather than by leukocyte-mediated inflammation. The etiology of PSVD appears to influence L-EV levels.

Venous thromboembolism (VTE) is a serious complication of pediatric acute lymphoblastic leukemia (ALL), primarily occurring during induction therapy and associated with acquired hemostatic abnormalities. However, the contribution of leukemic lymphoblasts to hypercoagulability remains unexplored. This study aimed to determine whether leukemic lymphoblasts express hemostatic factors that promote a hypercoagulable state and to assess the functional impact of lysed lymphoblasts on thrombin and fibrin generation.We examined the expression of 28 hemostatic factors at both mRNA and protein levels in four pediatric leukemic cell lines (T-ALL and B-ALL) and normal lymphocytes using RT-PCR and immunoblotting. To evaluate the overall functional effect, we conducted thrombin and fibrin generation assays by adding cell lysates to platelet-poor plasma in the absence of exogenous tissue factor or phospholipids.Leukemic lymphoblasts constitutively expressed the procoagulants tissue factor, factor VIII and factor XIIIa; the coagulation inhibitors antithrombin, ADAMTS13 and TFPI; and the pro-fibrinolytic and antifibrinolytic proteins uPA, TAFI, and α2-AP. Lysed, but not intact, leukemic lymphoblasts enhanced thrombin and fibrin generation, indicating a procoagulant state. Additionally, leukemic lysates exhibited a hypo-fibrinolytic state, as evidenced by prolonged fibrin clot lysis times.These findings suggest that leukemic lymphoblasts actively contribute to a hypercoagulable state in pediatric ALL by simultaneously increasing procoagulant activity and impairing fibrinolysis. This study provides novel insights into the mechanisms underlying VTE risk in pediatric ALL, highlighting the role of leukemic lymphoblasts in disrupting the hemostatic balance. · Leukemic lymphoblasts express hemostatic system factors at gene and protein levels.. · Leukemic lymphoblasts lysis directly contributes to hypercoagulability and hypofibrinolysis in thrombin and fibrin generation assays..

Traditionally, platelets were thought to originate solely in the bone marrow, but emerging evidence now indicates that the lung is a major site of platelet generation. Our previous work, along with studies by others, has revealed decreased platelet counts and enhanced platelet activation in BPD patients, linking platelets to the disease's pathogenesis. We investigated the protective effects and underlying mechanisms of umbilical cord blood (UCB) platelets in mitigating hyperoxia-induced lung injury in neonatal rats and in vitro. Compared with platelet-poor plasma (PPP), UCB-derived platelets (PLT) treatment preserved lung development, as evidenced by an increased density of secondary crests and reduced small arterial wall thickness. Given that secondary crest formation depends on myofibroblast activity, we further examined the cellular function of myofibroblasts isolated from the lungs of control and hyperoxic mice. We found that hyperoxia impaired myofibroblast function, particularly their migration capacity, which can be prevented by UCB platelet lysate. These findings suggest that UCB PLT preserve lung development by protecting myofibroblast migratory capacity, offering new insights into BPD pathogenesis and potential therapeutic strategies. Hyperoxia impairs myofibroblast function, particularly their migratory capacity, which can be prevented by umbilical cord blood platelet lysate. Umbilical cord blood platelets preserve lung development in hyperoxia-exposed newborn rats by increasing the density of secondary crests and mitigating vascular remodeling in small arteries. These findings underscore the promising therapeutic potential of umbilical cord blood-derived platelets for the management of BPD.