Platelets最新文献

Light transmission aggregometry (LTA) is commonly used to diagnose platelet disorders and has a specific pattern in Glanzmann thrombasthenia (GT). As there is currently no adequate test to assess the efficacy of platelet transfusion, we explored whether LTA can be used to monitor the platelet response following platelet transfusion. We retrospectively evaluated LTA results after platelet transfusion in four patients with GT. After transfusion of two units of platelets, aggregation assessed by LTA remained reduced for all platelet agonists except ristocetin, despite a satisfactory clinical effect on hemostasis. One patient received seven units, after which a change in LTA results was observed. In this heterogeneous case cohort, the LTA response did not correlate with the clinical response after platelet transfusion in GT. To draw definitive conclusions, a study in a larger population that controls for influencing factors - such as the timing and dose of platelet transfusion and the use of a standardized LTA procedure - should be conducted.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for various malignancies, but they are associated with a range of immunerelated adverse events, including rare hematological complications. Immune thrombocytopenia (ITP) has been reported with other antiPD1 agents such as nivolumab and pembrolizumab, but to date, no cases have been described with dostarlimab. We report the first case of ITP in a patient receiving dostarlimab for relapsed endometrial carcinoma. A 55yearold woman developed severe thrombocytopenia (3 × 10⁹/L) accompanied by rectal bleeding, resulting in a lifethreatening condition. Secondary causes were excluded, and bone marrow findings supported a diagnosis of ITP. Initial treatment with highdose corticosteroids and intravenous immunoglobulin achieved only a partial response, while sustained platelet recovery was obtained with the addition of romiplostim. The patient remained on dostarlimab following hematological recovery without further episodes of ITP. This case highlights a potentially lifethreatening adverse effect of a widely used immunotherapy and underscores the importance of early recognition and timely escalation of treatment in ICIinduced ITP.

The platelet is the most important cell in the bloodstream in providing endovascular immunity against Staphylococcus aureus bacteremia. Both quantitative and qualitative thrombocytopenia have been associated with increased mortality in patients with S. aureus bacteremia. Patients with end-stage renal disease are particularly vulnerable to both an increased risk of getting S. aureus bacteremia and endocarditis, but also in treatment failure resulting in prolonged infection and relapse. In this commentary, we highlight the important host-pathogen relationship between S. aureus and the human platelet. In particular, we describe virulence factor-mediated platelet clearance from the circulation and improvement in platelet counts as a marker of treatment success. P2Y12 inhibitors deployed in the treatment of cardiovascular disease have been shown to attenuate the effect of S. aureus on platelet clearance. Therefore, we believe that partnerships between investigators in cardiology, hematology, and infectious disease with particular focus on platelet pathophysiology are poised to improve outcomes in select patients with S. aureus endovascular infection.

Glanzmann thrombasthenia (GT), caused by defects in integrin αIIbβ3, is characterized by impaired platelet aggregation. While αIIbβ3 dysfunction is well-documented in hematologic pathology, its association with bone metabolism remains controversial. Here, we report a 14-year-old GT patient with a novel compound heterozygous mutation in ITGA2B (Arg358His and Leu466Pro) and asymptomatic radial osteoporosis. Platelet aggregation assays and flow cytometry confirmed type I GT with severely reduced CD41/CD61 expression (<5%). Structural modeling revealed that both mutations destabilize the β-propeller domain of αIIb, leading to protein degradation. Notably, dual-energy X-ray absorptiometry demonstrated osteoporosis, despite the absence of secondary causes. This case expands the genotypic spectrum of GT and provides clinical evidence linking ITGA2B mutations to abnormal bone metabolism.

Thrombopoietin (TPO) is the principal regulator of bone marrow platelet production and plays an important role in maintaining hematopoietic stem and progenitor cells. Predominantly produced in the liver, circulating TPO levels are primarily modulated through receptor-mediated clearance of TPO by target cells such as platelets. However, there is an additional component of TPO regulation at the transcriptional level, which may be affected in the setting of platelet-associated diseases. Current TPO knockout mouse models partially limit the study of transcriptional regulation because of disruption of the TPO genomic locus. Here, we describe a novel mouse model of TPO deficiency arising from a spontaneous mutation in a single base pair within exon 5 of the TPO gene. The resulting amino acid change (leucine to histidine at position 121) predicts a dramatic alteration in protein structure, ultimately resulting in a ~ 95% decrease of circulating TPO. The hematological phenotype of this new C57Bl/6(IMPC)J-TPO^L121H strain mimics that of other mouse models of TPO deficiency, but the genomic locus remains intact and therefore preserves normal TPO transcriptional regulation. We characterize the hematological phenotype of this new strain and discuss its applications as a model of transcriptional TPO regulation and clinical thrombocytopenia. Our findings highlight the theoretical possibility that TPO protein destabilizing mutations may explain rare cases of patient thrombocytopenia.

Platelets, traditionally known for their role in hemostasis, also contribute to inflammation, cancer, and intercellular communication through the release of platelet-derived extracellular vesicles (or platelet-derived microparticles; PMPs). Among these vesicles, a subpopulation containing functional mitochondria, known as mitoMPs, can be transferred to recipient cells, thereby modulating their metabolism and biological responses. This mitochondrial transfer plays a key role in various pathological processes, where it may either restore metabolic functions or enhance cancer cell proliferation, survival, and metabolic plasticity. In this study, we developed a permeabilization protocol combined with high-resolution respirometry to assess mitochondrial respiration in both platelets and PMPs. First, we found that saponin was a more effective permeabilizing agent than digitonin to measure mitochondrial respiration in these models. Moreover, our analysis revealed distinct respiratory profiles between platelets and PMPs and demonstrated that freeze-thaw cycles severely compromise mitochondrial functions in PMPs. Additionally, we performed proteomic profiling of PMPs to characterize their protein cargo, which associate with specific molecular pathways, particularly those associated with mitochondrial metabolism. These results provide novel insights into the biological functions of PMPs and their potential involvement in disease processes. Together, these findings advance the understanding of PMP-mediated mitochondrial transfer and intercellular communication and establish a foundation for future biomedical and therapeutic investigations.

While platelets for transfusion are traditionally stored at room temperature (20-24°C), cryopreservation at -80°C is attractive, as it facilitates an extension of the shelf-life from 7 days to several years. Cryopreserved platelets display enhanced procoagulant capacity, which may distort the balance between clot formation and resolution. Platelets were frozen at -80°C using DMSO and thawed and resuspended in fresh plasma before testing. Fresh components (day 1) were tested in parallel. The supernatant of thawed platelets contained a higher concentration of fibrinogen, plasminogen, TAFI, FXIII, PAI-1, and tPA, compared to fresh platelets. However, this was primarily due to the addition of fresh plasma at the time of platelet thawing, with the exception of PAI-1. Thawed platelets displayed a higher surface abundance of PAI-1 and FXIII, compared to fresh platelets. The clots formed by thawed platelets underwent retraction; although this was affected by time and platelet concentration. tPA-induced fibrinolysis, measured by thromboelastography (TEG), was not statistically different between fresh and thawed platelets. Although differences in the abundance of fibrinolytic mediators were observed in thawed platelets, compared to room temperature platelets, clot resolution properties were conserved. This work provides a more complete understanding of the overall hemostatic capacity of cryopreserved platelets.

Patients receiving hemodialysis (HD) are susceptible to bleeding and thrombosis. We assessed whether the T-TAS assay - which measures platelet thrombus formation (PL-AUC) and fibrin-rich thrombus formation (AR-OT) in whole blood under flow - could predict these complications in 176 chronic HD patients, monitoring bleeding and thromboembolic events over one year. During follow-up, 29 patients (16.5%) experienced at least one major or clinically relevant non-major bleeding (CRNMB) event, while 31 patients (17.6%) had at least one thromboembolic event. Patients with low thrombogenicity (PL-AUC below the median) had a more than fivefold increased risk of major bleed/CRNMB in multivariate analyses, and a C-statistic (ROC-AUC; 95% CI) for discrimination between future bleeding/no bleeding of 0.82 (0.74-0.90). AR-OT data showed comparable results. Further, the risk of thromboembolism was significantly lower in patients with PL-AUC below the median (multivariate OddsRisk [OR] ~0.20; C-statistic for thromboembolism/no thromboembolism of 0.73 [0.64-0.83]). Reduced fibrin-rich thrombus formation (AR-OT above median) was associated with ORs below 0.50 to develop thromboembolism in multivariate analyses (C-statistic 0.75 [0.65-0.85]). Excluding patients on oral antithrombotic agents (i.e. aspirin (n = 20) and warfarin (n = 14)), resulted in similar findings. In conclusion, T-TAS is a promising tool for assessing bleeding and thrombosis risk in HD patients.

Appropriate platelet function determines both the perioperative haemostasis and the risk of postoperative thrombotic complications in patients undergoing branched endovascular repair (bEVAR) of thoracoabdominal aortic aneurysm (TAAA). We aimed to assess the effect of bEVAR on platelet function and the predictive value of preoperative platelet function for postoperative bleeding. We measured platelet function using impedance aggregometry and total thrombus-formation analysis system in 50 consecutive patients, with TAAA undergoing elective bEVAR. After bEVAR, platelet reactivity was assessed using ASPI test, ADP test and TRAP test and thrombus size decreased, whereas time to clot formation increased, compared to baseline (p ≤ .042 for all). Preoperative platelet reactivity in the TRAP test was lower in patients who experienced post-operative bleeding, defined as ≥3 red blood cell units transfusion, compared to those who did not (p = .038). Baseline hemoglobin level <13 g/dl and TRAP test result ≤29.5 AUC increased the odds of bleeding by 5.4-fold and 6.8-fold, respectively, independent of other clinical variables. We conclude that in patients with TAAA undergoing bEVAR, platelet reactivity and platelet-rich thrombus formation decreased directly after the operation. Preoperative hemoglobin level and platelet reactivity in the TRAP test were independent predictors of postoperative bleeding complications.

Coronary artery disease is among the leading causes of morbidity and mortality worldwide, posing a significant threat to human health and life. Aspirin is widely used in the treatment of coronary artery disease, however, long-term use may increase the risk of bleeding. Urinary 11-dehydro-TXB2, a biomarker indicative of platelet activation, has been associated with thrombotic events, but its association with bleeding events remains unexplored. This study aimed to assess the predictive value of TXB2-M levels for bleeding events in patients with coronary artery disease undergoing aspirin therapy. Multifactorial logistic regression analysis was employed to evaluate the potential of TXB2-M levels as a reliable marker for bleeding risk following aspirin use. Among patients with coronary artery disease treated with aspirin, those with lower TXB2-M levels exhibited an increased risk of bleeding events within three years (Hazard Ratio: 0.46; 95% Confidence Interval: 0.26-0.79; P < 0.05). Additionally, variations in TXB2-M levels were observed across different demographic groups. This study reinforces the validity of TXB2-M levels as a biomarker for identifying patients at elevated risk of bleeding, thus facilitating the implementation of personalized treatment strategies to minimize bleeding risks while preserving the efficacy of antithrombotic therapy.