Platelets最新文献_第8页

First-in-human study to assess the safety, pharmacokinetics, and pharmacodynamics of BMS-986141, a novel, reversible, small-molecule, PAR4 agonist in non-Japanese and Japanese healthy participants. BMS-986141(一种新型、可逆的小分子PAR4激动剂)在非日本人和日本健康参与者中的安全性、药代动力学和药效学的首次人体研究

IF 3.3 3区医学

Platelets Pub Date : 2023-12-01 DOI: 10.1080/09537104.2023.2222846

Samira Merali, Zhaoqing Wang, Charles Frost, Stephanie Meadows-Shropshire, Dara Hawthorne, Jing Yang, Dietmar Seiffert

{"title":"First-in-human study to assess the safety, pharmacokinetics, and pharmacodynamics of BMS-986141, a novel, reversible, small-molecule, PAR4 agonist in non-Japanese and Japanese healthy participants.","authors":"Samira Merali, Zhaoqing Wang, Charles Frost, Stephanie Meadows-Shropshire, Dara Hawthorne, Jing Yang, Dietmar Seiffert","doi":"10.1080/09537104.2023.2222846","DOIUrl":"10.1080/09537104.2023.2222846","url":null,"abstract":"BMS-986141 is a novel, oral, protease-activated, receptor 4 (PAR4)-antagonist that exhibited robust antithrombotic activity and low bleeding risk in preclinical studies. The pharmacokinetic, pharmacodynamic, and tolerability profiles of BMS-986141 in healthy participants were assessed in a randomized, double-blind, placebo-controlled, single-ascending-dose (SAD; N = 60) study; a multiple-ascending-dose (MAD; N = 32) study; and a Japanese MAD (JMAD; N = 32) study. Exposure was dose-proportional for BMS-986141 2.5 mg and 150 mg; maximum concentrations were 17.6 ng/mL and 958 ng/mL; and areas under the curve (AUC) to infinity were 183 h* × ng/mL and 9207 h* × ng/mL, respectively. Mean half-life ranged from 33.7 to 44.7 hours across dose panels. The accumulation index following once-daily administration for 7 days suggested a 1.3- to 2-fold AUC increase at steady state. In the SAD study, BMS-986141 75 and 150 mg produced ≥80% inhibition of 25-100 µM PAR4 agonist peptide (AP)-induced platelet aggregation, without affecting PAR1-AP-induced platelet aggregation, through ≥24 hours postdose. In the MAD and JMAD studies, BMS-986141 doses ≥10 mg completely inhibited 12.5 μM and 25 μM PAR4-AP-induced platelet aggregation through 24 hours. This study found BMS-986141 was safe and well tolerated, with dose-proportional pharmacokinetics and concentration-dependent pharmacodynamics in healthy participants over a wide dose range. ClinicalTrials.gov ID: NCT02341638.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2222846"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9745065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy and safety of high dose recombinant human thrombopoietin in the treatment of immune thrombocytopenia. 大剂量重组人血小板生成素治疗免疫性血小板减少症的疗效和安全性。

IF 3.3 3区医学

Platelets Pub Date : 2023-12-01 Epub Date: 2023-11-08 DOI: 10.1080/09537104.2023.2271568

Xiuli Wang, Hui Bi, Lin Liu, Yuebo Liu, Liefen Yin, Jin Yao, Jingxing Yu, Wei Tao, Yueping Wei, Yu Li, Lingmei Yin, Hongli Mu, Yadong Du, Zeping Zhou

{"title":"Efficacy and safety of high dose recombinant human thrombopoietin in the treatment of immune thrombocytopenia.","authors":"Xiuli Wang, Hui Bi, Lin Liu, Yuebo Liu, Liefen Yin, Jin Yao, Jingxing Yu, Wei Tao, Yueping Wei, Yu Li, Lingmei Yin, Hongli Mu, Yadong Du, Zeping Zhou","doi":"10.1080/09537104.2023.2271568","DOIUrl":"10.1080/09537104.2023.2271568","url":null,"abstract":"The conventional dose of recombinant human thrombopoietin (rhTPO) in the treatment of immune thrombocytopenia (ITP) is 300 U/kg per day, but the clinical reaction rate is not satisfactory. Accordingly, we explored the efficacy and safety of increasing rhTPO dose in the treatment of ITP. A retrospective study was conducted to collect the clinical data of 105 ITP patients who were divided into two groups, a low-dose group (15 000 U/day) and a high-dose group (30 000 U/day) according to the dose of rhTPO. The total effective rate of the low-dose group and the high-dose group was 31/44 (70.45%) vs. 56/61 (91.80%) (P = .049), and the average time of using rhTPO in the high-dose group was shorter than that in the low-dose group (7 days vs. 10 days, P = .001). On the 7th and 14th day of treatment, the efficacy of the high-dose group was better than that of the low-dose group [45/61 (73.77%) vs. 17/44 (38.64%), P < .001; 55/60 (91.67%) vs. 30/44 (68.18%), P < .05)]. The incidence of treatment related adverse events in the low-dose group and the high-dose group was 6/44 (13.64%) vs. 6/61 (9.84%) (P > .05), which were mild and transient in nature. In our study, high-dose rhTPO had good efficacy and high safety in the treatment of ITP with the efficacy better than low-dose rhTPO especially at day 7.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2271568"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71522412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

C-type lectin-like receptor-2 (CLEC-2) is a key regulator of kappa-carrageenan-induced tail thrombosis model in mice. c型凝集素样受体-2 (clc -2)是kappa- carragean诱导小鼠尾部血栓形成模型的关键调控因子。

IF 3.3 3区医学

Platelets Pub Date : 2023-12-01 Epub Date: 2023-11-27 DOI: 10.1080/09537104.2023.2281941

Ryohei Yokomori, Toshiaki Shirai, Nagaharu Tsukiji, Saori Oishi, Tomoyuki Sasaki, Katsuhiro Takano, Katsue Suzuki-Inoue

{"title":"C-type lectin-like receptor-2 (CLEC-2) is a key regulator of kappa-carrageenan-induced tail thrombosis model in mice.","authors":"Ryohei Yokomori, Toshiaki Shirai, Nagaharu Tsukiji, Saori Oishi, Tomoyuki Sasaki, Katsuhiro Takano, Katsue Suzuki-Inoue","doi":"10.1080/09537104.2023.2281941","DOIUrl":"10.1080/09537104.2023.2281941","url":null,"abstract":"Kappa-carrageenan (KCG), which is used to induce thrombosis in laboratory animals for antithrombotic drug screening, can trigger platelet aggregation. However, the cell-surface receptor and related signaling pathways remain unclear. In this study, we investigated the molecular basis of KCG-induced platelet activation using light-transmittance aggregometry, flow cytometry, western blotting, and surface plasmon resonance assays using platelets from platelet receptor-deficient mice and recombinant proteins. KCG-induced tail thrombosis was also evaluated in mice lacking the platelet receptor. We found that KCG induces platelet aggregation with α-granule secretion, activated integrin αIIbβ3, and phosphatidylserine exposure. As this aggregation was significantly inhibited by the Src family kinase inhibitor and spleen tyrosine kinase (Syk) inhibitor, a tyrosine kinase-dependent pathway is required. Platelets exposed to KCG exhibited intracellular tyrosine phosphorylation of Syk, linker activated T cells, and phospholipase C gamma 2. KCG-induced platelet aggregation was abolished in platelets from C-type lectin-like receptor-2 (CLEC-2)-deficient mice, but not in platelets pre-treated with glycoprotein VI-blocking antibody, JAQ1. Surface plasmon resonance assays showed a direct association between murine/human recombinant CLEC-2 and KCG. KCG-induced thrombosis and thrombocytopenia were significantly inhibited in CLEC-2-deficient mice. Our findings show that KCG induces platelet activation via CLEC-2.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2281941"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138445980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of clinical characteristics and treatment efficacy in two pediatric cases of ANKRD26-related thrombocytopenia. 两例儿童ANKRD26相关血小板减少症的临床特征和治疗效果分析。

IF 3.3 3区医学

Platelets Pub Date : 2023-12-01 Epub Date: 2023-10-18 DOI: 10.1080/09537104.2023.2262607

Congfei Pang, Xiaomei Wu, Lauriane Nikuze, Hongying Wei

{"title":"Analysis of clinical characteristics and treatment efficacy in two pediatric cases of ANKRD26-related thrombocytopenia.","authors":"Congfei Pang, Xiaomei Wu, Lauriane Nikuze, Hongying Wei","doi":"10.1080/09537104.2023.2262607","DOIUrl":"10.1080/09537104.2023.2262607","url":null,"abstract":"ANKRD26-related thrombocytopenia (ANKRD26-RT or THC2, MIM 188 000), an autosomal dominant thrombocytopenia, is unresponsive to immunosuppressive therapy and susceptible to hematological malignancies. A large number of pediatric patients are diagnosed with immune thrombocytopenia (ITP) every year; however, thrombocytopenia of genetic origin is often missed. Extensive characterization of ANKRD26-RT will help prevent missed diagnosis and misdiagnosis. Furthermore, identification of ANKRD26-RT will help in the formulation of an accurate diagnosis and a treatment plan. In our study, we report cases of two Chinese pediatric patients with ANKRD26-RT and analyze their clinical characteristics, gene mutations, and treatment modalities. Both patients were 1-year-old and presented with mild bleeding (World Health Organization(WHO) score grade 1), different degrees of platelet reduction, normal mean platelet volume, and megakaryocyte maturation impairment not obvious. Genetic tests revealed that both patients had ANKRD26 gene mutations.Patient 1 had a mutation c.-140C>G of the 5' untranslated region (UTR), and patient 2 had a mutation of c.-127A>T of 5'UTR. Both patients were treated with eltrombopag, and the treatment was no response, with no adverse reactions.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2262607"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49681386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tissue inhibitors of metalloproteinases (TIMPs) modulate platelet ADAM10 activity. 金属蛋白酶组织抑制剂(TIMPs)调节血小板ADAM10活性。

IF 3.3 3区医学

Platelets Pub Date : 2023-12-01 Epub Date: 2023-11-30 DOI: 10.1080/09537104.2023.2288213

Christine Shu Mei Lee, Amandeep Kaur, Samantha J Montague, Sarah M Hicks, Robert K Andrews, Elizabeth E Gardiner

{"title":"Tissue inhibitors of metalloproteinases (TIMPs) modulate platelet ADAM10 activity.","authors":"Christine Shu Mei Lee, Amandeep Kaur, Samantha J Montague, Sarah M Hicks, Robert K Andrews, Elizabeth E Gardiner","doi":"10.1080/09537104.2023.2288213","DOIUrl":"https://doi.org/10.1080/09537104.2023.2288213","url":null,"abstract":"Platelet-specific collagen receptor glycoprotein (GP)VI is stable on the surface of circulating platelets but undergoes ectodomain cleavage on activated platelets. Activation-dependent GPVI metalloproteolysis is primarily mediated by A Disintegrin And Metalloproteinase (ADAM) 10. Regulation of platelet ADAMs activity is not well-defined however Tissue Inhibitors of Metalloproteinases (TIMPs) may play a role. As levels of TIMPs on platelets and the control of ADAMs-mediated shedding by TIMPs has not been evaluated, we quantified the levels of TIMPs on the surface of resting and activated platelets from healthy donors by flow cytometry and multiplex ELISA. Variable levels of all TIMPs could be detected on platelets. Plasma contained significant quantities of TIMP1 and TIMP2, but only trace amounts of TIMP3 and TIMP4. Recombinant TIMP3 strongly ablated resting and activated platelet ADAM10 activity, when monitored using a quenched fluorogenic peptide substrate with ADAM10 specificity. Whilst ADAM10-specific inhibitor GI254023X or ethylenediamine tetraacetic acid (EDTA) could modulate ligand-initiated shedding of GPVI, only recombinant TIMP2 achieved a modest (~20%) inhibition. We conclude that some platelet TIMPs are able to modulate platelet ADAM10 activity but none strongly regulate ligand-dependent shedding of GPVI. Our findings provide new insights into the regulation of platelet receptor sheddase activity.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2288213"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An oligogenic case of severe neonatal thrombocytopenia and a purportedly benign variant in GFI1B requiring reinterpretation. 严重新生儿血小板减少的少原性病例和GFI1B的良性变异需要重新解释。

IF 2.5 3区医学

Platelets Pub Date : 2023-12-01 DOI: 10.1080/09537104.2023.2237592

Max Frenkel, April Hall, M Stephen Meyn, Carol A Diamond

{"title":"An oligogenic case of severe neonatal thrombocytopenia and a purportedly benign variant in GFI1B requiring reinterpretation.","authors":"Max Frenkel, April Hall, M Stephen Meyn, Carol A Diamond","doi":"10.1080/09537104.2023.2237592","DOIUrl":"10.1080/09537104.2023.2237592","url":null,"abstract":"Although thrombocytopenia in neonatal intensive care patients is rarely due to inherited disorders, the number of genetic variants implicated in platelet defects has grown dramatically with increasing genome-wide sequencing. Here we describe a case of severe, oligogenic neonatal thrombocytopenia and reinterpret a reportedly benign mutation that is likely pathogenic. Despite this patient's synonymous mutation (GFI1B 576 C>T, Phe192=) being annotated as benign, GFI1B is a well-known regulator of megakaryopoiesis, this variant alters splicing and megakaryocyte maturation, and our analysis of existing genome-wide associated studies demonstrates that it likely causes gray platelet syndrome. This variant has not been reported in a case of life-threatening thrombocytopenia. We propose that the severity of this patient's phenotype is due to synergistic epistasis between the intrinsic platelet defect caused by this mutation and her concomitant inherited PMM2 congenital glycosylation disorder neither of which have been associated with such a severe phenotype. This case highlights the importance of whole-exome/genome sequencing for critically ill patients, reexamining variant interpretation when clinically indicated, and the need to study diverse genetic variation in hematopoiesis.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2237592"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10653983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9996743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The prospects of microphysiological systems in modeling platelet pathophysiology in cancer. 微生理系统在模拟肿瘤血小板病理生理中的应用前景。

IF 2.5 3区医学

Platelets Pub Date : 2023-12-01 DOI: 10.1080/09537104.2023.2247489

Lopamudra D Ghosh, Abhishek Jain

{"title":"The prospects of microphysiological systems in modeling platelet pathophysiology in cancer.","authors":"Lopamudra D Ghosh, Abhishek Jain","doi":"10.1080/09537104.2023.2247489","DOIUrl":"10.1080/09537104.2023.2247489","url":null,"abstract":"The contribution of platelets is well recognized in thrombosis and hemostasis. However, platelets also promote tumor progression and metastasis through their crosstalk with various cells of the tumor microenvironment (TME). For example, several cancer models continue to show that platelet functions are readily altered by cancer cells upon activation leading to the formation of platelet-tumor aggregates, triggering release of soluble factors from platelet granules and altering platelet turnover. Further, activated platelets protect tumor cells from shear forces in circulation and assault of cytotoxic natural killer (NK) cells. Platelet-secreted factors promote proliferation of malignant cells, metastasis, and chemoresistance. Much of our knowledge of platelet biology in cancer has been achieved with animal models, particularly murine. However, this preclinical understanding of the complex pathophysiology is yet to be fully realized and translated to clinical trials in terms of new approaches to treat cancer via controlling the platelet function. In this review, we summarize the current state of knowledge of platelet physiology obtained through existing in vivo and in vitro cancer models, the complex interactions of platelets with cancer cells in TME and the pathways by which platelets may confer chemoresistance. Since the FDA Modernization Act recently passed by the US government has made animal models optional in drug approvals, we critically examine the existing and futuristic value of employing bioengineered microphysiological systems and organ-chips to understand the mechanistic role of platelets in cancer metastasis and exploring novel therapeutic targets for cancer prevention and treatment.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2247489"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10578702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10115353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep learning, 3D ultrastructural analysis reveals quantitative differences in platelet and organelle packing in COVID-19/SARSCoV2 patient-derived platelets. 深度学习、3D超微结构分析揭示了新冠肺炎/SARSCoV2患者衍生血小板中血小板和细胞器包装的定量差异。

IF 2.5 3区医学

Platelets Pub Date : 2023-12-01 Epub Date: 2023-11-07 DOI: 10.1080/09537104.2023.2264978

Sagar S Matharu, Cassidy S Nordmann, Kurtis R Ottman, Rahul Akkem, Douglas Palumbo, Denzel R D Cruz, Kenneth Campbell, Gail Sievert, Jamie Sturgill, James Z Porterfield, Smita Joshi, Hammodah R Alfar, Chi Peng, Irina D Pokrovskaya, Jeffrey A Kamykowski, Jeremy P Wood, Beth Garvy, Maria A Aronova, Sidney W Whiteheart, Richard D Leapman, Brian Storrie

{"title":"Deep learning, 3D ultrastructural analysis reveals quantitative differences in platelet and organelle packing in COVID-19/SARSCoV2 patient-derived platelets.","authors":"Sagar S Matharu, Cassidy S Nordmann, Kurtis R Ottman, Rahul Akkem, Douglas Palumbo, Denzel R D Cruz, Kenneth Campbell, Gail Sievert, Jamie Sturgill, James Z Porterfield, Smita Joshi, Hammodah R Alfar, Chi Peng, Irina D Pokrovskaya, Jeffrey A Kamykowski, Jeremy P Wood, Beth Garvy, Maria A Aronova, Sidney W Whiteheart, Richard D Leapman, Brian Storrie","doi":"10.1080/09537104.2023.2264978","DOIUrl":"10.1080/09537104.2023.2264978","url":null,"abstract":"Platelets contribute to COVID-19 clinical manifestations, of which microclotting in the pulmonary vasculature has been a prominent symptom. To investigate the potential diagnostic contributions of overall platelet morphology and their α-granules and mitochondria to the understanding of platelet hyperactivation and micro-clotting, we undertook a 3D ultrastructural approach. Because differences might be small, we used the high-contrast, high-resolution technique of focused ion beam scanning EM (FIB-SEM) and employed deep learning computational methods to evaluate nearly 600 individual platelets and 30 000 included organelles within three healthy controls and three severely ill COVID-19 patients. Statistical analysis reveals that the α-granule/mitochondrion-to-plateletvolume ratio is significantly greater in COVID-19 patient platelets indicating a denser packing of organelles, and a more compact platelet. The COVID-19 patient platelets were significantly smaller -by 35% in volume - with most of the difference in organelle packing density being due to decreased platelet size. There was little to no 3D ultrastructural evidence for differential activation of the platelets from COVID-19 patients. Though limited by sample size, our studies suggest that factors outside of the platelets themselves are likely responsible for COVID-19 complications. Our studies show how deep learning 3D methodology can become the gold standard for 3D ultrastructural studies of platelets.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2264978"},"PeriodicalIF":2.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10809228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71485175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cryopreservation affects platelet macromolecular composition over time after thawing and differently impacts on cancer cells behavior in vitro. 低温保存对解冻后血小板大分子组成的影响以及对体外癌细胞行为的不同影响。

IF 3.3 3区医学

Platelets Pub Date : 2023-12-01 Epub Date: 2023-11-27 DOI: 10.1080/09537104.2023.2281943

Gaia Gavioli, Agnese Razzoli, Diana E Bedolla, Erminia Di Bartolomeo, Eleonora Quartieri, Barbara Iotti, Pamela Berni, Giovanni Birarda, Lisa Vaccari, Davide Schiroli, Chiara Marraccini, Roberto Baricchi, Lucia Merolle

{"title":"Cryopreservation affects platelet macromolecular composition over time after thawing and differently impacts on cancer cells behavior in vitro.","authors":"Gaia Gavioli, Agnese Razzoli, Diana E Bedolla, Erminia Di Bartolomeo, Eleonora Quartieri, Barbara Iotti, Pamela Berni, Giovanni Birarda, Lisa Vaccari, Davide Schiroli, Chiara Marraccini, Roberto Baricchi, Lucia Merolle","doi":"10.1080/09537104.2023.2281943","DOIUrl":"10.1080/09537104.2023.2281943","url":null,"abstract":"Cryopreservation affects platelets' function, questioning their use for cancer patients. We aimed to investigate the biochemical events that occur over time after thawing to optimize transfusion timing and evaluate the effect of platelet supernatants on tumor cell behavior in vitro. We compared fresh (Fresh-PLT) with Cryopreserved platelets (Cryo-PLT) at 1 h, 3 h and 6 h after thawing. MCF-7 and HL-60 cells were cultured with Fresh- or 1 h Cryo-PLT supernatants to investigate cell proliferation, migration, and PLT-cell adhesion. We noticed a significant impairment of hemostatic activity accompanied by a post-thaw decrease of CD42b+ , which identifies the CD62P--population. FTIR spectroscopy revealed a decrease in the total protein content together with changes in their conformational structure, which identified two sub-groups: 1) Fresh and 1 h Cryo-PLT; 2) 3 h and 6 h cryo-PLT. Extracellular vesicle shedding and phosphatidylserine externalization (PS) increased after thawing. Cryo-PLT supernatants inhibited cell proliferation, impaired MCF-7 cell migration, and reduced ability to adhere to tumor cells. Within the first 3 hours after thawing, irreversible alterations of biomolecular structure occur in Cryo-PLT. Nevertheless, Cryo-PLT should be considered safe for the transfusion of cancer patients because of their insufficient capability to promote cancer cell proliferation, adhesion, or migration.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2281943"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138445979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiple myeloma and its treatment contribute to increased platelet reactivity. 多发性骨髓瘤及其治疗有助于提高血小板反应性。

IF 3.3 3区医学

Platelets Pub Date : 2023-12-01 Epub Date: 2023-10-11 DOI: 10.1080/09537104.2023.2264940

Joanne L Mitchell, Dalia Khan, Rekha H Rana, Neline Kriek, Amanda J Unsworth, Tanya Sage, Alexander P Bye, Michael Laffan, Susan Shapiro, Anjan Thakurta, Henri Grech, Karthik Ramasamy, Jonathan M Gibbins

{"title":"Multiple myeloma and its treatment contribute to increased platelet reactivity.","authors":"Joanne L Mitchell, Dalia Khan, Rekha H Rana, Neline Kriek, Amanda J Unsworth, Tanya Sage, Alexander P Bye, Michael Laffan, Susan Shapiro, Anjan Thakurta, Henri Grech, Karthik Ramasamy, Jonathan M Gibbins","doi":"10.1080/09537104.2023.2264940","DOIUrl":"10.1080/09537104.2023.2264940","url":null,"abstract":"Multiple myeloma (MM) and its precursor states, smoldering myeloma (SM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with increased incidence of thrombosis, however the cause of this is unknown. Lenalidomide treatment of MM substantially improves patient survival, although significantly increases thrombotic risk by an unknown mechanism. This pilot study aimed to establish the impact of MM and its treatment with Lenalidomide on platelet function. We analyzed platelet function in MGUS, SM and MM compared to healthy controls. We report an increase in platelet reactivity in MGUS, SM, and MM where increases in fibrinogen binding, P-selectin exposure, altered receptor expression, elevated levels of aggregation and enhanced sensitivity to agonist stimulation were observed. We also demonstrate an increase in patient platelet reactivity post Lenalidomide treatment compared to pre-treatment. We show Lenalidomide treatment of platelets ex vivo increased reactivity that was associated with formation of larger thrombi at arterial shear rates but not venous shear rates. This study demonstrates a clear increase in platelet reactivity and prothrombotic potential in patients with MGUS, SM and MM which is elevated further upon treatment with Lenalidomide. Our observations suggest that more detailed studies are warranted to determine mechanisms of thrombotic complications to enable the development of new preventative strategies that specifically target platelets.","PeriodicalId":20268,"journal":{"name":"Platelets","volume":"34 1","pages":"2264940"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41210084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0