Pub Date : 2022-12-01DOI: 10.1080/09537104.2022.2151996
Soomin Kim, Yujin Kim, Shin-Hye Yu, Seo-Eun Lee, Jong Hyeok Park, Gayoung Cho, Chul Choi, Kyuboem Han, Chun-Hyung Kim, Young Cheol Kang
Platelets are known to improve the wound-repair capacity of mesenchymal stem cells (MSCs) by transferring mitochondria intercellularly. This study aimed to investigate whether direct transfer of mitochondria (pl-MT) isolated from platelets could enhance wound healing in vitro using a cell-based model. Wound repairs were assessed by 2D gap closure experiment in wound scratch assay using human dermal fibroblasts (hDFs). Results demonstrated that pl-MT were successfully internalized into hDFs. It increased cell proliferation and promoted the closure of wound gap. Importantly, pl-MT suppressed both intracellular and mitochondrial ROS production induced by hydrogen peroxide, cisplatin, and TGF-β in hDFs. Taken together, these results suggest that pl-MT transfer might be used as a potential therapeutic strategy for wound repair.
{"title":"Platelet-derived mitochondria transfer facilitates wound-closure by modulating ROS levels in dermal fibroblasts.","authors":"Soomin Kim, Yujin Kim, Shin-Hye Yu, Seo-Eun Lee, Jong Hyeok Park, Gayoung Cho, Chul Choi, Kyuboem Han, Chun-Hyung Kim, Young Cheol Kang","doi":"10.1080/09537104.2022.2151996","DOIUrl":"https://doi.org/10.1080/09537104.2022.2151996","url":null,"abstract":"<p><p>Platelets are known to improve the wound-repair capacity of mesenchymal stem cells (MSCs) by transferring mitochondria intercellularly. This study aimed to investigate whether direct transfer of mitochondria (pl-MT) isolated from platelets could enhance wound healing <i>in vitro</i> using a cell-based model. Wound repairs were assessed by 2D gap closure experiment in wound scratch assay using human dermal fibroblasts (hDFs). Results demonstrated that pl-MT were successfully internalized into hDFs. It increased cell proliferation and promoted the closure of wound gap. Importantly, pl-MT suppressed both intracellular and mitochondrial ROS production induced by hydrogen peroxide, cisplatin, and TGF-β in hDFs. Taken together, these results suggest that pl-MT transfer might be used as a potential therapeutic strategy for wound repair.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9564190","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}
Pub Date : 2022-11-17Epub Date: 2022-07-05DOI: 10.1080/09537104.2022.2091773
Musa Alzahrani, Saeed Al Turki, Waleed Al Rajban, Fatimah Alshalati, Fahad Almodaihsh, Khadega A Abuelgasim, Bader Alahmari, Thamer Al Bogami, Osama Ali, Talal Al Harbi, Mohammed A AlBalwi, Maram Alotaibi, Aamer Aleem, Ahmed Al Asker, Areej Al Mugairi
The P106L mutation in the human myeloproliferative leukemia virus oncogene (MPL) was shown to be associated with hereditary thrombocythemia in Arabs. The clinical and bone marrow (BM) features of P106L mutation are unknown. Genetic databases at two tertiary hospitals in Saudi Arabia were searched to identify patients with the MPL P106L mutation. Clinical data were collected retrospectively and the BM aspirates and biopsies were independently reviewed by two hematopathologists. In total, 115 patients were included. Median age was 33 years of which 31 patients were pediatric and 65 were female. The mutation was homozygous in 87 patients. Thrombocytosis was documented in 107 patients, with a median platelet count of 667 × 109/L. The homozygous genotype was associated with a higher platelet count. Thirty-three patients had an evaluable BM and clustering of megakaryocytes was observed in 30/33 patients. At the time of last follow-up, 114 patients were alive. The median follow-up was 7.8 years from the time of thrombocytosis. No patients developed disease progression to myelofibrosis. The P106L mutation was associated with marked thrombocytosis at a younger age and with a low risk of thrombosis, splenomegaly, and marrow fibrosis. The BM demonstrated normal or hypocellular marrow with megakaryocyte clusters.
{"title":"Pro106Leu MPL mutation is associated with thrombocytosis and a low risk of thrombosis, splenomegaly and marrow fibrosis.","authors":"Musa Alzahrani, Saeed Al Turki, Waleed Al Rajban, Fatimah Alshalati, Fahad Almodaihsh, Khadega A Abuelgasim, Bader Alahmari, Thamer Al Bogami, Osama Ali, Talal Al Harbi, Mohammed A AlBalwi, Maram Alotaibi, Aamer Aleem, Ahmed Al Asker, Areej Al Mugairi","doi":"10.1080/09537104.2022.2091773","DOIUrl":"https://doi.org/10.1080/09537104.2022.2091773","url":null,"abstract":"<p><p>The P106L mutation in the human myeloproliferative leukemia virus oncogene (MPL) was shown to be associated with hereditary thrombocythemia in Arabs. The clinical and bone marrow (BM) features of P106L mutation are unknown. Genetic databases at two tertiary hospitals in Saudi Arabia were searched to identify patients with the MPL P106L mutation. Clinical data were collected retrospectively and the BM aspirates and biopsies were independently reviewed by two hematopathologists. In total, 115 patients were included. Median age was 33 years of which 31 patients were pediatric and 65 were female. The mutation was homozygous in 87 patients. Thrombocytosis was documented in 107 patients, with a median platelet count of 667 × 10<sup>9</sup>/L. The homozygous genotype was associated with a higher platelet count. Thirty-three patients had an evaluable BM and clustering of megakaryocytes was observed in 30/33 patients. At the time of last follow-up, 114 patients were alive. The median follow-up was 7.8 years from the time of thrombocytosis. No patients developed disease progression to myelofibrosis. The P106L mutation was associated with marked thrombocytosis at a younger age and with a low risk of thrombosis, splenomegaly, and marrow fibrosis. The BM demonstrated normal or hypocellular marrow with megakaryocyte clusters.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40563150","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}
Pub Date : 2022-11-17Epub Date: 2022-07-05DOI: 10.1080/09537104.2022.2096211
Abdul Rehman Arif, Miaomiao Zhao, Wenlan Chen, Mei Xue, Shanshan Luo, Yadan Wang
MYH9-related disorder (MYH9-RD) is autosomal dominant thrombocytopenia caused by mutations in the MYH9 gene, which codes for the non-muscle myosin-IIA heavy chain. We present a case of a 24-year-old Chinese man with MYH9-RD who was initially misdiagnosed with immune thrombocytopenia. Whole-exome sequencing and Sanger sequencing revealed a novel missense mutation in the MYH9 gene at the position of c.4550 G > T (p.G1517V) in exon 32. The same phenotype was observed in the proband, his mother, and his brother, in addition to macrothrombocytopenia and Dohle-like bodies in neutrophil granulocytes without non-hematologic manifestations. Following failed treatment with eltrombopag, avatrombopag, which was not mentioned before in the MYH9-RD treatment, was administered to the patient, and thrombocytopenia improved. In this case report, we present a novel pathogenic mutation and show the potential of avatrombopag for temporarily increasing the platelet count in patients with MYH9-RD.
MYH9相关疾病(MYH9- rd)是由MYH9基因突变引起的常染色体显性血小板减少症,该基因编码非肌肉肌球蛋白- iia重链。我们报告一例24岁的中国男性MYH9-RD患者最初被误诊为免疫性血小板减少症。全外显子组测序和Sanger测序显示,MYH9基因c.4550位点出现了新的错义突变G > T (p.G1517V)在先证者及其母亲和兄弟中观察到相同的表型,除了中性粒细胞中大量血小板减少症和dohle样体,无非血液学表现。在eltrombopag治疗失败后,患者使用了先前在MYH9-RD治疗中未提及的avatrombopag,血小板减少症得到改善。在这个病例报告中,我们提出了一种新的致病突变,并展示了阿伐波帕暂时增加MYH9-RD患者血小板计数的潜力。
{"title":"Avatrombopag improves thrombocytopenia in MYH9-related disorder following eltrombopag treatment failure.","authors":"Abdul Rehman Arif, Miaomiao Zhao, Wenlan Chen, Mei Xue, Shanshan Luo, Yadan Wang","doi":"10.1080/09537104.2022.2096211","DOIUrl":"https://doi.org/10.1080/09537104.2022.2096211","url":null,"abstract":"<p><p>MYH9-related disorder (MYH9-RD) is autosomal dominant thrombocytopenia caused by mutations in the <i>MYH9</i> gene, which codes for the non-muscle myosin-IIA heavy chain. We present a case of a 24-year-old Chinese man with MYH9-RD who was initially misdiagnosed with immune thrombocytopenia. Whole-exome sequencing and Sanger sequencing revealed a novel missense mutation in the <i>MYH9</i> gene at the position of c.4550 G > T (p.G1517V) in exon 32. The same phenotype was observed in the proband, his mother, and his brother, in addition to macrothrombocytopenia and Dohle-like bodies in neutrophil granulocytes without non-hematologic manifestations. Following failed treatment with eltrombopag, avatrombopag, which was not mentioned before in the MYH9-RD treatment, was administered to the patient, and thrombocytopenia improved. In this case report, we present a novel pathogenic mutation and show the potential of avatrombopag for temporarily increasing the platelet count in patients with MYH9-RD.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40586932","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}
Pub Date : 2022-11-17DOI: 10.1080/09537104.2022.2069235
Hilaire Yam Fung Cheung, Luis A Moran, Albert Sickmann, Johan W M Heemskerk, Ángel Garcia, Steve P Watson
Src tyrosine kinases and spleen tyrosine kinase (Syk) have recently been shown to contribute to sustained platelet aggregation on collagen under arterial shear. In the present study, we have investigated whether Src and Syk are required for aggregation under minimal shear following activation of glycoprotein VI (GPVI) and have extended this to C-type lectin-like receptor-2 (CLEC-2) which signals through the same pathway. Aggregation was induced by the GPVI ligand collagen-related peptide (CRP) and the CLEC-2 ligand rhodocytin and monitored by light transmission aggregometry (LTA). Aggregation and tyrosine phosphorylation by both receptors were sustained for up to 50 min. The addition of inhibitors of Src, Syk or Bruton's tyrosine kinase (Btk) at 150 sec, by which time aggregation was maximal, induced rapid loss of tyrosine phosphorylation of their downstream proteins, but only Src kinase inhibition caused a weak (~10%) reversal in light transmission. A similar effect was observed when the inhibitors were combined with apyrase and indomethacin or glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, eptifibatide. On the other hand, activation of GPIIb-IIIa by GPVI in a diluted platelet suspension, as measured by binding of fluorescein isothiocyanate-labeled antibody specific for the activated GPIIb-IIIa (FITC-PAC1), was reversed on the addition of Src and Syk inhibitors showing that integrin activation is rapidly reversible in the absence of outside-in signals. The results demonstrate that Src but not Syk and Btk contribute to sustained aggregation as monitored by LTA, possibly as a result of inhibition of outside-in signaling from GPIIb-IIIa to the cytoskeleton through a Syk-independent pathway. This is in contrast to the role of Syk in supporting sustained aggregation on collagen under arterial shear.
{"title":"Inhibition of Src but not Syk causes weak reversal of GPVI-mediated platelet aggregation measured by light transmission aggregometry.","authors":"Hilaire Yam Fung Cheung, Luis A Moran, Albert Sickmann, Johan W M Heemskerk, Ángel Garcia, Steve P Watson","doi":"10.1080/09537104.2022.2069235","DOIUrl":"https://doi.org/10.1080/09537104.2022.2069235","url":null,"abstract":"<p><p>Src tyrosine kinases and spleen tyrosine kinase (Syk) have recently been shown to contribute to sustained platelet aggregation on collagen under arterial shear. In the present study, we have investigated whether Src and Syk are required for aggregation under minimal shear following activation of glycoprotein VI (GPVI) and have extended this to C-type lectin-like receptor-2 (CLEC-2) which signals through the same pathway. Aggregation was induced by the GPVI ligand collagen-related peptide (CRP) and the CLEC-2 ligand rhodocytin and monitored by light transmission aggregometry (LTA). Aggregation and tyrosine phosphorylation by both receptors were sustained for up to 50 min. The addition of inhibitors of Src, Syk or Bruton's tyrosine kinase (Btk) at 150 sec, by which time aggregation was maximal, induced rapid loss of tyrosine phosphorylation of their downstream proteins, but only Src kinase inhibition caused a weak (~10%) reversal in light transmission. A similar effect was observed when the inhibitors were combined with apyrase and indomethacin or glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, eptifibatide. On the other hand, activation of GPIIb-IIIa by GPVI in a diluted platelet suspension, as measured by binding of fluorescein isothiocyanate-labeled antibody specific for the activated GPIIb-IIIa (FITC-PAC1), was reversed on the addition of Src and Syk inhibitors showing that integrin activation is rapidly reversible in the absence of outside-in signals. The results demonstrate that Src but not Syk and Btk contribute to sustained aggregation as monitored by LTA, possibly as a result of inhibition of outside-in signaling from GPIIb-IIIa to the cytoskeleton through a Syk-independent pathway. This is in contrast to the role of Syk in supporting sustained aggregation on collagen under arterial shear.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10841366","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}
Pub Date : 2022-11-17Epub Date: 2022-06-29DOI: 10.1080/09537104.2022.2087868
Sean P Heffron, Joseph Windheim, Tessa J Barrett, Deepak Voora, Jeffrey S Berger
Aspirin's clinical efficacy may be influenced by body weight and mass. Although inadequate platelet inhibition by aspirin is suggested as responsible, evidence for this in non-diabetic patients is sparse. We investigated the influence of body weight and mass on aspirin's inhibition of platelet aggregation in healthy adults without diabetes. Cohort one (NYU, n = 84) had light transmission aggregometry (LTA) of platelet-rich plasma to submaximal adenosine diphosphate (ADP) and arachidonic acid (AA) before and following 1 week of daily 81 mg non-enteric coated aspirin. Subjects in the validation cohort (Duke, n = 66) were randomized to 81 mg or 325 mg non-enteric coated aspirin for 4 weeks, immediately followed by 4 weeks of the other dose, with LTA to submaximal collagen, ADP, and AA before and after each dosage period. Body mass index (BMI) range was 18.0-57.5 kg/m2 and 25% were obese. Inhibition of platelet aggregation was similar irrespective of BMI, body weight and aspirin dose. There was no correlation between platelet aggregation before or after aspirin with BMI or body weight. Our data demonstrate that aspirin produces potent inhibition of direct and indirect COX1-mediated platelet aggregation in healthy adults without diabetes regardless of body weight or mass - suggesting that other mechanisms explain lower preventive efficacy of low-dose aspirin with increasing body weight/mass.
阿司匹林的临床疗效可能受体重和质量的影响。虽然阿司匹林对血小板抑制不足被认为是原因之一,但在非糖尿病患者中这方面的证据很少。我们研究了体重和质量对非糖尿病健康成人阿司匹林抑制血小板聚集的影响。队列1 (NYU, n = 84)在每天服用81 mg非肠溶性阿司匹林1周前后,富血小板血浆对亚最大值二磷酸腺苷(ADP)和花生四烯酸(AA)的光透射聚集测定(LTA)。验证队列(Duke, n = 66)的受试者被随机分配到81 mg或325 mg非肠溶包衣阿司匹林4周,紧接着是另一个剂量4周,在每个给药期之前和之后的LTA对胶原、ADP和AA的亚最大值。体重指数(BMI)在18.0 ~ 57.5 kg/m2之间,25%为肥胖。无论BMI、体重和阿司匹林剂量如何,对血小板聚集的抑制作用是相似的。服用阿司匹林前后血小板聚集与BMI或体重之间没有相关性。我们的数据表明,在没有糖尿病的健康成年人中,无论体重或质量如何,阿司匹林都能有效抑制cox1介导的直接和间接血小板聚集,这表明其他机制可以解释低剂量阿司匹林随着体重/质量的增加而降低的预防效果。
{"title":"Platelet inhibition by low-dose aspirin is not influenced by body mass or weight.","authors":"Sean P Heffron, Joseph Windheim, Tessa J Barrett, Deepak Voora, Jeffrey S Berger","doi":"10.1080/09537104.2022.2087868","DOIUrl":"10.1080/09537104.2022.2087868","url":null,"abstract":"<p><p>Aspirin's clinical efficacy may be influenced by body weight and mass. Although inadequate platelet inhibition by aspirin is suggested as responsible, evidence for this in non-diabetic patients is sparse. We investigated the influence of body weight and mass on aspirin's inhibition of platelet aggregation in healthy adults without diabetes. Cohort one (NYU, n = 84) had light transmission aggregometry (LTA) of platelet-rich plasma to submaximal adenosine diphosphate (ADP) and arachidonic acid (AA) before and following 1 week of daily 81 mg non-enteric coated aspirin. Subjects in the validation cohort (Duke, n = 66) were randomized to 81 mg or 325 mg non-enteric coated aspirin for 4 weeks, immediately followed by 4 weeks of the other dose, with LTA to submaximal collagen, ADP, and AA before and after each dosage period. Body mass index (BMI) range was 18.0-57.5 kg/m<sup>2</sup> and 25% were obese. Inhibition of platelet aggregation was similar irrespective of BMI, body weight and aspirin dose. There was no correlation between platelet aggregation before or after aspirin with BMI or body weight. Our data demonstrate that aspirin produces potent inhibition of direct and indirect COX1-mediated platelet aggregation in healthy adults without diabetes regardless of body weight or mass - suggesting that other mechanisms explain lower preventive efficacy of low-dose aspirin with increasing body weight/mass.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9976777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9359542","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}
Pub Date : 2022-11-17DOI: 10.1080/09537104.2022.2107627
Brittney Williams, Jing Zhu, Lin Zou, Wei Chao
Thrombocytopenia is a common complication in sepsis and is associated with higher mortality. Activated platelets express CD62P, which facilitates platelet-leukocyte aggregate (PLA) formation and contributes to thrombocytopenia in sepsis. We have reported that thrombocytopenia in murine sepsis is partly attributable to TLR7 signaling, but the underlying mechanism is unclear. In the current study, we tested the hypothesis that TLR7 mediates platelet activation and PLA formation during sepsis. In vitro, whole blood from WT mice treated with loxoribine, a TLR7 agonist, exhibited a dose-dependent increase in activated platelets compared to the control (PBS with 0.05% DMSO) or loxoribine-treated TLR7-/- whole blood. In a murine model of sepsis, there was a significant increase in platelet activation and PLA formation 24 hours after cecal ligation and puncture (CLP) as evidenced by double positive expression of CD41+/CD62P+ and CD45+/CD62P+, respectively. The sepsis-induced PLA formation was significantly attenuated in TLR7-/- mice. Finally, in ex-vivo experiments, plasma isolated from septic mice induced WT platelet activation, but such effect was significantly attenuated in platelets deficient of TLR7. These findings demonstrate a pivotal role of TLR7 signaling in platelet activation and PLA formation during bacterial sepsis.
{"title":"Innate immune TLR7 signaling mediates platelet activation and platelet-leukocyte aggregate formation in murine bacterial sepsis.","authors":"Brittney Williams, Jing Zhu, Lin Zou, Wei Chao","doi":"10.1080/09537104.2022.2107627","DOIUrl":"https://doi.org/10.1080/09537104.2022.2107627","url":null,"abstract":"<p><p>Thrombocytopenia is a common complication in sepsis and is associated with higher mortality. Activated platelets express CD62P, which facilitates platelet-leukocyte aggregate (PLA) formation and contributes to thrombocytopenia in sepsis. We have reported that thrombocytopenia in murine sepsis is partly attributable to TLR7 signaling, but the underlying mechanism is unclear. In the current study, we tested the hypothesis that TLR7 mediates platelet activation and PLA formation during sepsis. In vitro, whole blood from WT mice treated with loxoribine, a TLR7 agonist, exhibited a dose-dependent increase in activated platelets compared to the control (PBS with 0.05% DMSO) or loxoribine-treated TLR7<sup>-/-</sup> whole blood. In a murine model of sepsis, there was a significant increase in platelet activation and PLA formation 24 hours after cecal ligation and puncture (CLP) as evidenced by double positive expression of CD41<sup>+</sup>/CD62P<sup>+</sup> and CD45<sup>+</sup>/CD62P<sup>+</sup>, respectively. The sepsis-induced PLA formation was significantly attenuated in TLR7<sup>-/-</sup> mice. Finally, in ex-vivo experiments, plasma isolated from septic mice induced WT platelet activation, but such effect was significantly attenuated in platelets deficient of TLR7. These findings demonstrate a pivotal role of TLR7 signaling in platelet activation and PLA formation during bacterial sepsis.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9833650/pdf/nihms-1860245.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10521674","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}
Pub Date : 2022-11-17Epub Date: 2022-09-22DOI: 10.1080/09537104.2022.2125504
Neda Rehan, Rehan Qayyum
While several small studies have found that selenium deficiency is associated with low platelet counts, they lack generalizability. We used data from the National Health and Nutrition Examination Surveys collected over a 12-year period. We examined the relationship between selenium quartiles and platelet count using survey-weighted linear regression models adjusting for age, sex, race, household income to poverty threshold income, highest education attainment, smoking status, red blood cell folate, and body mass index. Of the 21,764 participants, 51% were females, 23% African Americans, and 25% were >65 years of age. Mean (SD) platelet count was 243(64) 109/L and selenium was 183(32) µg/L. Women had significantly higher platelet count but lower selenium levels than men (258 vs. 227 109/L and 181 vs. 185 µg/L respectively; both P < 0.0001). In adjusted analysis, participants in the highest selenium quartile had 8.0x109/L higher platelet count as compared to those in the lowest selenium quartile (95%CI = 4.1 to 11.9; P < 0.0001). Gender modified the relationship between the two; although there was no difference in women, platelet count was higher in the highest than the lowest selenium quartile in men (interaction p-value = 0.001). These findings highlight the importance of selenium and gender in platelet biology which needs to be explored.
虽然一些小型研究发现硒缺乏与血小板计数低有关,但它们缺乏普遍性。我们使用的数据来自全国健康和营养调查收集了12年的时间。我们使用调查加权线性回归模型检验了硒四分位数与血小板计数之间的关系,该模型调整了年龄、性别、种族、家庭收入到贫困线收入、最高受教育程度、吸烟状况、红细胞叶酸和体重指数。在21764名参与者中,51%是女性,23%是非裔美国人,25%的人年龄>65岁。平均(SD)血小板计数为243(64)109/L,硒含量为183(32)µg/L。女性血小板计数明显高于男性,但硒水平明显低于男性(分别为258 vs. 227 109/L和181 vs. 185µg/L);与硒含量最低的四分位数组相比,p9 /L血小板计数均较高(95%CI = 4.1 ~ 11.9;P值= 0.001)。这些发现强调了硒和性别在血小板生物学中的重要性,这需要进一步探索。
{"title":"Sex-specific relationship between blood selenium levels and platelet count in a large cohort representative of the United States population.","authors":"Neda Rehan, Rehan Qayyum","doi":"10.1080/09537104.2022.2125504","DOIUrl":"https://doi.org/10.1080/09537104.2022.2125504","url":null,"abstract":"<p><p>While several small studies have found that selenium deficiency is associated with low platelet counts, they lack generalizability. We used data from the National Health and Nutrition Examination Surveys collected over a 12-year period. We examined the relationship between selenium quartiles and platelet count using survey-weighted linear regression models adjusting for age, sex, race, household income to poverty threshold income, highest education attainment, smoking status, red blood cell folate, and body mass index. Of the 21,764 participants, 51% were females, 23% African Americans, and 25% were >65 years of age. Mean (SD) platelet count was 243(64) 10<sup>9</sup>/L and selenium was 183(32) µg/L. Women had significantly higher platelet count but lower selenium levels than men (258 vs. 227 10<sup>9</sup>/L and 181 vs. 185 µg/L respectively; both <i>P</i> < 0.0001). In adjusted analysis, participants in the highest selenium quartile had 8.0x10<sup>9</sup>/L higher platelet count as compared to those in the lowest selenium quartile (95%CI = 4.1 to 11.9; <i>P</i> < 0.0001). Gender modified the relationship between the two; although there was no difference in women, platelet count was higher in the highest than the lowest selenium quartile in men (interaction <i>p</i>-value = 0.001). These findings highlight the importance of selenium and gender in platelet biology which needs to be explored.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33489266","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}
Pub Date : 2022-11-17Epub Date: 2022-08-14DOI: 10.1080/09537104.2022.2108541
Ziyue Mi, Li Gong, Yujie Kong, Peizhe Zhao, Yonghua Yin, Haixia Xu, Li Tian, Zhong Liu
Patients have a high risk of suffering adverse reactions after receiving platelet products stored for 5 days. Bioactive exosomes in platelet products can be accumulated during storage, which is associated with adverse reactions. MicroRNAs are one of the critical cargoes in exosomes, which participate in cell differentiation, metabolism, and immunomodulation. This study intends to elucidate and analyze the differential expression of exosomal microRNAs in apheresis platelet concentrates during storage and predict the potential functions of target genes. Apheresis platelet concentrates were used to isolate exosomes by ultracentrifugation. Exosomes were phenotyped by western blot, transmission electron microscopy, and nano flow cytometry. The differential expression of the exosomal microRNAs was obtained by a microarray test using four bags of apheresis platelets stored for 5 days compared with 1 day. The differentially expressed microRNAs between the two time points were identified, and their target genes were analyzed by miRWalk and miRDB. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the target genes' functions. Fifteen bags of apheresis platelet concentrates stored for 1 day and 5 days were used to verify the microarray results by quantitative reverse transcription-polymerase chain reactions (qRT-PCR). There were 134 microRNAs in total expressed differently in the two groups (day 1 and day 5), with 57 microRNAs up-regulated and 77 down-regulated (|fold change| > 2.0 and P < .05). Thirteen up-regulated microRNAs (hsa-miR-22-3p, hsa-miR-223-3p, hsa-miR-21-5p, hsa-miR-23a-3p, hsa-miR-320b, hsa-let-7a-5p, hsa-miR-25-3p, hsa-miR-126-3p, hsa-miR-320c, hsa-miR-342-3p, hsa-miR-320d, hsa-miR-328-3p, and hsa-miR-320e) detected in all samples were selected to validate the results. The qRT-PCR results showed that five (hsa-miR-22-3p, hsa-miR-223-3p, hsa-miR-21-5p, hsa-miR-23a-3p, and hsa-miR-320b) of them were increased more than 10-fold (P < .001); four (hsa-let-7a-5p, hsa-miR-25-3p, hsa-miR-126-3p, hsa-miR-320c) more than five-fold (P < .001); two (hsa-miR-342-3p and hsa-miR-320d) more than two-fold (P < .05); and two (hsa-miR-328-3p and hsa-miR-320e) more than two-fold (P > .05). Specifically, hsa-miR-22-3p increased 14.6-fold; hsa-miR-223-3p increased 13.0-fold; and hsa-miR-21-5p increased 12.0-fold. Based on bioinformatics functional analysis, target genes of top nine microRNAs (hsa-miR-22-3p, hsa-miR-223-3p, hsa-miR-21-5p, hsa-miR-23a-3p, hsa-miR-320b, hsa-let-7a-5p, hsa-miR-25-3p, hsa-miR-126-3p, and hsa-miR-320c) were annotated with positive regulation of cell proliferation and nervous system development, and mainly enriched in regulating pluripotency of stem cells signaling pathway, prolactin signaling pathway, and FoxO signaling pathway, etc. The prolactin, FoxO, ErbB, and TNF signaling pathway were relevant to immunomodulation. In particular, hsa-mi
患者在接受储存5天的血小板产品后发生不良反应的风险很高。血小板产物中的生物活性外泌体可在储存过程中积累,这与不良反应有关。microrna是外泌体的重要载体之一,参与细胞分化、代谢和免疫调节。本研究旨在阐明和分析单采血小板浓缩物储存过程中外泌体microRNAs的差异表达,并预测靶基因的潜在功能。采用单采血小板浓缩液超离心分离外泌体。外泌体通过western blot、透射电镜和纳米流式细胞术进行表型分析。外泌体microRNAs的差异表达通过微阵列测试获得,使用4袋单采血小板储存5天与1天。鉴定两个时间点差异表达的microrna,并通过miRWalk和miRDB分析其靶基因。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)分析来预测目标基因的功能。分别保存1天和5天的15袋单采血小板浓缩液,用定量逆转录聚合酶链反应(qRT-PCR)验证微阵列结果。两组(第1天和第5天)共有134个microrna表达差异,其中上调57个,下调77个(|fold change| > 2.0, P P P P P > 0.05)。具体来说,hsa-miR-22-3p增加14.6倍;hsa-miR-223-3p增加13.0倍;hsa-miR-21-5p升高12.0倍。基于生物信息学功能分析,前9位microrna靶基因(hsa-miR-22-3p、hsa-miR-223-3p、hsa-miR-21-5p、hsa-miR-23a-3p、hsa-miR-320b、hsa-let-7a-5p、hsa-miR-25-3p、hsa-miR-126-3p、hsa-miR-320c)被注释为正向调控细胞增殖和神经系统发育,主要富集调控干细胞信号通路、泌乳素信号通路、FoxO信号通路等多能性。催乳素、FoxO、ErbB和TNF信号通路与免疫调节有关。尤其是贮藏期间,hsa-miR-22-3p的表达差异最大,变化了14.6倍,这可能是一个关键的中介。
{"title":"Differential expression of exosomal microRNAs in fresh and senescent apheresis platelet concentrates.","authors":"Ziyue Mi, Li Gong, Yujie Kong, Peizhe Zhao, Yonghua Yin, Haixia Xu, Li Tian, Zhong Liu","doi":"10.1080/09537104.2022.2108541","DOIUrl":"https://doi.org/10.1080/09537104.2022.2108541","url":null,"abstract":"<p><p>Patients have a high risk of suffering adverse reactions after receiving platelet products stored for 5 days. Bioactive exosomes in platelet products can be accumulated during storage, which is associated with adverse reactions. MicroRNAs are one of the critical cargoes in exosomes, which participate in cell differentiation, metabolism, and immunomodulation. This study intends to elucidate and analyze the differential expression of exosomal microRNAs in apheresis platelet concentrates during storage and predict the potential functions of target genes. Apheresis platelet concentrates were used to isolate exosomes by ultracentrifugation. Exosomes were phenotyped by western blot, transmission electron microscopy, and nano flow cytometry. The differential expression of the exosomal microRNAs was obtained by a microarray test using four bags of apheresis platelets stored for 5 days compared with 1 day. The differentially expressed microRNAs between the two time points were identified, and their target genes were analyzed by miRWalk and miRDB. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the target genes' functions. Fifteen bags of apheresis platelet concentrates stored for 1 day and 5 days were used to verify the microarray results by quantitative reverse transcription-polymerase chain reactions (qRT-PCR). There were 134 microRNAs in total expressed differently in the two groups (day 1 and day 5), with 57 microRNAs up-regulated and 77 down-regulated (|fold change| > 2.0 and <i>P</i> < .05). Thirteen up-regulated microRNAs (hsa-miR-22-3p, hsa-miR-223-3p, hsa-miR-21-5p, hsa-miR-23a-3p, hsa-miR-320b, hsa-let-7a-5p, hsa-miR-25-3p, hsa-miR-126-3p, hsa-miR-320c, hsa-miR-342-3p, hsa-miR-320d, hsa-miR-328-3p, and hsa-miR-320e) detected in all samples were selected to validate the results. The qRT-PCR results showed that five (hsa-miR-22-3p, hsa-miR-223-3p, hsa-miR-21-5p, hsa-miR-23a-3p, and hsa-miR-320b) of them were increased more than 10-fold (<i>P</i> < .001); four (hsa-let-7a-5p, hsa-miR-25-3p, hsa-miR-126-3p, hsa-miR-320c) more than five-fold (<i>P</i> < .001); two (hsa-miR-342-3p and hsa-miR-320d) more than two-fold (<i>P</i> < .05); and two (hsa-miR-328-3p and hsa-miR-320e) more than two-fold (<i>P</i> > .05). Specifically, hsa-miR-22-3p increased 14.6-fold; hsa-miR-223-3p increased 13.0-fold; and hsa-miR-21-5p increased 12.0-fold. Based on bioinformatics functional analysis, target genes of top nine microRNAs (hsa-miR-22-3p, hsa-miR-223-3p, hsa-miR-21-5p, hsa-miR-23a-3p, hsa-miR-320b, hsa-let-7a-5p, hsa-miR-25-3p, hsa-miR-126-3p, and hsa-miR-320c) were annotated with positive regulation of cell proliferation and nervous system development, and mainly enriched in regulating pluripotency of stem cells signaling pathway, prolactin signaling pathway, and FoxO signaling pathway, etc. The prolactin, FoxO, ErbB, and TNF signaling pathway were relevant to immunomodulation. In particular, hsa-mi","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40615633","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}
Pub Date : 2022-11-17Epub Date: 2022-09-01DOI: 10.1080/09537104.2022.2091772
Xue Li, Nanyi Li, Guangjie Zhao, Xiaoqin Wang
Iron deficiency anemia (IDA) affects more than 1.2 billion individuals globally. In addition to anemia, reactive thrombocytosis is also a common clinical hematological condition in patients with IDA. However, some case reports have described the thrombotic complications in association with IDA-induced thrombocytosis. Patients with a high risk of thrombosis need prompt identification and effective treatment to prevent thrombotic complications. While iron replacement treatment has been shown to decrease platelet count in this context, there is limited published evidence on how iron supplementation affects the thrombocytosis caused by IDA. We retrospectively examined the clinical records of 440 patients with IDA from an RCT completed from 1 January 2016, to 30 December 2017, and data obtained from this study was used for post hoc analysis to examine the effect of iron on platelet count in IDA-induced thrombocytosis.The mean ± standard deviation (SD) platelet counts of the 440 patients with IDA was 310.23 ± 98.72 × 109/L. With baseline platelet counts>450 × 109 /L as the cutoff for thrombocytosis, patients were divided into 2 groups: 36 (8.1%) in the IDA with thrombocytosis group (mean ± SD platelet count, 521.67 ± 73.85 × 109/L) and the remaining 404 in the IDA without thrombocytosis group (mean ± SD platelet count, 291.39 ± 76.11 × 109/L).Differences were found in baseline characteristics including white blood cell (WBC) count, hemoglobin (Hb) level, mean corpuscular volume (MCV), transferrin saturation (TSAT), serum iron (SI) level, and total iron-binding capacity (TIBC) between the two groups (P < .05). From baseline to 8 weeks of continuous iron supplementation treatment, the mean platelet counts in both groups were decreased at 2-week treatment intervals. And in the IDA with thrombocytosis group, half of the patients resolved thrombocytosis after 2 weeks of iron supplementation, and the counts of all patients with thrombocytosis decreased below 450 × 109 /L within 6 weeks.In conclusion, the rate of reactive thrombocytosis in patients with IDA was 8.1%. IDA patients with thrombocytosis showed more severe anemia, lower ferritin, and more advanced iron deficiency than those without thrombocytosis. Platelet counts of half of the patients with thrombocytosis reduced below cut off of 450 × 109/L for thrombocytosis after 2 weeks of treatment, and all patients resolved thrombocytosis after 6 weeks. Our study provided clinical evidence for more effective and individualized iron management in the future. IDA patients with thrombocytosis should take active iron treatment and increase follow-up frequency to prevent thrombotic events. For patients with persistent thrombocytosis, a concomitant clonal process should be considered.
{"title":"Effect of iron supplementation on platelet count in adult patients with iron deficiency anemia.","authors":"Xue Li, Nanyi Li, Guangjie Zhao, Xiaoqin Wang","doi":"10.1080/09537104.2022.2091772","DOIUrl":"https://doi.org/10.1080/09537104.2022.2091772","url":null,"abstract":"<p><p>Iron deficiency anemia (IDA) affects more than 1.2 billion individuals globally. In addition to anemia, reactive thrombocytosis is also a common clinical hematological condition in patients with IDA. However, some case reports have described the thrombotic complications in association with IDA-induced thrombocytosis. Patients with a high risk of thrombosis need prompt identification and effective treatment to prevent thrombotic complications. While iron replacement treatment has been shown to decrease platelet count in this context, there is limited published evidence on how iron supplementation affects the thrombocytosis caused by IDA. We retrospectively examined the clinical records of 440 patients with IDA from an RCT completed from 1 January 2016, to 30 December 2017, and data obtained from this study was used for post hoc analysis to examine the effect of iron on platelet count in IDA-induced thrombocytosis.The mean ± standard deviation (SD) platelet counts of the 440 patients with IDA was 310.23 ± 98.72 × 10<sup>9</sup>/L. With baseline platelet counts>450 × 10<sup>9</sup> /L as the cutoff for thrombocytosis, patients were divided into 2 groups: 36 (8.1%) in the IDA with thrombocytosis group (mean ± SD platelet count, 521.67 ± 73.85 × 10<sup>9</sup>/L) and the remaining 404 in the IDA without thrombocytosis group (mean ± SD platelet count, 291.39 ± 76.11 × 10<sup>9</sup>/L).Differences were found in baseline characteristics including white blood cell (WBC) count, hemoglobin (Hb) level, mean corpuscular volume (MCV), transferrin saturation (TSAT), serum iron (SI) level, and total iron-binding capacity (TIBC) between the two groups (<i>P</i> < .05). From baseline to 8 weeks of continuous iron supplementation treatment, the mean platelet counts in both groups were decreased at 2-week treatment intervals. And in the IDA with thrombocytosis group, half of the patients resolved thrombocytosis after 2 weeks of iron supplementation, and the counts of all patients with thrombocytosis decreased below 450 × 10<sup>9</sup> /L within 6 weeks.In conclusion, the rate of reactive thrombocytosis in patients with IDA was 8.1%. IDA patients with thrombocytosis showed more severe anemia, lower ferritin, and more advanced iron deficiency than those without thrombocytosis. Platelet counts of half of the patients with thrombocytosis reduced below cut off of 450 × 10<sup>9</sup>/L for thrombocytosis after 2 weeks of treatment, and all patients resolved thrombocytosis after 6 weeks. Our study provided clinical evidence for more effective and individualized iron management in the future. IDA patients with thrombocytosis should take active iron treatment and increase follow-up frequency to prevent thrombotic events. For patients with persistent thrombocytosis, a concomitant clonal process should be considered.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40341416","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}
Pub Date : 2022-11-17Epub Date: 2022-07-18DOI: 10.1080/09537104.2022.2078490
Nahreen Tynngård, Aseel Alshamari, Freja Månsson, Sofia Ramström
In flow cytometry, individual cells are investigated. Platelet activation is normally reported in form of percentage of platelets expressing the marker (positive platelets) and/or mean/median fluorescence intensity (MFI) for the entire analyzed population. None of these take into account the variance of the marker expression between individual platelets. This can be obtained as data on coefficient of variation (CV). This study explores if CV provides additional information regarding platelet function. Samples from platelet concentrates (PCs) prepared by apheresis- (n = 13) and interim platelet unit (IPU) technique (n = 26) and stored for 6-7 days were included and compared. Spontaneous- and agonist-induced expression of activation markers (fibrinogen binding and exposure of P-selectin, LAMP-1, and CD63) was investigated as percentage positive platelets, MFI and CV. Spontaneous expression of P-selectin as percentage positive platelets and MFI was higher for IPU PCs than apheresis PCs, which in contrast had higher agonist-induced activation. CV for spontaneous fibrinogen binding and P-selectin exposure was larger for apheresis PCs, while IPU PCs generally had larger CV for P-selectin, LAMP-1, and CD63 after agonist stimulation. Our findings show that CV adds additional information when assessing platelet activation by providing data on the variation in activation responses within the platelet population.
{"title":"Variation in activation marker expression within the platelet population - a new parameter for evaluation of platelet flow cytometry data.","authors":"Nahreen Tynngård, Aseel Alshamari, Freja Månsson, Sofia Ramström","doi":"10.1080/09537104.2022.2078490","DOIUrl":"https://doi.org/10.1080/09537104.2022.2078490","url":null,"abstract":"<p><p>In flow cytometry, individual cells are investigated. Platelet activation is normally reported in form of percentage of platelets expressing the marker (positive platelets) and/or mean/median fluorescence intensity (MFI) for the entire analyzed population. None of these take into account the variance of the marker expression between individual platelets. This can be obtained as data on coefficient of variation (CV). This study explores if CV provides additional information regarding platelet function. Samples from platelet concentrates (PCs) prepared by apheresis- (n = 13) and interim platelet unit (IPU) technique (n = 26) and stored for 6-7 days were included and compared. Spontaneous- and agonist-induced expression of activation markers (fibrinogen binding and exposure of P-selectin, LAMP-1, and CD63) was investigated as percentage positive platelets, MFI and CV. Spontaneous expression of P-selectin as percentage positive platelets and MFI was higher for IPU PCs than apheresis PCs, which in contrast had higher agonist-induced activation. CV for spontaneous fibrinogen binding and P-selectin exposure was larger for apheresis PCs, while IPU PCs generally had larger CV for P-selectin, LAMP-1, and CD63 after agonist stimulation. Our findings show that CV adds additional information when assessing platelet activation by providing data on the variation in activation responses within the platelet population.</p>","PeriodicalId":20268,"journal":{"name":"Platelets","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40505653","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}