American Journal of Hematology最新文献

{"title":"Baseline Hemoglobin Values and Clinical Outcomes in Acute Venous Thromboembolism: Insights From the RIETE Registry","authors":"Carmine Siniscalchi, Pierpaolo Di Micco, Antonella Tufano, Maria Luisa Peris, Patricia López-Miguel, Alicia Alda-Lozano, Pilar Llamas, Diego Durán Barata, Yaser Jenab, Manuel Monreal, the RIETE Investigators","doi":"10.1002/ajh.27707","DOIUrl":"10.1002/ajh.27707","url":null,"abstract":"<p>Venous thromboembolism (VTE) is a major global health concern and a leading cause of morbidity and mortality. While anticoagulation effectively reduces the risk of recurrent VTE, it is associated with an inherent risk of bleeding. Identifying patient characteristics that influence these risks is critical for personalized management. Baseline hemoglobin (Hb) values have emerged as a potential prognostic marker [<span>1-5</span>], reflecting both underlying comorbidities and hemostatic alterations. However, the impact of Hb values on both thrombotic and bleeding complications in anticoagulated VTE patients remains insufficiently characterized.</p><p>We analyzed data from 111,646 patients with acute VTE included in the RIETE registry, a large multinational prospective cohort (ClinicalTrials.gov identifier: NCT02832245) [<span>6</span>]. Patients were stratified into Hb quintiles: < 11.4, 11.4–12.6, 12.7–13.6 (reference), 13.7–14.7, and > 14.7 g/dL. We assessed 90-day rates of recurrent VTE, major bleeding, arterial ischemic events (myocardial infarction, ischemic stroke, or limb amputation), and all-cause mortality. Multivariable logistic regression models were adjusted for demographic and clinical characteristics, including VTE risk factors, initial VTE presentation, comorbidities, renal function, leukocyte and platelet counts, anticoagulant strategy, and concomitant medications.</p><p>Patients with lower Hb values were more likely to be female (64%), older, and have a lower body mass index, while those in the highest Hb quintile were predominantly male (81%) and younger. The initial presentation of VTE varied, with presentation as PE becoming more frequent with increasing Hb values, whereas upper-limb DVT was more prevalent in the lowest Hb group (< 11.4 g/dL). Comorbidities such as active cancer, chronic heart failure, renal failure, and prior ischemic stroke were more common in patients with lower Hb values compared to those with higher values. Conversely, unprovoked VTE was more frequent in higher Hb quintiles.</p><p>The risk of adverse events declined progressively with increasing Hb values. In the lowest Hb quintile, 90-day rates of recurrent VTE, major bleeding, arterial ischemic events, and all-cause mortality were 2.2%, 4.1%, 0.5%, and 16%, respectively. In contrast, corresponding rates in the highest Hb quintile were 1.3%, 0.9%, 0.2%, and 3.2% (Table 1). Major bleeding and mortality rates were approximately five times higher in the lowest Hb quintile than in the highest, whereas VTE recurrence and arterial ischemic events were nearly twice as frequent. The major bleeding-to-VTE recurrence ratio was highest in the lowest quintile (1.86) and lowest in the highest quintile (0.49), indicating that bleeding risk outweighed thrombotic risk in anemic patients, whereas the opposite trend was observed in those with elevated Hb values.</p><p>Multivariable analysis confirmed that patients in the lowest Hb quintile had significantly incre","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 8","pages":"1444-1447"},"PeriodicalIF":10.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27707","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimal Depth of the Treatment Response Before Allogeneic Hematopoietic Transplantation for Chronic Myeloid Leukemia in Chronic Phase","authors":"Yosuke Okada, Takeshi Kondo, Takuya Miyazaki, Yutaka Shimazu, Yosuke Minami, Fumihiko Ouchi, Shinichi Kako, Masatsugu Tanaka, Tetsuya Nishida, Shin-Ichiro Fujiwara, Naoyuki Uchida, Hirohisa Nakamae, Yuta Hasegawa, Keisuke Kataoka, Shingo Yano, Mamiko Sakata-Yanagimoto, Ayumu Ito, Jun Ishikawa, Yoshinobu Kanda, Koji Kawamura, Takahiro Fukuda, Yoshiko Atsuta, Takayoshi Tachibana","doi":"10.1002/ajh.27706","DOIUrl":"10.1002/ajh.27706","url":null,"abstract":"<p>The outcomes of chronic myeloid leukemia (CML) have dramatically improved since the introduction of tyrosine kinase inhibitors (TKIs) [<span>1, 2</span>]. The development of TKIs has improved the life expectancy in CML patients, which is approaching that in the general population. However, resistance and intolerance to TKIs can still occur, and allogeneic hematopoietic cell transplantation (allo-HCT) is still a therapeutic option for CML. According to the European LeukemiaNet 2020 recommendations, CML patients in the first chronic phase (CP1) who are resistant or intolerant to multiple TKIs, those who progress to the accelerated phase (AP) or blast phase (BP) during treatment, and those who initially present with BP are recommended to receive allo-HCT [<span>3</span>]. Regarding disease status, it is well known that CML patients in chronic phase (CML-CP) have favorable outcomes compared to those in the AP or BP [<span>4</span>]. However, it is not yet clear whether a deeper treatment response in CML-CP results in better outcomes after allo-HCT.</p><p>In this study, we aimed to clarify the optimal depth of the treatment response at allo-HCT for CML-CP. Based on the Japanese nationwide registry database, we retrospectively analyzed transplant outcomes in CML-CP who received their first allo-HCT and who had received TKI therapy before allo-HCT. Details of additional methods are provided in the Supporting Information. Between 2002 and 2022, 1413 patients who were aged 16 years or older received their first allo-HCT, and 689 patients met the inclusion criteria. Disease status at diagnosis was CP or AP in 350 and BP in 339 patients (de novo BP group). Among the patients whose disease status at diagnosis was CP or AP, disease status at allo-HCT was CP1 in 207 (insufficient response group) and second CP (CP2) or later in 143 (disease progression group; Figure S1).</p><p>Regarding the depth of the treatment response, the number of patients with major molecular response (MMR) at allo-HCT has increased in recent years, whereas the number of patients with complete cytogenetic response (CCyR) or complete hematologic response (CHR) has decreased (<i>p</i> < 0.001, Table 1). Accordingly, second- and third-generation TKIs before allo-HCT (<i>p</i> < 0.001) and post allo-HCT TKI maintenance (<i>p</i> < 0.001) were more commonly administered in patients with MMR compared to the rates in those with CCyR or CHR. The relationship between the highest generation of TKIs before allo-HCT and transplantation years was shown in Figure S2. The details of TKIs before and after allo-HCT were provided in Table S1.</p><p>In the entire cohort, disease-free survival (DFS) at 3 years was higher in patients with MMR (76.3%, 95% confidence interval (CI): 70.6–80.9) than in those with CCyR (65.1%, 95% CI: 56.6–72.3) or CHR (64.8%, 95% CI: 58.3–70.5, <i>p</i> = 0.017). Overall survival (OS) at 3 years was also higher in patients with MMR (82.6%, 95% CI: 77.4–86.7) than in ","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 8","pages":"1440-1443"},"PeriodicalIF":10.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27706","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Switching From Race-Based to Race-Neutral Spirometry Reference Equations in Children With Sickle Cell Anemia","authors":"Jose A. Mejias-Figueroa, Mark Rodeghier, Michael R. DeBaun","doi":"10.1002/ajh.27704","DOIUrl":"10.1002/ajh.27704","url":null,"abstract":"<p>The American Thoracic Society now recommends race-neutral spirometry reference equations, as proposed by the Global Lung Initiative, which estimates lung function based solely on age, height, and sex [<span>1</span>]. However, the impact of this shift from race-based to race-neutral reference equations on the established relationship in children with sickle cell anemia between increasing age and decreasing FEV<sub>1</sub>% predicted is unknown [<span>2</span>]. To address this knowledge gap in patient care management, we tested the following hypothesis: FEV1% predicted declines with age in children and adolescents with sickle cell anemia when using the new race-neutral pulmonary function test reference equations. All participants provided appropriate assent and parental written informed consent.</p><p>We re-analyzed the Sleep and Asthma Cohort (SAC) dataset, as previously done by our team [<span>2</span>]. The SAC cohort was a multi-center observational study comprising children and adolescents with sickle cell anemia, unselected for respiratory disease. The participants ranged from 4 to 18 years of age and were enrolled and followed between 2005 and 2011 at three clinical centers: Washington University School of Medicine in St. Louis, Missouri; Case Western Reserve University in Cleveland, Ohio; and UCL Great Ormond Street Institute of Child Health in London, UK.</p><p>Participants were either HbSS (<i>N</i> = 240) or HbSβ<sup>0</sup> (<i>N</i> = 12). Children were not eligible for participation in the study if they received long-term blood transfusion therapy, received overnight oxygen or continuous positive airway pressure (CPAP) support, had chronic lung disease other than asthma, or were known to be HIV positive. We carefully screened all participants for asthma. Asthma classification was based on physician diagnosis and current prescription of asthma medication, consistent with previous methods [<span>3</span>]. After the start of the study, data from participants who initiated chronic blood transfusion therapy were censored from that point forward due to the known decrease in pain events following the initiation of chronic transfusion therapy.</p><p>Pulmonary function tests (PFTs) were obtained when participants were at least 4 weeks after discharge from the hospital for SCA complications and at baseline health without current illness, pain, or acute respiratory symptoms. Pulmonary function testing (spirometry and body plethysmography) was done at study enrollment and then at least annually during the study period. All PFTs were centrally adjudicated for acceptable quality as per the American Thoracic Society guidelines. Predicted values were determined for each participant using the previously recommended GLI 2012 Race-based reference equations and the newly recommended GLI 2023 Race-neutral reference equations. We used linear mixed-effects models to evaluate the association between age and pulmonary function.</p><p>A total of 223 part","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 8","pages":"1453-1455"},"PeriodicalIF":10.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27704","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoferremic Response to Chronic Inflammation Is Controlled via the Hemojuvelin/Hepcidin/Ferroportin Axis and Does Not Involve Hepcidin-Independent Regulation of Fpn mRNA","authors":"Siqi Liu,&nbsp;Sofiya Tsyplenkova,&nbsp;Carine Fillebeen,&nbsp;Kostas Pantopoulos","doi":"10.1002/ajh.27710","DOIUrl":"10.1002/ajh.27710","url":null,"abstract":"<p>The iron regulatory hormone hepcidin contributes to the pathogenesis of anemia of inflammation (AI) by inhibiting the iron exporter ferroportin in target cells, causing hypoferremia. Under acute inflammation, hepcidin induction requires hemojuvelin (Hjv), a bone morphogenetic protein co-receptor, while <i>Fpn</i> mRNA is also suppressed in a hepcidin-independent manner. However, it is unclear whether, during chronic inflammation, Hjv and hepcidin-independent <i>Fpn</i> mRNA regulation are critical for hypoferremia and AI. To address these questions, wild type and <i>Hjv</i>^{<i>−/−</i>} mice, a model of hemochromatosis, were fed for 8 weeks an adenine-rich diet to develop chronic kidney disease (CKD). Renal inflammation, accessed by increased <i>Il6</i> mRNA expression, did not differ among genotypes. Hjv disruption did not mitigate the severity of kidney injury but suppressed the inflammatory induction of liver hepcidin. CKD triggered hypoferremia and mild anemia in wild type mice; however, <i>Hjv</i>^{<i>−/−</i>} littermates maintained high serum iron and normal hemoglobin, consistent with a protective effect of Hjv/hepcidin deficiency. Notably, tissue <i>Fpn</i> mRNA levels were not affected by the inflammatory milieu of CKD. Following injection of wild type or <i>Hjv</i>^{<i>−/−</i>} mice with heat-killed <i>Brucella abortus</i>, <i>Fpn</i> mRNA was suppressed during the acute phase of inflammation but quickly recovered and persisted in the chronic phase. We conclude that Hjv deficiency reduces hepcidin levels and mitigates anemia in the CKD model, providing further support for pharmacological targeting of Hjv for the treatment of AI. Moreover, our data demonstrate that <i>Fpn</i> mRNA suppression only occurs under acute but not chronic inflammatory conditions and therefore cannot substantially contribute to AI pathogenesis.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 8","pages":"1323-1333"},"PeriodicalIF":10.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27710","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Allogeneic Hematopoietic Stem Cell Transplantation on Sickle Cell Retinopathy and Maculopathy: A Prospective, Observational Study","authors":"Rajani P. Brandsen,&nbsp;Elisabeth Dovern,&nbsp;Bart J. Biemond,&nbsp;Roselie M. H. Diederen,&nbsp;Erfan Nur","doi":"10.1002/ajh.27705","DOIUrl":"10.1002/ajh.27705","url":null,"abstract":"&lt;p&gt;Sickle cell retinopathy (SCR) represents a significant ocular manifestation of sickle cell disease (SCD) that can dramatically impair visual acuity. SCR can be divided into non-proliferative SCR and proliferative SCR. Non-proliferative SCR involves abnormalities of the peripheral retina such as vascular occlusion without neovascularization, typical scarring (“black sunbursts”) and intraretinal hemorrhages (“salmon patches”). Proliferative SCR represents the more severe form of SCR, characterized by neovascularization. This can lead to vitreous hemorrhage or retinal detachment, which can temporarily or permanently impair visual acuity. In more recent years, modern imaging techniques such as spectral-domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA) have also revealed subclinical changes in the central part of the retina (the macula) in asymptomatic patients with SCD [&lt;span&gt;1&lt;/span&gt;]. These changes are referred to as sickle cell maculopathy (SCM) and include macular thinning, enlargement of the foveal avascular zone (FAZ) and lower vessel densities. Both SCR and SCM are progressive in nature and associated with increasing age [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Allogeneic hematopoietic stem cell transplantation (HSCT) is the only established curative treatment option for patients with SCD. Improvements in non-myeloablative regimens have led to excellent disease-free and overall survival in transplanted adults with SCD, also in the setting of haploidentical HSCT [&lt;span&gt;3&lt;/span&gt;]. SCD-related organ damage is one of the main indications for HSCT, but data on long-term outcomes regarding the progression of organ complications is scarce [&lt;span&gt;4&lt;/span&gt;]. This is particularly true for adult patients, who frequently already have developed (sub-)clinical organ damage before HSCT.&lt;/p&gt;&lt;p&gt;Evidence concerning the behavior of SCR and SCM after HSCT is especially scarce. The only study on SCR after HSCT was conducted in children with SCD and did not include SCM [&lt;span&gt;5&lt;/span&gt;]. This leaves a significant gap in understanding how these conditions evolve in adults with SCD undergoing HSCT. We hypothesized that HSCT has the potential to stabilize pre-existing SCR and will prevent the development of new SCR in patients with SCD. Therefore, the aim of this study was to evaluate the natural course of SCR and SCM in an adult cohort of SCD patients undergoing HSCT.&lt;/p&gt;&lt;p&gt;In this prospective observational study in adults with SCD (HbSS, HbSC, HbSβ&lt;sup&gt;0&lt;/sup&gt; and HbSβ&lt;sup&gt;+&lt;/sup&gt; genotype), retinopathy and maculopathy were assessed before and at least 1 year post-transplant. All SCD patients undergoing non-myeloablative matched sibling donor (MSD) and haploidentical bone marrow transplantation were included [&lt;span&gt;3, 6&lt;/span&gt;]. Patients undergoing MSD transplantation received a 3-month preconditioning with azathioprine/hydroxyurea, followed by alemtuzumab (1 mg/kg) and 3 Gy total body irradiation (TBI) [&lt;span&gt;6&lt;/span&gt;]. The condition","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 8","pages":"1448-1452"},"PeriodicalIF":10.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27705","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic Hematopoietic Stem Cell Transplantation for Elderly Acute Lymphoblastic Leukemia Patients: A Registry Study From the Société Francophone de Greffe de Moelle et Thérapie Cellulaire (SFGM-TC)","authors":"Yves Chalandon,&nbsp;Raynier Devillier,&nbsp;Ariane Boumendil,&nbsp;Stephanie Nguyen,&nbsp;Claude-Eric Bulabois,&nbsp;Patrice Ceballos,&nbsp;Eolia Brissot,&nbsp;Marie-Thérèse Rubio,&nbsp;Hélène Labussière-Wallet,&nbsp;Johan Maertens,&nbsp;Patrice Chevallier,&nbsp;Natacha Maillard,&nbsp;Xavier Poiré,&nbsp;Cristina Castilla-Llorente,&nbsp;Yves Beguin,&nbsp;Jérôme Cornillon,&nbsp;Sébastien Maury,&nbsp;Tony Marchand,&nbsp;Etienne Daguindau,&nbsp;Jacques-Olivier Bay,&nbsp;Pascal Turlure,&nbsp;Magalie Joris,&nbsp;Anne-Lise Menard,&nbsp;Karin Bilger,&nbsp;Gaelle Guillerm,&nbsp;Sylvie François,&nbsp;Ali Bazarbachi,&nbsp;Sylvain Chantepie,&nbsp;Philippe Lewalle,&nbsp;Ambroise Marçais,&nbsp;Michael Loschi,&nbsp;Malek Benakli,&nbsp;Paul Chauvet,&nbsp;Edouard Forcade,&nbsp;Anne Huynh,&nbsp;Marie Robin,&nbsp;Stavroula Masouridi-Levrat","doi":"10.1002/ajh.27701","DOIUrl":"10.1002/ajh.27701","url":null,"abstract":"<div>\u0000 \u0000 <p>There are very limited data regarding the outcomes of elderly patients with acute lymphoblastic leukemia (ALL) who undergo allogeneic hematopoietic stem cell transplantation (alloHSCT). A total of 316 ALL patients aged ≥ 60 years who underwent alloHSCT between 2010 to 2022 were identified in the SFGM-TC registry. The primary objective was to evaluate progression-free survival (PFS), non-relapse mortality (NRM), relapse incidence (RI), and graft-versus-host disease (GvHD)-free relapse-free survival (GRFS), as well as their risk factors. The median age was 63.8 years (range 60–75.8), 49.8% of patients had Philadelphia-positive B-ALL (Ph + ALL), and 70.9% were in first complete remission (CR1) at transplantation. The donor was an unrelated donor in 52.1%, a matched related donor (MRD) in 26.3%, and a haplo-identical donor in 17.7%. Reduced-intensity conditioning (RIC) was administered to 64.6% of patients, while total body irradiation (TBI) was used in 35.8%. The 3-year overall survival (OS) was 46% (95% CI 40%–53%). The 3-year PFS, NRM, RI, and GRFS were 41% (95% CI 35%–48%), 23% (95% CI 18%–28%), 36% (95% CI 31%–42%), and 30% (95% CI 25%–37%), respectively. Multivariable analyses confirmed poorer OS and PFS in patients with advanced disease, with an HR of 1.79 (95% CI 1.22–2.64), <i>p</i> = 0.0032. Additionally, the ALL subtype significantly impacted outcomes, with an HR of 1.99 (95% CI 1.42–2.79) for non-Ph + ALL. This study suggests that alloHSCT is a viable option for elderly ALL patients, as age itself did not impact outcomes. However, advanced disease and non-Ph + ALL were associated with significantly worse survival.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 7","pages":"1173-1184"},"PeriodicalIF":10.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing Outcomes in Relapsed and Refractory Multiple Myeloma: Personalized Approaches and Adverse Event Management","authors":"Eirini Katodritou, Evangelos Terpos, Suzanne Lentzsch, Shaji Kumar","doi":"10.1002/ajh.27646","DOIUrl":"https://doi.org/10.1002/ajh.27646","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"60 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PIEZO1 Activation-Mediated Generation of Transgene-Free Long-Term Hematopoietic Stem Cells","authors":"Giorgia Scapin,&nbsp;Jennifer L. Cillis,&nbsp;Marie C. Goulard,&nbsp;Taylor C. Patch,&nbsp;Cintia E. Gomez Limia,&nbsp;Yichen Ding,&nbsp;Wenqiang Du,&nbsp;Priyanka R. Dharampuriya,&nbsp;Elliott J. Hagedorn,&nbsp;Heidi Anderson,&nbsp;Gabriel A. Musso,&nbsp;Caitlyn R. Curley,&nbsp;Emily M. Teets,&nbsp;Calum A. MacRae,&nbsp;Lalit Sehgal,&nbsp;Tzung K. Hsiai,&nbsp;Bradley W. Blaser,&nbsp;Dhvanit I. Shah","doi":"10.1002/ajh.27689","DOIUrl":"10.1002/ajh.27689","url":null,"abstract":"<div>\u0000 \u0000 <p>The development of engraftable, long-term reconstituting hematopoietic stem cells (LT-HSC) from human pluripotent stem cells (hPSC) has been a long-sought goal. Since HSCs are formed by a subset of endothelial cells in the ventral part of the dorsal aorta, we analyzed heartbeat-mediated pulsatile displacement experienced by the walls of the dorsal aorta in zebrafish embryos. We found that pulsation-mediated circumferential stretch was restricted to the ventral part of the dorsal aorta and activated Piezo1 to stimulate LT-HSC formation. Stimulation of pulsation or Yoda1-mediated Piezo1 activation promoted the formation of <i>de novo</i> LT-HSCs from hemogenic endothelial cells derived from murine embryos or human pluripotent stem cells. These HSCs gave long-term multilineage reconstitution of hematopoietic cells upon transplantation into immunocompromised mice. The formation of transgene-free human LT-HSCs that can engraft and reconstitute the hematopoietic system will facilitate the generation of off-the-shelf HSCs from hPSCs for use in cellular therapies.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 6","pages":"963-979"},"PeriodicalIF":10.1,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombotic Thrombocytopenic Purpura (TTP) Survivors Exhibit Impaired Stress Perfusion on Cardiac MRI","authors":"Senthil Sukumar,&nbsp;Leah Danish,&nbsp;Yuchi Han,&nbsp;Spero Cataland","doi":"10.1002/ajh.27702","DOIUrl":"10.1002/ajh.27702","url":null,"abstract":"<p>Stress images are on the left and rest images are on the right. The top row is a TTP subject and the bottom row is a control subject. The color maps show myocardial blood flow (MBF) in ml/g/min with brighter colors indicating higher perfusion. Stress imaging of the TTP patient shows decreased MBF compared with control, primarily noted in the subendocardium. The rest images do not show any significant difference in MBF at rest.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 7","pages":"1256-1258"},"PeriodicalIF":10.1,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27702","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thrombocytopenia and Anemia After Cardiac Surgery","authors":"Myriam Beshai,&nbsp;Nour Alhomsi,&nbsp;Theodore E. Warkentin","doi":"10.1002/ajh.27696","DOIUrl":"10.1002/ajh.27696","url":null,"abstract":"&lt;p&gt;\u0000 &lt;b&gt;An 83-year-old Caucasian female with hypertension, dyslipidemia, and diabetes presented to the hospital with acute chest pain, nausea, and diaphoresis; she had a previous history of coronary angioplasty (9 years prior). Acute non-ST segment elevation myocardial infarction (NSTEMI) was diagnosed based upon non-specific T wave abnormalities and high-sensitivity troponin-I rise (peak, 780 ng/mL; reference range [RR], &lt; 40). She received enteric-coated aspirin (160 mg first dose; subsequently, 81 mg daily) and 2.5 mg of fondaparinux daily by subcutaneous injection. Heart catheterization, performed with 3000 units (U) of unfractionated heparin [UFH], revealed triple-vessel coronary artery disease (including 80% stenosis in the left anterior descending artery), with left ventricle function preserved; coronary artery bypass graft (CABG) surgery was scheduled.&lt;/b&gt;\u0000 &lt;/p&gt;&lt;p&gt;CABG surgery is common in the United States (400 000 procedures per year) [&lt;span&gt;1&lt;/span&gt;]. While percutaneous coronary intervention may be used to treat NSTEMI, CABG is often performed for triple-vessel coronary disease with stenosi(e)s greater than 70%. Patlolla and coworkers [&lt;span&gt;2&lt;/span&gt;] reported better long-term survival in patients undergoing CABG surgery within 7 days following NSTEMI versus CABG surgery performed later. This patient was judged to be a relatively good candidate for CABG. This patient was treated in a Canadian hospital, and thus the antithrombin-dependent pentasaccharide anticoagulant, fondaparinux—which is approved in Canada for coronary artery thrombosis prophylaxis in STEMI patients based upon efficacy and safety (versus enoxaparin) in this clinical setting [&lt;span&gt;3&lt;/span&gt;]—was administered (note: fondaparinux is not approved for coronary thrombosis prophylaxis by the U.S. Food and Drug Administration).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Prior to CABG surgery, the last doses of fondaparinux and aspirin were given 2 and 3 days before surgery, respectively.&lt;/b&gt; &lt;b&gt;Immediately pre-surgery, her complete blood count (CBC) showed: platelet count 200 × 10&lt;sup&gt;9&lt;/sup&gt;/L (reference range [RR], 150–400), hemoglobin 10.8 g/dL (RR, 11.5–16.5), and white blood cell (WBC) count 8.3 × 10&lt;sup&gt;9&lt;/sup&gt;/L (RR, 4.0–11.0), with normal automated WBC differential.&lt;/b&gt; &lt;b&gt;She was typed as blood group A, RhD-positive (A+), without red blood cell (RBC) alloantibodies (by indirect Coombs' test); a direct antiglobulin test (DAT, i.e., direct Coombs) was also negative.&lt;/b&gt; &lt;b&gt;She underwent CABG, with three arteries bypassed, and received a total of 35 000 U of UFH intraoperatively. Her intraoperative and early postoperative course was complicated by bleeding: on the day of surgery, she was transfused a total of 3 units of A+ red cell concentrates (RCCs), and 3 more A+ RCCs during the first two postoperative days.&lt;/b&gt; &lt;b&gt;Her platelet count dropped by 55% to 89 × 10&lt;sup&gt;9&lt;/sup&gt;/L on the day of surgery, and hemoglobin levels dropped by 42% to 6.3 g/dL (nadir) on the day of surgery (","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 8","pages":"1425-1431"},"PeriodicalIF":10.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27696","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}