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https://www.readbyqxmd.com/read/29739038/effects-of-analyzer-detection-method-ethnicity-and-reference-individuals-on-reference-interval-of-immature-platelet-fraction
#1
Ming-Feng Wu, Hsien-Hsu Hsieh, Wei-Chang Huang, Kun-Mu Lu, Jun-Hong Lin, Yi-Ching Lin, Jiunn-Min Wang, Tseng-Hsi Lin
BACKGROUND: Immature platelet fraction (IPF) is a new biomarker for thrombopoiesis and inflammation. However, the reference interval (RI) is wildly discrepant among published reports. This study aimed to establish the RI of IPF for a population in Taiwan and evaluate the effects the detection method of the analyzer, ethnicity, and reference individuals have on the RI of IPF. METHODS: The RI of absolute IPF (A-IPF) and IPF% were established with healthy subjects from the outpatient services of the Health Management Department of Taichung Veterans General Hospital between January 1, 2015 and March 1, 2016...
May 1, 2018: Clinical Laboratory
https://www.readbyqxmd.com/read/29720539/its-reticulated-the-liver-at-the-heart-of-atherosclerosis
#2
Prabhakara R Nagareddy, Sunil K Noothi, Michelle Christine Flynn, Andrew Murphy
Platelets play a critical role in both the initiation and progression of atherosclerosis, and even more so in the ensuing atherothrombotic complications. Low-dose aspirin remains the mainstay of antiplatelet therapy in high-risk patients by reducing the risk of myocardial ischemia (MI), stroke, or death due to cardiovascular disease (CVD). However, antiplatelet therapies lose their efficacy in people with diabetes mellitus (DM), increasing the risk of future atherothrombotic events. The molecular mechanisms that promote platelet hyperactivity remain unclear but could be due to glycation-induced conformational changes of platelet membranes resulting in impaired aspirin entry, or less-efficient acetylation/compensatory increase in COX-2 expression in newborn platelets...
May 2, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29708814/protective-effect-of-the-c-mpl-agonist-romiplostim-on-megakaryocytopoiesis-of-human-cd34-hematopoietic-progenitor-cells-exposed-to-ionizing-radiation
#3
Satoru Monzen, Shunta Kimura, Masaru Yamaguchi, Ikuo Kashiwakura
A thrombopoiesis-stimulating protein, the myeloproliferative leukemia virus protooncogene (Mpl) ligand romiplostim (RP), is currently approved as a therapeutic agent for idiopathic thrombocytopenic purpura in many countries. Although the action of the initial MPL ligand thrombopoietin (TPO) on human megakaryocytic regeneration from irradiated human hematopoietic stem cells has been examined, there are few reports on the action of RP. In the present study, freshly prepared nonirradiated and 2-Gy X-irradiated human CD34 positive (CD34+ ) cells from placental umbilical cord blood were cultured with a combination of RP and various cytokines...
April 30, 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29666579/d-dencichine-regulates-thrombopoiesis-by-promoting-megakaryocyte-adhesion-migration-and-proplatelet-formation
#4
Shilan Ding, Min Wang, Song Fang, Huibo Xu, Huiting Fan, Yu Tian, Yadong Zhai, Shan Lu, Xin Qi, Fei Wei, Guibo Sun, Xiaobo Sun
Life-threatening chemotherapy-induced thrombocytopenia can increase the risk of bleeding due to a dramatic low platelet count, which may limit or delay treatment schedules in cancer patients. The pressing need for the rapid alleviation of the symptoms of thrombocytopenia has prompted us to search for novel highly effective and safe thrombopoietic agents. Pharmacological investigations have indicated that dencichine can prevent and treat blood loss and increase the number of platelets. On the basis of the neurotoxicity of dencichine, D-dencichine is artificially synthesized in the laboratory...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29617409/microvasculature-directed-thrombopoiesis-in-a-3d-in-vitro-marrow-microenvironment
#5
Surya Kotha, Sijie Sun, Amie Adams, Brian Hayes, Kiet T Phong, Ryan Nagao, Jo-Anna Reems, Dayong Gao, Beverly Torok-Storb, José A López, Ying Zheng
Vasculature is an interface between the circulation and the hematopoietic tissue providing the means for hundreds of billions of blood cells to enter the circulation every day in a regulated fashion. The precise mechanisms that control the interactions of hematopoietic cells with the vessel wall are largely undefined. Here, we report on the development of an in vitro 3D human marrow vascular microenvironment (VME) to study hematopoietic trafficking and the release of blood cells, specifically platelets. We show that mature megakaryocytes from aspirated marrow as well as megakaryocytes differentiated in culture from CD34+ cells can be embedded in a collagen matrix containing engineered microvessels to create a thrombopoietic VME...
2018: PloS One
https://www.readbyqxmd.com/read/29522790/thrombopoietin-tpo-induces-thrombocytic-colony-formation-of-kidney-cells-synergistically-with-kit-ligand-a-and-a-non-secretory-tpo-variant-exists-in-common-carp
#6
Fumihiko Katakura, Yuji Sugie, Kiyotaka Hayashi, Kohei Nishiya, Jiro Miyamae, Masaharu Okano, Teruyuki Nakanishi, Tadaaki Moritomo
The development of mammalian megakaryocytes and platelets is regulated by numerous cytokine signals, primarily through the thrombopoietin (TPO)/c-MPL axis. Although non-mammalian vertebrates are known to possess nucleated thrombocytes functionally equivalent to mammalian platelets, the dynamics of the thrombocyte development remains unclear. Here we identified TPO and a splice variant (TPO-v) caused by the intron retention in common carp (Cyprinus carpio). Both the tpo and its variant transcripts were highly expressed in heart and liver...
July 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29519806/cancer-and-platelet-crosstalk-opportunities-and-challenges-for-aspirin-and-other-antiplatelet-agents
#7
REVIEW
Xiaohong Ruby Xu, George M Yousef, Heyu Ni
Platelets have long been recognized as key players in hemostasis and thrombosis; however, growing evidence suggests that they are also significantly involved in cancer, the second leading cause of mortality worldwide. Preclinical and clinical studies showed that tumorigenesis and metastasis can be promoted by platelets through a wide variety of crosstalk between platelets and cancer cells. For example, cancer changes platelet behavior by directly inducing tumor-platelet aggregates, triggering platelet granule and extracellular vesicle release, altering platelet phenotype and platelet RNA profiles, and enhancing thrombopoiesis...
April 19, 2018: Blood
https://www.readbyqxmd.com/read/29476485/bone-imaging-platelet-formation-dynamics
#8
Asuka Sakata, Satoshi Nishimura
Bone imaging using multiphoton microscopy enables dynamic observation of platelet formation in living animals. Two-photon excitation microscopy is superior to confocal microscopy as it enables deeper tissue penetration, efficient light detection, and reduced phototoxicity. Using this microscopy approach, thrombopoiesis by megakaryocytes is clearly visualized in the skull at significant depth from the surface. Here we describe our microscopy setup and dye recipe for visualization of bone marrow in the mouse skull...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29461915/a-novel-method-for-automated-assessment-of-megakaryocyte-differentiation-and-proplatelet-formation
#9
M Salzmann, B Hoesel, M Haase, M Mussbacher, W C Schrottmaier, J B Kral-Pointner, M Finsterbusch, A Mazharian, A Assinger, J A Schmid
Transfusion of platelet concentrates represents an important treatment for various bleeding complications. However, the short half-life and frequent contaminations with bacteria restrict the availability of platelet concentrates and raise a clear demand for platelets generated ex vivo. Therefore, in vitro platelet generation from megakaryocytes represents an important research topic. A vital step for this process represents accurate analysis of thrombopoiesis and proplatelet formation, which is usually conducted manually...
June 2018: Platelets
https://www.readbyqxmd.com/read/29421274/autonomous-role-of-wiskott-aldrich-syndrome-platelet-deficiency-in-inducing-autoimmunity-and-inflammation
#10
Lucia Sereni, Maria Carmina Castiello, Francesco Marangoni, Achille Anselmo, Dario di Silvestre, Sara Motta, Elena Draghici, Stefano Mantero, Adrian J Thrasher, Silvia Giliani, Alessandro Aiuti, Pierluigi Mauri, Luigi D Notarangelo, Marita Bosticardo, Anna Villa
BACKGROUND: Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by eczema, infections, and susceptibility to autoimmunity and malignancies. Thrombocytopenia is a constant finding, but its pathogenesis remains elusive. OBJECTIVE: To dissect the basis of the WAS platelet defect, we used a novel conditional mouse model (CoWas) lacking Wiskott-Aldrich syndrome protein (WASp) only in the megakaryocytic lineage in the presence of a normal immunologic environment, and in parallel we analyzed samples obtained from patients with WAS...
February 6, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29410193/inflammation-associated-cytokines-igfbp1-and-rantes-impair-the-megakaryocytic-potential-of-hscs-in-pt-patients-after-allo-hsct
#11
Cuicui Liu, Yiqing Yang, Dan Wu, Wenxia Zhang, Hongtao Wang, Pei Su, Jianfeng Yao, Chen Liang, Sizhou Feng, Mingzhe Han, Fuxu Wang, Erlie Jiang, Jiaxi Zhou
Prolonged isolated thrombocytopenia (PT) is a severe complication in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Whether the megakaryoctic potential of hematopoietic stem cells (HSCs) in bone marrow is intact and what factors drive the pathological process of PT remain elusive. A retrospective study in patients (n = 285) receiving HSCT revealed that the occurrence of PT was approximately 8% and the number of platelets and megakaryocytes in PT patients is much lower compared with control subjects...
February 1, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29407773/preclinical-evaluation-of-the-mono-pegylated-recombinant-human-interleukin-11-in-cynomolgus-monkeys
#12
Kuo-Ming Yu, Johnson Yiu-Nam Lau, Manson Fok, Yuk-Keung Yeung, Siu-Ping Fok, Suxing Zhang, Peizhen Ye, Kezhi Zhang, Xiaobo Li, Juan Li, Qin Xu, Wing-Tak Wong, Qui-Lim Choo
The mono-PEGylated recombinant human interleukin-11 (rhIL-11) was evaluated for its pharmacology and toxicology profile in non-human primates. This PEGylated IL-11 (PEG-IL11) showed a much prolonged circulating half-life of 67h in cynomolgus monkeys as compared to its un-PEGylated counterpart (~3h) through subcutaneous administration, implicating that a single injection of the recommended dose will effectively enhance thrombopoiesis in humans for a much longer period of time compared to rhIL-11 in humans (t1/2 =6...
March 1, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29396859/n-acetyl-l-cysteine-improves-bone-marrow-endothelial-progenitor-cells-in-prolonged-isolated-thrombocytopenia-patients-post-allogeneic-hematopoietic-stem-cell-transplantation
#13
Yuan Kong, Min-Min Shi, Yuan-Yuan Zhang, Xie-Na Cao, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang
Prolonged isolated thrombocytopenia (PT) is a serious complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). According to murine studies, endothelial progenitor cells (EPCs) play a crucial role in the regulation of hematopoiesis and thrombopoiesis in the bone marrow (BM) microenvironment. We previously showed that the reduced frequency of BM EPCs was an independent risk factor for the occurrence of PT following allo-HSCT. However, the functional role of BM EPCs and methods to improve the impaired BM EPCs in PT patients are unknown...
February 2, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29381746/time-course-of-immature-platelet-count-and-its-relation-to-thrombocytopenia-and-mortality-in-patients-with-sepsis
#14
Kansuke Koyama, Shinshu Katayama, Tomohiro Muronoi, Ken Tonai, Yuya Goto, Toshitaka Koinuma, Jun Shima, Shin Nunomiya
INTRODUCTION: The pathogenesis of thrombocytopenia in patients with sepsis is not fully understood. The aims of this study were to investigate changes in thrombopoietic activity over time by using absolute immature platelet counts (AIPC) and to examine the impact of platelet production on thrombocytopenia and mortality in patients with sepsis. METHODS: This retrospective observational study included adult patients with sepsis admitted to the intensive care unit at a university hospital...
2018: PloS One
https://www.readbyqxmd.com/read/29380037/a-novel-heterozygous-itgb3-p-t720del-inducing-spontaneous-activation-of-integrin-%C3%AE-iib%C3%AE-3-in-autosomal-dominant-macrothrombocytopenia-with-aggregation-dysfunction
#15
Naohiro Miyashita, Masahiro Onozawa, Koji Hayasaka, Takahiro Yamada, Ohsuke Migita, Kenichiro Hata, Kohei Okada, Hideki Goto, Masao Nakagawa, Daigo Hashimoto, Kaoru Kahata, Takeshi Kondo, Shinji Kunishima, Takanori Teshima
We identified a novel heterozygous ITGB3 p.T720del mutation in a pedigree with macrothrombocytopenia exhibiting aggregation dysfunction. Platelet aggregation induced by ADP and collagen was significantly reduced, while ristocetin aggregation was normal. Integrin αIIbβ3 was partially activated in a resting status, but platelet expression of αIIbβ3 was downregulated. Functional analysis using a cell line showed spontaneous phosphorylation of FAK in αIIb/β3 (p.T720del)-transfected 293T cells in suspension conditions...
April 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29364213/megakaryocyte-differentiation-and-platelet-formation-from-human-cord-blood-derived-cd34-cells
#16
Jose Perdomo, Feng Yan, Halina H L Leung, Beng H Chong
Platelet production occurs principally in the bone marrow in a process known as thrombopoiesis. During thrombopoiesis, hematopoietic progenitor cells differentiate to form platelet precursors called megakaryocytes, which terminally differentiate to release platelets from long cytoplasmic processes termed proplatelets. Megakaryocytes are rare cells confined to the bone marrow and are therefore difficult to harvest in sufficient numbers for laboratory use. Efficient production of human megakaryocytes can be achieved in vitro by culturing CD34+ cells under suitable conditions...
December 27, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29358086/meis1-regulates-hemogenic-endothelial-generation-megakaryopoiesis-and-thrombopoiesis-in-human-pluripotent-stem-cells-by-targeting-tal1-and-fli1
#17
Hongtao Wang, Cuicui Liu, Xin Liu, Mengge Wang, Dan Wu, Jie Gao, Pei Su, Tatsutoshi Nakahata, Wen Zhou, Yuanfu Xu, Lihong Shi, Feng Ma, Jiaxi Zhou
Human pluripotent stem cells (hPSCs) provide an unlimited source for generating various kinds of functional blood cells. However, efficient strategies for generating large-scale functional blood cells from hPSCs are still lacking, and the mechanism underlying human hematopoiesis remains largely unknown. In this study, we identified myeloid ectopic viral integration site 1 homolog (MEIS1) as a crucial regulator of hPSC early hematopoietic differentiation. MEIS1 is vital for specification of APLNR+ mesoderm progenitors to functional hemogenic endothelial progenitors (HEPs), thereby controlling formation of hematopoietic progenitor cells (HPCs)...
February 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29327472/mesenchymal-stem-cell-deficiency-influences-megakaryocytopoiesis-through-the-tnfaip3-nf-%C3%AE%C2%BAb-smad-pathway-in-patients-with-immune-thrombocytopenia
#18
Yun He, Lin-Lin Xu, Fei-Er Feng, Qian-Ming Wang, Xiao-Lu Zhu, Chen-Cong Wang, Jia-Min Zhang, Hai-Xia Fu, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
Immune thrombocytopenia (ITP) is an autoimmune disease. Mesenchymal stem cells (MSCs) play important roles in the physiology and homeostasis of the haematopoietic system, including supporting megakaryocytic differentiation from CD34+ haematopoietic progenitor cells. Tumour necrosis factor alpha-induced protein 3 (TNFAIP3, also termed A20) plays a key role in terminating NF-κB signalling. Human genetic studies showed that the polymorphisms of the TNFAIP3 gene may contribute to ITP susceptibility. In this study, we showed a significant decrease in TNFAIP3 and increase in NF-κB/SMAD7 in ITP-MSCs...
February 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29296828/gene-editing-rescue-of-a-novel-mpl-mutant-associated-with-congenital-amegakaryocytic-thrombocytopenia
#19
Cédric Cleyrat, Romain Girard, Eun H Choi, Éric Jeziorski, Thierry Lavabre-Bertrand, Sylvie Hermouet, Serge Carillo, Bridget S Wilson
Thrombopoietin (Tpo) and its receptor (Mpl) are the principal regulators of early and late thrombopoiesis and hematopoietic stem cell maintenance. Mutations in MPL can drastically impair its function and be a contributing factor in multiple hematologic malignancies, including congenital amegakaryocytic thrombocytopenia (CAMT). CAMT is characterized by severe thrombocytopenia at birth, which progresses to bone marrow failure and pancytopenia. Here we report unique familial cases of CAMT that presented with a previously unreported MPL mutation: T814C (W272R) in the background of the activating MPL G117T (K39N or Baltimore) mutation...
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296823/mature-murine-megakaryocytes-present-antigen-mhc-class-i-molecules-to-t-cells-and-transfer-them-to-platelets
#20
Anne Zufferey, Edwin R Speck, Kellie R Machlus, Rukhsana Aslam, Li Guo, Mark J McVey, Michael Kim, Rick Kapur, Eric Boilard, Joseph E Italiano, John W Semple
Megakaryocytes (MKs) are bone marrow-derived cells that are primarily responsible for generating platelets for the maintenance of hemostasis. Although MK can variably express major histocompatibility complex (MHC) class I and II molecules during their differentiation, little is known whether they can elicit nonhemostatic immune functions such as T-cell activation. Here, we demonstrate that mature CD34- MHC class II- CD41+ MKs can endocytose exogenous ovalbumin (OVA) and proteolytically generate its immunogenic peptide ligand, which is crosspresented on their surface in association with MHC class I molecules...
September 12, 2017: Blood Advances
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