MBChB, FRACP, FRCPA Mark P. Smith (Consultant Haematologist and Deputy Director), MD, PhD Elisabeth M. Cramer (Maître de Conférence des Universités (Paris), Practicien Hospitalier) , MBBChir, MA, MD Geoffrey F. Savidge (Director, Professor of Coagulation Medicine)
{"title":"7 Megakaryocytes and platelets in α-granule disorders","authors":"MBChB, FRACP, FRCPA Mark P. Smith (Consultant Haematologist and Deputy Director), MD, PhD Elisabeth M. Cramer (Maître de Conférence des Universités (Paris), Practicien Hospitalier) , MBBChir, MA, MD Geoffrey F. Savidge (Director, Professor of Coagulation Medicine)","doi":"10.1016/S0950-3536(97)80054-6","DOIUrl":"10.1016/S0950-3536(97)80054-6","url":null,"abstract":"<div><p>This chapter summarizes research data contributing to current understanding of disorders affecting α-granules of megakaryocytes and platelets. Diagnostic features of the gray platelet syndrome are well defined. Combined evidence suggests a defect, specific to the megakaryocyte cell lineage, causing a cytoskeletal abnormality and defective targeting of endogenously synthesized proteins to the α-granule. The abnormalities linked by signal transduction pathways. von Willebrand disease and afibrinogenaemia are disorders which highlight the functional importance of platelet storage pools of von Willebrand factor and fibrinogen, essential ligands in the process of adhesion and aggregation. The abnormality in the factor V Quebec disorder leads to a degradation of most proteins contained within the α-granule. The familial platelet disorder Paris-Trousseau thrombocytopenia is the only α-granule disorder associated with a cytogenetic abnormality, and it presents a useful model for exploring the genetic influence on regulation of thrombopoiesis. Study of these syndromes has elucidated aspects of the physiology of normal megakaryocyte maturation and platelet formation, including storage organelle biosynthesis.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 1","pages":"Pages 125-148"},"PeriodicalIF":0.0,"publicationDate":"1997-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80054-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20100553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MD, PhD Paquita Nurden (Haematologist), Christel Poujol (Research Assistant), PhD Alan T. Nurden (Reseach Director)
{"title":"1 The evolution of megakaryocytes to platelets","authors":"MD, PhD Paquita Nurden (Haematologist), Christel Poujol (Research Assistant), PhD Alan T. Nurden (Reseach Director)","doi":"10.1016/S0950-3536(97)80048-0","DOIUrl":"10.1016/S0950-3536(97)80048-0","url":null,"abstract":"<div><p>Megakaryocytes (MKs) arise from pluripotent stem cells by a process of cell division, endoreplication and maturation. Progressively, the MK cytoplasm is invaded by the demarcation membrane system speculated to delimit pre-formed platelets. One theory is that the passage of entire MKs (or fragments) into the blood stream is followed by their physical break-up into platelets in the pulmonary circulation. A second theory is that MKs produce beaded processes (proplatelets) which then separate into platelets. Functionally vital platelet receptors such as GPIIb-IIIa and GPIb-IX complexes are specific markers of the MK lineage. CD34 and CD4 are present in progenitors but progressively disappear as MKs mature. Stroma cells secrete cytokines, produce extracellular matrix proteins and mediate cellular contact interactions that regulate MK development. Studies on thrombopoietin and the use of transgenic mouse models are helping to clarify MK biology.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 1","pages":"Pages 1-27"},"PeriodicalIF":0.0,"publicationDate":"1997-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80048-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20101950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MD, PhD Jean-Pierre Cazenave (Director) , MD, PhD Christian Gachet (Chargé de Recherche)
{"title":"9 Anti-platelet drugs: do they affect megakaryocytes?","authors":"MD, PhD Jean-Pierre Cazenave (Director) , MD, PhD Christian Gachet (Chargé de Recherche)","doi":"10.1016/S0950-3536(97)80056-X","DOIUrl":"10.1016/S0950-3536(97)80056-X","url":null,"abstract":"<div><p>Anti-platelet drugs are used in clinical medicine to prevent thromboembolic complications of cardiovascular diseases. Among anti-platelet drugs, very little is known of their possible effects on megakaryocytes. ASA is the only compound for which it has clearly been demonstrated that its mechanism of action involves acetylation of the Ser 529 residue in cyclo-oxygenase in platelets and megakaryocytes. Because megakaryocytes possess membrane receptors for ADP, the thienopyridine metabolites of ticlopidine and clopidogrel may modify these receptors as in platelets and hence prevent ADP binding and further activation. Megakaryocytes also have GPIIb-IIIa receptors for the adhesive protein fibrinogen and may be accessible in vivo to GPIIb-IIIa antagonists such as the monoclonal antibody abciximab. Drugs such as heparin or the phosphodiesterase inhibitor anagrelide can either inhibit or stimulate megakaryocytopoiesis and platelet production, while cytokines such as thrombopoietin affect megakaryocytopoiesis, platelet production and platelet function by potentiating the activation of platelets by other agonists.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 1","pages":"Pages 163-180"},"PeriodicalIF":0.0,"publicationDate":"1997-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80056-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20100555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MD Sylvia Bellucci (Maître de Conférences des Universités, Practicien Hospitalier)
{"title":"8 Megakaryocytes and inherited thrombocytopenias","authors":"MD Sylvia Bellucci (Maître de Conférences des Universités, Practicien Hospitalier)","doi":"10.1016/S0950-3536(97)80055-8","DOIUrl":"10.1016/S0950-3536(97)80055-8","url":null,"abstract":"<div><p>Inherited thrombocytopenias may be divided into two groups. In the first group, there is no marked thrombocytopathy. Although numerous in the bone marrow, megakaryocytes often are abnormal cytologically. A dysmegakaryocytopoiesis with defective platelet production is suggested but remains to be evidenced. In the second group, thrombocytopenias are accompanied with variable thrombocytopathy. The functional and biochemical platelet abnormalities responsible for these different thrombocytopathies often are well elucidated. The study of the relations with the occurrence of thrombocytopenia constitutes an interesting field of investigation.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 1","pages":"Pages 149-162"},"PeriodicalIF":0.0,"publicationDate":"1997-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80055-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20100554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MD Hidehiko Saito (Chairman and Professor of Medicine)
{"title":"3 Megakaryocytic cell lines","authors":"MD Hidehiko Saito (Chairman and Professor of Medicine)","doi":"10.1016/S0950-3536(97)80050-9","DOIUrl":"10.1016/S0950-3536(97)80050-9","url":null,"abstract":"<div><p>Megakaryocytic cell lines, established from the blood of patients with leukaemia, provide us with a unique opportunity to study the proliferation, differentiation and maturation of megakaryocytes. Eighteen human and three animal cell lines that express some megakaryocytic features have been described in the literature. Many of these cell lines have primitive multiphenotypic properties of erythroid, myeloid and megakaryocytic cells, while some show more restricted megakaryocyte-specific markers. The most consistent cell marker of megakaryocytic cell lines is the presence of platelet membrane glycoprotein (GPIIb-IIIa) in human cell lines and that of acetylcholinesterase in mouse or rat cell lines. The expressions of GPIb, von Willebrand factor and platelet peroxidase are variable among different cell lines, perhaps reflecting different stages of differentiation or a neoplastic nature of immortal cell lines. Treatment of many of these cell lines with phorbol esters leads to enhanced expression of the megakaryocytic programme.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 1","pages":"Pages 47-63"},"PeriodicalIF":0.0,"publicationDate":"1997-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80050-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20101952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MD Bernd van der Loo (Honorary Research Fellow), MD, FRCP, FESC John F. Martin (British Heart Foundation Professor of Cardiovascular Science)
{"title":"6 Megakaryocytes and platelets in vascular disease","authors":"MD Bernd van der Loo (Honorary Research Fellow), MD, FRCP, FESC John F. Martin (British Heart Foundation Professor of Cardiovascular Science)","doi":"10.1016/S0950-3536(97)80053-4","DOIUrl":"10.1016/S0950-3536(97)80053-4","url":null,"abstract":"<div><p>Platelets are anucleate cells with no DNA. They are derived from their precursor, the megakaryocyte (MK), whose differentiation is characterized by nuclear polyploidization through a process called endomitosis. Changes in the MK-platelet-haemostasis axis may precede acute thrombotic events. Changes in MK ploidy distribution may be associated with the production of large platelets. Mean platelet volume (MPV) is an important biological variable as it is a determinant of platelet reactivity. Large platelets are denser and more active haemostatically. MPV is increased in patients after myocardial infarction (MI) and is a predictor of a further ischaemic event and death when measured after MI. It has been suggested that changes not only in platelets but also in the parental MK are associated with chronic and acute vascular events.</p><p>The regulation of megakaryocytopoiesis depends on several haematopoietic factors such as thrombopoietin. An understanding of the signalling system that controls platelet number and size might give insight into a role of platelet production in thrombogenesis and atherogenesis.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 1","pages":"Pages 109-123"},"PeriodicalIF":0.0,"publicationDate":"1997-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80053-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20100552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MD Jean Briere (Professor of Medicine, Head), MD Jean-Jacques Kiladjian (Assistant), MD Edith Peynaud-Debayle (Assistant)
{"title":"4 Megakaryocytes and platelets in myeloproliferative disorders","authors":"MD Jean Briere (Professor of Medicine, Head), MD Jean-Jacques Kiladjian (Assistant), MD Edith Peynaud-Debayle (Assistant)","doi":"10.1016/S0950-3536(97)80051-0","DOIUrl":"10.1016/S0950-3536(97)80051-0","url":null,"abstract":"<div><p>Increased megakaryocyte (MK) proliferation in bone marrow is a feature common to the three Ph-negative myeloproliferative disorders (MPDs), i.e. essential thrombocythaemia (ET), polycythaemia vera (PV), and myelofibrosis with splenic myeloid metaplasia (MMM), and to chronic myelocytic leukaemia (CML). Enlarged MKs with multilobulated nuclei and cell clustering in close proximity are the hallmark of all the Ph negative MPDs. Clonality of haematopoietic cells, based on X chromosome inactivation, can now be studied in a majority of female patients in all nucleated cell fractions as well as in platelets. Cytofluorometric studies have demonstrated a shift towards higher ploidy classes in PV and ET MKs which may be useful in discriminating between both primary and reactive thrombocytosis and CML patients which show a significant shift to lower MK ploidy values.</p><p>The role of MK proliferation on the evolution of myelofibrosis common to MPDs has been firmly established. Implication of platelet-derived growth factor (PDGF)in myelofibrosis has already been demonstrated. More recently transforming growth factor β (TGFβ) synthesized and secreted by MK has been implicated in fibroblasts stimulation.</p><p>A significant increase in circulating colony-forming units of MKs (CFU-MK) has been repeatedly observed in MPDs as well as a spontaneous MK colony formation in a majority of ET patients. Hypersensitivity to thrombopoietin (TPO) in relation to a functional defect of the TPO-MPL pathway may play a major role in spontaneous MK growth.</p><p>There is no currently available test of platelet functions able to predict the risk of occurrence of thrombotic or haemorrhagic complications in MPD patients. However, the role of platelet activation in the pathogenesis of ischaemic erythromelalgia has been established and a correlation between presenting haemorrhagic manifestations and platelet counts in excess of 1000 × 10<sup>9</sup>/l has been found.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 1","pages":"Pages 65-88"},"PeriodicalIF":0.0,"publicationDate":"1997-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80051-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20101953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MD Zhen-Yi Wang (Professor of Haematology and Pathophysiology, Honorary Director) , MD Zhi-Xiang Shen (Professor, Chief)
{"title":"5 Megakaryocytes and platelets in immune thrombocytopenic purpura","authors":"MD Zhen-Yi Wang (Professor of Haematology and Pathophysiology, Honorary Director) , MD Zhi-Xiang Shen (Professor, Chief)","doi":"10.1016/S0950-3536(97)80052-2","DOIUrl":"10.1016/S0950-3536(97)80052-2","url":null,"abstract":"<div><p>In idiopathic thrombocytopenic purpura, 90% of the patients have an elevated platelet-associated immunoglobulin. The most important related antigens are glycoprotein IIb-IIIa (GPIIb-IIIa) (16.7–83.3%), GPIb-IX (13.3–83%), GPIb (3.3–47.1%) and GPIIIa (21.6–33.3%), and less commonly GPIa-IIa, GPIV and GPV. Other related antigens can be platelet granule membrane protein, phospholipid, intraplatelet and cytoplasmic antigens, and rarely human platelet antigen (HPA) la and HLA-DR antigens. The marrow megakaryocytes are usually normal or increased in number with maturation impairment. There are discrepancies regarding megakaryocytopoiesis in vitro. A low dose of heparin could elevate the platelet number in certain cases. The expression of c-<em>sis</em> was reported to be inhibited in ITP, when the plasma β-thromboglobin-platelet factor 4 level was elevated.</p><p>In secondary immune thrombocytopenia, platelet antibodies can be (1) alloantibodies against the (HPA) system and (2) autoantibodies most commonly against platelet GPIIb-IIIa or GPIb-IX. Other antigens can be 30–52 kDa proteins of the platelet membrane. Platelet survival is usually shortened, and marrow megakaryocytes are normal in number. Megakaryocyte colony-forming units could be reduced.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 1","pages":"Pages 89-107"},"PeriodicalIF":0.0,"publicationDate":"1997-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80052-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20101954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PhD Françoise Wendling (Research Director), MD, PhD Zhong-Chao Han (Head of Department Professor Associé des Universités Professor of Haematology)
{"title":"2 Positive and negative regulation of megakaryocytopoiesis","authors":"PhD Françoise Wendling (Research Director), MD, PhD Zhong-Chao Han (Head of Department Professor Associé des Universités Professor of Haematology)","doi":"10.1016/S0950-3536(97)80049-2","DOIUrl":"10.1016/S0950-3536(97)80049-2","url":null,"abstract":"<div><p>The recently cloned physiological regulator of megakaryocytopoiesis, known as Mpl ligand, thrombopoietin (TPO), megakaryocyte growth and development factor (MGDF) or megapoietin, is undergoing preclinical and clinical trials. This factor is an extremely potent thrombocytopoietic agent in vivo in normal animals, and accelerates platelet recovery in some but not all models of myelosuppression. Together with its apparent lack of adverse effects, the preclinical data suggest that TPO might permit the use of higher doses of chemotherapy in dose-intensive regimens and be useful in patients with ineffective platelet production or production abnormalities. The direct effects of TPO on primitive and various myeloid committed haematopoietic progenitor cells predict that TPO may be used in combination with other cytokines in a variety of clinical disorders. Along with the progress made in the understanding of the positive regulation of megakaryocytopoiesis, accumulating data demonstrate that platelet production is also controlled by negative regulators with potential clinical applications. Some of these regulators are effective in the treatment of essential thrombocythaemia and myeloproliferative disorders, while others seem capable of protecting progenitor cells from the cytotoxicity of chemotherapeutic drugs.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"10 1","pages":"Pages 29-45"},"PeriodicalIF":0.0,"publicationDate":"1997-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(97)80049-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20101951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
求助内容：
应助结果提醒方式：