Fraxiparin, a low-molecular-weight heparin, stimulates megakaryocytopoiesis in vitro and in vivo in mice

Summary. The effect of a low-molecular-weight heparin, faxiparin (Nadroparinŕ;), on murine megakaryocytopoiesis in vitro and in vivo was studied in comparison with unfractionated heparin. The addition of fraxiparin at 1–20 IU/ml into plasma clot cultures but not serum-free agar culture significantly enhanced MK colony growth. Furthermore, fraxiparin was found to potentiate the stimulating activity of aplastic anaemia serum (AAS) but not stem cell factor (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo), on MK colony growth in vitro , and to neutralize the inhibitory effect of platelet factor 4 (PF4) in vitro and in vivo . Fraxiparin also acted synergistically with heparin confactor II and antithrombin III to promote megakaryocyte colony formation. Intraperitoneal administration of fraxiparin twice daily for 4d at 0.1–25IU/injection increased in mice the level of blood platelet counts and the number of single MKs and CFU-MK in bone marrow. These data demonstrate that fraxiparin is able to positively regulate megakaryocytopoiesis.     

The production of JAK2 wild‐type platelets is not downregulated in patients with JAK2 V617F mutant‐positive essential thrombocythaemia

To clarify the relationship between the levels of JAK2 wild‐type (WT) and V617F mutant‐positive platelets in patients with essential thrombocythaemia (ET), we quantified mutant levels in purified cells from 10 V617F‐positive patients prior to receiving cytoreductive therapy. Mutant levels were significantly higher in platelet than neutrophil RNA (P = 0·002), but the mutation was still only present in a sub‐population of platelets (median 54%). When the absolute number of WT platelets was calculated, it was always within or above the normal platelet range, indicating that there is an aberration in the negative feedback to JAK2 WT platelets in ET.     

Refractory immune thrombocytopenic purpura: current strategies for investigation and management

There is currently no consensus on how best to manage refractory immune thrombocytopenic purpura (ITP). In part, this reflects the need for individualized treatment due to the wide spectrum of patients' requirements and responsiveness to therapies. The objective of this review is to provide a clinically useful guide to current management strategies. This article suggests investigations to identify factors that may exacerbate thrombocytopenia and underlie poor therapeutic responses, and highlights emerging therapies, including the thrombopoietic agents, which are anticipated to dramatically alter the natural history of "refractory" ITP. Morbidity, mortality and heath-related quality of life are also discussed.     

下肢深静脉血栓形成的临床护理体会

目的:探讨下肢深静脉血栓形成的原因及护理体会。方法:对38例下肢深静脉血栓患者临床护理的具体做法及体会进行总结。结果:治愈33例,好转5例。结论:经过细心护理,提供针对性护理对策,帮助患者尽快恢复健康。     

Intravital imaging of megakaryocytes

Abstract

The dynamics of platelet formation could only be investigated since the development of two-photon microscopy in combination with suitable fluorescent labeling strategies. In this review paper, we give an overview of recent advances in fluorescence imaging of the bone marrow that have contributed to our understanding of platelet biogenesis during the last decade. We make a brief survey through the perspectives and limitations of today’s intravital imaging, but also discuss complementary methods that may help to piece together the puzzle of megakaryopoiesis and platelet formation.     

Circulating Thrombopoietin in Clonal Versus Reactive Thrombocytosis

Introduction: The aim of this study is to assess circulating thrombopoietin concentrations in patients with both clonal and reactive thrombocytosis (RT), which are two distinct categories of extreme platelet production circumstances. Investigation of the thrombopoietin levels in clonal versus reactive thrombocytosis may help us to understand the interactions of this key regulatory cytokine and the conditions in which abnormally increased platelet formation exist.

Materials and methods: Thrombopoietin levels were measured in patients with platelet counts greater than 500 × 10³ μl^?1 The study population consisted of 21 patients with RT (13 with iron deficiency anemia, and 8 with rheumatoid arthritis), 24 patients with clonal thrombocytosis (six with essential thrombocytosis, three with myelofibrosis, eight with chronic myelogenous leukemia, and seven with polycythemia vera (PV)) and 16 healthy subjects were used as controls.

Results: The median plasma thrombopoietin concentration was 100.5 pg ml^?1 in patients with RT, 467pg ml^?1 in patients with clonal thrombocytosis and 62.65pgml^?1 in the control group. The thrombopoietin concentration was found to be higher in the patients with primary thrombocytosis when compared to the control group (p = 0.001), as well as in patients with RT (p = 0.002). However, there was no statistically significant difference between the patients with RT and the control group (p = 0.14). There was no correlation between thrombopoietin levels and the platelet counts in patients with clonal thrombocytosis, including essential thrombo- cythemia (ET).

Conclusion: Increased levels of thrombopoietin were found in patients with clonal thrombocytosis versus patients with RT and control subjects as well. Defective clearance of thrombopoietin by megakaryocytes and platelets due to a reduced number of thrombopoietin receptors may be the causative mechanism behind this. These results indicate that plasma thrombopoietin levels may be helpful in distinguishing between clonal and reactive thrombocytosis.     

复杂冠状动脉病变介入治疗后应用替罗非班预防急性支架血栓的疗效及安全性

目的观察替罗非班预防复杂冠状动脉病变患者介入治疗后急性、亚急性支架血栓的疗效,以及评价其安全性。方法将2008年1月至2012年12月在高州市人民医院住院的200例冠状动脉粥样硬化性心脏病(冠心病)复杂冠状动脉病变介入治疗后患者按随机数字表法随机分为2组:治疗组100例,在阿司匹林、氯吡格雷常规基础上予替罗非班负荷量,后维持量24 h;对照组100例,在阿司匹林、氯吡格雷常规基础上,术后用低分子肝素抗凝治疗3 d。观察两组支架血栓及出血并发症。结果治疗组冠状动脉病变中B2、C型病变分别为63例、37例,对照组为70例、30例。治疗组与对照组植入支架的数量及植入支架的总长度比较,差异均无统计学意义[(3.1±1.3)枚vs.(2.9±1.2)枚,P>0.05;(32.4±13.8)mm vs.(33.2±12.7)mm,P>0.05]。治疗组急性支架血栓形成低于对照组,差异有统计学了意义[2%(2/100)vs.7%(7/100),χ2=45.82,P<0.05]。两组出血并发症的发生率比较,差异无统计学意义[12%(12/100)vs.9%(9/100),χ2=5.18,P>0.05]。结论复杂冠状动脉病变患者PCI治疗后使用替罗非班是安全的,且降低了支架内急性、亚急性血栓发生率。     

Thrombopoiesis and Structural Rearrangements of the Long Arm of Chromosome 3. Review arid Analysis of Data on 64 Published Patients

During the least 10 years a growing number of case reports arid small patient series have demonstrated an association between certain structural changes of the q arm of chromosom'e no. 3 (insertion, inversion, translocation (3; 3) or translocation with other chromosomes) and signs of increased platelet production and morphologic megakaryocyte abnormalitieis. Analysis of published data on 64 such patients now demonstrate that rearrangements between the two chromosomes 3 are associated with significantly higher platelet counts and higher frequencies of megakaryocytes in the marrow than are translocations between no. 3 and other chromosomes. Further, the megakaryocyte hyperplasia is due primarily to abnormally small megakaryocytes, often with hypolobulated nuclei. These quantitative,and qualitative changes of thrombopoiesis are associated with coincident breaks in 3q21 an8d 3q26 and juxtaposition of these bands so that the band sequence 3q21::q26 is formed. Apparently, this band sequence specifically stimulates and changes thrombopoiesis.