The genetics of platelet count and volume in humans

The last decade has witnessed an explosion in the depth, variety, and amount of human genetic data that can be generated. This revolution in technical and analytical capacities has enabled the genetic investigation of human traits and disease in thousands to now millions of participants. Investigators have taken advantage of these advancements to gain insight into platelet biology and the platelet’s role in human disease. To do so, large human genetics studies have examined the association of genetic variation with two quantitative traits measured in many population and patient based cohorts: platelet count (PLT) and mean platelet volume (MPV). This article will review the many human genetic strategies—ranging from genome-wide association study (GWAS), Exomechip, whole exome sequencing (WES), to whole genome sequencing (WGS)—employed to identify genes and variants that contribute to platelet traits. Additionally, we will discuss how these investigations have examined and interpreted the functional implications of these newly identified genetic factors and whether they also impart risk to human disease. The depth and size of genetic, phenotypic, and other -omic data are primed to continue their growth in the coming years and provide unprecedented opportunities to gain critical insights into platelet biology and how platelets contribute to disease.     

长春新碱联合糖皮质激素治疗11例婴儿期Kasabach-Merritt综合征

目的 探讨Kasabach-Merritt（K-M）综合征的有效治疗方案。方法 收集2015—2017年首都医科大学附属北京儿童医院皮肤科收治的11例K-M综合征患儿的临床资料,分析长春新碱联合糖皮质激素治疗的疗效。结果 11例患儿就诊年龄1～212（87.91 ± 72.01） d,男4例、女7例。血管瘤多呈紫红色斑块,质地偏硬,其中5例瘤体周围伴有皮肤紫癜。血小板计数（4 ~ 32） × 109/L。给予口服泼尼松（2 ~ 5） mg·kg-1·d-1与静脉注射长春新碱每周0.05 mg/kg联合治疗。10例患儿应用糖皮质激素联合长春新碱治疗（1.8 ± 1.23）周后血小板达到正常,治疗（3.6 ± 1.26）周后纤维蛋白原恢复正常,治疗（3.9 ± 0.74）周后血管瘤开始软化或缩小。1例治疗5周后,血小板计数仍没有恢复正常,联合使用静脉栓塞后,血小板恢复正常,并可维持。结论 长春新碱联合糖皮质激素治疗可控制K-M综合征患儿瘤体发展,促进血小板恢复。     

血小板减少合并缺血性卒中的诊治进展

在临床中，如果免疫性血小板减少（immune thrombocytopenia，ITP）、肝素诱发的血小板减少 （heparin-induced thrombocytopenia，HIT）、血栓性血小板减少性紫癜（thrombotic thrombocytopenic purpura， TTP）等血小板减少疾病患者合并缺血性卒中，其治疗存在矛盾。本文对血小板减少的病因机制及血小 板减少合并急性缺血性卒中时静脉溶栓、机械取栓及抗血小板治疗等方面的研究进展进行了综述。     

Danazol in acquired amegakaryocytic thrombocytopenic purpura: A case report

Summary Acquired amegakaryocytic thrombocytopenic purpura is a rare disease. Most reported patients did not respond to any therapeutical approach. Recently we observed a striking improvement of this disorder in a female patient shortly after therapy with danazol had been initiated. This observation and its possible implication for the treatment of amegakaryocytic thrombocytopenia are reported herein.     

Rapid determination of anti-heparin/platelet factor 4 antibody titers in the diagnosis of heparin-induced thrombocytopenia

PURPOSE: Heparin-induced thrombocytopenia is mediated by antibodies directed against the heparin-platelet factor 4 (heparin/PF4) complex. Our aim was to investigate whether rapid measurement of anti-heparin/PF4 antibodies could improve the diagnostic workup of patients with suspected heparin-induced thrombocytopenia. METHODS: We examined 148 consecutive patients in our laboratory between January 1995 and June 2001 for suspected heparin-induced thrombocytopenia. Clinical data allowed retrospective assessment of the likelihood of heparin-induced thrombocytopenia. Antibodies against the heparin/PF4 complex were detected by a rapid particle gel immunoassay. RESULTS: Anti-heparin/PF4 antibodies were detected in 69 (47%) of the 148 patients, at dilution titers from 1 to 256. Clinically "likely" or "very likely" heparin-induced thrombocytopenia was significantly more common in patients with titers >or=4 (95% [39/41]) than in those with undetectable antibodies (13% [9/70]; P <0.0001), a titer of 1 (18% [4/22]; P <0.0001), or a titer of 2 (33% [2/6]; P = 0.001). All 19 samples with a positive platelet aggregation test had anti-heparin/PF4 antibody titers of at least 4, including 15 samples with titers >or=32. Thromboembolic complications in heparin-treated patients were significantly more prevalent in patients with titers >or=4 (63% [26/41]) than in those with undetectable antibodies (8% [6/79]; P <0.0001) or a titer of 1 (9% [2/22]; P <0.0001). Of the 11 patients with a titer of 1 who were maintained on heparin, none developed worse thrombocytopenia or thromboembolic complications. CONCLUSION: Anti-heparin/PF4 antibody titers, which can be measured rapidly and reproducibly using a particle gel immunoassay, can be used as a confirmatory test to complement a clinical likelihood score among patients with suspected heparin-induced thrombocytopenia.     

Abnormal hematological indices in cirrhosis

Abnormalities in hematological indices are frequently encountered in cirrhosis. Multiple causes contribute to the occurrence of hematological abnormalities. Recent studies suggest that the presence of hematological cytopenias is associated with a poor prognosis in cirrhosis. The present article reviews the pathogenesis, incidence, prevalence, clinical significance and treatment of abnormal hematological indices in cirrhosis.     

血液肿瘤化疗后血清可溶性白细胞介素-11水平的变化及其意义

目的 观察血液肿瘤化疗后血清可溶性白细胞介素-11(sIL-11)水平与血小板数量改变的关系,探索能维持血小板安全水平的sIL-11临界值,以指导临床治疗.方法 收集血液肿瘤患者化疗前后的血标本,测定sIL-11和血小板水平,观察两者变化间关系并进行统计学分析.结果 99例患者完成研究.化疗后患者的sIL-11水平逐步升高,第6天达到峰值后逐渐下降;血小板数量随时间逐步降低,第10天达到最低值,然后逐渐上升;在血小板达到最低之前sIL-11已达峰值;患者化疗后sIL-11越高,血小板数量越有可能维持于较高水平.根据血小板水半最低值将病例分为两组比较,具较高血小板组有较高sIL-11峰值.其sIL-11平均增长速度快,血小板达到最低值的时间较晚,高sIL-11峰值的病例较多.多元回归显示化疗后血小板低于临界值的影响因素有:sIL-11达到最大值的日平均增长速度和化疗第4天sIL-11低于2000Pg/ml.结论 血液肿瘤患者化疗后sIL-11水平与血小板数量的变化存在相关关系,可以通过测量sIL-11的变化来预测血小板数量的变化趋势.化疗第4天sIL-11<2000 Pg/ml的患者发生严重血小板减少的可能性大,建议给予rhIL-11治疗或输注血小板治疗.     

血小板减少症产妇的护理

目的:探讨血小板减少产妇的护理。方法:对我院住院的3例血小板减少症产妇的临床资料进行分析,总结血小板减少症产妇的治疗和护理体会。结果:无1例发生严重并发症,疗效满意。结论:对血小板减少症的产妇,加强生命体征监测,防止出血及感染,提高母婴生存质量。     

Recombinant factor VIIa reduces bleeding in severely thrombocytopenic rabbits

Severe thrombocytopenia is a common complication to intensive chemotherapeutic regimens. For bleeding episodes associated with severe thrombocytopenia, the current standard treatment is platelet transfusion. However, due to several transfusion complications such as transfusion-transmitted diseases, platelet refractoriness and immunomodulation, as well as increasing problems with sufficient supply of platelet products, it is imperative to search for alternatives to platelet transfusion. To test the efficacy of recombinant activated human coagulation factor VII (rFVIIa, NovoSeven) in thrombocytopenia, a preclinical study was conducted in thrombocytopenic rabbits. Thrombocytopenia was induced by a combination of gamma-irradiation and the use of platelet antibodies, and the effect of rFVIIa on nail cuticle bleeding was determined. Administration of rFVIIa at 2 mg/kg significantly shortened the prolonged bleeding time in thrombocytopenic animals (rFVIIa vs. control, median 23 min 41 s vs. 60 min, p=0.016) as well as significantly reducing the blood loss (rFVIIa vs. control, median: 8.8 vs. 12.2 nmol hemoglobin/ml, p=0.016). This effect was also reflected by a significant reduction of the prothrombin time, activated partial thromboplastin time, as well as improvement in clotting parameters in an in vitro thromboelastography thrombocytopenia model. Histopathological evaluation of kidney biopsies for the presence of micro thrombi did not reveal evidence of prothrombotic effects of rFVIIa in this model. These data demonstrate the haemostatic efficacy of rFVIIa in a rabbit model of severe thrombocytopenia. Clinical trials will be needed to further explore the potential of NovoSeven as a haemostatic agent in thrombocytopenic patients.