病毒性肝炎血小板减少机制探讨

病毒性肝炎患者血小板减少十分常见，在各型慢性肝炎和肝硬化中发生率约为37％～77％，在重症肝炎和暴发性肝衰竭患者中也有约50％的患者发生。长期以来，人们始终很自然的认为脾大及脾功能亢进是肝病血小板减少的主要原因。近年来，随着有关血小板生成素及免疫研究的不断深入，对病毒性肝炎血小板减少的原因有了一些新的认识，其机制较为复杂，为多种因素综合作用的结果。为合理治疗病毒性肝炎血小板减少，本文就其发病机制做一些探讨。     

病毒感染与血小板减少性紫癜

血小板减少性紫癜是临床上最常见的出血性疾病 ,根据中国医学科学院血液病研究所统计的血液病构成中 ,血小板减少性紫癜占出血性疾病的 70 %左右。其中 80 %急性型患者常发生于病毒感染性疾病之后 ,即“病毒感染相关性血小板减少”。患者血液中可检测出抗血小板抗体 ,因此被称为自身免疫性血小板减少性紫癜。目前发现多种病毒与血小板减少性紫癜的发病有关 ,其中包括疱疹病毒、人类微小病毒Ｂ19、麻疹病毒、流行性腮腺炎病毒、风疹病毒和肝炎病毒。病毒感染引起的血小板减少性紫癜机制复杂 ,尚处于研究之中。现在多数学者认为早期病毒感染引…     

病毒性肝炎血小板减少症影响因素的研究

目的探讨病毒性肝炎血小板减少症的发病机制.方法 84例病毒性肝炎患者和20名健康志愿者分为3组,A组(48例病毒性肝炎并血小板减少症患者)、B组(36例病毒性肝炎血小板正常患者)和C组(20名健康志愿者),分别采用酶联免疫吸附法、流式细胞术、腹部彩色B超检测3组血清血小板生成素(TPO)水平、血小板相关免疫球蛋白(PAIg)及其类别PAIgG、PAIgA、PAIgM水平、脾脏大小,采用骨髓穿刺术对其中74例行骨髓细胞学检查.结果血清TPO水平A组低于C组(P<0.01)和B组(P<0.05),严重肝病血清TPO水平与血小板数相关(r=0.374,P<00.01).PAIg、PAIgG水平A组明显高于B组(P<0.001)和C组(P<0.01),血小板数与PAIg水平呈负相关(r=0.446,P<0.01),血小板数与PAIgG水平亦呈负相关(r=-0.462,P<0.01).脾脏肿大发生率A组(77.1%)明显高于B组(47.2%,P<0.01),C组无脾脏肿大发生,血小板数与脾脏大小呈负相关(r=-0.5 81,P<0.01).74例骨髓象显示A组有4例呈骨髓抑制象改变,B组和C组无一例有上述改变.结论严重肝功能受损时血清TPO水平下降,与血小板数减少直接相关.PAIg介导的自身免疫机制在病毒性肝炎血小板减少症中可能起重要作用.脾脏肿大是引起病毒性肝炎血小板减少的因素.初步发现慢性肝病有骨髓抑制现象,可能成为引起病毒性肝炎血小板减少的因素之一.     

新型布尼亚病毒感染致消化道大出血1例

正新型布尼亚病毒,又称发热伴血小板减少综合征病毒(severe fever with thrombocytopenia syndrome bunyavirus,SFTSV),是2009年由我国学者首次从蜱虫体内发现并报道的一种新型RNA病毒[1],可导致以发热、血小板减少及多器官功能障碍为主要表现的临床综合征,发病率及病死率较高,预后差。该病毒感染后可导致肌痛[2]、消化道出血[3]、神经系统异常[2]等临床表现,本文报道1例新型布尼亚病毒     

血小板生成减少引起的血小板减少症

纯巨核细胞生成障碍引起的血小板减少是一种少见的疾病，其特征是骨髓巨核细胞明显减少或完全缺乏导致血小板减少，而其他血细胞成分很少累及。巨核细胞生成障碍性血小板减少患者伴有其他细胞系轻度异常，大红细胞或红细胞生成障碍较少见，这些异常可能是骨髓增生异常或再生障碍性贫血(下称再障)的一个前驱表现。获得性巨核细胞生成障碍可能与以下因素有关，如某些病毒如微小病毒、人类免疫缺陷病毒(HIV-1)等感染；某些药物如噻嗪类利尿剂、雌激素、     

干扰素诱导的严重血小板减少性紫癜临床特点分析27例

目的:分析干扰素α(interferon α,IFNα)导致的严重血小板减少性紫癜患者临床特点.方法:检索PubMed和CNKI数据库26例及我院所见1例IFNα导致的严重血小板减少性紫癜,共27例,根据发病机制分成免疫性血小板减少性紫癜(immune thrombocytopenic purpura,ITP)及血栓性血小板减少性紫癜(thromboticthrombocytopenic purpura,TTP)2组,分析临床表现、实验室检查特点、治疗和转归.结果:ITP组24例主要表现为出血倾向,血小板显著减少,血小板抗体或血小板相关IgG明显升高,骨髓增生活跃,停IFNα及应用免疫抑制剂治疗后血小板于1-2 wk上升,预后较好.TTP组3例主要表现为发热,血小板显著减少,溶血性贫血,神经系统损害及肾脏损害.血浆置换是主要的治疗手段,预后差,死亡率高.ITP及TTP多发生在IFNα抗丙肝治疗过程中.结论:IFNα抗病毒过程中可能出现ITP或TTP两种严重血小板减少性紫癜的发生,须提高认识给予及时正确处理.     

病毒性肝炎血液学变化的研究进展

病毒性肝炎导致血液细胞学的改变十分常见。随着病情的加重,红细胞、血小板、白细胞等指标均会明显下降。长期以来人们始终认为脾大及脾功能亢进是肝病血液学指标减少的主要原因。随着近年来有关骨髓造血、自身抗体及相关细胞因子的深入研究,对于病毒性肝炎所致血液细胞学改变的原因有了一些新的认识,其主要是多种因素综合作用的结果,机制比较复杂。本文主要从其血液学改变的具体表现及发病机制做一些探讨。     

肝硬化患者的血小板参数检测及其临床意义

乙型病毒性肝炎后肝硬化的病人血小板减少是众所周知的。由于乙型肝炎病毒(HBV)感染后，可损害骨髓的造血功能和机体的免疫功能，引起不同程度的单核-巨噬细胞系统功能减弱，脾功能亢进，尤其是HBV抑制巨核细胞增殖，在病毒或毒素的作用下会导致血小板超微结构的异常。为了解肝硬化患者血小板的变化情况，     

脾切除治疗原发性免疫性血小板减少症

1概况原发性免疫性血小板减少症(immune throm-bocytopenia,ITP)即特发性血小板减少性紫癜是临床上最常见的出血性疾病,主要是由于抗血小板抗体导致血小板破坏过多而引起血小板减少。脾脏是ITP患者血小板破坏的主要场所,也可能是血小板抗体产生的主要器官。被抗体结合的血小板,通过脾脏时在脾窦滞留,被单核-巨噬细胞系统吞噬、清除是ITP患者血小板破坏的主要机制。因此脾切除术很早就应用于ITP的治疗。ITP的一线治疗目前已经取得共识,主要是皮质激素和静脉用免疫球蛋白(IVIg)。皮质激素应用于ITP的     

发热伴血小板减少综合征流行现状及诊疗新进展

发热伴血小板减少综合征(SFTS)是一种传染性人畜共患病,属于出血热的一种,由布尼亚病毒科的一种新型白蛉病毒SFTS病毒(SFTSV)引起。出血热的主要症状是发热、血小板减少、白细胞减少和胃肠道异常。有时在非常严重的情况下,也可能发生全身器官衰竭,SFTS患者的平均死亡率接近10%。SFTS发病机制尚未完全明确,目前仍无针对该病毒的治疗方法。保护自己不受感染最简单的方法是避免被蜱虫叮咬。目前,该疾病已经演变成为世界各国人类的严重健康问题。收集SFTS的流行病学资料,了解SFTS的疾病特点和诊疗进展,以帮助应对这种疾病。本综述将从流行病学史、发病机制、临床表现、诊断及鉴别诊断和治疗最新策略展开逐一阐述。     

Comparative study on infection-induced thrombocytopenia among returned travellers

Background

Thrombocytopenia is a frequent finding among ill returned travellers and may be caused by a large number of different conditions, including infectious diseases specific or typical for tropical and subtropical regions. In order to assess the diagnostic significance of thrombocytopenia we investigated a large cohort of returned travellers.

Methods

This was a comparative study in which data collected on 19,473 returned travellers who consulted the outpatient travel clinic of the the University of Munich Hospital between 1999 and 2009 were analysed. Of these, 732 (3.8%) travellers were diagnosed with thrombocytopenia, and their data were compared with those of the remaining 18,741 travellers with normal platelet counts.

Results

Thrombocytopenia was significantly more frequent among patients with malaria (63%), acute human immunodeficiency virus infection (48%), dengue fever/dengue haemorrhagic fever (DF/DHF; 47%), Epstein?CBarr virus infectious mononucleosis (23%), paratyphoid/typhoid fever (14%), and rickettsiosis (12%). Malaria and DF/DHF caused 25% of all cases of thrombocytopenia (platelet count <140,000/??l) and 75% of all cases of severe thrombocytopenia (platelet count <30,000/??l). Sex, age, country of origin, duration and type of travel were not significantly correlated with thrombocytopenia. The most frequent travel destinations were Asia (42%), Africa (33%), and Latin America (14%). Travellers to Sub-Saharan Africa (high risk for malaria) and to South/South-east Asia (high risk for DF/DHF) had the highest relative risk for thrombocytopenia.

Conclusion

Platelet count among returned travellers is an essential screening parameter, as thrombocytopenia is highly correlated with important infectious diseases, particularly with malaria and DF/DHF.     

Life-threatening thrombocytopenia associated with acute Epstein-Barr virus infection in an older adult

Acute Epstein-Barr virus (EBV) infection commonly induces hematological abnormalities, most notably atypical lymphocytosis ("infectious mononucleosis"). In addition, mild decreases in platelet counts are commonly encountered in uncomplicated cases; however, severe thrombocytopenia is exceedingly rare. Here, we describe a 58-year-old white man who presented with cervical lymphadenopathy, thrombocytopenia, and a bleeding diathesis with minimal platelet counts of 0.5 x 10(9)/l. The diagnosis of acute EBV was serologically confirmed. Because of the bleeding diathesis and the prior ingestion of aspirin, treatment was started with intravenous methylprednisolone and immunoglobulins. Platelet counts normalized within 7 days, and the patient fully recovered. Although more common in children, adolescents, and young adults, acute EBV infection may also occur in older adults, and this differential diagnosis should be considered in every patient presenting with acute thrombocytopenia. In this report we also briefly summarize the literature on EBV-associated severe thrombocytopenia.     

Fetal thrombocytopenia: a retrospective survey of 5,194 fetal blood samplings

Fetal platelet counts were retrospectively studied in a series of 5,194 consecutive fetal blood samplings (FBS). The mean value was 245 +/- 65 x 10(9)/L, without significant variation between 17 and 41 weeks' gestation. After exclusion of false thrombocytopenia due to contamination with amniotic fluid, 247 fetuses had platelet counts less than 150 x 10(9)/L. In 70 cases, thrombocytopenia was due to congenital infectious diseases (toxoplasmosis, rubella, and cytomegalovirus). It was related to immune causes in 45 cases: anti-HPA-1a (n = 23), anti- HPA-5b (n = 2) or possible anti-HLA (n = 2) alloimmunizations, and immune thrombocytopenic purpura (n = 18). Chromosomal abnormality was the etiology in 43 cases (trisomy 13, 18, and 21, Turner's syndrome, triploidy), and other disorders (multiple birth defects, intrauterine growth retardation, rhesus disease, and gestational thrombocytopenia) in 62 cases. No specific cause for the low platelet count could be established in 27 fetuses (range, 115 to 149 x 10(9)/L). Severe thrombocytopenia (< or = 50 x 10(9)/L) occurred mainly in immune cases (16%), congenital infectious diseases (7%), and chromosomal abnormalities (1%). Diagnosis, prognosis, and management of fetal thrombocytopenia are presented in the different clinical situations. In this series, FBS was never associated with serious bleeding, and no fetal exsanguination was observed.     

Platelet activation and binding of complement components to platelets induced by immune complexes

Clinical disorders such as malignant diseases, infectious diseases or autoimmune diseases are associated with circulating immune complexes. These immune complexes can activate the complement system in the blood or interact with complement or Fc receptors on the surface of cells. Complement activation may cause cytolysis and the immune complex interaction with receptors may cause activation of cells. We have used flow cytometry and labelled chicken antibodies to study the in vitro effects of model immune complexes on platelets and show that such immune complexes activate platelets and deposit Clq, C4 and C5 on them. Either low levels or no C3 could be detected on the platelets by flow cytometry. The immune complexes also induced formation of microparticles from purified platelets. Flow cytometry might become a useful tool in estimation of risk of thrombosis or thrombocytopenia in patients with autoimmune disease. Chicken antibodies are superior to mammalian antibodies for the measurement of platelet bound plasma proteins as they do not induce complement activation or platelet activation.     

Causes of thrombocytopenia in chronic hepatitis C viral infection

We retrospectively studied 89 patients with chronic hepatitis C virus (HCV) infection, including 50 chronic hepatitis (CH) cases, 18 liver cirrhosis (LC) cases, and 21 LC with hepatocellular carcinoma (LC + HCC) cases, with regard to various factors related with thrombocytopenia. The platelet count decreased with the stage advancement of liver diseases. Multiple regression analysis revealed that splenomegaly and von Willebrand factor (vWF) were explanatory variables that correlated with thrombocytopenia. Splenomegaly appears to be the most responsible factor, although there are a considerable number of thrombocytopenic cases without splenomegaly, suggesting other factors may also be responsible. The vWF level is inversely correlated with the platelet count. Soluble thrombomodulin, a marker of endothelial dysfunction, increases with the advancement of liver fibrosis. It is positively correlated with vWF and inversely with the platelet count. Our present results imply that vascular endothelial dysfunction is also involved in thrombocytopenia during chronic HCV infection.     

New technologies for the inactivation of infectious pathogens in cellular blood components and the development of platelet substitutes

Despite the increased safety of blood components, achieved through improved donor selection and testing, transfusion recipients remain at risk of transfusion-associated diseases. Transfusion of cellular blood components has been implicated in transmission of viral, bacterial and protozoan diseases. While it is commonly recognized that hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), and retroviruses, such as human immunodeficiency virus (HIV) and the human lymphotrophic viruses (HTLV), can be transmitted through cellular components, other pathogens are emerging as potentially significant transfusion-associated infectious agents. For example, transmission of protozoan infections due to trypanosomes and Babesia have been reported. In addition to viral and protozoan infectious agents, cases of bacterial contamination of platelet and red cell concentrates continue to be reported and may be an under-reported transfusion complication. More importantly, new infectious agents continue to enter the donor population, and there is an inherent time delay before the new pathogens are definitively identified and new tests implemented in order to maintain consistent safety of the blood supply. The paradigm for this problem is the HIV pandemic.During the past decade a number of methods for inactivating infectious pathogens in platelet concentrates have been investigated as a strategy to improve the safety of platelet transfusion therapy. One method of treating platelet concentrates to inactive pathogens has now reached the advanced clinical trial phase in the United States and Europe. Similar efforts with a new class of compounds are underway for red cell concentrates, and two of these are in early phase trials. In addition to studies with allogeneic platelets and red cells, a number of laboratories have described methods for developing platelet substitutes or modified platelets to avoid the use of traditional platelet concentrates as a means to improve safety.     

HIV-related thrombocytopenias

Thrombocytopenia is a relatively frequent hematological complication in patients infected with the human immunodeficiency virus type 1. Occurring in all risk groups (homosexuals, intravenous drug addicts, hemophiliacs, heterosexuals) this complication has an overall prevalence varying between 5 and 15%. Only a relatively small proportion of patients have severe thrombocytopenia (6 to 24%), and life-endangering bleeding symptoms are not frequent. Accordingly, aggressive treatment is seldom indicated. Corticosteroids should be avoided because they may further compromise the deteriorated immune system of these patients. Splenectomy is efficacious as in patients with non-human immunodeficiency virus related immune thrombocytopenic purpura and infectious complications are not a prominent problem following the operation. Antiretroviral treatment with zidovudine and/or highly active protease inhibitors increases platelet count, but the control of thrombocytopenia is often transient when these drugs are stopped. Other treatments such as alpha-interferon and thrombopoietin require further experiences. On the whole, thrombocytopenia is generally a relatively mild complication of the human immunodeficiency virus infection and aggressive treatment is often unwarranted.     

Specific Autoantibodies to Platelet Glycoproteins in Epstein-Barr Virus—Associated Immune Thrombocytopenia

In this study, we detected autoantibodies to platelet glycoproteins GPIIb/IIIa and GPIb/IX on platelets and in plasma in a patient with immune thrombocytopenia associated with Epstein-Barr virus-related infectious mononucleosis. In addition, we present our findings on the effectiveness of intravenous immunoglobulin therapy for immune thrombocytopenia associated with Epstein-Barr virus.     

Platelet kinetics in immune thrombocytopenic purpura and human immunodeficiency virus thrombocytopenia

Platelet kinetics studies are capable of measuring in vivo platelet survival and platelet turnover rates. These studies can be helpful in elucidating mechanisms of thrombocytopenia, particularly in complicated clinical situations. Numerous studies over the past 30 years have established the abnormalities in platelet kinetics associated with immune thrombocytopenic purpura (ITP). It is now well known that many patients infected with HIV type-1 will develop thrombocytopenia, and that at least 10% will develop a thrombocytopenic disorder clinically indistinguishable from immune thrombocytopenic purpura. Platelet kinetics studies in this group of patients may prove of great benefit in understanding the mechanisms underlying thrombocytopenia and in making accurate diagnoses. For all patients with ITP-like disorders, these studies may also prove helpful in understanding and improving current therapies.     

Management of thrombocytopenia due to liver cirrhosis:A review

Thrombocytopenia is a common complication in liver disease and can adversely affect the treatment of liver cirrhosis,limiting the ability to administer therapy and delaying planned surgical/diagnostic procedures because of an increased risk of bleeding.Multiple factors,including splenic sequestration,reduced activity of the hematopoietic growth factor thrombopoietin,bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents,and antiviral treatment with interferon-based therapy,can contribute to the development of thrombocytopenia in cirrhotic patients.Of these factors,the major mechanisms for thrombocytopenia in liver cirrhosis are(1)platelet sequestration in the spleen;and(2)decreased production of thrombopoietin in the liver.Several treatment options,including platelet transfusion,interventional partial splenic embolization,and surgical splenectomy,are now available for severe thrombocytopenia in cirrhotic patients.Although thrombopoietin agonists and targeted agents are alternative tools for noninvasively treating thrombocytopenia due to liver cirrhosis,their ability to improve thrombocytopenia in cirrhotic patients is under investigation in clinical trials.In this review,we propose a treatment approach to thrombocytopenia according to our novel concept of splenic volume,and we describe the current management of thrombocytopenia due to liver cirrhosis.