低分子肝素诱导的血小板减少一例并文献复习

目的对1例使用低分子肝素钠后出现血小板减少的患者进行分析,以提高临床对肝素诱导的血小板减少症（Heparin-induced thrombocytopenia,HIT）的认识。方法回顾性分析及复习相关文献。结果在使用肝素或低分子肝素过程中可能引起血小板减少,严重者可伴血栓形成,需高度重视。结论一旦出现HIT,须及时停用肝素或低分子肝素,换为非肝素类抗凝剂。     

重症医学科病人中肝素诱导的血小板减少症

肝素诱导的血小板减少症(HIT)是一种与肝素相关的严重副反应。其中Ⅱ型HIT是一种免疫介导的常发生在使用普通肝素、但较少发生在使用低分子量肝素病人中的血栓形成并发症,可见于各临床专科,但易被临床医师忽视或漏诊,特别是重症医学科危重病人普遍存在血小板减少现象且通常可由HIT外的其它病症所致,诊断较为困难。应用4T评分表有助于这类病人的确诊与治疗用药的选择。确诊HIT需实验室检查发现存在HIT抗体,而血小板功能检测与抗原检测相结合可提高诊断试验的特异性和敏感度。HIT治疗较棘手,严重者会危及生命,故临床疑诊HIT即应尽早开始替代抗凝治疗,治疗药物可选择直接凝血酶抑制剂和Xa因子抑制剂。     

FDA最新药物

FDA批准bivalirudin注射剂的新适应证2005年11月30日,FDA批准了bivalirudin注射剂(商品名Angiomax,Medicines公司)的新适应证,用于治疗经皮腔内冠状动脉成形术(PTCA)后由肝素所致的血小板减少症和血小板减少性血栓综合征(HIT/HITTS)。血小板减少症和血小板减少性血栓综合征是一种肝素诱导的免疫反应,表现为循环中血小板的减少,以及血栓形成危险性的增加,从而可导致肢体缺血(需要截肢)、心肌梗死、卒中、肺栓塞和死亡。根据FDA所示,用bivalirudin代替肝素治疗,可能会改善HIT/HITTS患者或HIT/HITTS高危患者的预后。由于在临床…     

先天性心脏病术后肝素诱导性血小板减少症一例并文献复习

肝素诱导血小板减少症（heparin-induced thrombocytopenia,HIT）是使用肝素治疗的副作用之一。血小板因子4与肝素形成复合物时,常由IgG型抗体介导并引起血小板活化,最终激活凝血系统,促使大量凝血酶生成,机体处于高凝状态,实际上HIT是一类促血栓形成疾病[1]。然而,     

肝素致血小板减少症

在美国,肝素钠注射剂产品的标签上最近补充了一则警告语,提示肝素致血小板减少症(HIT)可能延迟发生,进一步建议用此类产品时应密切监测不同程度的血小板减少症出现,若血小板计数跌至100000/mm3以下或血栓形成复发,则此肝素产品应立即停用,考虑改用其他抗凝药。先前肝素产品标签上也有关于致血小板减少症的警告语,而此次修订的新警告语还强调,HIT为一种抗体介导的严重不良反应,由不可逆的血小板凝聚所致,并可进而发展为静脉和动脉血栓形成,即所谓肝素致血小板减少与血栓形成(HITT)。这些新警告语已在近期的美国FDA MedWatch网站公布。…     

来吡鲁定治疗肝素所致血小板减少症

来吡鲁定(lepirudin,商品名Refludan)是凝血酶的直接抑制剂,已由美国FDA批准用于肝素引起的血小板减少症及血栓栓塞并发症的患者。 在接受肝素治疗超过4d时,有1％～2％病人会发生极为严重的肝素所致血小板减少症(HIT)。这时体内就会形成对抗肝素-血小板蛋白复合体的抗体。在有肝素存在的情况下,这些抗体会激活血小板,迅速引起严重的血小板减少症并损害血管内皮,出现血栓形成前的状态。HIT如未得到治疗,则可导致动静脉血栓形成、肺栓塞、急性心肌梗死、周围动脉阻塞及中风,其病死率为20％～30％。     

肝素好用诱导的血小板减少症怎么处理

正近期,来自德国格赖夫斯瓦尔德大学的Greinacher博士通过一则病例介绍了肝素诱导的血小板减少症,全文发表在NEJM上。病例介绍患者,女,64岁,因感染性心内膜炎入院,予静脉抗生素治疗,病情稳定,但血小板计数从入院第7天的161×109/L降至第9天的60×109/L。患者自入院开始每天注射40 mg低分子肝素,如此病例,如何进一步评估和治疗?概念引出:肝素诱导的血小板减少症肝素诱导的血小板减少症(HIT)是以血小板减少和血栓形成为主要特征的免疫性疾病,其发病率约为1/5000,接受普通肝素治疗7-10天的患者     

肝素诱导血小板减少症的新进展

<正>肝素以其使用方便、生产过程简单和价格低廉等特点,已成为临床工作中较常用的抗凝药物。主要用于急性冠脉综合征、介入检查及治疗、心脏外科手术、静脉血栓栓塞、外周血管栓塞、透析和体外循环等抗凝治疗。肝素诱发血小板减少,并可继发致命性血栓形成,称为肝素诱导的血小板减少症(HIT)[1]。Levy等[1]研究发现,约38%~78%HIT患者形成血栓,其中截肢10%,20%~30%患者在     

低分子量肝素引起HIT发生率的前瞻性队列研究

与普通肝素拥有大量文献资料相比,低分子量肝素引起的肝素致血小板减少症(HIT)的发生率尚未较好地确定。此试验中有来自17个医学中心的1 754例患者使用低分子量肝素用于预防或治疗血栓栓塞疾病,同时监测其血小板计数。     

1例利伐沙班治疗肝素诱导的血小板减少症的用药分析

本文通过对1例肺栓塞患者使用肝素治疗过程中发生血小板减少症后,选用利伐沙班进行治疗,进而探讨利伐沙班对肝素诱导的血小板减少症(HIT)的疗效。通过使用利伐沙班,患者肺栓塞得到安全、有效的治疗,血小板计数及其他指标均恢复正常。故对肺栓塞患者使用肝素时需要严格检测实验室指标,以便及时防治不良反应的发生;同时,利伐沙班作为一种新型口服抗凝药,在治疗HIT及肺栓塞方面发挥了重要的作用。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.