药物所致的血小板减少症

药物所致的血小板减少症为药物治疗过程中的一种常见副作用。主要分为两型 :一为骨髓被药物毒性作用抑制所致 ,二为药物通过免疫机制破坏血小板所致 ,后者中以肝素、奎宁、奎尼丁、金盐与磺胺类药物发病较高。临床症状极不一致 ,血小板减少至 (1.0～ 80 )× 10 9/L ,轻者无症状 ,重者可因颅内出血或因肝素导致内皮细胞的免疫损害 ,合并危及生命的肺栓塞与动脉血栓形成致死。诊断主要依靠 :①药物治疗期间血小板减少 ;②停药后血小板减少消除。严重患者血清中可检出药物依赖性血小板抗体 ,但敏感性不高而常呈假阴性。治疗之首要是立即停用相关药物 ,严重病例可相机使用输注血小板、激素、丙球甚或血浆置换     

Relapsing thrombotic thrombocytopenic purpura in association with recurrent pancreatitis

We report the case of a 28-year-old woman who presented with two episodes of acute pancreatitis 3 years apart both of which were complicated by the development of thrombotic thrombocytopenic purpura (TTP). On each occasion the TTP was successfully managed with plasmapheresis. Although TTP has been reported as causing acute pancreatitis, the induction of TTP by pancreatitis is rare. As far as we are aware this is the first reported case of recurrent TTP in association with acute pancreatitis. It is possible that circulating pancreatic proteases may have induced the TTP by modifying von Willebrand factor enabling spontaneous platelet membrane receptor binding resulting in intravascular platelet aggregation.     

Thrombocytopenia associated with chronic liver disease

Thrombocytopenia (platelet count <150,000/microL) is a common complication in patients with chronic liver disease (CLD) that has been observed in up to 76% of patients. Moderate thrombocytopenia (platelet count, 50,000/microL-75,000/microL) occurs in approximately 13% of patients with cirrhosis. Multiple factors can contribute to the development of thrombocytopenia, including splenic platelet sequestration, bone marrow suppression by chronic hepatitis C infection, and antiviral treatment with interferon-based therapy. Reductions in the level or activity of the hematopoietic growth factor thrombopoietin (TPO) may also play a role. Thrombocytopenia can impact routine care of patients with CLD, potentially postponing or interfering with diagnostic and therapeutic procedures including liver biopsy, antiviral therapy, and medically indicated or elective surgery. Therapeutic options to safely and effectively raise platelet levels could have a significant effect on care of these patients. Several promising novel agents that stimulate TPO and increase platelet levels, such as the oral platelet growth factor eltrombopag, are currently in development for the prevention and/or treatment of thrombocytopenia. The ability to increase platelet levels could significantly reduce the need for platelet transfusions and facilitate the use of interferon-based antiviral therapy and other medically indicated treatments in patients with liver disease.     

Anticardiolipin antibodies in patients with autoimmune diseases: Isotype distribution and clinical associations

Summary A prospective study of IgG and IgM isotypes of anticardiolipin antibodies (aCL) was performed in a series of 167 patients with various autoimmune diseases, including rheumatic and nonrheumatic disorders, and in a group of 100 healthy blood donors. The IgG aCL serum was regarded as positive if a binding index (BI) greater than 2.85 (3.77 SD) was detected and a BI greater than 4.07 (3.90 SD) was defined as positive for IgM aCL. Forty patients (24%) were found to be positive for IgG and/or IgM aCL. IgG aCL were detected in 23% of patients with systemic lupus erythematosus (SLE), in 9% with idiopathic thrombocytopenic purpura, in 7% with progressive systemic sclerosis, and in 6% with dermatomyositis-polymyositis. IgM aCL were present in 43% patients with primary biliary cirrhosis, in 33% with rheumatoid arthritis, in 22% with SLE, and in 8% with giant-cell arteritis. IgG aCL were found to have a significant association with thrombosis and thrombocytopenia, and IgM and aCL with haemolytic anaemia and neutropenia, in SLE but not in the other autoimmune diseases. The identification of these differences in the aCL isotype associations, depending on the autoimmune disorder, may improve the clinical usefulness of these tests.     

应用重组人血小板生成素减少肝硬化患者术前血小板输注疗效初步研究*

目的 以输注血小板改善肝硬化并发血小板减少症患者出血风险的疗效不确切,且可能导致潜在的并发症。本研究的目的是探讨应用重组人血小板生成素注射液(rhTPO)能否减少肝硬化患者术前输注血小板。方法 2017年1月～2019年4月在西京医院消化内科住院并进行手术治疗的乙型肝炎肝硬化患者40例和肝细胞癌患者36例,均需行食管静脉曲张套扎和/或胃底静脉曲张组织胶注射术或经肝动脉化疗栓塞术(TACE)治疗。术前给予rhTPO 15000U皮下注射,1次/d,连续应用10 d。结果 在76例患者中,血小板计数为40～50×10⁹/L组23例,血小板计数<40×10⁹/L组53例;两组患者在治疗第8 d时,外周血血小板计数较基线明显升高【>50×10⁹/L,分别为(76.0±26.6)×10⁹/L和(54.4±24.3)×10⁹/L]。在治疗第12 d,两组外周血血小板计数达到高峰[分别为(95±34.8)×10⁹/L和(67.9±25.1)×10⁹/L],在治疗后第30 d,血小板计数降至基线水平;应用rhTPO治疗后,保证了手术的顺利进行,对血凝功能无明显影响,两组未观察到门静脉血栓形成。结论 rhTPO可作为肝硬化并发血小板减少症患者术前血小板输注的替代疗法,能降低术中出血风险,且安全,值得临床进一步验证。     

血小板减少症对重症监护病房危重患者预后的判断研究

目的：探讨血小板减少症对重症监护病房（ICU）危重患者预后的判断意义。方法选择2012年1月～2013年3月广东省南雄市人民医院ICU危重患者152例作为研究对象,分析患者入院24 h内急性生理学及慢性健康状况评分Ⅱ（APACHEⅡ）评分与血小板计数的关系,并按照患者的临床预后分为死亡组50例和存活组102例,比较2组的血小板计数。结果 APACHEⅡ评分0～20分的ICU危重患者血小板计数为（86.10±16.43）×10^9/L,21～40分为（65.58±15.24）×10^9/L,＞40分为（49.81±12.20）×10^9/L,ICU危重患者的血小板计数与APACHEⅡ评分显著相关（r=-1.476,P＜0.05）,APACHEⅡ评分越高,血小板减少越显著;死亡组血小板计数为（58.21±8.90）×10^9/L,显著低于存活组的（65.45±10.11）×10^9/L,差异有统计学意义（t=4.310,P＜0.05）。结论 ICU危重患者静脉血小板计数随着APACHEⅡ评分的增高而减少,是危重病严重程度的监测指标,血小板减少症可以作为判断ICU危重患者预后的临床项目。     

重组人血小板生成素治疗恶性血液病化疗后血小板减少简

目的 评价重组人血小板生成素（rhTPO）对恶性血液病化疗后血小板减少的疗效和安全性.方法 化疗后血小板计数≤20×10^9/L的25例急性白血病和恶性淋巴瘤患者,接受方案和剂量相同的两周期化疗,采用病例自身对照研究方法,第一周期（对照组）化疗后出现血小板计数≤20×10^9/L时给予输注血小板悬液;第二个周期（治疗组）化疗结束后,在前述治疗基础上,当血小板计数≤50×10^9/L时给予皮下注射rhTP0 15 000 u,每日1次,连续7d,若未见效,最多延长至14 d;血小板计数≥75×10^9/L或血小板绝对数升高50×10^9/L时停药.监测血常规、肝肾功能、凝血功能、心电图.结果 治疗组和对照组血小板最低平均值为12.4±6.7×10^9/L和（10.8±9.0）×10^9/L,两组差异无统计学意义（P＞0.05）.血小板计数≤20×10^9/L的持续时间治疗组和对照组分别为4.8±1.3 d和6.5±1.7d（P＜0.05）.血小板恢复至≥50×10^9/L、≥75×10^9/L、≥100×10^9/L所需的天数治疗组分别为7.4±1.4 d、9.5±1.5d、11.7±1.8 d,短于对照组的10.3±1.6 d、12.4 ±2.0 d、15.4±2.8 d,两组差异有统计学意义（P＜0.05）.治疗组血小板输注量为13.0±6.8u,对照组血小板输注量为18.5 ±7.6 u,差异有统计学意义（P＜0.05）.治疗组未见严重不良反应.结论 rhTPO能有效促进血小板的恢复,减轻化疗引起的血小板减少程度和持续时间,减少血小板的输注量.     

Immortalized porcine liver sinusoidal endothelial cells: an in vitro model of xenotransplantation-induced thrombocytopenia

Wang Z‐Y, Paris LL., Chihara RK., Tector AJ., Burlak C. Immortalized porcine liver sinusoidal endothelial cells: an in vitro model of xenotransplantation‐induced thrombocytopenia. Xenotransplantation 2012; 19: 249–255.. © 2012 John Wiley & Sons A/S. Abstract: Background: Xenotransplantation has the potential to solve the critical shortage of human organs available for allotransplantation. The major barrier to porcine liver xenotransplantation is sequestration of human platelets causing thrombocytopenia. Porcine liver sinusoidal endothelial cells (LSEC) bind and phagocytose human platelets at least in part through binding of the asialoglycoprotein receptor 1 (ASGR1). Our purpose was to generate an immortalized porcine LSEC (iLSEC) line that mimics primary LSEC in ASGR1 expression and phagocytosis of human platelets. Porcine iLSEC would enable continued study of xenotransplantation‐induced thrombocytopenia in vitro with fewer animals sacrificed. Methods:  Primary domestic porcine LSEC were transduced with lentiviral vector expressing the large and small T antigen of SV40 (SV40 TAg). The phenotype and genotype of the immortalized LSEC were compared with primary LSEC. Results:  A total of eight clones expressing SV40 TAg were isolated, and one clone was subcultured and analyzed for growth, phenotype, and function during passages 15–40. Expression of the SV40 TAg was confirmed by confocal microscopy and western blot. MTS cell proliferation assay demonstrated that the clone rapidly grew in culture medium with 2–10% fetal bovine serum. iLSEC expressed the endothelial cell marker, CD31, as determined by confocal microscopy and flow cytometry. Activation of iLSEC by treatment with lipopolysaccharide (LPS) resulted in upregulation of the inflammatory cytokine interleukin 6 (IL 6) by qPCR and ELISA. iLSEC phagocytosed human serum albumin and latex beads as measured by flow cytometry. Human platelets were phagocytosed by immortalized porcine LSEC. Conclusions:  Immortalized porcine LSEC retain a phagocytic phenotype, making them a good model for the study of xenotransplantation‐induced thrombocytopenia and may provide further insight into the phagocytic role of LSEC.     

Assessment of a modified 4T scoring system for heparin-induced thrombocytopenia in critically ill patients

Purpose

The purpose of the study is to determine if a modified 4T (m4T) scoring system, which omits clinical evaluation of other thrombocytopenic etiologies, is different from the 4T scoring system's probability to predict a positive heparin-induced thrombocytopenia (HIT) laboratory test in the intensive care unit.

Materials and methods

This is a single-centered retrospective analysis of critically ill adults who had an enzyme-linked immunosorbent assay antiplatelet factor 4 antibody (ELISA anti-PF4 Ab) ordered. Patients were identified as HIT positive (optical density, ≥ 0.40) or HIT negative (optical density, < 0.40) based on the ELISA anti-PF4 Ab. Both 4T and m4T scores were calculated, and the diagnostic accuracy was compared using paired receiver operating characteristic curves.

Results

A total of 1487 adult intensive care unit patients with an ELISA anti-PF4 Ab ordered between January 2007 and December 2009 were eligible for study enrollment. Application of exclusion criteria and random selection yielded a total of 232 patients included for analysis (58 HIT-positive and 174 HIT-negative patients). The area under the curve for the 4T and m4T scores were 0.683 (95% confidence interval, 0.604-0.762) and 0.680 (95% confidence interval, 0.600-0.759), respectively (P = .065).

Conclusion

This study does not show a difference in the probability of the m4T and 4T scoring systems to predict a positive ELISA anti-PF4 Ab test in the critically ill patient population. Further prospective studies are needed to validate the m4T scoring system.     

Reduction of linezolid-associated thrombocytopenia by the dose adjustment based on the risk factors such as basal platelet count and body weight

The aim of the present study was to evaluate the efficacy of dose modification based on the risk factor for linezolid-induced thrombocytopenia. A multivariate logistic regression analysis performed in the observational study showed that low body weight of <55 kg (odds ratio [OR]: 33.2, 95% confidence interval [CI]: 2.16–510.1, P = 0.012) and the baseline platelet count of <200 × 10³/mm³ (OR: 24.9, 95% CI: 1.53–404.7, P = 0.024) were found to be risk factors for linezolid-induced thrombocytopenia. In the subsequent intervention study, in which daily dose of linezolid was set to 20 mg/kg in patients with either one of the risk factors or 1200 mg in those without any risk factor, the onset of thrombocytopenia was significantly prolonged in the intervention study group (P = 0.043), without reducing clinical efficacy. These findings suggest that dose adjustment of linezolid is effective in preventing thrombocytopenia without reducing its clinical efficacy in patients having risk factors.