造血干细胞移植相关的血栓性微血管病研究进展

血栓性微血管病（TMA）是以微血管性溶血性贫血（MAHA）（伴红细胞碎片）、外周血小板减少、微血管血栓形成和多器官功能衰竭为表现的临床综合征，常引起肾功能损害及中枢神经系统异常，死亡率很高。溶血性尿毒综合征（HUS）和血栓性血小板减少性紫癜（TTP）均属于这一范畴。造血干细胞移植（HSCT）相关的内皮细胞损伤也可以导致TMA的发生，是HSCT后的严重并发症，与移植患者的预后密切相关，1980年由Powles等首次报道。移植相关的血栓性微血管病（TA—TMA）临床表现与经典TTP类似，但预后更差，目前已经受到该领域学者的广泛关注，我们就近年来的有关研究进展作一综述。     

移植相关血栓性微血管病的研究进展

移植相关血栓性微血管病(TA-TMA),是一类以微血管病性溶血性贫血、肾功能不全和神经系统异常为主要特征的造血干细胞移植(HSCT)并发症.TA TMA发病机制可能与移植预处理、病原微生物感染、钙调磷酸酶及雷帕霉素靶蛋白(mTOR)抑制剂、移植物抗宿主病(GVHD)、细胞因子、补体及中性粒细胞胞外陷阱(NET)等多种因素相关.临床对TA-TMA的诊断标准,目前仍局限于有创性较大的组织病理学诊断,缺乏有创性较小的特异性生物标志物诊断手段.目前,治疗性血浆置换、GVHD预防药物的调整、去纤苷、利妥昔单抗及依库珠单抗等,可能是治疗TA-TMA的有效手段.随着对TA-TMA发病机制研究的深入,制定其标准诊断和治疗方案正受到国内外广泛关注.笔者拟就TA-TMA的研究进展综述如下.     

移植相关血栓性微血管病的研究进展

移植相关血栓性微血管病是指发牛于移植以后，以微血管病性溶血性贫血、消耗性血小板减少以及脏器功能不全为临床特征的一组疾病的总称。内皮细胞损伤为其发病的中心环节。临床表现呈高度异质性，其诊断的确立通常是困难的。目前尚无肯定的治疗措施。预后好组可表现为自限性病程，而预后差组往往合并多种并发症，死于严重的GVHD、感染及原发病复发等。     

移植相关血栓性微血管病的研究进展

移植相关血栓性微血管病是指发生于移植以后,以微血管病性溶血性贫血、消耗性血小板减少以及脏器功能不全为临床特征的一组疾病的总称。内皮细胞损伤为其发病的中心环节。临床表现呈高度异质性,其诊断的确立通常是困难的。目前尚无肯定的治疗措施。预后好组可表现为自限性病程,而预后差组往往合并多种并发症,死于严重的GVHD、感染及原发病复发等。     

造血干细胞移植相关性肠道血栓性微血管病的护理

目的探讨造血干细胞移植后并发肠道血栓性微血管病的护理对策。方法回顾性总结3例造血干细胞移植后并发肠道血栓性微血管病患者的发病情况及采取的相关护理措施。结果 248例造血干细胞移植患者术后并发肠道血栓性微血管病3例,发生率为0.01%,3例患者均死亡。结论血栓性微血管病的病死率极高、预后很差,医护人员应提高对该病的认识,做到早诊断、早治疗,护士要做好各项治疗配合及护理工作,以降低病死率。     

造血干细胞移植后移植物抗宿主病合并移植相关血栓性微血管病患儿的护理

总结1例STAT1基因突变致结核分枝杆菌感染合并噬血细胞综合征患儿的护理体会.护理重点为做好早期筛查识别原发性免疫缺陷疾病,对患儿进行保护性隔离、营养管理,做好药物护理和舒适护理.经积极治疗和护理,患儿病情得到控制,好转出院;1个月后门诊随访,体温正常,胃纳好转,体质量增长1.0 kg.     

11例造血干细胞移植相关血栓性微血管病患者临床特征分析

目的分析造血干细胞移植(HSCT)后移植相关血栓性微血管病(TA-TMA)患者的临床特征。方法选取行HSCT的患者185例,确诊11例TA-TMA患者,作为病例组。从185例患者中随机选取30例年龄、移植方式、人类白细胞抗原配型相合的非TA-TMA患者,作为对照组。比较2组破碎红细胞比例,并分析11例TA-TMA患者的实验室指标结果及临床特征。结果在185例行HSCT的患者中,确诊11例(5.9%,11/185)TA-TMA患者,年龄33(7～45)岁,移植后发病时间76(22～152)d。病例组破碎红细胞比例为3.3%,高于对照组(0.4%)(P0.05)。11例TA-TMA患者血红蛋白(Hb)水平、血小板(PLT)计数呈进行性降低、减少。乳酸脱氢酶(LDH)、血清肌酐(Cr)、血清总胆红素(TB)、C反应蛋白(CRP)、降钙素原(PCT)、环孢素A(CsA)水平均升高。8例伴有急、慢性移植物抗宿主病(GVHD),6例患者24 h尿蛋白阳性。除1例患者未检出病毒DNA之外,其他患者均伴有1种及以上病毒血症,至随访结束仅4例存活。结论TA-TMA是骨髓移植后极为严重的一种并发症,患者如果合并GVHD,则预后较差,综合多项实验室指标结果有利于TA-TMA的早期诊断、治疗,降低死亡率。     

异基因造血干细胞移植相关血栓性微血管病患者的病情观察及护理

目的探讨异基因造血干细胞移植相关血栓性微血管病(transplantation-associated thrombotic micmangiopathy,TA-TMA)的病情观察重点及护理对策。方法回顾性总结7例TA-TMA患者的发病情况及相关护理措施。结果 7例患者异基因造血干细胞移植(allo-hematopoietic stem cell transplantation,allo-HSCT)后22～169d确诊为发生TA-TMA。4例TA-TMA患者癫痫发作,其中3例治疗有效,1例患者合并植入功能不良、纯红细胞再生障碍性贫血,拒绝血浆置换等进一步治疗出院后死亡。3例肠道TA-TMA患者中2例治疗有效(表现为腹痛缓解,乳酸脱氢酶及破碎红细胞计数恢复正常值),但所有患者均合并肠道移植物抗宿主病(graft versus host disease,GVHD),病情加重直至出现消化道大出血及多脏器功能衰竭死亡。结论 TA-TMA的病死率高、预后差,早诊断及早治疗有助于降低病死率,护士需要熟知该疾病的早期临床表现,早期预警,做好病情观察及疾病专科护理工作,以提高造血干细胞移植成功率。     

Acute phase after haematopoietic stem cell transplantation: bleeding and thrombotic complications

The transplantation of allogeneic or autologous haematopoietic stem cells is an established treatment for many malignant and non-malignant diseases of the bone marrow. Intensive cytoreductive regimens administered before transplantation induce prolonged and severe cytopenia of all haematopoietic lineages. Thrombocytopenia leads to an increased risk of bleeding, which may be further aggravated by consumption of plasmatic factors as a result of tumour lysis or after antibody administration. At the same time, patients after transplantation are also at increased risk of thrombotic complications. Endothelial damage induced by radio- and chemotherapy, indwelling catheters, prolonged immobilization and a high incidence of systemic infection all contribute to the frequent occurrence of thromboembolic events in this population. This review discusses the incidence and risk factors for haemorrhagic and thrombotic complications after stem cell transplantation. Special emphasis is given to complications occurring specifically in the context of transplantation such as diffuse alveolar haemorrhage, haemorrhagic cystitis, veno-occlusive disease, and transplant associated microangiopathy.     

Diagnosis of intestinal graft-versus-host disease and thrombotic microangiopathy after allogeneic stem cell transplantation

Severe diarrhea is a serious complication after allogeneic hematopoietic stem cell transplantation (HSCT). Acute graft-versus-host disease (GVHD) has been one of the major causes of diarrhea after HSCT, which is triggered by donor-derived cytotoxic T-lymphocytes. On the other hand, intestinal thrombotic microangiopathy (TMA) sometimes coexists with acute GVHD, and intensified immunosuppression to treat acute GVHD could exacerbate intestinal TMA, presumably through the vascular endothelial cell damage. The differential diagnosis between intestinal TMA and acute GVHD of the gut has mainly relied on the pathological findings, as clinical diagnosis of intestinal TMA has not been established. Therefore, we aimed to assess the feasibility of our clinical diagnosis for the patients with diarrhea after HSCT. We made tentative clinical criteria for intestinal TMA and acute GVHD of the gut, based on the clinical manifestations, laboratory data and colonoscopic findings, and started treatment before pathological diagnosis were made. Subsequently, a pathologist retrospectively assessed the accuracy of clinical diagnosis in a blind manner. In this study, we enrolled 19 patients complicating watery diarrhea after HSCT, and diagnosed as having acute GVHD (n = 10), intestinal TMA (n = 3), or both (n = 6) according to our criteria. We demonstrated that our clinical diagnosis for intestinal TMA and acute GVHD of the gut was overall correct, in terms of the response to the therapy and the pathological diagnosis. The present study may provide a clue on making clinical diagnosis of patients with watery diarrhea after HSCT, which enables us to start a prompt therapy.     

Thrombotic microangiopathy following stem cell transplantation

Stem cell transplantation associated microangiopathy (TA-TMA) occurs in about 7% of all transplantations. While it resembles in all its features idiopathic TTP or HUS, response to plasma therapy is poor. The overall mortality of patients afflicted with TA-TMA is about 80%. Comparative studies aimed at discovering risk factors for the development of TA-TMA and defined different entities according to clinical, laboratory and outcome parameters. It is thought to be of multifactorial aetiology with the central event of endothelial damage. Intensive chemotherapy and radiation for bmt-preparation, infection in the immunocompromised host and graft versus host disease in conjunction with immunosuppressive therapy i. e. cyclosporine turn the haemostatic balance into a procoagulant state. Therapeutic strategies deduced from idiopathic TTP were disappointing with the only consensus in the withdrawal of cyclosporine from TA-TMA patients. Future trials are directed to ameliorate endothelial dysfunction.     

Natural killer cells in haematopoietic stem cell transplantation

Natural killer cells represent the predominant lymphoid cell in the peripheral blood for many months after allogeneic or autologous stem cell transplant and their role in immunity to pathogens during this period is established. However, following the largely unsuccessful trials of NK and IL-2 activated NK cells for the treatment of haematological malignancies in the 1980's and 90's, their role in tumour immunology was discredited. Over the past ten years we have come to understand some of the complex regulatory pathways involved in NK cell activation and we are now in a position to capitalise upon this knowledge. This review presents our current state of understanding of NK cell regulation and highlights the role of these cells in engraftment, graft-versus-host disease, anti-leukaemia activity and post-transplant infection.     

Late effects on haemostasis after haematopoietic stem cell transplantation

Allogeneic and autologous hematopoietic stem cell transplantations are important therapeutic options for patients with hematologic disorders. Hemostatic complications are frequent after hematopoietic stem cell transplantation with a considerable morbidity and mortality. The incidence of bleedings and thrombosis is highest in the first few weeks after transplantation, but may also occur later. However, beyond the first year of transplantation only limited data are available. In long-term survivors the risk for premature atherosclerosis increases over time after allogeneic hematopoietic stem cell transplantation and it is higher than in the age-adjusted general population and in recipients of autologous transplantation.