造血干细胞移植相关性肠道血栓性微血管病:临床病理学特征、诊断标准和治疗

异基因造血干细胞移植（allo-HSCT）后肠道血栓性微血管病（TMA）是一种少见的、致死性的、临床表现酷似肠道GVHD的合并症，此前国内尚无报道。自2002年5月至2004年7月，在本研究所接受allo-HSCT的患者总计373例，其中184例为HLA配型全相合，189例为HLA配型至少1个位点不合的亲缘供者移植。为探索TMA的临床及其病理学特征，本研究将其中30例allo-HSCT后因严重腹泻接受结肠镜以及病理检查的患者活检组织样本进行复检研究。结果发现，7例患者样本具有TMA特征性病理学改变，占活检例数的23．3％（7／30）。全部患者均伴有巨细胞病毒（CMV）血症和CMV疾病（CMV-IP5例、CMV肠炎2例）；5例伴有乳酸脱氢酶（LDH）增高。TMA组织学特征是多发性微血管管腔内血小板-纤维素血栓；血管内皮细胞肿胀、剥脱，伴有或不伴有血管周围出血。3例样本兼有TMA和GVHD的病理学特征；4例具备TMA的病理学特征而无GVHD的组织学改变。3例患者临床表现酷似急性缺血性肠炎，均有间断性或持续性鲜血便、明显腹痛伴有迅速发展的溶血性贫血、顽固性血小板减少、肝静脉阻塞综合征（VOD）、毛细血管渗漏综合征以及低蛋白血症。在移植后活存101-254天。结论：诊治肠道GVHD的同时应排查TMA，病理学特征可资鉴别；与此同时，初步研究首次证实TMA和TMA-GVHD各自具有特定病理特征，其治疗反应及转归也有差异。

HSC Transplantation-associated Intestinal Thrombotic Microangiopathy: Clinical Pathological Features, Diagnosis Criteria and Treatment

Thrombotic microangiopathy (TMA) is a lethal transplantation-associated complication which exactly likes acute intestinal graft-versus-host disease (GVHD) in the clinical manifestation. 373 consecutive patients with hematological diseases received family HLA matched or mismatched HCT from May, 2002 to July, 2004. To analyse the clinical and pathological characteristics of TMA, 30 patients who suffered from severe diarrhea and received colonoscopic examination and gut biopsy were retrospectively analyzed. The results indicated that 7 patients originally diagnosed as gut GVHD showed the pathological evidence of enteric TMA. The incidence of TMA was 7 out of 30 specimen (23.3%). Pathological evidence of enteric TMA shown microvascular disorder characterized by thrombus in the capillary without infiltration of lymphocytes and perivascular hemorrhages in the mucosa, swelling and focal denudation of epithelial cells. All patients with TMA were associated with cytomegalovirus (CMV) antigenemia /disease. Among these patients, 4 cases, who only showed TMA without the evidence of gut GVHD pathologically, displayed treatment-resistant bloody diarrhea, renal failure, veno-occlusive disease, hemorrhagic cystitis, hemolytic anemia as well as thrombocytopenia. But the other 3 cases, with co-existence of both TMA and GVHD pathological characteristics had better treatment response. Survival analysis indicated that 3 patients with TMA-GVHD survived for 461 to 536 days but three out of four TMA patients died from VOD with liver failure as well as multiple organ failure during 101 to 254 days after HCT. In conclusion, to better diagnose those patients with severe and refractory diarrhea following HCT, pathological examination may indicate crux evidence to identify intestinal TMA from gut GVHD. Furthermore, this primary report has first evidenced that TMA and TMA-GVHD are two pathologically well-recognized subtypes with the difference between the pathylogical characteristics, treatment response and clinical outcomes.