原发性骨髓纤维化伴阵发性睡眠性血红蛋白尿1例并文献复习

Primary myelofibrosis with paroxysmal nocturnal hemoglobinuria: a case report and literature review

分析原发性骨髓纤维化(primary myelofibrosis,PMF)伴阵发性睡眠性血红蛋白尿(paroxysmal nocturnal hemoglobinuria,PNH)患者的临床特征,应用细胞化学染色及银染色等行骨髓象及骨髓病理检查,应用流式细胞术(FCM)检测红细胞及粒细胞表面的CD55、CD59,对粒、单核细胞进行荧光标记的嗜水气单胞菌素前体的变异体(FLAER)检测,为进一步确诊,应用高通量测序技术(又称二代测序)进行基因检测。该患者临床上表现为重度脾大、贫血,查骨髓象考虑PMF之可能,骨髓病理示骨髓纤维化(myelofibrosis,MF)3级。基因检测示:BCR/ABL融合基因阴性,JAK2 V617F基因突变阳性。故诊断为:PMF。给予达那唑、十一酸睾酮、促红细胞生成素(erythropoietin,EPO)、沙利度胺、血制品支持等治疗过程中出现血制品输注无效,伴茶色尿,完善相关检查:血常规示网织红细胞偏高,直接胆红素、间接胆红素偏高,抗人球蛋白试验(Coombs test)2次均为阴性,FCM示CD55、CD59降低,FLAER示粒、单表达缺陷,PIG-A基因突变阳性,故最终诊断为:PMF合并PNH。

The clinical characteristics of the pathogenesis of primary myelofibrosis(PMF)with paroxysmal nocturnal hemoglobinuria(PNH)were analyzed.Bone marrow imaging and bone marrow pathology were carried out by means of cytochemical staining and silver staining.Flow cytometry(FCM)was used to detect CD55 and CD59 on the surface of erythrocytes and granulocytes.And the granulocytes and monocytes were detected by FLAER.For further diagnosis,high-throughput sequencing technology(also known as the second generation sequencing)was used for genetic testing.The patient was clinically characterized by severe splenomegaly and anemia,which might be diagnosed with PMF by bone marrow examination.However,bone marrow pathology showed myelofibrosis(MF)grade 3.Genetic testing showed that BCR/ABL fusion gene was negative and JAK2 V617F positive.Therefore,the patient was diagnosed with PMF.Then,the patient was treated with danazol,testosterone undecanoate,erythropoietin(EPO),thalidomide,and blood product support.While the blood product infusion was ineffective during treatment and brown urine appeared,but the relevant examination was improved.The blood routine test showed that high reticulocyte,direct bilirubin,indirect bilirubin were high,the Coombs test was negative for twice,FCM showed the reduction of CD55 and CD59,and FLAER presented the expression defect of granulocytes and monocytes.And PIG-A gene mutation was found positive.Therefore,the patient was diagnosed as PMF with PNH.