摘要：
目的 探讨获得性血友病(AH)A的病因、临床特点、治疗方法及疗效.方法 选择2007年6月至2016年5月,凉山彝族自治州第一人民医院血液科收治的4例AHA患者为研究对象.回顾性分析这4例AHA患者的临床特点、实验室检查结果、治疗方法及疗效等临床资料,并结合相关文献,探讨AHA诊治的研究进展.结果 ①4例患者均以皮肤淤斑及肌肉血肿为主要表现.患者1,四肢脉搏微弱,血压为80 mmHg/40 mmHg(1 mmHg=0.133 kPa);血常规检查结果示,血红蛋白(Hb)水平为69 g/L;凝血功能分析结果示,活化部分凝血活酶时间(APTT)为82.8 s,凝血因子FⅧ活性＜1.0％,凝血因子FⅧ抑制物滴度为3.20 Bu/mL,凝血因子FⅨ活性为1.0％;风湿三项检测结果示,类风湿因子(RF)水平为219.0 U/L,C反应蛋白(CRP)水平为46.19 mg/L.患者2,四肢脉搏微弱,血压为80 mmHg/50 mmHg;血常规检查结果示,Hb水平为58 g/L;凝血功能分析结果示,APTT＞248.0 s,凝血因子FⅧ活性＜2.0％,凝血因子FⅧ抑制物滴度为5.50 Bu/mL,凝血因子FⅨ活性为4.5％,凝血因子FⅪ活性为13.6％,凝血因子FⅫ活性为7.0％,凝血因子FⅨ抑制物滴度为0.98 Bu/mL;免疫学检查结果示,抗干燥综合征(SS)A抗体(+++)、抗SSB抗体(+++)、抗RO52抗体(+++),抗酸性核蛋白抗体(++),抗核抗体(ANA)滴度为1∶3 200.患者3,血压为104 mmHg/66 mmHg;血常规检查结果示,Hb水平为46 g/L;凝血功能分析结果示,APTT明显延长为104.4 s,凝血因子FⅧ活性为4.4％,FⅧ抑制物滴度为6.20 Bu/mL;免疫学检查结果示:ANA滴度为1∶3 200,抗SSA抗体(+),抗线粒体M2抗体(+),ACA(-).患者4,血压为106 mmHg/72 mmHg;血常规检测结果示,白细胞计数为23.21×109/L,中性粒细胞比例为90％,Hb水平为58 g/L;凝血功能分析结果示,APTT为96.9s,凝血因子FⅧ活性为3.7％,凝血因子FⅧ抑制物滴度为3.30 Bu/mL;胸部CT结果示,右肺下叶外压性肺不张,左下肺小范围感染灶.②根据病史、体征及相关实验室检查结果,患者1诊断为AHA合并失血性贫血、失血性休克、类风湿关节炎(RA).患者2诊断为AHA合并失血性贫血,失血性休克,系统性红斑狼疮(SLE).患者3诊断为AHA合并失血性贫血、SS.患者4诊断为AHA合并失血性贫血、高血压病、重症肺炎、Ⅰ型呼吸衰竭.③患者1接受新鲜冰冻血浆(400～600 mL/d)、冷沉淀(10 U/d)输注,并接受扩容,血管活性药物治疗.随后患者接受甲泼尼龙(80 mg/d×8 d),联合甲氨蝶呤(10 mg/d×4d),静脉注射免疫球蛋白(IVIG) (5.0 g/d×5 d)治疗.患者病情好转后复发.患者接受新鲜冰冻血浆(400～600 mL/d)及冷沉淀(8～10 U/d)、来氟米特(10 mg/d)、甲泼尼龙(80 mg/d)、环磷酰胺(0.6 g/d×3 d).患者病情好转后再次复发.患者再次接受新鲜冰冻血浆(400～600 mL/d),甲泼尼龙(80 mg/d×3 d),环磷酰胺(0.6 g/d×3 d)治疗后,患者出血症状好转,APTT恢复至正常参考值范围内,获得完全缓解(CR).患者2接受新鲜冰冻血浆(600～800 mL/d×1d,400～600 mL/d×1 d)输注,扩容,血管活性药物治疗,并接受甲泼尼龙(80 mg/d×7 d)治疗.由于疗效不佳,治疗方案改为甲泼尼龙(500 mg/d×3d)联合环磷酰胺(0.8 g/d×2d),同时继续输注新鲜冰冻血浆(600～800 mL/d)治疗.治疗后,患者出血症状好转,但是APTT仍无明显好转,患者获得部分缓解(PR).患者3接受新鲜冰冻血浆(600～800 mL/d×3 d),甲泼尼龙(80 mg/d×7 d)治疗.由于疗效不佳,治疗方法改为甲泼尼龙(500 mg/d×3 d)联合环磷酰胺(0.6 g/d×2 d)治疗.治疗后,患者出血症状获得缓解,APTT恢复至正常参考值范围内,患者获得CR.患者4接受抗感染治疗,并且输注新鲜冰冻血浆(600～800 mL/d)及悬浮红细胞(1.5 U/d×2 d).患者出血症状无明显好转,治疗过程中患者并发感染性休克、Ⅰ型呼吸衰竭、心功能不全,接受甲泼尼龙(80 mg/d)及扩容、升血压、解痉平喘、纠正心功能衰竭等多重治疗.因患者感染程度较重,故未接受免疫抑制剂治疗.患者对治疗无反应,家属选择放弃治疗,患者出院后死亡.结论 AHA患者出血倾向严重,多以皮肤及肌肉血肿形成为主,免疫性疾病为常见原因,治疗多采用糖皮质激素、免疫抑制剂,疗效较好.%Objective To investigate the etiology,clinical features,treatment and curative effect of acquired hemophilia (AH) A.Methods From June 2007 to May 2016,a total of 4 AHA patients who were admitted to Department of Hematology,First People's Hospital of Liangshan Yi Autonomous Prefecture were included in this study.The clinical characteristics,laboratory examination results,treatment methods and curative effect of the 4 AHA patients were analyzed retrospectively,and the research progress of diagnosis and treatment of AHA was discussed in combination with relevant literature.Results ① Skin stasis and muscle hematoma were the main manifestations in 4 AHA patients.Case 1 had a weak pulse in all extremities and a blood pressure of 80 mmHg/40 mmHg (1 mmHg =0.133 kPa).Blood routine examination results showed that level of hemoglobin (Hb) was 69 g/L.Blood coagulation function analysisresults showed activated partial thromboplastin time (APTT) was 82.8 s,FⅧ activity＜1.0％,titer of FⅧ inhibitor was 3.20 Bu/mL,FⅨ activity was 1.0％.Rheumatoid arthritis (RA) test results showed level of rheumatoid factor (RF) was 219.0 U/L,and level of C reaction protein (CRP) was 46.19 mg/L.Case 2 had a weak pulse in all extremities and a blood pressure of 80 mmHg/50 mmHg.Blood routine examination results showed that the Hb level was 58 g/L.Blood coagulation function analysis results showed APTT＞ 248.0 s,FⅧ activity＜2.0％,titer of FⅧ inhibitor was 5.50 Bu/mL,FⅨ activity was 4.5％,FⅪ activity was 13.6％,FⅫ activity was 7.0％,titer of FⅨ inhibitor was 0.98 Bu/mL.Immunological test showed Sjogrensyndrome (SS) antibody (+++),SSB antibody (+++),RO52 antibody (+++),acidic nucleoprotein antibody (++),titer of antinuclear antibody (ANA) was 1 ∶ 3 200.Case 3 had a blood pressure of 104 mmHg/66 mmHg.Blood routine examination results showed that Hb level was 46 g/L.Blood coagulation function analysis results showed APTT was 104.4 s,FⅧ activity was 4.4％,titer of FⅧ inhibitor was 6.20 Bu/mL.Immunological test showed titer of ANA was 1 ∶ 3 200,SSA antibody (+),mitochondria M2 antibody (+),anti-centromere antibody (ACA) (-).Case 3 had a blood pressure of 106 mmHg/72 mmHg.Blood routine examination results showed that white cell count was 23.21 × 109/L,neutrophil proportion was 90％,Hb level was 58 g/L.Blood coagulation function analysis results showed APTT was 96.9 s,FⅧ activity was 3.7％,titer of FⅧ inhibitor was 3.30 Bu/mL.Chest CT results showed right lower lung lobe with extrapyramidal atelectasis,left lower lung with small range of infection foci.② According to the medical history,physical signs and relevant laboratory examination results,case 1 was diagnosed as AHA with hemorrhagic anemia,hemorrhagic shock,RA.Case 2 was diagnosed as AHA with hemorrhagic anemia,hemorrhagic shock,and systemic lupus erythematosus (SLE).Case 3 was diagnosed as AHA with hemorrhagic anemia,SS.Case 4 was diagnosed as AHA with hemorrhagic anemia,hypertension disease,severe pneumonia,type Ⅰ respiratory failure.③ Case 1 received fresh frozen plasma (400-600 mL/d),cryoprecipitate (10 U/d),and received dilation,vasoactive drug treatment.Then,patient was treated with methyl prednisolone (80 mg/d × 8 d),combined with methotrexate (10 mg/d × 4 d),intravenous immunoglobulin (IVIG) (5.0 g/d × 5 d).The patient relapsed after improvement of disease.The patient was treated with fresh frozen plasma (400-600 mL/d),cryoprecipitate (10 U/d),leflunomide (10 mg/d),methyl prednisolone (80 mg/d),cyclophosphamide (0.6 g/d × 3 d).The patient relapsed after improvement of disease again.The patient was treated with fresh frozen plasma (400-600 mL/d),methyl prednisolone (80 mg/d × 3 d),cyclophosphamide (0.6 g/d × 3 d).The patient' s bleeding symptoms improved and APTT returned to the normal reference range,and the patient achieved complete remission (CR).Case 2 received fresh frozen plasma (600-800 mL/d× 1 d,400-600 mL/d× 1 d),and treatment of dilation,vasoactive drug,methyl prednisolone (80 mg/d×7 d).Due to poor curative effect,treatment changed to methyl prednisolone (500 mg/d × 3 d),combined with cyclophosphamide (0.8 g/d×2 d),and fresh frozen plasma (400-600 mL/d).After treatment,the patient's bleeding symptoms improved without APTT improvement,and the patient achieved partial remission (PR).Case 3 received fresh frozen plasma (600-800 mL/d× 3 d),and methyl prednisolone (80 mg/d× 7 d).Due to poor curative effect,treatment changed to methyl prednisolone (500 mg/d×3 d) combined with cyclophosphamide (0.6 g/d× 2 d).After treatment,the patient's bleeding symptoms improved and APTT returned to the normal reference range,and the patient achieved CR.Case 4 received anti-infective therapy,and fresh frozen plasma (600-800 mL/d),red cells suspension (1.5 U/d × 2 d).The patient's bleeding symptoms didn't improve.During the treatment,the patient developed septic shock,type Ⅰ respiratory failure,cardiac insufficiency,and received methyl prednisolone (80 mg/d),dilation,vasoactive drug,and treatment to relieve spasmolysis and heart failure.The patient was not treated with immunosuppressive therapy because of severe infection.After treatment,the patient had no response,and family members chose to give up treatment and the patient died after discharge.Conclusions AHA patients have a severe bleeding tendency,along with skin and muscle hematoma.Immunological diseases are the common cause.Most common treatments of AHA were glucocorticoid hormone,immunosuppressive agents with good efficacy.
