Objective: To explore the diagnosis and treatment of acquired hemophilia A (AHA) based on the analysis of clinical data.
Methods: A retrospective analysis was conducted on the clinical manifestations, laboratory characteristics, treatment, and outcomes of 25 patients diagnosed with AHA who were admitted to the Second Hospital of Hebei Medical University.
Results: Among all patients, 11 cases had secondary factors, including 5 cases of autoimmune diseases, 3 cases of pregnancy-related disease, 1 case of pemphigoid, 1 case of Graves' disease, and 1 case of monoclonal gammaglobulinemia of unknown significance (MGUS). The bleeding sites include the skin, mucous membrane, muscle, joint cavity and brain tissue. Twenty-three patients were treated with prednisone combined with cyclophosphamide (CP regimen), one patient with rituximab combined with cyclophosphamide because of femoral head necrosis, and one case with rituximab monotherapy because of gastrointestinal bleeding after prednisone treatment. Among them, 23 cases achieved complete remission (CR), 2 cases were partial remission (PR), and 8 cases relapsed after CR. All of 10 patients including 2 cases with PR and 8 relapsed cases after CR were treated with rituximab. At last, 8 patients achieved CR, and 2 patients (both were patients with recurrence after first CR) achieved PR. These two patients achieving PR were treated with low-dose rituximab combined with bortezomib (RB regimen). One patient reached CR after 4 cycles and the other reached CR after 6 cycles of RB regimen. After CR, 4 of the 10 patients treated with rituximab received maintenance therapy with rituximab monotherapy for 1.5 to 2 years, in which, none of them relapsed. Among the 6 patients who did not receive maintenance therapy, 4 patients relapsed after CR, and the median time to relapse was 15 months. Eight patients treated with CP regimen developed common infections, and two patients treated with rituximab developed severe pneumonia. All 25 patients survived until the end of follow-up.
Conclusion: Skin ecchymosis, mucous hemorrhage and muscle hematoma are the most common hemorrhagic manifestations in AHA, and joint hemorrhage and cerebral hemorrhage can also occur. CP regimen is the preferred option of first-line therapy for AHA. Rituximab can be used for patients with steroid contraindication or who failed to respond to the above therapy or relapsed after effective treatment, and maintenance therapy is recommended to reduce the risk of recurrence. Meanwhile, close attention should be paid to the occurrence of infection events during rituximab treatment. Rituximab in combination with bortezomib can also be used in patients with refractory or relapsing AHA.
题目: 单中心25例获得性血友病A临床分析.
目的: 基于临床资料分析探讨获得性血友病A(AHA)的诊治。.
方法: 回顾性分析我中心收治的25例AHA患者的临床表现、实验室特点、治疗和转归。.
结果: 所有患者中11例存在继发因素，包括自身免疫性疾病5例，妊娠相关3例，类天疱疮1例，Graves病1例，意义未明的单克隆丙种球蛋白血症（MGUS）1例。出血部位包括皮肤、黏膜、肌肉、关节腔及脑组织。23例患者接受醋酸泼尼松联合环磷酰胺（CP方案）治疗，1例因存在股骨头坏死选用利妥昔单抗联合环磷酰胺方案，1例因应用醋酸泼尼松后出现消化道出血改用利妥昔单抗治疗。完全缓解（CR）23例，部分缓解（PR）2例，CR后复发8例。10例患者（包括2例PR及8例CR后复发）均采用利妥昔单抗治疗，8例达CR，2例达PR（均为CR后复发患者），PR患者均采用小剂量利妥昔单抗联合硼替佐米（RB方案）治疗，1例于4周期后达CR，另1例于6周期后达CR。应用利妥昔单抗治疗的10例患者达CR后有4例接受利妥昔单抗单药维持治疗有效未复发，维持治疗时间为1.5-2年；未维持治疗的6例患者中4例出现CR后复发，中位复发时间为15个月。应用CP方案的患者有8例出现普通感染，给予利妥昔单抗治疗的患者有2例发生了重症肺炎。25例患者至随访结束均存活。.
结论: AHA以皮肤瘀斑、黏膜出血、肌肉血肿最常见，亦可发生关节出血、脑出血。一线治疗首选CP方案。对于激素有禁忌或上述治疗无效以及有效后复发的患者可应用利妥昔单抗治疗，且建议维持治疗，以减少复发风险，同时治疗过程中应密切注意感染事件的发生。对于难治复发患者还可考虑应用利妥昔单抗联合硼替佐米的治疗方案。.
Keywords: acquired hemophilia A; coagulation factor FⅧ inhibitor; rituximab.