获得性血友病A合并静脉血栓形成一例并文献复习

Acquired hemophilia A with venous thrombosis:report of a case and review of the literature

目的通过分析1例获得性血友病A(AHA)合并静脉血栓形成患者的临床资料并复习相关文献,提高对该病的认识。方法结合1例胃印戒细胞癌患者相关的AHA合并下肢深静脉血栓形成的临床资料及文献报道,对本病的病因学、发病机制、临床表现、诊断和治疗进行讨论。结果 AHA是由针对凝血因子Ⅷ的自身抗体导致的罕见出血性疾病,多见于老年人;与其相关的常见疾病是自身免疫性疾病、恶性肿瘤,约50%的AHA患者既往身体健康。出血最常累及软组织。AHA患者存在的各种促血栓形成因素(先天性、获得性)均有助于静脉血栓形成。AHA患者的治疗包括凝血因子替代止血治疗和抗体清除治疗,静脉血栓的抗凝治疗则有可能加重患者出血倾向。本例患者为一66岁男性胃癌患者,术前APTT延长,术后软组织血肿,血浆凝血因子Ⅷ活性(FⅧ:C)下降,FⅧ抗体滴度128BU,予糖皮质激素、丙种球蛋白、环磷酰胺(CTX)抑制抗体生成、输注FⅧ、凝血酶原复合物(PCC)止血;此后,出现右下肢静脉血栓形成;停用PCC,并予胃癌联合化疗,出血和血栓症状消失,凝血功能恢复正常。结论 AHA合并静脉血栓形成临床罕见,治疗相互矛盾。及时识别这两种疾病同时存在并采取综合性、个体化治疗措施是成功治疗的关键。

Objective To understand better the clinical features of acquired hemophilia A with venous thrombosis. Methods The etiology, pathogenesis, symptom, diagnosis, and treatment of acquired hemophilia A with venous thrombosis were discussed after retrospectively analysis of the prestentions of the case report and the literature. Results Acquired hemophilia A is a rare bleeding disease caused by antoantibodies directed against clotting factor Ⅷ. This autoimmune disorder most commonly occurs in the elderly. In approximately 50% of cases, it is idiopathic,while the remaining cases may be associated with autoimmune diseases, underlying hematologic or solid cancers. Hemorrhages in patients with acquired hemophilia A involve most frequently soft tissues. The associate prothrombotic risk factors （both congenital, but mainly acquired）are probably responsible for the occurrence of thrombosis in some of acquired hemophilia A patients. The two treatment priorities are to arrest the acute bleeding with substitution therapy and to eradicate the factor Ⅷ autoantibody with immunosuppressive therapy. Anti- coagulation and anti-thrombosis therapy may enhance the bleeding tendency in acquired hemophilia A patients. The report case was an 66-year-old man with gastric cancer. He had a prolonged APTr pre-operation and soft tissue hematoma post-operation. F Ⅷ inhibitor title was 128 Bethesda Unit. He was treated with prednisone, cyclophosphamide, and high-dose intravenous immunoglobulin to eradicate the inhibitor, factor concentrates （human F Ⅷ concentrates and prothrombin complex concentrate ） transfusion to arrest the acute bleeding. Transfusion of prothrombin complex concentrate was discontinued after his right femoral and calf muscular venous thrombosis developed. He was treated with combined chemotherapy containing Paclitaxel for three cycles. The signs of hematoma and thrombosis disappeared and coagulation tests returned to normal with inhibitor undetected. Conclusions Acquired hemophilia A with venous thrombosis is a very rare occurrence of hemorrhagic diathesis andveno-occlusive disorder with treatments incompatible. Correct diagnosis and comprehensive and individual therapies are the key to successive treatment.