Acquired hemophilia A and delta storage pool deficiency in a patient with indolent non-Hodgkin lymphoma

B-cell lymphoproliferative diseases may be associated with acquired hemostasis disorders, such as acquired hemophilia A (AHA) caused by autoantibodies that neutralize factor VIII activity, and δ-storage pool deficiency, an abnormality of platelet function due to defective dense granules and impaired secretion. We describe the case of a 67-year-old man in whom these two acquired bleeding disorders were concomitantly present as the first clinical manifestation of an indolent non-Hodgkin lymphoma. Immunosuppressive therapy with prednisone was initially started to eradicate anti-FVIII antibodies, subsequently boosted with cyclophosphamide and rituximab, these medications being also chosen to treat the associated indolent lymphoma. Bleeding symptoms were first tackled with limited benefit by using rFVIIa and then rescued using recombinant porcine FVIII. After a 6 month’s follow-up lymphoma and AHA were in remission and platelet function was improved. This case underlines the need of multiple and complex diagnostic and therapeutic approaches to rare acquired bleeding disorders associated with lymphoproliferative diseases.

B细胞淋巴增殖性疾病（B-cell lymphoproliferative diseases）可与获得性止血障碍相关，例如由可中和凝血因子VIII（factor VIII）活性的自身抗体所致的获得性血友病A（acquired hemophilia A，AHA），以及δ颗粒储存池缺陷（δ-storage pool deficiency）——一种因致密颗粒缺陷与分泌功能受损引发的血小板功能异常。我们报告1例67岁男性患者，其同时罹患上述两种获得性出血性疾病，以此作为惰性非霍奇金淋巴瘤（indolent non-Hodgkin lymphoma）的首发临床表现。初始予泼尼松（prednisone）行免疫抑制治疗以清除抗凝血因子VIII自身抗体，后续加用环磷酰胺（cyclophosphamide）与利妥昔单抗（rituximab），上述药物亦可用于治疗伴发的惰性淋巴瘤。出血症状最初予重组凝血因子VIIa（rFVIIa）治疗获益有限，随后改用重组猪源凝血因子VIII（recombinant porcine FVIII）才得以有效控制。经6个月随访，患者淋巴瘤与获得性血友病A均获缓解，血小板功能亦得到改善。本例提示，针对淋巴增殖性疾病伴发的罕见获得性出血性疾病，需采用多维度且复杂的诊断与治疗策略。