探讨妊娠合并布鲁菌病继发获得性再生障碍性贫血(AA)患者的临床特点、治疗及预后。

选择2020年2月大连医科大学附属第二医院收治的1例足月妊娠合并布鲁菌病继发获得性AA患者(患者1)为研究对象。采用回顾性分析方法，分析其临床病例资料。以"妊娠""布鲁菌病""获得性再生障碍性贫血""pregnancy""brucellosis""acquired aplastic anemia"为中、英文关键词，在中国知网数据库、万方数据知识服务平台及PubMed数据库中，检索妊娠合并布鲁菌病继发获得性AA患者相关文献的结果显示，均无妊娠合并布鲁菌病继发获得性AA的文献报道，再以"妊娠""布鲁菌病""pregnancy""brucellosis""case report"为中、英文关键词，对上述数据库进行检索。对上述文献检索时限均设定为上述数据库建库至2026年3月。对国内外文献报道的妊娠合并布鲁菌病患者临床资料进行综合分析。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》。

①本研究患者1为女性、33岁，因"停经37^＋2周，阴道少量血性分泌物1 d"于本院治疗。患者1长期生活于布鲁菌病流行地区，家中饲养大量牛、羊，10年前曾因发热、乏力就诊于当地医院，血液菌群培养及骨髓检查结果均提示布鲁菌呈阳性，孕前及孕期血清学检查结果亦均提示布鲁菌抗体呈阳性。本次孕期出现乏力、大汗、恶心、关节疼痛及皮肤淤斑，逐渐出现严重血细胞减少，孕期血小板计数(PLT)为(5~20)×10⁹/L(较正常参考值异常降低)，血红蛋白(Hb)水平为52~70 g/L(较正常参考值异常降低)，对其采取间断输注血小板及红细胞治疗后，疗效维持时间有限。采取利福平治疗后，患者1的PLT一过性升高至100×10⁹/L，但因胃肠道不良反应未完成足疗程治疗。本次入院后，其实验室检查结果显示，白细胞计数(WBC)为4.05×10⁹/L(正常)，PLT为5×10⁹/L(降低)，Hb水平为52 g/L(降低)，布鲁菌免疫球蛋白(Ig)G抗体呈阳性。经多学科协作团队会诊后，对其采取丙种免疫球蛋白(20 g/d)及地塞米松(6 mg/12 h)治疗，并输注血小板2 U及红细胞4 U治疗后，PLT升高至59×10⁹/L、Hb升高至58 g/L，仍然均低于正常参考值。于蛛网膜下腔阻滞麻醉下进行急诊剖宫产术，新生儿生后1 min Apgar评分为10分，出生体重为2 750 g，脐带血全血细胞计数正常，脐带血布鲁菌IgG抗体呈阳性。胎盘病理学检查结果提示，胎盘绒毛毛细血管充血、小灶性梗死及少量炎性细胞浸润。术后患者1的PLT再次下降，根据中国医学科学院血液病医院对其进行的骨髓穿刺的复查结果，并结合临床表现将其诊断为布鲁菌病继发获得性AA。对患者1采取重组促红细胞生成素、免疫抑制剂及糖皮质激素治疗措施后，上述各项指标好转出院。对患者1分娩后42 d及6个月随访结果显示，PLT维持于约为20×10⁹/L水平，无明显出血表现。②根据本研究设定的文献检索策略，共计检索到6篇关于妊娠合并布鲁菌病患者的研究文献，涉及6例妊娠合并布鲁菌病患者(患者2~7)，加上患者1，共计7例妊娠合并布鲁菌病患者被纳入进行综合分析。这7例患者平均年龄为28岁，初产妇为5例、经产妇为2例；主要临床表现为关节痛(5例)、乏力(4例)、多汗(3例)、发热(2例)；1例于孕龄为6^＋个月时，采取米索前列醇引产，6例分娩活产新生儿，其中4例为早产，2例为足月产。

妊娠合并布鲁菌病继发获得性AA临床极其罕见，患者的发病机制复杂，布鲁菌病可对母体和胎儿均构成严重威胁，早期诊断和及时干预至关重要。对于妊娠合并布鲁菌病患者的治疗，需多学科协作团队综合分析其抗感染及妊娠管理措施，降低继发获得性AA的母儿风险。

To explore the clinical characteristics, treatment and prognosis of patients with acquired aplastic anemia (AA) secondary to brucellosis in pregnancy.

A case of patient with brucellosis in full-term pregnancy leading to secondary acquired AA (patient 1) admitted to the Second Affiliated Hospital of Dalian Medical University in February 2020 was selected as the study subject. A retrospective analysis method was employed to analyze her clinical data. Using " pregnancy" " brucellosis" " acquired aplastic anemia" as Chinese and English keywords, the search results of relevant literature on acquired AA secondary to brucellosis in pregnancy in CNKI database, Wanfang Data Knowledge Service Platform and PubMed database showed that there were no relevant reports on acquired AA secondary to brucellosis in pregnancy. Therefore, " pregnancy" " brucellosis" and " case report" were used as Chinese and English keywords to search the above databases. The literature retrieval time was set from the establishment of each database to March 2026. The clinical data of patients with brucellosis in pregnancy reported at home and abroad were comprehensively analyzed. The procedures followed in this study was complied with the requirements of the Helsinki Declaration of the World Medical Association revised in 2013.

① Patient 1 was a 33-year-old female, who was treated in our hospital due to " 37^{+ 2} weeks of amenorrhea and a small amount of vaginal bloody secretions for 1 day". Patient 1 had lived in a brucellosis-endemic area for a long time and had a history of contact with cattle and sheep. She was treated for fever and fatigue 10 years ago, and blood culture and bone marrow examination indicated brucellosis infection. Serological examination before and during this pregnancy indicated positive Brucella antibody. During this pregnancy, she experienced fatigue, profuse sweating, nausea, joint pain and skin ecchymosis, and gradually developed severe cytopenia. The platelet count (PLT) during pregnancy was (5-20)×10⁹/L (abnormally lower than the normal reference value), and the hemoglobin (Hb) level was 52-70 g/L (abnormally lower than the normal reference value). She received intermittent platelet and red blood cell transfusions, with transient effects. After treatment with rifampicin, the PLT transiently increased to 100×10⁹/L, but the full course of treatment was not completed due to gastrointestinal adverse reactions. Laboratory examination after this admission showed white blood cell count (WBC) was 4.05×10⁹/L, PLT was 5×10⁹/L, Hb was 52 g/L, and positive Brucella immunoglobulin (Ig)G antibody. After multidisciplinary team consultation, she was treated with intravenous immunoglobulin (20 g/d) and dexamethasone (6 mg/12 h), along with supportive treatment of 2 U platelets and 4 U red blood cells. After the PLT rose to 59×10⁹/L and Hb rose to 58 g/L, an emergency cesarean section was performed under subarachnoid block anesthesia. The newborn was in good condition at birth, with an Apgar score of 10 points at 1 minute after birth, a birth weight of 2 750 g, a normal umbilical cord blood complete blood cell count, and positive umbilical cord blood Brucella IgG antibody. Placental pathological examination showed congestion of placental villous capillaries, small focal infarction and a small amount of inflammatory cell infiltration. The PLT of patient 1 decreased again after cesarean section. After further hematological evaluation, bone marrow examination was rechecked at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Combined with the bone marrow examination results, clinical manifestations and exclusion of other secondary factors, she was diagnosed as acquired AA secondary to brucellosis. And after treatment with recombinant erythropoietin, immunosuppressants and glucocorticoids, the above parameters improved, and she was discharged. Follow-up results at 42 days and 6 months postoperatively for patient 1 showed that the PLT remained at approximately 20×10⁹/L, with no obvious bleeding manifestations. ② According to the literature search strategy set in this study, a total of 6 articles related to patients with brucellosis in pregnancy were retrieved, involving 6 patients with brucellosis in pregnancy (patients 2-7). Together with patient 1, a total of 7 patients were included for comprehensive analysis. The average age of these 7 patients was 28 years, including 5 primiparas and 2 multiparas. The main clinical manifestations were joint pain (5 cases), fatigue (4 cases), hyperhidrosis (3 cases), and fever (2 cases). One case underwent misoprostol induction at 6⁺ months of gestation, and 6 cases delivered live newborns, including 4 cases of premature delivery and 2 cases of full-term delivery.

Acquired AA secondary to brucellosis in pregnancy is extremely rare, and its pathogenesis is complex. Brucellosis in pregnancy can pose a serious threat to both the pregnant mother and the fetus, and early diagnosis and timely intervention are crucial. For the treatment of brucellosis in pregnancy, multidisciplinary team collaboration is required, and comprehensive consideration of anti-infection, supportive treatment and hematological management is needed to reduce the risk of secondary AA.