Placental abruption as a trigger of DIC in women with HELLP syndrome: a population-based study

Disseminated Intravascular Coagulation (DIC) is a life-threatening condition. Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome is one of the obstetrical syndromes mostly associated with DIC and thus, high rates of fatal complications. There is a lack of information regarding epidemiologic and clinical characteristics of women who developed HELLP syndrome with and without DIC. Additionally, until now, there is no adapted and widely accepted way to diagnose DIC among pregnant women presenting with HELLP syndrome, despite the evident maternal mortality linked to the disease. <b>Objectives: (</b>1) Address the gaps in knowledge regarding the prevalence, epidemiologic and clinical characteristics of women with HELLP syndrome who develop DIC; and (2) determine the risk factors for the development of DIC among women with HELLP syndrome. This was a population-based retrospective cohort study, including all women who delivered at the Soroka University Medical Center between the years 2001–2017. The study population was divided into three groups: (1) comparison group (<i>n</i> = 207,266 deliveries); (2) HELLP syndrome without DIC (<i>n</i> = 320); (3) HELLP syndrome with DIC (<i>n</i> = 21). The diagnosis of DIC was based on the ICD-9 code as recorded in the obstetrical database of the Soroka University Medical Center. The coding is based on the diagnosis made by the attending physician during hospitalization. (1) The rate of HELLP syndrome in the study population was 0.16% (341/207,607), of them 6.16% (21/341) had DIC; (2) among patients with HELLP syndrome, those with DIC had a higher median gravidity and parity; (3) a higher rate of severe maternal morbidity including blood product transfusion, placental abruption, eclampsia, acute renal failure and maternal death was observed in those who had HELLP syndrome and DIC compared to those with HELLP syndrome without DIC and the comparison group (<i>p</i>-value &lt;.001 for comparison among the three groups); (4) among women with HELLP syndrome, those with DIC had a longer median PT difference, higher serum creatinine and lower AST as well as ALT median concentrations than those without DIC; (5) patients with HELLP syndrome and DIC had a higher rate of stillbirth and postpartum death than patients in the other groups (<i>p</i>-value &lt;.001 for comparison among the three groups); and (6) placental abruption was an independent risk factor for the development of DIC in women with HELLP syndrome (<i>p</i>-value &lt;.001). (1) Among women with HELLP syndrome, those who developed DIC had a higher rate of maternal and neonatal morbidity and mortality than those without DIC; and (2) placental abruption, but not abnormal liver function, was an independent risk factor for the development of DIC in women with HELLP syndrome.

弥散性血管内凝血（Disseminated Intravascular Coagulation，DIC）是一种危及生命的病症。溶血、肝酶升高伴血小板减少（Hemolysis, Elevated Liver enzymes and Low Platelets, HELLP）综合征是与DIC密切相关的产科综合征之一，此类患者的致死性并发症发生率较高。目前针对伴或不伴DIC的HELLP综合征孕妇的流行病学及临床特征相关研究数据仍较为匮乏。此外，尽管该病与显著的孕产妇死亡相关，但迄今为止仍缺乏适用于HELLP综合征孕妇人群且被广泛认可的DIC诊断方案。**研究目标：**（1）填补HELLP综合征合并DIC孕妇的患病率、流行病学及临床特征相关研究空白；（2）明确HELLP综合征孕妇发生DIC的危险因素。本研究为基于人群的回顾性队列研究，纳入2001年至2017年间在索罗卡大学医学中心（Soroka University Medical Center）分娩的所有孕妇。研究队列分为三组：（1）对照组（*n* = 207,266例分娩）；（2）不伴DIC的HELLP综合征组（*n* = 320例）；（3）伴DIC的HELLP综合征组（*n* = 21例）。DIC的诊断依据索罗卡大学医学中心产科数据库中记录的国际疾病分类第9版（International Classification of Diseases 9th Revision, ICD-9）编码，该编码基于住院期间接诊医师作出的临床诊断。本研究结果如下：（1）研究队列中HELLP综合征的发生率为0.16%（341/207,607），其中6.16%（21/341）合并DIC；（2）在HELLP综合征孕妇中，合并DIC者的中位孕产次数及产次更高；（3）与不伴DIC的HELLP综合征组及对照组相比，伴DIC的HELLP综合征孕妇出现严重孕产妇不良结局的比例更高，包括输注血液制品、胎盘早剥、子痫、急性肾衰竭及孕产妇死亡（三组比较*p* < 0.001）；（4）在HELLP综合征孕妇中，合并DIC者的中位凝血酶原时间（Prothrombin Time, PT）差值、血清肌酐水平更高，而天冬氨酸氨基转移酶（Aspartate Aminotransferase, AST）及丙氨酸氨基转移酶（Alanine Aminotransferase, ALT）的中位浓度更低；（5）伴DIC的HELLP综合征孕妇的死胎及产后死亡发生率高于其他两组（三组比较*p* < 0.001）；（6）胎盘早剥是HELLP综合征孕妇发生DIC的独立危险因素（*p* < 0.001）。综上，（1）在HELLP综合征孕妇中，合并DIC者的孕产妇及新生儿不良结局发生率均高于未合并DIC者；（2）胎盘早剥而非肝功能异常，是HELLP综合征孕妇发生DIC的独立危险因素。