血管性血友病因子抗原：遗传性血栓性血小板减少性紫癜妇女发生严重妊娠并发症的生物标志物？

von Willebrand factor antigen: a biomarker for severe pregnancy complications in women with hereditary thrombotic thrombocytopenic purpura?

机构信息

Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben-Gurion University of the Negev, Be'er-Sheva, Israel.

Transfusion Medicine Institute, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er-Sheva, Israel; Hematology Institute, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er-Sheva, Israel.

出版信息

J Thromb Haemost. 2023 Jun;21(6):1623-1629. doi: 10.1016/j.jtha.2023.02.022. Epub 2023 Mar 6.

DOI:10.1016/j.jtha.2023.02.022

PMID:36889591

Abstract

BACKGROUND

Hereditary thrombotic thrombocytopenic purpura (hTTP) is associated with severe obstetric morbidity (SOM) during pregnancy. Treatment with fresh frozen plasma (FFP) mitigates the risk in some women, but others respond poorly and continue to suffer obstetric complications.

OBJECTIVES

To determine a possible association between SOM and elevated nonpregnant von Willebrand factor (NPVWF) antigen levels in women with hTTP and whether the latter can predict the response to FFP transfusion.

METHODS

This was a cohort-based study of women with hTTP due to homozygous c.3772delA mutation of ADAMTS-13 who had pregnancies both with and without FFP treatment. Occurrences of SOM were determined from medical records. Generalized estimated equation logistic regressions and receiver operating characteristic curve analysis determined the NPVWF antigen levels associated with the development of SOM.

RESULTS

Fourteen women with hTTP had 71 pregnancies; of which 17 (24%) culminated in pregnancy loss and 32 (45%) were complicated by SOM. FFP transfusions were administered in 32 (45%) of the pregnancies. Treated women had decreased SOM (28% vs 72%, p < .001) and preterm thrombotic thrombocytopenic purpura exacerbations (18% vs 82%, p < .001) and higher median NPVWF antigen levels than those of women with uncomplicated pregnancies (p = .018). Among the treated women, median NPVWF antigen levels were higher in those with SOM than in those without SOM (225% vs 165%, p = .047). Logistic regression models demonstrated a significant 2-way association between elevated NPVWF antigen levels (for SOM, odds ratio, 1.08; 95% CI, 1.001-1.165; p = .046) and SOM (for elevated NPVWF antigen levels, odds ratio, 1.6; 95% CI, 1.329-1.925; p < .001). The receiver operating characteristic curve analysis demonstrated that an NPVWF antigen level of 195% had 75% sensitivity and 72% specificity for SOM.

CONCLUSION

Elevated NPVWF antigen levels are associated with SOM in women with hTTP. Women with levels >195% may benefit from increased surveillance and more intensive FFP treatment during pregnancy.

摘要

背景

遗传性血栓性血小板减少性紫癜（hTTP）与妊娠期间的严重产科发病率（SOM）有关。在一些女性中，使用新鲜冷冻血浆（FFP）治疗可以降低风险，但其他女性反应不佳，继续遭受产科并发症的困扰。

目的

确定 hTTP 女性 SOM 与非妊娠状态下 von Willebrand 因子（NPVWF）抗原水平升高之间是否存在关联，以及后者是否可以预测 FFP 输血的反应。

方法

这是一项基于队列的研究，纳入了因 ADAMTS-13 基因 c.3772delA 突变导致 hTTP 的女性，这些女性有伴有和不伴有 FFP 治疗的妊娠。从病历中确定 SOM 的发生情况。广义估计方程逻辑回归和接收者操作特征曲线分析确定与 SOM 发生相关的 NPVWF 抗原水平。

结果

14 名 hTTP 女性有 71 次妊娠，其中 17 次（24%）以妊娠丢失告终，32 次（45%）出现 SOM。32 次妊娠（45%）给予了 FFP 输血。治疗组 SOM 发生率降低（28% vs 72%，p <.001），早产血栓性血小板减少性紫癜恶化率降低（18% vs 82%，p <.001），NPVWF 抗原水平中位数高于无并发症妊娠女性（p =.018）。在治疗组中，SOM 女性的 NPVWF 抗原水平中位数高于无 SOM 女性（225% vs 165%，p =.047）。Logistic 回归模型显示，NPVWF 抗原水平升高（SOM 的比值比，1.08；95%置信区间，1.001-1.165；p =.046）和 SOM 之间存在显著的双向关联。受试者工作特征曲线分析显示，NPVWF 抗原水平为 195%时，对 SOM 的敏感性为 75%，特异性为 72%。