Wiewel-Verschueren Sophie, Mulder André B, Meijer Karina, Mulder René
a Division of Thrombosis and Haemostasis, Department of Hematology , University of Groningen, University Medical Center Groningen , Groningen , The Netherlands.
b Department of Obstetrics and Gynaecology , University of Groningen, University Medical Center Groningen , Groningen , The Netherlands.
J Obstet Gynaecol. 2017 Oct;37(7):912-918. doi: 10.1080/01443615.2017.1312303. Epub 2017 Jun 13.
In a previous study it was shown that lower factor XI (FXI) levels in women with heavy menstrual bleeding (HMB). Our aim was to determine the single-nucleotide variants (SNVs) in the F11 gene in women with HMB. In addition, an extensive literature search was performed to determine the clinical significance of each SNV. Patients referred for HMB (PBAC-score >100) were included. With direct sequencing analysis of all 15 exons and flanking introns of the F11 gene, 29 different non-structural SNVs were detected in 49 patients with HMB. Interestingly, most of these SNVs have previously been associated with venous thrombosis instead of bleeding. These findings have not helped to elucidate the molecular basis of HMB. They also question the specificity of previously reported F11 variations in patients with thrombosis. More studies are needed to explain the lower FXI levels seen in patients with HMB. IMPACT STATEMENT Women with mild deficiencies of factor XI (FXI) (< 70%) are prone to excessive bleeding during menstruation. Bleeding manifestations are not well correlated with plasma FXI levels and bleeding episodes can vary widely among patients with similar low FXI levels. In a previous study we showed that women with heavy menstrual bleeding (HMB) had normal, but on average, lower levels of FXI than controls. In light of these findings, we performed F11 gene analysis to determine the single-nucleotide variants (SNVs) in women with HMB and performed an extensive literature search to determine the clinical significance of each SNV. By direct sequencing analysis of the F11 gene we found 29 different non-structural SNVs in 49 women with heavy menstrual bleeding. Remarkably, a number of these SNVs have previously been implicated in thrombosis. These findings have not helped to elucidate the molecular basis of lower FXI levels in HMB. They also question the specificity of previously reported F11 variations in patients with thrombosis. More studies are needed to explain the lower FXI levels seen in patients with HMB.
在先前的一项研究中发现，月经过多（HMB）女性的凝血因子XI（FXI）水平较低。我们的目的是确定HMB女性F11基因中的单核苷酸变异（SNV）。此外，还进行了广泛的文献检索以确定每个SNV的临床意义。纳入了因HMB前来就诊（PBAC评分>100）的患者。通过对F11基因的所有15个外显子和侧翼内含子进行直接测序分析，在49例HMB患者中检测到29种不同的非结构性SNV。有趣的是，这些SNV中的大多数先前都与静脉血栓形成而非出血有关。这些发现无助于阐明HMB的分子基础。它们还对先前报道的血栓形成患者中F11变异的特异性提出了质疑。需要更多的研究来解释HMB患者中出现的较低FXI水平。影响声明：凝血因子XI（FXI）轻度缺乏（<70%）的女性在月经期间容易出现过度出血。出血表现与血浆FXI水平相关性不佳，在FXI水平相似的患者中，出血发作可能差异很大。在先前的一项研究中，我们表明月经过多（HMB）的女性FXI水平正常，但平均低于对照组。鉴于这些发现，我们进行了F11基因分析，以确定HMB女性中的单核苷酸变异（SNV），并进行了广泛的文献检索，以确定每个SNV的临床意义。通过对F11基因的直接测序分析，我们在49例月经过多的女性中发现了29种不同的非结构性SNV。值得注意的是，其中一些SNV先前与血栓形成有关。这些发现无助于阐明HMB中较低FXI水平的分子基础。它们还对先前报道的血栓形成患者中F11变异的特异性提出了质疑。需要更多的研究来解释HMB患者中出现的较低FXI水平。
