Background Low von Willebrand factor (VWF) refers to subjects with plasma levels of 30 to 50 IU/dL. The mechanism of low VWF is poorly understood. We chose to determine the clinical presentation, laboratory phenotype, and underlying mechanisms of low VWF. Material and Methods We included 250 patients characterized with low VWF. The International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) was used to assess clinical symptoms. To determine the underlying mechanisms of low VWF, we used as markers the VWF propeptide (VWFpp) assay and FVIII:C/VWF:Ag ratio for VWF synthesis and the VWFpp/VWF:Ag ratio for VWF clearance. Results were compared with those of 120 healthy controls. Cases with abnormal screening tests were further evaluated for coagulation factor levels and platelet disorders. Results The median age of the cohort was 35 years (range 3–85), 21% were children (n = 53), 34% were adult males (n = 85), and 45% (n = 112) were adult females. According to the ISTH-BAT, abnormal bleeding was found in 35% of children, 47% of males, and 49% of females. No association was found between VWF activity levels and ISTH-BAT. Patients showed an overall decreased VWF synthesis/secretion and an enhanced VWF clearance was identified in 33% of them. In 89 patients (36%), there were other hemostasis-related defects, but there was no difference in the ISTH-BAT between the two groups. Conclusion Our findings indicate that reduced VWF synthesis/secretion and enhanced VWF clearance are major mechanisms of low VWF levels. Patients with low VWF have significant bleeding manifestations. While other hemostasis defects occurred together with low VWF, this combination did not exacerbate clinical symptoms.

中文翻译：

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低 VWF 患者的临床和实验室表现及潜在机制

背景 低血管性血友病因子 (VWF) 是指血浆水平为 30 至 50 IU/dL 的受试者。低 VWF 的机制尚不清楚。我们选择确定低 VWF 的临床表现、实验室表型和潜在机制。材料和方法 我们纳入了 250 名具有低 VWF 特征的患者。使用国际血栓和止血协会出血评估工具（ISTH-BAT）来评估临床症状。为了确定低 VWF 的潜在机制，我们使用 VWF 前肽 (VWFpp) 测定和 VWF 合成的 FVIII:C/VWF:Ag 比率以及 VWF 清除的 VWFpp/VWF:Ag 比率作为标记。结果与 120 名健康对照者的结果进行了比较。筛查测试异常的病例进一步评估凝血因子水平和血小板疾病。结果 该队列的中位年龄为 35 岁（范围 3-85），其中 21% 为儿童（n = 53），34% 为成年男性（n = 85），45%（n = 112）为成年女性。根据 ISTH-BAT 的数据，35% 的儿童、47% 的男性和 49% 的女性发现异常出血。未发现 VWF 活动水平与 ISTH-BAT 之间存在关联。患者的 VWF 合成/分泌总体下降，其中 33% 的患者 VWF 清除率增强。89 名患者（36%）存在其他止血相关缺陷，但两组之间的 ISTH-BAT 没有差异。结论 我们的研究结果表明，VWF 合成/分泌减少和 VWF 清除增强是低 VWF 水平的主要机制。VWF低的患者有明显的出血表现。虽然其他止血缺陷与低 VWF 一起发生，但这种组合并没有加剧临床症状。