a Department of Anesthesiology and Department of Transfusion Medicine , Cell Therapeutics and Hemostaseology, Ludwig-Maximilians University , Munich , Germany.
b Baxalta Innovations GmbH , Vienna , Austria , now part of Shire.
Platelets. 2019;30(2):264-270. doi: 10.1080/09537104.2017.1420153. Epub 2018 Jan 10.
Recombinant von Willebrand factor (rVWF), which was licensed in the United States in 2015, has the multimeric distribution of freshly secreted VWF with ultralarge (UL) and high molecular weight multimers (HMWM) from endothelial cells and megakaryocytes since it has never been exposed to ADAMTS13 or any other proteolytic enzyme. Measurement of closure time (CT) using the platelet function analyzer-200 (PFA-200) is highly sensitive to the presence of UL VWF multimers in added VWF concentrates. The PFA-200 is fully automated and can be used as a reliable point-of-care method to evaluate primary hemostasis. Although it is sensitive to presence of UL VWF multimers, there could be significant clinical utility when used to monitor rVWF replacement therapy. The ability to monitor and optimize the dosing of rVWF contributes to patient safety, especially in situations where the bleeding and thrombotic risk needs to be carefully balanced (e.g., cardiac assist device).
The aim of this in-vitro study was to demonstrate the detectability of rVWF spiked in VWF-deficient blood from patients with severe von Willebrand disease (VWD) with quantitative and functional pathologies using a functional testing device. We hypothesized that (1) whole blood samples from VWD patients spiked with rVWF would show a normalization in PFA-CT and (2) that a dose-response relationship could be demonstrated.
We selected 12 patients diagnosed with VWD from our database. A therapeutic dose of rVWF product (1 IU/ml) was spiked in VWD patients´ whole blood samples and PFA-CTs were measured. Furthermore, we investigated PFA-CTs under incremental doses of rVWF (0.1, 0.2, and 0.5 IU/ml). The PFA-CTs were normalized in VWD patients´ whole blood samples spiked with rVWF. Additionally, incremental doses of rVWF resulted in a progressive and dose-dependent PFA-CT correction.
Our in-vitro data indicate that the PFA-200 is a useful tool to detect rVWF. As the PFA-CT correction is dose dependent, the rVWF might be reliably monitored with a point-of-care analytical method during replacement therapy.
2015 年在美国获得许可的重组 von Willebrand 因子（rVWF）从未接触过 ADAMTS13 或任何其他蛋白水解酶，因此它具有内皮细胞和巨核细胞中新鲜分泌的 VWF 的多聚体分布，包括超大（UL）和高分子量多聚体（HMWM）。使用血小板功能分析仪-200（PFA-200）测量闭合时间（CT）对添加的 VWF 浓缩物中 UL VWF 多聚体的存在高度敏感。PFA-200 是全自动的，可以用作可靠的即时护理方法来评估初级止血。尽管它对 UL VWF 多聚体的存在敏感，但在监测 rVWF 替代治疗时可能具有重要的临床应用价值。监测和优化 rVWF 的剂量有助于患者安全，尤其是在需要仔细平衡出血和血栓形成风险的情况下（例如，心脏辅助装置）。
本体外研究旨在使用功能测试设备证明在患有严重 von Willebrand 病（VWD）的 VWF 缺乏患者的全血样本中添加 rVWF 的可检测性，这些患者具有定量和功能病理学。我们假设（1）添加 rVWF 的 VWD 患者的全血样本的 PFA-CT 将正常化，（2）可以证明剂量反应关系。
我们从我们的数据库中选择了 12 名被诊断患有 VWD 的患者。将 rVWF 产品的治疗剂量（1IU/ml）添加到 VWD 患者的全血样本中，并测量 PFA-CT。此外，我们研究了递增剂量的 rVWF（0.1、0.2 和 0.5IU/ml）下的 PFA-CT。添加 rVWF 的 VWD 患者全血样本的 PFA-CT 正常化。此外，递增剂量的 rVWF 导致 PFA-CT 逐渐和剂量依赖性校正。
我们的体外数据表明 PFA-200 是一种有用的工具，可以检测 rVWF。由于 PFA-CT 校正与剂量相关，因此在替代治疗期间，rVWF 可能可以通过即时护理分析方法可靠地监测。
