Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Synergy America, Inc., Duluth, Georgia, USA.
Haemophilia. 2021 Sep;27(5):823-829. doi: 10.1111/hae.14352. Epub 2021 Jun 5.
Antibodies inhibiting von Willebrand factor (VWF) develop in a subset of patients with type 3 von Willebrand disease (VWD3) and may be detected by their inhibition of ristocetin cofactor activity (VWF:RCo). Some also inhibit factor VIII activity (VIII:C).
To describe monitoring of ten VWD3 patients for VWF inhibitors using a quantitative assay.
VWF inhibitor was measured by comparing VWF:RCo activity of a mix of patient and pooled normal plasma (PNP) with a mix of buffer and PNP, using agglutination of fixed normal platelets in microtiter plates or lyophilized platelets in an aggregometer. VIII:C inhibitor was measured by Bethesda assay. Preanalytical heat treatment of patient plasma was used during treatment episodes.
Four of 10 patients monitored developed VWF inhibitors, two detected during bleeding episodes refractory to treatment and two on routine screening. Data from the first five patients were used to establish an arbitrary unit, VWU, defined as the amount of inhibitor per millilitre of patient plasma inactivating 25% of the activity of 1 mL of PNP. In three of four patients, both VWF:RCo and VIIII:C were inhibited at some time points, although VIII:C inhibition sometimes disappeared. In one patient, no VIII:C inhibition was seen. Two patients remained inhibitor positive more than 15 years after inhibitor detection, one became negative following immune tolerance induction, and one was deceased.
VWF inhibitors can be quantitatively monitored in VWD3 patients. Preanalytical heat treatment may be required for their detection post infusion.
抗血管性血友病因子 (VWF) 抗体在部分 3 型血管性血友病 (VWD3) 患者中产生，其可能通过抑制瑞斯托霉素辅因子活性 (VWF:RCo) 被检测到。部分抗体还抑制 VIII 因子活性 (VIII:C)。
描述使用定量检测方法对 10 例 VWD3 患者的 VWF 抑制剂进行监测。
通过比较患者与混合正常血浆 (PNP) 的混合物与缓冲液和 PNP 的混合物中 VWF:RCo 活性，使用固定正常血小板在微量板中的凝集或在凝集仪中的冻干血小板，定量检测 VWF 抑制剂。VIII:C 抑制剂通过 Bethesda 法测定。在治疗期间，患者血浆的预分析热处理用于治疗发作。
10 例患者中有 4 例监测到 VWF 抑制剂，其中 2 例在出血发作且对治疗无反应时检测到，2 例在常规筛查时检测到。前 5 例患者的数据用于建立一个任意单位，VWU，定义为每毫升患者血浆中抑制 1ml PNP 25%活性的抑制剂量。在 4 例患者中的 3 例中，VWF:RCo 和 VIIII:C 均在某些时间点被抑制，尽管 VIII:C 抑制有时消失。在 1 例患者中，未见 VIII:C 抑制。2 例患者在检测到抑制剂后超过 15 年仍为阳性，1 例在诱导免疫耐受后转为阴性，1 例死亡。
VWD3 患者的 VWF 抑制剂可定量监测。输注后可能需要进行预分析热处理以检测其抑制剂。
