Ther of Von Willebrand Disease w/Single-donor Cryoprecipitate Collected by Apher

Apher 收集的冯·维勒布兰德病与单一供体冷沉淀物

• 批准号: 6431830
• 负责人: SUSAN F LEITMAN-KLINMAN
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431830
• 关键词: adolescence (12-20); arginine vasopressin; blood /lymphatic pharmacology; blood donor; blood transfusion; citrates; clinical research; cryopreservation; extended care; health services research tag; human subject; patient care management; precipitation; von Willebrand factor; von Willebrand's disease

Von Willebrands Disease (vWD) is the most common inherited bleeding disorder. We have studied the efficacy and feasibility of treating a child with type III severe vWD solely with cryoprecipitate prepared by repeated DDAVP-stimulated plasma exchange donation from a single, dedicated, paternal donor. An infant presented with massive hemorrhage at circumcision. The child was found to have FVIII:C 4 percent, FVIII:Ag 20 percent, vWF:RCo 21 percent, vWF:Ag 3 percent, indicative of severe vWD. His father carried an allele with a defect at the level of vWF mRNA expression but had a negative bleeding history with normal coagulation values. Cryoprecipitate was prepared from serial DDAVP-stimulated plasma exchange donation using peripheral venous access, ACD-A anticoagulant, and autologous cryoprecipitate-depleted plasma as replacement fluid. Exchange volume was 9,620 plus or minus 2,191 (m plus or minus SD, range 4,715-13,500) ml during the first 37 plasma exchange donations that the donor made during the 13 years since the childs birth. Repeated plasma exchange donation was well tolerated, with adverse effects including mild headache and flushing due to the DDAVP, and citrate toxicity. Cryoprecipitate was stored for less than 1 to 102 months at minus 70 (C. 90 percent of the cryoprecipitate was transfused after 1 year of storage, with a mean collection to transfusion interval of 2.4 years. Cryoprecipitate tested after 13 to 77 months of storage showed 48 to 124 percent of the original FVIII activity; decreased activity was noted with increasing length of storage. Over 13 years, 114,309 units of FVIII were collected in this manner. Most recently, we have standardized plasma exchange donation to involve processing of exactly 4,500 ml of plasma, which yields a mean of 14 bags of cryoprecipitate, each having a FVIII content of 262 plus or minus 62 units). Manufacture of plasma exchange donation-derived FVIII resulted in an estimated 50 percent cost reduction compared with similar doses of commercial factor concentrates. All bleeding episodes that occurred in the patient since birth were successfully managed with cryoprecipitate derived by this method. Remarkably, at age 13, the child has received only one donor exposure throughout his entire life, that of the paternal donor of his cryoprecipitate. Cryoprecipitate prepared by repeated plasma exchange donation of a vWD carrier provided excellent hemostatic function, even after prolonged storage intervals of greater than 1 year. Plasma exchange donation of a committed donor may be the safest option for long-term management of vWD, and provides a cost-effective alternative to commercial factor concentrates.

血管性血友病（vWD）是最常见的遗传性出血性疾病。我们研究了单独使用冷沉淀治疗III型重度vWD儿童的有效性和可行性，冷沉淀是通过重复DDAVP刺激的血浆置换捐献从单一的、专用的、父亲供体制备的。一名婴儿在包皮环切术时出现大出血。该儿童被发现患有FVIII：C 4%，FVIII：Ag 20%，vWF：RCo 21%，vWF：Ag 3%，表明严重vWD。他的父亲携带一个等位基因，在vWF mRNA表达水平上有缺陷，但有阴性出血史，凝血值正常。使用外周静脉通路、ACD-A抗凝剂和自体冷沉淀去除血浆作为置换液，从连续DDAVP刺激的血浆交换捐献中制备冷沉淀。在查尔兹出生后的13年中，在前37次血浆置换捐献中，置换量为9，620 ± 2，191（m ± SD，范围4，715 - 13，500）ml。重复血浆置换捐献耐受性良好，不良反应包括DDAVP引起的轻度头痛和潮红以及柠檬酸盐毒性。冷沉淀物在-70 ℃下储存不到1至102个月。90%的冷沉淀物在储存1年后输注，平均收集至输注间隔为2.4年。储存13至77个月后检测的冷沉淀物显示原始FVIII活性的48%至124%;随着储存时间的增加，活性降低。在13年中，以这种方式收集了114，309个单位的FVIII。最近，我们对血浆置换捐献进行了标准化，涉及精确处理4，500 ml血浆，平均产生14袋冷沉淀物，每袋的FVIII含量为262 ± 62单位。与类似剂量的商业因子浓缩物相比，血浆交换供体来源的FVIII的生产估计可降低50%的成本。自出生以来，患者发生的所有出血事件均成功地用该方法获得的冷沉淀进行了处理。值得注意的是，在13岁时，这个孩子一生中只接受过一次供体暴露，那就是他的冷沉淀物的父亲供体。通过vWD载体的重复血浆交换捐赠制备的冷沉淀物提供了优异的止血功能，即使在超过1年的长期储存间隔后。血浆置换捐赠的承诺捐赠者可能是最安全的选择长期管理vWD，并提供了一个具有成本效益的替代商业因子浓缩物。