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

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由单一、专门的父亲供者反复使用ddavp刺激的血浆交换捐赠制备的低温沉淀治疗III型严重vWD儿童的疗效和可行性。包皮环切术中出现大量出血的婴儿。该患儿发现FVIII: c4%， FVIII:Ag 20%, vWF:RCo 21%, vWF:Ag 3%，提示严重vWD。其父亲携带一个vWF mRNA表达水平缺陷的等位基因，但出血史阴性，凝血值正常。低温沉淀是通过外周静脉通路、ACD-A抗凝剂和自体无低温沉淀血浆作为替代液，由连续的ddavp刺激血浆交换捐献制备的。在孩子出生后的13年中，献血者进行的前37次血浆交换捐赠中，交换量为9,620±2,191 (m±SD，范围4,715-13,500)ml。反复血浆交换捐献耐受性良好，不良反应包括轻度头痛和由于DDAVP引起的潮红，以及柠檬酸盐毒性。低温沉淀在零下70℃下保存不到1 ~ 102个月，保存1年后90%的低温沉淀输注，平均收集至输注间隔为2.4年。冷冻沉淀储存13 ~ 77个月后，FVIII活性恢复到原来的48% ~ 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单位FVIII。最近，我们对血浆交换捐献进行了标准化，包括处理4500毫升血浆，平均产生14袋低温沉淀，每袋FVIII含量为262±62单位)。与类似剂量的商业浓缩因子相比，血浆交换捐献来源的FVIII的生产成本估计降低了50%。自出生以来发生的所有出血事件均成功地用该方法获得的低温沉淀处理。值得注意的是，在13岁时，这个孩子一生中只接受过一次捐赠者的接触，那就是他的冷冻沉淀的父亲捐赠者。通过反复血浆交换捐献vWD载体制备的低温沉淀具有优异的止血功能，即使在延长储存间隔超过1年之后也是如此。对于vWD的长期管理而言，承诺供体的血浆交换捐赠可能是最安全的选择，并且提供了一种具有成本效益的替代商业因子浓缩物的选择。

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.