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

血管性血友病是最常见的遗传性出血性疾病。我们已经研究了单独使用冷沉淀物治疗III型重度vWD的有效性和可行性，该冷沉淀物是由单一的、奉献的、父亲的供体多次DDAVP刺激的血浆交换供体制备的。一名婴儿在包皮环切术中出现大出血。FVIII：C4%，FVIII：Ag20%，vWF：RCO 21%，vWF：Ag3%，表明严重的vWD。他的父亲携带有vWF mRNA表达水平缺陷的等位基因，但有阴性出血史，凝血值正常。用外周静脉通路、ACD-A抗凝剂和自体去冷沉淀血浆作为替换液，从DDAVP刺激的连续血浆置换中制备冷沉淀物。在孩子出生后13年的前37次血浆交换中，换血量为9,620正负2,191(m正负SD，范围4,715-13,500)毫升。反复血浆置换的耐受性良好，不良反应包括DDAVP引起的轻微头痛和潮红，以及柠檬酸盐毒性。冷沉淀物在-70℃下储存不到1-102个月。90%的冷沉淀物在储存1年后输注，平均收集到输液间隔为2.4年。储存13至77个月后测试的冷沉淀物显示FVIII活性为原始FVIII的48%至124%；随着储存时间的延长，活性降低。在13年的时间里，以这种方式收集了114,309个FVIII单位。最近，我们对血浆交换捐献进行了标准化处理，只需处理4,500毫升血浆，平均产生14袋冷沉淀物，每袋的FVIII含量为262个正负62个单位)。血浆交换捐赠衍生的FVIII的制造与类似剂量的商业因子浓缩物相比，成本估计降低了50%。患者自出生以来发生的所有出血事件都通过这种方法获得的冷沉淀物成功地处理了。值得注意的是，在孩子13岁的时候，他一生中只接触过一次捐赠者，就是他的冷沉淀物的父亲捐赠者。用vWD载体反复血浆交换制备的冷沉淀物具有良好的止血功能，即使在超过1年的长时间储存后也是如此。对于vWD的长期治疗，承诺捐赠者的血浆交换可能是最安全的选择，并提供了一种替代商业因子浓缩物的经济高效的替代方案。

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.