Marlar R A, Sills R H, Groncy P K, Montgomery R R, Madden R M
Blood Center of Southeastern Wisconsin, Milwaukee.
Am J Hematol. 1992 Sep;41(1):24-31. doi: 10.1002/ajh.2830410106.
Homozygous protein C (PC) deficiency is a rare genetic defect that usually results in fatal thrombotic complications (purpura fulminans and DIC), but it can be successfully managed with oral anticoagulants or PC replacement. The successful use of PC replacement for two individuals is described. The activity and antigen levels of PC in fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) are also reported. The concentration of PC in FFP is 87 +/- 15 units/dl. PC is present in all PCC analyzed; however, a ten-fold difference between the various brands and/or lots is noted. The PC activity and antigen correlates well with no significant levels of APC. Upon infusion of FFP into two homozygous PC-deficient children, the PC levels obtained were less than or equal to 30 units/dl post-infusion and undetectable after 12-18 hr. With infusions of PCC, plasma levels of PC obtained were 100-145 units/dl and less than 10 units/dl after 48 hr. The percent recovery and half-lives of PC from FFP and PCC were 49.8% and 7.8 hr, and 84% and 7.4 hr, respectively. One infant was treated every 48 hr for 2 years without significant purpura fulminans or DIC complications. The levels of the other PC system components did not change during the infusion of the PC-rich material. Based on this information, a specific replacement protocol has been developed using a PC-rich concentrate. However, several problems may arise with the "less pure" PC-rich concentrates: catheter-tip thrombosis, related large vessel thrombosis and blood-transmitted diseases. With a specific PC concentrate, replacement therapy is a viable alternative for the long-term management/treatment of homozygous PC deficiency.
纯合子蛋白C（PC）缺乏症是一种罕见的遗传缺陷，通常会导致致命的血栓并发症（暴发性紫癜和弥散性血管内凝血），但可以通过口服抗凝剂或补充PC成功治疗。本文描述了两名患者成功使用PC替代疗法的情况。同时还报告了新鲜冰冻血浆（FFP）和凝血酶原复合物浓缩物（PCC）中PC的活性和抗原水平。FFP中PC的浓度为87±15单位/分升。在所有分析的PCC中均检测到PC；然而，不同品牌和/或批次之间存在10倍的差异。PC活性和抗原与活化蛋白C（APC）的无显著水平密切相关。向两名纯合子PC缺乏症儿童输注FFP后，输注后PC水平低于或等于30单位/分升，12 - 18小时后检测不到。输注PCC后，血浆PC水平为100 - 145单位/分升，48小时后低于10单位/分升。FFP和PCC中PC的回收率和半衰期分别为49.8%和7.8小时，以及84%和7.4小时。一名婴儿每48小时接受治疗，持续2年，未出现明显的暴发性紫癜或弥散性血管内凝血并发症。在输注富含PC的物质过程中，其他PC系统成分的水平没有变化。基于这些信息，已开发出使用富含PC的浓缩物的特定替代方案。然而，“纯度较低”的富含PC的浓缩物可能会出现几个问题：导管尖端血栓形成、相关的大血管血栓形成和血液传播疾病。使用特定的PC浓缩物，替代疗法是纯合子PC缺乏症长期管理/治疗的可行选择。
