Gordon E M, Mungo R, Goldsmith J C
Division of Hematology-Oncology, Children's Hospital of Los Angeles, California.
Am J Pediatr Hematol Oncol. 1993 Feb;15(1):107-10. doi: 10.1097/00043426-199302000-00015.
The management of oral bleeding in hemophilia A patients with high titer inhibitors can be challenging. Simultaneous administration of activated prothrombin complex concentrates and antifibrinolytic agents is potentially dangerous because both agents have thrombogenic properties. We report sustained control of life-threatening lingual hemorrhage in a hemophilic patient with a high titer inhibitor (100 Bethesda Units/ml) on continuous infusion of a monoclonal antibody-purified factor VIII concentrate (75 U/kg/h).
In vivo hemostasis was achieved without an initial increment in free plasma factor VIII:C. The biphasic nature of recovered factor VIII:C indicated initial antigen-antibody formation, a saturation point, then a rapid rise of free factor VIII in plasma. In vitro, rapid loss of factor VIII activity was noted in mixtures of patient's plasma and purified factor VIII during incubation at 37 degrees C. When an excess of purified factor VIII was added to patient's plasma, a plateau of stable residual factor VIII activity followed the initial loss of factor VIII activity, suggesting a second-order reaction.
This type I kinetic response is typical of alloantibodies induced by exposure to factor VIII concentrates.
对高滴度抑制物的甲型血友病患者进行口腔出血管理具有挑战性。同时给予活化凝血酶原复合物浓缩剂和抗纤溶药物具有潜在危险性，因为这两种药物都有促血栓形成的特性。我们报告了一名高滴度抑制物（100贝塞斯达单位/毫升）的血友病患者，通过持续输注单克隆抗体纯化的凝血因子VIII浓缩剂（75单位/千克/小时），危及生命的舌部出血得到持续控制。
在未使游离血浆凝血因子VIII：C初始增加的情况下实现了体内止血。恢复的凝血因子VIII：C的双相性质表明最初形成抗原 - 抗体，达到饱和点，然后血浆中游离因子VIII迅速上升。在体外，在37℃孵育期间，患者血浆与纯化的凝血因子VIII的混合物中观察到凝血因子VIII活性迅速丧失。当向患者血浆中加入过量的纯化凝血因子VIII时，凝血因子VIII活性最初丧失后，稳定的残余凝血因子VIII活性出现平台期，提示为二级反应。
这种I型动力学反应是接触凝血因子VIII浓缩剂诱导的同种抗体的典型表现。
