Alten Jeffrey A, Benner Kim, Green Kelsey, Toole Benjamin, Tofil Nancy M, Winkler Margaret K
University of Alabama at Birmingham, 1600 7th Ave South, ACC 504, Birmingham, AL 35233, USA.
Pediatrics. 2009 Mar;123(3):1066-72. doi: 10.1542/peds.2008-1685.
Our goal was to report our institutional experience with recombinant factor VIIa for the treatment and/or prevention of bleeding in nonhemophiliac children.
This was a retrospective case series in a tertiary pediatric referral hospital.
During 1999-2006, 135 patients received recombinant factor VIIa for off-label use. The median number of doses was 2; the median dose was 88 mug/kg. The most common diagnoses among patients receiving recombinant factor VIIa were disseminated intravascular coagulation/sepsis (28), surgical bleeding (19), procedural prophylaxis (16), and trauma (15). The median volume of blood products administered 24 hours before recombinant factor VIIa treatment was 29.7 vs 11.7 mL/kg 24 hours after treatment. Only 1 high-risk patient had significant bleeding after receiving prophylactic recombinant factor VIIa before an invasive procedure. Nonsurvivors had significantly increased incidence of multiple organ dysfunction syndrome (75%) compared with survivors (23%). The largest group of patients (n = 28) received recombinant factor VIIa for bleeding and/or coagulopathy because of disseminated intravascular coagulation; the mortality in this group was 26 (93%) of 28. Eleven patients received multiple doses of recombinant factor VIIa to treat bleeding complications after hematopoietic stem cell transplant, without improvement in blood use. Mortality in medical patients was 58% vs 16% in surgical patients. Three patients had significant thrombotic adverse events after receiving recombinant factor VIIa, resulting in 2 deaths and 1 leg amputation.
Off-label use of recombinant factor VIIa significantly decreases blood-product administration; surgical patients had control of life-threatening bleeding with low associated mortality. Prophylactic recombinant factor VIIa may be effective in preventing bleeding if given before invasive procedures in children at high risk. Prolonged use of recombinant factor VIIa for bleeding complications after hematopoietic stem cell transplant is not effective in preventing packed red blood cell transfusion. Presence of disseminated intravascular coagulation and mulitorgan dysfunction syndrome may help predict futility of recombinant factor VIIa treatment. Off-label use of recombinant factor VIIa is associated with thromboembolic events in children.
我们的目标是报告我院使用重组凝血因子VIIa治疗和/或预防非血友病儿童出血的经验。
这是一项在三级儿科转诊医院进行的回顾性病例系列研究。
1999年至2006年期间，135例患者接受了重组凝血因子VIIa的非标签使用。给药剂量中位数为2次；剂量中位数为88μg/kg。接受重组凝血因子VIIa治疗的患者中最常见的诊断为弥散性血管内凝血/脓毒症（28例）、手术出血（19例）、操作前预防（16例）和创伤（15例）。在重组凝血因子VIIa治疗前24小时输注血液制品的中位数体积为29.7ml/kg，而治疗后24小时为11.7ml/kg。只有1例高危患者在侵入性操作前接受预防性重组凝血因子VIIa后发生了严重出血。与幸存者（23%）相比，非幸存者多器官功能障碍综合征的发生率显著增加（75%）。最大的患者组（n = 28）因弥散性血管内凝血导致出血和/或凝血病而接受重组凝血因子VIIa治疗；该组死亡率为28例中的26例（93%）。11例患者接受多次剂量的重组凝血因子VIIa治疗造血干细胞移植后的出血并发症，但输血情况并未改善。内科患者的死亡率为58%，而外科患者为16%。3例患者在接受重组凝血因子VIIa后发生了严重的血栓不良事件，导致2例死亡和1例截肢。
重组凝血因子VIIa的非标签使用显著减少了血液制品的使用；外科患者的危及生命的出血得到了控制，相关死亡率较低。预防性使用重组凝血因子VIIa在高危儿童侵入性操作前给药可能有效预防出血。造血干细胞移植后长期使用重组凝血因子VIIa治疗出血并发症对预防输注浓缩红细胞无效。弥散性血管内凝血和多器官功能障碍综合征的存在可能有助于预测重组凝血因子VIIa治疗的无效性。重组凝血因子VIIa的非标签使用与儿童血栓栓塞事件有关。
