Iorio Alfonso, Marchesini Emanuela, Marcucci Maura, Stobart Kent, Chan Anthony Kc
Clinical Epidemiology and Biostatistic Department, McMaster University, 1280 Main Street West, CRL - 140, Hamilton, ON, Canada, L8S 4K1.
Cochrane Database Syst Rev. 2011 Sep 7(9):CD003429. doi: 10.1002/14651858.CD003429.pub4.
The hallmark of severe hemophilia is recurrent bleeding into joints and soft tissues with progressive joint damage, notwithstanding on-demand treatment. Prophylaxis has long been used but not universally adopted because of medical, psychosocial, and cost controversies.
To determine the effectiveness of clotting factor concentrate prophylaxis in the management of people with hemophilia A or B.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register. In addition, we searched major electronic databases (MEDLINE, EMBASE, CENTRAL), handsearched relevant journals and abstract books and reference lists of relevant articles.Last search of Group's Coagulopathies Trials Register: 07 April 2011.
Randomised controlled trials and quasi-randomised controlled trials evaluating people with severe hemophilia A or hemophilia B receiving prophylactic clotting factor concentrates.
Two authors independently reviewed studies for eligibility, assessed risk of bias and extracted data.
Six studies (including 142 participants) were eligible for inclusion. Two compared three-times-a-week prophylactic administration with on-demand treatment in children with hemophilia. Pooled results from these two studies showed a rate ratio of 0.30 (95% confidence interval; 0.12 to 0.76) for all bleedings and 0.22 (95% confidence interval 0.08 to 0.63) for joint bleedings favouring prophylaxis. Results on the number of patients with preserved joints after three to seven years of follow-up were not pooled due to significant heterogeneity. Three of the remaining four studies evaluated hemophilia A; one showed a statistically significant decrease in frequency of joint bleeds with prophylaxis compared to placebo, with a rate difference of -10.73 (95% confidence interval -16.55 to -4.91) bleeds per year. Two studies compared two prophylaxis regimens, failing to demonstrate an advantage of one regimen over the other in terms of bleeding frequency. The fourth study evaluated hemophilia B and showed fewer joint bleeds with weekly (15 IU/kg) versus bi-weekly (7.5 IU/kg) prophylaxis, rate difference -3.30 (95% confidence interval -5.50 to -1.10) bleeds per year. Non-significant increases in both inhibitor and infectious complications were observed in patients on prophylaxis, which occurred more often when using long-term venous access.
AUTHORS' CONCLUSIONS: There is strong evidence from randomised controlled trials and observational trials that prophylaxis preserves joint function in children with hemophilia as compared to on-demand treatment. There is insufficient evidence from randomised controlled trials to confirm the observational evidence that prophylaxis decreases bleeding and related complications in patients with existing joint damage. Well-designed randomised controlled trials and prospective observational controlled studies are needed to establish the best prophylactic regimen and to assess the effectiveness of prophylactic clotting factor concentrates in adult patients.
重度血友病的特征是尽管进行了按需治疗，但仍反复出现关节和软组织出血，并伴有进行性关节损伤。预防性治疗早已被使用，但由于医学、心理社会和成本等方面的争议，尚未得到普遍采用。
确定凝血因子浓缩物预防性治疗对甲型或乙型血友病患者的疗效。
我们检索了Cochrane囊性纤维化和遗传疾病小组的凝血障碍试验注册库。此外，我们还检索了主要的电子数据库（MEDLINE、EMBASE、CENTRAL），手工检索了相关期刊、摘要书籍以及相关文章的参考文献列表。小组凝血障碍试验注册库的最后一次检索时间为2011年4月7日。
评估重度甲型或乙型血友病患者接受预防性凝血因子浓缩物治疗的随机对照试验和半随机对照试验。
两位作者独立审查研究的入选资格，评估偏倚风险并提取数据。
六项研究（包括142名参与者）符合纳入标准。两项研究比较了血友病儿童每周三次预防性给药与按需治疗的效果。这两项研究的汇总结果显示，所有出血的率比为0.30（95%置信区间：0.12至0.76），关节出血的率比为0.22（95%置信区间0.08至0.63），支持预防性治疗。由于存在显著异质性，未汇总三至七年随访后关节保留患者数量的结果。其余四项研究中有三项评估了甲型血友病；其中一项显示，与安慰剂相比，预防性治疗使关节出血频率有统计学显著降低，每年的率差为-10.73（95%置信区间-16.55至-4.91）次出血。两项研究比较了两种预防性治疗方案，未能证明一种方案在出血频率方面优于另一种方案。第四项研究评估了乙型血友病，结果显示每周（15 IU/kg）预防性治疗比每两周（7.5 IU/kg）预防性治疗的关节出血更少，每年的率差为-3.30（95%置信区间-5.50至-1.10）次出血。接受预防性治疗的患者中，抑制剂和感染性并发症均有非显著增加，长期静脉通路使用时更常发生。
随机对照试验和观察性试验有强有力的证据表明，与按需治疗相比，预防性治疗可保留血友病儿童的关节功能。随机对照试验缺乏足够证据来证实观察性证据，即预防性治疗可减少现有关节损伤患者的出血及相关并发症。需要精心设计的随机对照试验和前瞻性观察性对照研究来确定最佳预防性治疗方案，并评估预防性凝血因子浓缩物对成年患者的疗效。
