Objective: To study the risk factors, characteristics and treatment of factor Ⅷ (F Ⅷ) inhibitor in Chinese children with hemophilia A (HA) through a retrospective case-control survey; To investigate the bleeding phenotype before and after inhibitor formation.
Methods: The clinical data of outpatients and inpatients with HA children from January 2010 to December 2014 were collected. A case control study was performed to investigate the risk factors for inhibitor formation.
Results: A total of 445 HA children were enrolled with 82(18.4%) severe, 269(60.5%) moderate, and 94(21.1%) mild cases; 26(5.8% ) patients, among whom 13 were severe HA and 13 moderate HA, had inhibitor (9 low titer inhibitors, and 17 high titer inhibitors). No inhibitor was found in mild HA patients. Intensive treatment (P= 0.030, HR=4.435, 95% CI 1.150-17.094) was a risk factor for inhibitor generation. After inhibitor formation, 2 patients received small dose rituximab for inhibitor eradication, and one of them also received ITI therapy. When bleeding, 65.2% (15/23) inhibitors received PCC treatment to stop the bleeding, 8.7% (2/23) inhibitors didn't receive any medication, and 26.1% (6/23) inhibitors chose intermittent small dose FⅧ treatment; Among those patients who didn't received inhibitor eradication, 87.5%(7/8) patients with low titer inhibitor showed gradual disappearance, and the median time was 3 months; 84.6% (11/13) patients with high-titer inhibitors remained positive in 12-48 months showing a gradual decrease with time; 7.7% (1/13) high titer inhibitors showed gradual disappearance in 2 years. The annual traumatic and provoked bleeding frequency for joints, skin and soft tissue showed no difference after inhibitor formation.
Conclusion: Intensive F Ⅷ treatment was a risk factor for inhibitor formation. The inhibitor didn' t increase bleeding frequency in HA children.
目的: 探讨中国血友病A(HA）患儿凝血因子Ⅷ（FⅧ）抑制物发生的危险因素、治疗及转归以及抑制物对HA患儿出血特征的影响。
方法: 回顾性分析2010年1月至2014年12月445例HA患儿的临床资料。采用病例对照研究方法分析抑制物发生的危险因素。
结果: 在纳入研究的445例HA患儿中，重型患者82例（18.4%），中间型患者269例（60.5%），轻型患者94例（21.1%）。抑制物阳性26例（5.8%，失访3例），低滴度抑制物9例，高滴度抑制物17例，其中重型、中间型患者各13例。高强度替代治疗是抑制物产生的危险因素[P=0.030，HR值为4.435(95% CI 1.150~17.094）]；抑制物产生后2例患者接受小剂量利妥昔单抗清除抗体治疗，其中1例联合免疫耐受治疗3个月。出血时65.2%（15/23）的患者选择凝血酶原复合物治疗，8.7%（2/23）选择制动、冰敷、抬高患肢等保守治疗措施，26.1%（6/23）选择间断输注小剂量FⅧ治疗。未接受抗体清除治疗的患者中，87.5%（7/8）低滴度抑制物转阴，抑制物中位持续时间为3(1~3）个月，84.6%（11/13）的高滴度抑制物随时间呈下降趋势，在未进行抗体清除治疗的情况下持续12~48个月仍未转阴，7.7%（1/13）的高滴度抑制物2年后转阴。抑制物产生前后患儿关节年出血率、非关节年出血率、自发年出血率、创伤性年出血率差异无统计学意义。
结论: 高强度替代治疗是HA患儿抑制物产生的危险因素；抑制物并不能增加HA患儿出血频率。