【摘要】 目的 探讨重组人凝血因子Ⅷ制剂小剂量短程预防性输注能否有效减少中重度血友病A患儿关节出血问题。 方法 对2008年11月-2009年4月期间就诊的13例年龄3~11岁的中重度血友病A患儿，均在为期2个月内接受重组人凝血因子Ⅷ 2次/周、间隔3 d、每次7.5~10.0 U/kg的静脉预防性输注，记录治疗前2个月与治疗2个月时关节出血次数，以及同一关节反复发生出血的情况。 结果 治疗前关节出血的发生次数为（3.77±2.13）次，治疗后关节出血的发生次数为（0.46±0.87）次，治疗前后比较，差异有统计学意义（Plt;0.01）；治疗前靶关节出血的发生率为35.7％，治疗后靶关节出血的发生率为0.0%，治疗前后比较，差异有统计学意义（Plt;0.01）。患儿治疗成本约510~680元/（kg?2个月）。 结论 重组人凝血因子Ⅷ制剂小剂量短疗程预防性输注能有效减少中重度血友病A患儿关节出血次数，同时可有效减少靶关节出血的发生率，从而在一定程度上保护关节的功能。治疗费用相对可接受。【Abstract】 Objective To evaluate the efficacy of low-dose short-course infusion of recombinant human factor Ⅷ concentration in treating joint bleeding in children with severe and moderate hemophilia A. Methods Thirteen children aged 3 to 11 years old with severe or moderate hemophilia A were included in the present study from November 2008 to April 2009. For children in the treatment group, they were treated with low-dose short-course infusion of recombinant human factor Ⅷ concentration with a dose of 7.5-10.0 U/kg twice weekly as secondary prophylaxis for two months. The incidence of joint bleeding 2 months before treatment (control group) and during the 2 months of treatment (treatment group) was observed. Moreover, the incidence of their target joint bleeding was measured in both groups. Results Children in the control group had (3.77±2.13) joint bleedings while children in the treatment group had (0.46±0.87) joint bleedings, which was obviously lower than those in the control group (Plt;0.01). Meanwhile, the incidence of target joint bleeding in the treatment group was 0%, which was obviously lower than that in the control group (35.7%) (Plt;0.01). In the treatment group, the costs of treatment were about RMB 510-680 yuan/kg every 2 months. Conclusions Treatment with low-dose short-course infusion of recombinant human factor Ⅷ concentration can effectively decrease joint bleeding in children with severe and moderate hemophilia A, and can effectively decrease the incidence of target joint bleeding. Therefore, this method may play an important role in protection of the joint function in those patients at an acceptable cost.
Objective To evaluate the safety repeated intravitreal injection of bevacizumab (Avastin) with different dosage in rabbitsprime;eyes. Methods Fourteen chinchilla rabbits were randomly divided into 3 groups, including both eyes of 2 rabbits in the control group,the right eyes of the other 12 rabbits in the experimental group,and the left eyes of the 12 rabbits in the experimental control group. The eyes in the experimental group underwent intravitreal injection of bevacizumab with the dosage of 2.5 mg/0.1 ml and 5.0 mg/0.2 ml of bevacizumab; the eyes in the experimental control group underwent intravitreal injection of normal saline with the same dosage as in the experimental group. Injections were performed every two weeks and lasted six weeks. Clinical observation and retinal function tests were performed before and two days after every injection. The eyes were sacrificed 1 week and 4 weeks after last intravitreal injection respectively.Electron and optical microscope and TUNEL were performed.Results After intravitreal injection,no obvious anterior chamber flare, abnormal change of the ocular fundus, or vitreous opacity and hemorrhage was observed in all of the eyes.No change was found by indirect ophthalmoscope,Bultrasonic inspection, ultrasound biomicroscopy and optical coherence tomography. The number of anterior chamber flare before and after the injection with the dosage of 2.5 and 5.0 mg, the difference among the 3 groups didnprime;t differ much from each other (Pgt;0.05).Amplitude and pattern of ERG responses and flash VEP were similar between the control and experimental groups (Pgt;0.05). Some inflammatory cells were found in the some bevacizumabinjected eyes 1 week after injection, and vanished 3 weeks later. The histological configuration of the retina didnprime;t change in both experimental control and the control group. Electron microscopy showed that plasma cells were presented and vacuolelike change was observed in part of the photoreceptor cells in 5.0 mg experimental group 1 week after injections.Cellular apoptosis was observed in the photoreceptor cell layer. The number of apoptotic cells was more in 5.0 mg experimental group than that in the control and experimental control group 1 week after injections (Plt;0.01). Conclusion Multiintravitreal injection with 5.0 mg bevacizumab may have mild toxicity to the retina in the rabbits.