Hakobyan N, Valentino L A, Cong L, Enockson C, Song X Q, Desai S, Radtke R, Fogg L F
Department of Pediatrics, Rush University Medical Center, Chicago, IL, USA.
Rush University, Chicago, IL, USA.
Haemophilia. 2016 Sep;22(5):790-8. doi: 10.1111/hae.12950. Epub 2016 Jul 25.
The prophylactic administration of clotting factor concentrate is currently the most effective strategy for the prevention of joint bleeding. As new agents with different mechanisms of action and administration schedules are developed, it will be important to study them in relevant preclinical models.
The aim of this study was the standardization of a mouse haemarthrosis model in a haemophilia mouse and the development and validation of a comprehensive bleeding assessment system, the Bleeding Severity Score (BSS).
Four outcome measurements were assessed, two of which, the extra-articular bleeding score and intra-articular bleeding score, were determined to be the most reliable and were summarized into a BSS which was validated using a mouse haemarthrosis variability model.
Using this model, the haemostatic effect of prospective drugs can be assessed in a clinically relevant joint bleeding model and will significantly increase the value of preclinical studies.
目前，预防性给予凝血因子浓缩物是预防关节出血最有效的策略。随着具有不同作用机制和给药方案的新型药物的研发，在相关临床前模型中对其进行研究将具有重要意义。
本研究的目的是在血友病小鼠中标准化小鼠关节积血模型，并开发和验证一个全面的出血评估系统——出血严重程度评分（BSS）。
评估了四项结局指标，其中两项，即关节外出血评分和关节内出血评分，被确定为最可靠的指标，并汇总为BSS，该评分通过小鼠关节积血变异性模型进行了验证。
使用该模型，可以在临床相关的关节出血模型中评估前瞻性药物的止血效果，并将显著提高临床前研究的价值。
