文献类型：期刊文献

英文题名：Timely and large dose of clotting factor IX provides better joint wound healing after hemarthrosis in hemophilia B mice

作者：He, Ping[1];Zhang, Feixu[1];Zhong, Chen[1];Li, Min[1];Zheng, Jing[1];Hua, Baolai[2];Sun, Junjiang[1,3,4]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai, Peoples R China;[2]Yangzhou Univ, Dept Hematol, Clin Med Coll, Yangzhou, Jiangsu, Peoples R China;[3]Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27515 USA;[4]Univ N Carolina, Eshelman Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC 27515 USA

年份：2019

卷号：110

期号：1

起止页码：59

外文期刊名：INTERNATIONAL JOURNAL OF HEMATOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000471635500009)】；

基金：The authors acknowledge the Animal Histopathology and Laboratory Medicine Core at UNC-CH for histology processing. This work was partly supported by a research grant from Asklepios BioPharmaceutical (to J.S.). H.B.L. is supported by Beijing Municipal Natural Science Foundation (No 7162151) and the Novo Nordisk Hemophilia China Research Fund. It is also supported by "the Fundamental Research Funds for the Central Universities". Parts of work were supervised by Dr. Paul E Monahan during his work in UNC-Chapel Hill. We acknowledge the language editing from Editage (http://www.editage.com).

语种：英文

外文关键词：Hemophilia; Hemarthrosis; Thrombin; Prothrombin; Factor IX

摘要：Bleeding into the joints represents the major morbidity of severe hemophilia and predisposes it to hemophilic arthropathy (HA). In a reproducible hemarthrosis mouse model, we found distinct changes in thrombin activity in joint tissue homogenate following exposure of the joint to blood in wide type (WT) and hemophilic B mice. Specifically, at early time points (4h and 24h) after hemarthrosis, thrombin activity in WT mice quickly peaked at 4h, and returned to baseline after 1 week. In hemophilia B mice, there was no/minimal thrombin activity in joint tissues at 4h and 24h, whereas at 72h and thereafter, thrombin activity kept rising, and persisted at a higher level. Nevertheless, prothrombin had not decreased in both WT and hemophilia. The pattern was also confirmed by Western blotting and immunostaining. To optimize the protection against development of HA, we tested different treatment regimens by administration of clotting factor IX into hemophilia B mouse after hemarthrosis induction, including a total of 600IU/kg FIX within the first 24h or the whole 2-week period. We concluded that timely (in the first 24h) and sufficient hemostasis correction is critical for a better protection against the development of hemophilic arthropathy.