Novel, high incidence exercise-induced muscle bleeding model in hemophilia B mice: rationale, development and prophylactic intervention
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Novel, high incidence exercise-induced muscle bleeding model in hemophilia B mice : rationale, development and prophylactic intervention. / Tranholm, M.; Kristensen, Annemarie Thuri; Broberg, M. L.; Groth, Mette Perch.
In: Journal of Thrombosis and Haemostasis, Vol. 13, No. 1, 2015, p. 82-91.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Novel, high incidence exercise-induced muscle bleeding model in hemophilia B mice
T2 - rationale, development and prophylactic intervention
AU - Tranholm, M.
AU - Kristensen, Annemarie Thuri
AU - Broberg, M. L.
AU - Groth, Mette Perch
N1 - © The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.
PY - 2015
Y1 - 2015
N2 - INTRODUCTION: Muscle hematomas are the second most common complication of hemophilia and insufficient treatment may result in serious and even life-threatening complications. Hemophilic dogs and rats do experience spontaneous muscle bleeding, but currently, no experimental animal model is available specifically investigating spontaneous muscle bleeds in a hemophilic setting.AIM: The objective of this study was to develop a model of spontaneous muscle bleeds in hemophilia B mice. We hypothesized that treadmill exercise would induce muscle bleeds in hemophilia B mice but not in normal non-hemophilic mice and that treatment with recombinant factor IX (rFIX) before treadmill exercise could prevent the occurrence of pathology.METHODS: A total of 203 mice (123 F9-KO and 80 C57BL/6NTac) were included in three separate studies: (i) the model implementation study investigating the bleeding pattern in hemophilia B mice after treadmill exercise; (ii) a study evaluating the pharmacokinetics of recombinant FIX (rFIX) in hemophilia B mice and based on these data; (iii) the treatment study, which tested therapeutic intervention with rFIX. At termination of the treadmill studies the presence of bleeds was evaluated.RESULTS: Treadmill exercise resulted in a high incidence of muscle bleeds in F9-KO mice but not in C57BL/6NTac mice. Treating hemophilia B mice with rFIX before treadmill exercise prevented muscle bleeds.CONCLUSION: A novel model of muscle bleeds in hemophilia B mice, responsive to rFIX, has been developed.
AB - INTRODUCTION: Muscle hematomas are the second most common complication of hemophilia and insufficient treatment may result in serious and even life-threatening complications. Hemophilic dogs and rats do experience spontaneous muscle bleeding, but currently, no experimental animal model is available specifically investigating spontaneous muscle bleeds in a hemophilic setting.AIM: The objective of this study was to develop a model of spontaneous muscle bleeds in hemophilia B mice. We hypothesized that treadmill exercise would induce muscle bleeds in hemophilia B mice but not in normal non-hemophilic mice and that treatment with recombinant factor IX (rFIX) before treadmill exercise could prevent the occurrence of pathology.METHODS: A total of 203 mice (123 F9-KO and 80 C57BL/6NTac) were included in three separate studies: (i) the model implementation study investigating the bleeding pattern in hemophilia B mice after treadmill exercise; (ii) a study evaluating the pharmacokinetics of recombinant FIX (rFIX) in hemophilia B mice and based on these data; (iii) the treatment study, which tested therapeutic intervention with rFIX. At termination of the treadmill studies the presence of bleeds was evaluated.RESULTS: Treadmill exercise resulted in a high incidence of muscle bleeds in F9-KO mice but not in C57BL/6NTac mice. Treating hemophilia B mice with rFIX before treadmill exercise prevented muscle bleeds.CONCLUSION: A novel model of muscle bleeds in hemophilia B mice, responsive to rFIX, has been developed.
U2 - 10.1111/jth.12775
DO - 10.1111/jth.12775
M3 - Journal article
C2 - 25370152
VL - 13
SP - 82
EP - 91
JO - Journal of Thrombosis and Haemostasis
JF - Journal of Thrombosis and Haemostasis
SN - 1538-7933
IS - 1
ER -
ID: 131363246