Muscle Bleeding

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M P Groth - One of the best experts on this subject based on the ideXlab platform.

  • novel high incidence exercise induced Muscle Bleeding model in hemophilia b mice rationale development and prophylactic intervention
    Journal of Thrombosis and Haemostasis, 2015
    Co-Authors: Mikael Tranholm, Annemarie T Kristensen, M L Broberg, M P Groth
    Abstract:

    Summary 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.

  • Novel, high incidence exercise‐induced Muscle Bleeding model in hemophilia B mice: rationale, development and prophylactic intervention
    Journal of Thrombosis and Haemostasis, 2014
    Co-Authors: Mikael Tranholm, Annemarie T Kristensen, M L Broberg, M P Groth
    Abstract:

    Summary 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.

Mikael Tranholm - One of the best experts on this subject based on the ideXlab platform.

  • novel high incidence exercise induced Muscle Bleeding model in hemophilia b mice rationale development and prophylactic intervention
    Journal of Thrombosis and Haemostasis, 2015
    Co-Authors: Mikael Tranholm, Annemarie T Kristensen, M L Broberg, M P Groth
    Abstract:

    Summary 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.

  • Novel, high incidence exercise‐induced Muscle Bleeding model in hemophilia B mice: rationale, development and prophylactic intervention
    Journal of Thrombosis and Haemostasis, 2014
    Co-Authors: Mikael Tranholm, Annemarie T Kristensen, M L Broberg, M P Groth
    Abstract:

    Summary 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.

M L Broberg - One of the best experts on this subject based on the ideXlab platform.

  • novel high incidence exercise induced Muscle Bleeding model in hemophilia b mice rationale development and prophylactic intervention
    Journal of Thrombosis and Haemostasis, 2015
    Co-Authors: Mikael Tranholm, Annemarie T Kristensen, M L Broberg, M P Groth
    Abstract:

    Summary 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.

  • Novel, high incidence exercise‐induced Muscle Bleeding model in hemophilia B mice: rationale, development and prophylactic intervention
    Journal of Thrombosis and Haemostasis, 2014
    Co-Authors: Mikael Tranholm, Annemarie T Kristensen, M L Broberg, M P Groth
    Abstract:

    Summary 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.

Annemarie T Kristensen - One of the best experts on this subject based on the ideXlab platform.

  • novel high incidence exercise induced Muscle Bleeding model in hemophilia b mice rationale development and prophylactic intervention
    Journal of Thrombosis and Haemostasis, 2015
    Co-Authors: Mikael Tranholm, Annemarie T Kristensen, M L Broberg, M P Groth
    Abstract:

    Summary 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.

  • Novel, high incidence exercise‐induced Muscle Bleeding model in hemophilia B mice: rationale, development and prophylactic intervention
    Journal of Thrombosis and Haemostasis, 2014
    Co-Authors: Mikael Tranholm, Annemarie T Kristensen, M L Broberg, M P Groth
    Abstract:

    Summary 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.

Ingrid Pabinger - One of the best experts on this subject based on the ideXlab platform.

  • Inhibitor development in two patients with mild haemophilia A – spontaneous disappearance and no recurrence of the inhibitor after re-challenge
    Wiener klinische Wochenschrift, 2012
    Co-Authors: Sylvia E. Reitter-pfoertner, Klaus Lechner, Birgit Horvath, Raute Sunder-plassmann, Christine Mannhalter, Ingrid Pabinger
    Abstract:

    Inhibitors against factor VIII (FVIII) complicate the treatment of patients with haemophilia. In mild haemophilia, the development of antibodies against FVIII is rare. However, the occurrence of an inhibitor in mild haemophilia changes the Bleeding phenotype from mild to severe, and thus becomes a major clinical problem. We report on two patients with mild haemophilia A (FVIII level 8 and 27%, respectively), who have a missense mutation in exon 16 (G to A transition in codon 1773) and exon 22 (T to C transition in codon 2096), respectively. Both mutations have not been described in the Haemophilia A Mutation, Structure Test and Resource Site. Our patients developed high titer inhibitors following an intensive FVIII replacement therapy due to a Muscle Bleeding and after a polytrauma. During the presence of the inhibitor, AICC or FVIIa was successfully used as bypassing agent. In both patients the inhibitor disappeared spontaneously. Years after the development of the inhibitor, the patients again received FVIII concentrates. Reappearance of the inhibitor was not observed in either patient. The reported cases indicate that inhibitors in patients with mild haemophilia might be transient and disappear spontaneously. Therefore, the necessity of immune tolerance therapy, which is costly and strenuous for the patients, should be critically examined for each individual patient and a watch and wait strategy might be advisable. Hemmkörper gegen den Gerinnungsfaktor VIII (FVIII) verkomplizieren die Behandlung von Hämophiliepatienten. Die Inzidenz von Inhibitoren bei Patienten mit leichter Hämophilie ist gering. Dennoch führt deren Auftreten durch eine Änderung des Blutungsphänotyps meist zu einem größeren klinischen Problem. Wir berichten über zwei Patienten mit leichter Hämophilie A (FVIII-Spiegel 8 bzw. 27 %) auf Basis einer Missense Mutation in Exon 16 (G --> A Mutation in Codon 1773) bzw. Exon 22 (T --> C Mutation in Codon 2096). Beide Mutationen sind bisher nicht vorbeschrieben. Unsere Patienten entwickelten nach intensiver Behandlung mit FVIII-Konzentraten – aufgrund einer Muskelblutung bzw. nach Polytrauma – hochtitrige Hemmkörper. Während des Vorhandenseins der Hemmkörper wurden AICC (Anti-Inhibitor Coagulant Complex) bzw. FVIIa erfolgreich zur Blutungskontrolle bzw. -behandlung verwendet. Bei beiden Patienten kam es zu einem spontanen Verschwinden des Hemmkörpers. Jahre nach Auftreten des Inhibitors erhielten die Patienten erneut Faktorkonzentrate. Der Hemmkörper trat allerdings bei keinem der beiden Patienten wieder auf. Die geschilderten Fälle zeigen, dass Hemmkörper bei Patienten mit leichter Hämophilie transient sein können und ein spontanes Verschwinden möglich ist. Daher sollte die Notwendigkeit einer Immuntoleranztherapie, welche kostenintensiv und mühsam für den Patienten ist, für jeden Patienten kritisch hinterfragt werden und eine "Watch and Wait"-Strategie kann durchaus ratsam sein.

  • Inhibitor development in two patients with mild haemophilia A – spontaneous disappearance and no recurrence of the inhibitor after re-challenge
    Wiener Klinische Wochenschrift, 2012
    Co-Authors: Sylvia E. Reitter-pfoertner, Klaus Lechner, Birgit Horvath, Raute Sunder-plassmann, Christine Mannhalter, Ingrid Pabinger
    Abstract:

    Inhibitors against factor VIII (FVIII) complicate the treatment of patients with haemophilia. In mild haemophilia, the development of antibodies against FVIII is rare. However, the occurrence of an inhibitor in mild haemophilia changes the Bleeding phenotype from mild to severe, and thus becomes a major clinical problem. We report on two patients with mild haemophilia A (FVIII level 8 and 27%, respectively), who have a missense mutation in exon 16 (G to A transition in codon 1773) and exon 22 (T to C transition in codon 2096), respectively. Both mutations have not been described in the Haemophilia A Mutation, Structure Test and Resource Site. Our patients developed high titer inhibitors following an intensive FVIII replacement therapy due to a Muscle Bleeding and after a polytrauma. During the presence of the inhibitor, AICC or FVIIa was successfully used as bypassing agent. In both patients the inhibitor disappeared spontaneously. Years after the development of the inhibitor, the patients again received FVIII concentrates. Reappearance of the inhibitor was not observed in either patient. The reported cases indicate that inhibitors in patients with mild haemophilia might be transient and disappear spontaneously. Therefore, the necessity of immune tolerance therapy, which is costly and strenuous for the patients, should be critically examined for each individual patient and a watch and wait strategy might be advisable.

  • Inhibitor development in two patients with mild haemophilia A - spontaneous disappearance and no recurrence of the inhibitor after re-challenge.
    Wiener klinische Wochenschrift, 2012
    Co-Authors: Sylvia E. Reitter-pfoertner, Klaus Lechner, Birgit Horvath, Raute Sunder-plassmann, Christine Mannhalter, Ingrid Pabinger
    Abstract:

    Inhibitors against factor VIII (FVIII) complicate the treatment of patients with haemophilia. In mild haemophilia, the development of antibodies against FVIII is rare. However, the occurrence of an inhibitor in mild haemophilia changes the Bleeding phenotype from mild to severe, and thus becomes a major clinical problem. We report on two patients with mild haemophilia A (FVIII level 8 and 27%, respectively), who have a missense mutation in exon 16 (G to A transition in codon 1773) and exon 22 (T to C transition in codon 2096), respectively. Both mutations have not been described in the Haemophilia A Mutation, Structure Test and Resource Site. Our patients developed high titer inhibitors following an intensive FVIII replacement therapy due to a Muscle Bleeding and after a polytrauma. During the presence of the inhibitor, AICC or FVIIa was successfully used as bypassing agent. In both patients the inhibitor disappeared spontaneously. Years after the development of the inhibitor, the patients again received FVIII concentrates. Reappearance of the inhibitor was not observed in either patient. The reported cases indicate that inhibitors in patients with mild haemophilia might be transient and disappear spontaneously. Therefore, the necessity of immune tolerance therapy, which is costly and strenuous for the patients, should be critically examined for each individual patient and a watch and wait strategy might be advisable.