Magnetic resonance imaging in boys with severe hemophilia A: Serial and end-of-study findings from the Canadian Hemophilia Primary Prophylaxis Study

Jennifer Stimec; Saunya Dover; Eleanor Pullenayegum; Victor S. Blanchette; Andrea S. Doria; Brian M. Feldman; Manuel Carcao; Georges E. Rivard; Sara J. Israels; Anthony K. Chan; MacGregor Steele; Stephanie Cloutier; Robert J. Klaassen; Victoria E. Price; Roona Sinha; Nicole Laferriere; Elizabeth Paradis; John K.M. Wu; Paul Babyn

doi:10.1002/rth2.12565

Magnetic resonance imaging in boys with severe hemophilia A: Serial and end-of-study findings from the Canadian Hemophilia Primary Prophylaxis Study

Jennifer Stimec, Saunya Dover, Eleanor Pullenayegum, Victor S. Blanchette, Andrea S. Doria, Brian M. Feldman, Manuel Carcao, Georges E. Rivard, Sara J. Israels, Anthony K. Chan, MacGregor Steele, Stephanie Cloutier, Robert J. Klaassen, Victoria E. Price, Roona Sinha, Nicole Laferriere, Elizabeth Paradis, John K.M. Wu, Paul Babyn

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

Abstract

Background: This study examined the structural outcomes for joints of boys with severe hemophilia A receiving frequency/dose-escalated primary prophylaxis using magnetic resonance imaging (MRI), and the importance of interval MRI changes. Methods: Forty-six subjects (27 with interval studies) were evaluated by radiographs (X-rays) and mid- and end-of-study MRIs (using the International Prophylaxis Study Group scale), as part of the Canadian Hemophilia Prophylaxis Study. The primary outcome was the presence of MRI osteochondral findings. Results: The median (range) time on study at the end-of-study MRI examination was 9.6 (4.8–16.0) years, during which 18 of 46 subjects (39%) had osteochondral changes in at least one joint. An interval change in MRI score of at least 1 point was observed in 44% of joints (43 ankles, 21 elbows, 4 knees); at least one joint showed this change in all 27 subjects. Self-reported interval hemarthrosis was associated with a higher likelihood of interval osteochondral change (odds ratio [OR], 1.49; 95% confidence interval [CI] = 1.08–2.06). Presence of synovial hypertrophy or hemosiderin on interval MRIs was associated with an OR of 4.71 (95% CI, 1.92–11.57) and 5.25 (95% CI, 2.05–13.40) of later osteochondral changes on MRI. Discussion: MRI changes were seen in 39% of subjects. Interval index joint bleeding was associated with an increased risk of later MRI changes, and earlier soft-tissue changes were associated with subsequent osteochondral changes.

Original language	English
Article number	e12565
Journal	Research and Practice in Thrombosis and Haemostasis
Volume	5
Issue number	7
DOIs	https://doi.org/10.1002/rth2.12565
Publication status	Published - Oct 2021
Externally published	Yes

Bibliographical note

Funding Information:
The Canadian Hemophilia Primary Prophylaxis Study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and the Bayer/Canadian Blood Services/Hema‐Quebec Partnership Fund. Subsequent renewals were funded by Bayer Inc.

Funding Information:
VB reports that he is chair of the International Prophylaxis Study Group (IPSG), a cooperative study group that is funded by education grants from Bayer Healthcare, Bioverativ/Sanofi, Novo Nordisk, Pfizer, Shire/Takeda, and Spark Therapeutics to the Hospital for Sick Children (“SickKids”) Foundation. He has received fees for participation in advisory boards/education events supported by Amgen, Bayer, Novo Nordisk, Pfizer, Roche, and Shire/Takeda and for participation in data safety monitoring boards for Octapharma and Shire/Takeda. He has received investigator‐initiated, industry‐supported research grants from Novo Nordisk, Bioverativ/Sanofi, and Shire/Takeda. AD reports research grants from Baxalta‐Shire, Novo Nordisk, Terry Fox Foundation, PSI Foundation, Society of Pediatric Radiology, and Garron Family Cancer Centre; and education grants from the Radiological Society of North America. She is a member of the International Prophylaxis Study Group and OMERACT Special Interest Group in MRI in Juvenile Idiopathic Arthritis (JIA). BF reports grants from Bayer and the Canadian Institutes of Health Research (CIHR). MC reports grants from Bayer, grants and personal fees from Bioverativ/Sonofi, Novo Nordisk; and Takeda; and personal fees from CSL‐Behring, Pfizer, Roche, LFB, and Grifols. RK reports personal fees from Agios Pharmaceuticals Inc, Amgen Inc, Hoffman‐LaRoche LTD, Shire Pharma Canada ULC, Novo Nordisk Canada Inc, Octapharma AG, Takeda, and Sanofi. MS reports personal fees from Octapharma, Takeda, and Meducom. JKMW reports grants and nonfinancial support from Bayer. The remaining authors have nothing to disclose.

Funding Information:
The Canadian Hemophilia Primary Prophylaxis Study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and the Bayer/Canadian Blood Services/Hema-Quebec Partnership Fund. Subsequent renewals were funded by Bayer Inc.

Publisher Copyright:
© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH)

ASJC Scopus Subject Areas

Hematology

PubMed: MeSH publication types

Journal Article

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Stimec, J., Dover, S., Pullenayegum, E., Blanchette, V. S., Doria, A. S., Feldman, B. M., Carcao, M., Rivard, G. E., Israels, S. J., Chan, A. K., Steele, M., Cloutier, S., Klaassen, R. J., Price, V. E., Sinha, R., Laferriere, N., Paradis, E., Wu, J. K. M., & Babyn, P. (2021). Magnetic resonance imaging in boys with severe hemophilia A: Serial and end-of-study findings from the Canadian Hemophilia Primary Prophylaxis Study. Research and Practice in Thrombosis and Haemostasis, 5(7), Article e12565. https://doi.org/10.1002/rth2.12565

Magnetic resonance imaging in boys with severe hemophilia A: Serial and end-of-study findings from the Canadian Hemophilia Primary Prophylaxis Study. / Stimec, Jennifer; Dover, Saunya; Pullenayegum, Eleanor et al.
In: Research and Practice in Thrombosis and Haemostasis, Vol. 5, No. 7, e12565, 10.2021.

Research output: Contribution to journal › Article › peer-review

Stimec, J, Dover, S, Pullenayegum, E, Blanchette, VS, Doria, AS, Feldman, BM, Carcao, M, Rivard, GE, Israels, SJ, Chan, AK, Steele, M, Cloutier, S, Klaassen, RJ, Price, VE, Sinha, R, Laferriere, N, Paradis, E, Wu, JKM & Babyn, P 2021, 'Magnetic resonance imaging in boys with severe hemophilia A: Serial and end-of-study findings from the Canadian Hemophilia Primary Prophylaxis Study', Research and Practice in Thrombosis and Haemostasis, vol. 5, no. 7, e12565. https://doi.org/10.1002/rth2.12565

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title = "Magnetic resonance imaging in boys with severe hemophilia A: Serial and end-of-study findings from the Canadian Hemophilia Primary Prophylaxis Study",

abstract = "Background: This study examined the structural outcomes for joints of boys with severe hemophilia A receiving frequency/dose-escalated primary prophylaxis using magnetic resonance imaging (MRI), and the importance of interval MRI changes. Methods: Forty-six subjects (27 with interval studies) were evaluated by radiographs (X-rays) and mid- and end-of-study MRIs (using the International Prophylaxis Study Group scale), as part of the Canadian Hemophilia Prophylaxis Study. The primary outcome was the presence of MRI osteochondral findings. Results: The median (range) time on study at the end-of-study MRI examination was 9.6 (4.8–16.0) years, during which 18 of 46 subjects (39%) had osteochondral changes in at least one joint. An interval change in MRI score of at least 1 point was observed in 44% of joints (43 ankles, 21 elbows, 4 knees); at least one joint showed this change in all 27 subjects. Self-reported interval hemarthrosis was associated with a higher likelihood of interval osteochondral change (odds ratio [OR], 1.49; 95% confidence interval [CI] = 1.08–2.06). Presence of synovial hypertrophy or hemosiderin on interval MRIs was associated with an OR of 4.71 (95% CI, 1.92–11.57) and 5.25 (95% CI, 2.05–13.40) of later osteochondral changes on MRI. Discussion: MRI changes were seen in 39% of subjects. Interval index joint bleeding was associated with an increased risk of later MRI changes, and earlier soft-tissue changes were associated with subsequent osteochondral changes.",

author = "Jennifer Stimec and Saunya Dover and Eleanor Pullenayegum and Blanchette, {Victor S.} and Doria, {Andrea S.} and Feldman, {Brian M.} and Manuel Carcao and Rivard, {Georges E.} and Israels, {Sara J.} and Chan, {Anthony K.} and MacGregor Steele and Stephanie Cloutier and Klaassen, {Robert J.} and Price, {Victoria E.} and Roona Sinha and Nicole Laferriere and Elizabeth Paradis and Wu, {John K.M.} and Paul Babyn",

note = "Funding Information: The Canadian Hemophilia Primary Prophylaxis Study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and the Bayer/Canadian Blood Services/Hema‐Quebec Partnership Fund. Subsequent renewals were funded by Bayer Inc. Funding Information: VB reports that he is chair of the International Prophylaxis Study Group (IPSG), a cooperative study group that is funded by education grants from Bayer Healthcare, Bioverativ/Sanofi, Novo Nordisk, Pfizer, Shire/Takeda, and Spark Therapeutics to the Hospital for Sick Children (“SickKids”) Foundation. He has received fees for participation in advisory boards/education events supported by Amgen, Bayer, Novo Nordisk, Pfizer, Roche, and Shire/Takeda and for participation in data safety monitoring boards for Octapharma and Shire/Takeda. He has received investigator‐initiated, industry‐supported research grants from Novo Nordisk, Bioverativ/Sanofi, and Shire/Takeda. AD reports research grants from Baxalta‐Shire, Novo Nordisk, Terry Fox Foundation, PSI Foundation, Society of Pediatric Radiology, and Garron Family Cancer Centre; and education grants from the Radiological Society of North America. She is a member of the International Prophylaxis Study Group and OMERACT Special Interest Group in MRI in Juvenile Idiopathic Arthritis (JIA). BF reports grants from Bayer and the Canadian Institutes of Health Research (CIHR). MC reports grants from Bayer, grants and personal fees from Bioverativ/Sonofi, Novo Nordisk; and Takeda; and personal fees from CSL‐Behring, Pfizer, Roche, LFB, and Grifols. RK reports personal fees from Agios Pharmaceuticals Inc, Amgen Inc, Hoffman‐LaRoche LTD, Shire Pharma Canada ULC, Novo Nordisk Canada Inc, Octapharma AG, Takeda, and Sanofi. MS reports personal fees from Octapharma, Takeda, and Meducom. JKMW reports grants and nonfinancial support from Bayer. The remaining authors have nothing to disclose. Funding Information: The Canadian Hemophilia Primary Prophylaxis Study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and the Bayer/Canadian Blood Services/Hema-Quebec Partnership Fund. Subsequent renewals were funded by Bayer Inc. Publisher Copyright: {\textcopyright} 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH)",

year = "2021",

month = oct,

doi = "10.1002/rth2.12565",

language = "English",

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issn = "2475-0379",

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TY - JOUR

T1 - Magnetic resonance imaging in boys with severe hemophilia A

T2 - Serial and end-of-study findings from the Canadian Hemophilia Primary Prophylaxis Study

AU - Stimec, Jennifer

AU - Dover, Saunya

AU - Pullenayegum, Eleanor

AU - Blanchette, Victor S.

AU - Doria, Andrea S.

AU - Feldman, Brian M.

AU - Carcao, Manuel

AU - Rivard, Georges E.

AU - Israels, Sara J.

AU - Chan, Anthony K.

AU - Steele, MacGregor

AU - Cloutier, Stephanie

AU - Klaassen, Robert J.

AU - Price, Victoria E.

AU - Sinha, Roona

AU - Laferriere, Nicole

AU - Paradis, Elizabeth

AU - Wu, John K.M.

AU - Babyn, Paul

N1 - Funding Information: The Canadian Hemophilia Primary Prophylaxis Study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and the Bayer/Canadian Blood Services/Hema‐Quebec Partnership Fund. Subsequent renewals were funded by Bayer Inc. Funding Information: VB reports that he is chair of the International Prophylaxis Study Group (IPSG), a cooperative study group that is funded by education grants from Bayer Healthcare, Bioverativ/Sanofi, Novo Nordisk, Pfizer, Shire/Takeda, and Spark Therapeutics to the Hospital for Sick Children (“SickKids”) Foundation. He has received fees for participation in advisory boards/education events supported by Amgen, Bayer, Novo Nordisk, Pfizer, Roche, and Shire/Takeda and for participation in data safety monitoring boards for Octapharma and Shire/Takeda. He has received investigator‐initiated, industry‐supported research grants from Novo Nordisk, Bioverativ/Sanofi, and Shire/Takeda. AD reports research grants from Baxalta‐Shire, Novo Nordisk, Terry Fox Foundation, PSI Foundation, Society of Pediatric Radiology, and Garron Family Cancer Centre; and education grants from the Radiological Society of North America. She is a member of the International Prophylaxis Study Group and OMERACT Special Interest Group in MRI in Juvenile Idiopathic Arthritis (JIA). BF reports grants from Bayer and the Canadian Institutes of Health Research (CIHR). MC reports grants from Bayer, grants and personal fees from Bioverativ/Sonofi, Novo Nordisk; and Takeda; and personal fees from CSL‐Behring, Pfizer, Roche, LFB, and Grifols. RK reports personal fees from Agios Pharmaceuticals Inc, Amgen Inc, Hoffman‐LaRoche LTD, Shire Pharma Canada ULC, Novo Nordisk Canada Inc, Octapharma AG, Takeda, and Sanofi. MS reports personal fees from Octapharma, Takeda, and Meducom. JKMW reports grants and nonfinancial support from Bayer. The remaining authors have nothing to disclose. Funding Information: The Canadian Hemophilia Primary Prophylaxis Study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and the Bayer/Canadian Blood Services/Hema-Quebec Partnership Fund. Subsequent renewals were funded by Bayer Inc. Publisher Copyright: © 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH)

PY - 2021/10

Y1 - 2021/10

N2 - Background: This study examined the structural outcomes for joints of boys with severe hemophilia A receiving frequency/dose-escalated primary prophylaxis using magnetic resonance imaging (MRI), and the importance of interval MRI changes. Methods: Forty-six subjects (27 with interval studies) were evaluated by radiographs (X-rays) and mid- and end-of-study MRIs (using the International Prophylaxis Study Group scale), as part of the Canadian Hemophilia Prophylaxis Study. The primary outcome was the presence of MRI osteochondral findings. Results: The median (range) time on study at the end-of-study MRI examination was 9.6 (4.8–16.0) years, during which 18 of 46 subjects (39%) had osteochondral changes in at least one joint. An interval change in MRI score of at least 1 point was observed in 44% of joints (43 ankles, 21 elbows, 4 knees); at least one joint showed this change in all 27 subjects. Self-reported interval hemarthrosis was associated with a higher likelihood of interval osteochondral change (odds ratio [OR], 1.49; 95% confidence interval [CI] = 1.08–2.06). Presence of synovial hypertrophy or hemosiderin on interval MRIs was associated with an OR of 4.71 (95% CI, 1.92–11.57) and 5.25 (95% CI, 2.05–13.40) of later osteochondral changes on MRI. Discussion: MRI changes were seen in 39% of subjects. Interval index joint bleeding was associated with an increased risk of later MRI changes, and earlier soft-tissue changes were associated with subsequent osteochondral changes.

AB - Background: This study examined the structural outcomes for joints of boys with severe hemophilia A receiving frequency/dose-escalated primary prophylaxis using magnetic resonance imaging (MRI), and the importance of interval MRI changes. Methods: Forty-six subjects (27 with interval studies) were evaluated by radiographs (X-rays) and mid- and end-of-study MRIs (using the International Prophylaxis Study Group scale), as part of the Canadian Hemophilia Prophylaxis Study. The primary outcome was the presence of MRI osteochondral findings. Results: The median (range) time on study at the end-of-study MRI examination was 9.6 (4.8–16.0) years, during which 18 of 46 subjects (39%) had osteochondral changes in at least one joint. An interval change in MRI score of at least 1 point was observed in 44% of joints (43 ankles, 21 elbows, 4 knees); at least one joint showed this change in all 27 subjects. Self-reported interval hemarthrosis was associated with a higher likelihood of interval osteochondral change (odds ratio [OR], 1.49; 95% confidence interval [CI] = 1.08–2.06). Presence of synovial hypertrophy or hemosiderin on interval MRIs was associated with an OR of 4.71 (95% CI, 1.92–11.57) and 5.25 (95% CI, 2.05–13.40) of later osteochondral changes on MRI. Discussion: MRI changes were seen in 39% of subjects. Interval index joint bleeding was associated with an increased risk of later MRI changes, and earlier soft-tissue changes were associated with subsequent osteochondral changes.

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Magnetic resonance imaging in boys with severe hemophilia A: Serial and end-of-study findings from the Canadian Hemophilia Primary Prophylaxis Study

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