Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients: Results of the INSIGHT case-control study

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Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients : Results of the INSIGHT case-control study. / van Velzen, Alice S.; Eckhardt, C. L.; Peters, M.; Leebeek, F. W. G.; Escuriola-Ettingshausen, C.; Hermans, C; Keenan, Russell D.; Astermark, J.; Male, Christoph; Peerlinck, K; le Cessie, Saskia; Van der Bom, J. G.; Fijnvandraat, K.

I: Journal of Thrombosis and Haemostasis, Vol. 15, Nr. 7, 03.07.2017, s. 1422-1429.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

van Velzen, AS, Eckhardt, CL, Peters, M, Leebeek, FWG, Escuriola-Ettingshausen, C, Hermans, C, Keenan, RD, Astermark, J, Male, C, Peerlinck, K, le Cessie, S, Van der Bom, JG & Fijnvandraat, K 2017, 'Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients: Results of the INSIGHT case-control study', Journal of Thrombosis and Haemostasis, vol. 15, nr. 7, s. 1422-1429. https://doi.org/10.1111/jth.13711

APA

van Velzen, A. S., Eckhardt, C. L., Peters, M., Leebeek, F. W. G., Escuriola-Ettingshausen, C., Hermans, C., ... Fijnvandraat, K. (2017). Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients: Results of the INSIGHT case-control study. Journal of Thrombosis and Haemostasis, 15(7), 1422-1429. https://doi.org/10.1111/jth.13711

CBE

van Velzen AS, Eckhardt CL, Peters M, Leebeek FWG, Escuriola-Ettingshausen C, Hermans C, Keenan RD, Astermark J, Male C, Peerlinck K, le Cessie S, Van der Bom JG, Fijnvandraat K. 2017. Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients: Results of the INSIGHT case-control study. Journal of Thrombosis and Haemostasis. 15(7):1422-1429. https://doi.org/10.1111/jth.13711

MLA

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Author

van Velzen, Alice S. ; Eckhardt, C. L. ; Peters, M. ; Leebeek, F. W. G. ; Escuriola-Ettingshausen, C. ; Hermans, C ; Keenan, Russell D. ; Astermark, J. ; Male, Christoph ; Peerlinck, K ; le Cessie, Saskia ; Van der Bom, J. G. ; Fijnvandraat, K. / Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients : Results of the INSIGHT case-control study. I: Journal of Thrombosis and Haemostasis. 2017 ; Vol. 15, Nr. 7. s. 1422-1429.

RIS

TY - JOUR

T1 - Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients

T2 - Journal of Thrombosis and Haemostasis

AU - van Velzen, Alice S.

AU - Eckhardt, C. L.

AU - Peters, M.

AU - Leebeek, F. W. G.

AU - Escuriola-Ettingshausen, C.

AU - Hermans, C

AU - Keenan, Russell D.

AU - Astermark, J.

AU - Male, Christoph

AU - Peerlinck, K

AU - le Cessie, Saskia

AU - Van der Bom, J. G.

AU - Fijnvandraat, K.

PY - 2017/7/3

Y1 - 2017/7/3

N2 - Essentials: Research suggests that intensive treatment episodes may increase the risk to develop inhibitors. We performed an international nested case-control study with 298 non-severe hemophilia A patients. Surgery and a high dose of factor VIII concentrate were associated with increased inhibitor risk. Physicians need to review arguments for factor VIII dose and elective surgery extra critically. Summary: Background: Inhibitor development is a major complication of treatment with factor VIII concentrates in hemophilia. Findings from studies among severe hemophilia A patients suggest that intensive treatment episodes increase the risk of developing inhibitors. Objectives: We set out to assess whether intensive treatment is also associated with an increased risk of inhibitor development among non-severe hemophilia A patients. Patients/Methods: We performed a nested case-control study. A total of 75 inhibitor patients (cases) and 223 control patients were selected from 2709 non-severe hemophilia A patients (FVIII:C, 2-40%) of the INSIGHT cohort study. Cases and controls were matched for date of birth and cumulative number of exposure days (EDs) to FVIII concentrates. Conditional logistic regression was used to calculate both unadjusted and adjusted odds ratios (aOR); the latter were adjusted for a priori specified confounders. Results: Peak treatment of 5 or 10 consecutive EDs did not increase inhibitor risk (aOR, 1.0; 95% confidence interval (CI), 0.4-2.5; and aOR, 1.8; CI, 0.6-5.5, respectively). Both surgical intervention (aOR, 4.2; CI, 1.7-10.3) and a high mean dose (> 45 IU kg-1/ED) of FVIII concentrate (aOR, 7.5; CI, 1.6-35.6) were associated with an increased inhibitor risk. Conclusions: Our findings suggest that high-dose FVIII treatment and surgery increase the risk of inhibitor development in non-severe hemophilia A. Together with the notion that non-severe hemophilia A patients are at a lifelong risk of inhibitor development, we suggest that in the future physicians will review the arguments for the FVIII dose and elective surgery extra critically.

AB - Essentials: Research suggests that intensive treatment episodes may increase the risk to develop inhibitors. We performed an international nested case-control study with 298 non-severe hemophilia A patients. Surgery and a high dose of factor VIII concentrate were associated with increased inhibitor risk. Physicians need to review arguments for factor VIII dose and elective surgery extra critically. Summary: Background: Inhibitor development is a major complication of treatment with factor VIII concentrates in hemophilia. Findings from studies among severe hemophilia A patients suggest that intensive treatment episodes increase the risk of developing inhibitors. Objectives: We set out to assess whether intensive treatment is also associated with an increased risk of inhibitor development among non-severe hemophilia A patients. Patients/Methods: We performed a nested case-control study. A total of 75 inhibitor patients (cases) and 223 control patients were selected from 2709 non-severe hemophilia A patients (FVIII:C, 2-40%) of the INSIGHT cohort study. Cases and controls were matched for date of birth and cumulative number of exposure days (EDs) to FVIII concentrates. Conditional logistic regression was used to calculate both unadjusted and adjusted odds ratios (aOR); the latter were adjusted for a priori specified confounders. Results: Peak treatment of 5 or 10 consecutive EDs did not increase inhibitor risk (aOR, 1.0; 95% confidence interval (CI), 0.4-2.5; and aOR, 1.8; CI, 0.6-5.5, respectively). Both surgical intervention (aOR, 4.2; CI, 1.7-10.3) and a high mean dose (> 45 IU kg-1/ED) of FVIII concentrate (aOR, 7.5; CI, 1.6-35.6) were associated with an increased inhibitor risk. Conclusions: Our findings suggest that high-dose FVIII treatment and surgery increase the risk of inhibitor development in non-severe hemophilia A. Together with the notion that non-severe hemophilia A patients are at a lifelong risk of inhibitor development, we suggest that in the future physicians will review the arguments for the FVIII dose and elective surgery extra critically.

KW - Case-control study

KW - Factor VIII

KW - Hemophilia A

KW - Inhibitor

KW - Risk factors

UR - http://www.scopus.com/inward/record.url?scp=85020136275&partnerID=8YFLogxK

U2 - 10.1111/jth.13711

DO - 10.1111/jth.13711

M3 - Article

VL - 15

SP - 1422

EP - 1429

JO - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 7

ER -