Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A

Research output: Contribution to journalArticle

Standard

Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A. / Collins, P. W.; Blanchette, V. S.; Fischer, K.; Bjorkman, S.; Oh, M.; Fritsch, S.; Schroth, P.; Spotts, G.; Astermark, Jan; Ewenstein, B.

In: Journal of Thrombosis and Haemostasis, Vol. 7, No. 3, 2009, p. 413-420.

Research output: Contribution to journalArticle

Harvard

APA

CBE

MLA

Vancouver

Author

Collins, P. W. ; Blanchette, V. S. ; Fischer, K. ; Bjorkman, S. ; Oh, M. ; Fritsch, S. ; Schroth, P. ; Spotts, G. ; Astermark, Jan ; Ewenstein, B. / Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A. In: Journal of Thrombosis and Haemostasis. 2009 ; Vol. 7, No. 3. pp. 413-420.

RIS

TY - JOUR

T1 - Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A

AU - Collins, P. W.

AU - Blanchette, V. S.

AU - Fischer, K.

AU - Bjorkman, S.

AU - Oh, M.

AU - Fritsch, S.

AU - Schroth, P.

AU - Spotts, G.

AU - Astermark, Jan

AU - Ewenstein, B.

PY - 2009

Y1 - 2009

N2 - Background: The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level < 1 IU dL(-1). Studies to date, however, have not demonstrated a strong link between FVIII level and the bleeding rate. Objectives: To assess the effect of FVIII level on break-through bleeding in patients with severe hemophilia A on prophylaxis. Patients/methods: This study analysed data from 44 patients aged 1-6 and 99 patients aged 10-65 years with severe hemophilia A (FVIII < 1 IU dL(-1)) who were treated with prophylactic FVIII as part of clinical studies assessing pharmacokinetics, safety and efficacy of a recombinant FVIII (Advate((R))). Each patient had pharmacokinetic measurements and FVIII infusions recorded, and these were used to calculate time spent with a FVIII below 1, 2 and 5 IU dL(-1). Results: The data demonstrate that increasing time with a FVIII below 1 IU dL(-1) is associated with increased total bleeds and hemarthroses. Lack of adherence to the intended frequency of FVIII infusion was the most important determinant of low FVIII and increased bleeding. In children aged 1-6 years, the rate of bleeding was also influenced by FVIII half-life and clearance. Conclusions: These data have important implications for the management of patients with severe hemophilia.

AB - Background: The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level < 1 IU dL(-1). Studies to date, however, have not demonstrated a strong link between FVIII level and the bleeding rate. Objectives: To assess the effect of FVIII level on break-through bleeding in patients with severe hemophilia A on prophylaxis. Patients/methods: This study analysed data from 44 patients aged 1-6 and 99 patients aged 10-65 years with severe hemophilia A (FVIII < 1 IU dL(-1)) who were treated with prophylactic FVIII as part of clinical studies assessing pharmacokinetics, safety and efficacy of a recombinant FVIII (Advate((R))). Each patient had pharmacokinetic measurements and FVIII infusions recorded, and these were used to calculate time spent with a FVIII below 1, 2 and 5 IU dL(-1). Results: The data demonstrate that increasing time with a FVIII below 1 IU dL(-1) is associated with increased total bleeds and hemarthroses. Lack of adherence to the intended frequency of FVIII infusion was the most important determinant of low FVIII and increased bleeding. In children aged 1-6 years, the rate of bleeding was also influenced by FVIII half-life and clearance. Conclusions: These data have important implications for the management of patients with severe hemophilia.

KW - pharmacokinetics

KW - hemophilia A

KW - bleeding

KW - factor VIII

KW - prophylaxis

U2 - 10.1111/j.1538-7836.2008.03270.x

DO - 10.1111/j.1538-7836.2008.03270.x

M3 - Article

VL - 7

SP - 413

EP - 420

JO - Journal of Thrombosis and Haemostasis

T2 - Journal of Thrombosis and Haemostasis

JF - Journal of Thrombosis and Haemostasis

SN - 1538-7933

IS - 3

ER -