Haemophilia. 2018;24(Suppl. 2):3–17. wileyonlinelibrary.com/journal/hae
© 2018 John Wiley & Sons Ltd
Over the past decades, haemophilia management has constantly
evolved, with prophylaxis now considered the treatment of choice.
In several studies, prophylaxis treatment was demonstrated supe-
rior to on- demand, decreasing the number of bleeds while enhanc-
ing the patients’ quality of life.
Two major randomized prospective
trials clearly showed that prophylaxis was effective in reducing joint
bleeding and life- threatening haemorrhages while lowering the risk for
haemarthroses and structural joint damage.
Official bodies like the
World Federation of Haemophilia (WFH)
have meanwhile advocated
prophylaxis as the optimal approach for severe haemophilia.
The first prophylactic treatments were initiated in Sweden in 1958.
The Malmö protocol sought to enable patients to live a life “as nor-
mal as possible” by maintaining factor (F) levels above 1 IU/dL,
thereby converting the bleeding pattern of severe haemophilia into
that of a milder type. Swedish prophylaxis practice is initiated as early
Accepted: 19 November 2017
Unité d’Hémostase Clinique, Hôpital
Cardiologique Louis Pradel, CRTH de Lyon,
CHU de Lyon, France
INSERM, UMR 1059, Pôle Biologie-
Pathologie, Hôpital Nord, CHU de Saint-
The Royal London Haemophilia Centre, Barts
and The London School of Medicine, Blizard
Institute, QMUL, London, UK
Yesim Dargaud, CRTH de Lyon, Hôpital
Cardiologique Louis Pradel, Unité
d’Hémostase Clinique, CHU de Lyon, France.
This publication was sponsored by CSL
Over the past decades, haemophilia management has continually evolved, with proph-
ylaxis now considered the treatment of choice. Prophylaxis primarily seeks to prevent
bleeding and haemarthrosis episodes from occurring and avert the otherwise inevita-
ble haemophilic arthropathy. Yet, numerous unanswered issues remain. These con-
cern dose levels, dosing intervals, ways of integrating variability in bleeding phenotype,
patient age, joint status, lifestyle, physical activity, treatment adherence and individual
responses to FVIII or FIX concentrates. Individualized prophylaxis may thus be para-
mount. One crucial tool that may allow more accurate prophylaxis regimens to be im-
plemented is the individual pharmacokinetic (PK) study. Therefore, physicians in
charge of managing those living with haemophilia must be comfortable with PK profil-
ing in order to be in a position to tailor patients’ treatment, taking into account PK
data, while minimizing patients’ inconvenience, discomfort, as well as, possibly, treat-
ment costs. For optimization of prophylaxis, recent development of recombinant mol-
ecules with more attractive PK properties, such as prolonged elimination half- life,
increases the choice of dosing regimens, enabling decreased frequency of dosing for
some, if deemed appropriate. For each patient, PK parameters can be determined, in-
cluding trough levels, AUC, and time spent under a predefined threshold, with addi-
tional pharmacodynamic (PD) parameters possibly established by means of a global
coagulation test like the thrombin generation test. Most importantly, target PK/PD
parameters will need to consider clinical variables like patient age, body weight, joint
status, treatment adherence, number of bleeding episodes, activity index or lifestyle.
Bayesian model, extended half-life coagulation factor, haemophilia, individualized
pharmacokinetics, prophylaxis, quality of life, thrombin generation test