Influence of factor VIII concentrate infusion on platelet activation, inflammatory parameters and endothelial parameters; a pilot study

Inflammatory and endothelial parameters:
Nowadays, life expectancy of hemophilia patients approaches that of the general
male population. Consequently, aging hemophilia patients are increasingly
confronted with age-related co-morbidity, including ischemic cardiovascular
disease. Although the incidence and prevalence of ischemic cardiovascular
disease appear to be increasing in hemophilia patients, several cohort studies
reported a reduced mortality caused by ischemic heart disease in hemophilia
patients as compared to the general male population. Not much is known about
the causes or mechanisms behind the reduced mortality due to ischemic heart
disease. One hypothesis is that hemophilia patients develop less
atherosclerosis than persons without hemophilia.
The majority of patients with severe hemophilia A are using prophylactic
treatment with clotting factor concentrate. This continuous partial correction
may dilute the possible protective effect of FVIII deficiency on
atherosclerosis. In this pilot study, we will investigate whether infusion of
FVIII concentrate influences levels of inflammatory and endothelial parameters,
important in the development of atherosclerosis, in patients with severe
hemophilia A.

Platelet activity and responsiveness
There is a great diversity of bleeding patterns within the group of patients
with severe hemophilia. This indicates that the bleeding pattern is influenced
by other factors than the residual FVIII concentration. An element of the
coagulation system, which to our knowledge has not yet been studied in the
context of bleeding pattern variability in hemophilia A, is the functioning of
blood platelets.
In a future study, we will determine the role of platelet functioning in the
bleeding pattern of patients with severe hemophilia A, by comparing the degree
of platelet activation and platelet responsiveness of patients with a mild
bleeding pattern to those of patients with a severe bleeding pattern. In this
pilot study, we want to observe if FVIII concentrate infusion, which is used on
a regular basis by many haemophilia patients, influences platelet activation
and responsiveness. If factor VIII concentrate infusion influences platelet
activation and responsiveness, this must be incorporated into future study
protocols.

Inflammatory and endothelial parameters
To investigate the influence of factor VIII concentrate infusion on
inflammatory and endothelial parameters in patients with severe hemophilia A.

Platelet activity and responsiveness
To investigate the influence of factor VIII concentrate infusion on platelet
activation and responsiveness in patients with severe hemophilia A.

The study population will consist of patients with severe hemophilia A,
scheduled for an elective operation.
It is a standard pre-operative procedure to administer a high dose of FVIII
concentrate several hours before the operation to increase FVIII activity.
Before and 15 minutes after FVIII concentrate infusion, blood is collected to
measure FVIII activity. In this pilot study, we will collect extra blood before
and 15 minutes after FVIII concentrate infusion. An extra venapunture is needed
to collect blood 1 hour after FVIII infusion.

By using patients with severe hemophilia A, scheduled for an elective
operation, we only need to collect extra blood on 2 occasions and perform 1
extra venapuncture. Patients do not have to come to the hospital especially for
this study, because they are already here for their operation. Pre-operative
factor VIII infusion is part of the standard procedure. We can conclude that
both risk and burden for the patient is low.
The results of this study will not be directly beneficial for the participating
patients. This study will contribute to the knowledge about the effects of
treatment with factor VIII concentrate, which is necessary for the
interpretation of future studies on the development of atherosclerosis in
hemophilia patients and on assessment of bleeding phenotype in patients with
severe hemophilia.