HET ANTAGONEREN VAN HET EFFECT VAN DABIGATRAN® MET PROTHROMBIN COMPLEX CONCENTRATE (BERIPLEX®) GEMETEN MET TWEE NIEUWE HUIDBLOEDINGSTESTEN

There is currently no registered antidote for the reversal of Dabigatran in
case of bleeding or when emergency surgical intervention is necessary.
Prothrombin complex concentrate (PCC) is used for decades in the management of
Vitamin-k antagonist associated bleeding and potentially may be effective in
reversing the anticoagulant effect of Dabigatran.

To determine whether a single dose of 50 IE/Kg PCC is effective in reversing
the anticoagulant effect of Dabigatran Etexilate 300mg b.i.d. taken for 2.5
days, as assessed by two modified skin bleeding assays: the "shed blood" and
"washed blood" methods.

cross-over randomized double-blind controlled trial, n=12

Patients will take Dabigatran etexilate 300mg b.i.d. for 2.5 days (5 doses) after which they will be randomized to receive a single intravenous dose of PCC (Beriplex) 50IE/Kg or matched volume placebo. After a minimum 10 day wash-out period patients will take Dabigatran etexilate 300mg b.i.d. for 2.5 days (5 doses) and will be randomized to the alternative treatment.

Treatment with any anticoagulant is associated with a higher bleeding risk,
though minimal in this case. The treatment with PCC has the potential of
thromboembolic complications. At the site of venous catheter placement a
haematoma might be caused.

The bleeding risk associated with Dabigatran treatment during 2.5 days is very
low also taking into account the young age, sexe and expected good kidney
function of the test subjects.
The treatment with PCC has been proven safe in similarly designed studies.

Nonetheless patients will be instructed to prevent potentially harmfull
activities during the use of anticoagulation and will be observed during and 6
hours after PCC infusion.