Fixed versus variable dosing strategy of prothrombin complex concentrate for bleeding complications of vitamin K antagonists

There is no consensus on the optimal dosing strategy for PCC. In clinical
practice, both fixed and variable protocols are used. In an observational,
prospective, two-cohort comparison of dosing PCC in bleeding complications of
vitamin K antagonists (VKA), we showed that a lower fixed dose was at least as
successful from a clinical point of view as a higher variable dose. The lower
fixed dose can be administered more quickly, is cheaper and might decrease the
risk of thrombotic complications.

To test whether the clinical outcome of lower fixed dose of PCC is superior to
higher variable dose of PCC, for VKA related bleeding in a randomized setting.
Secondary objectives include the comparison of INR after administration of PCC,
time to administration, mortality, other complications and drivers of costs.

Randomized controlled trial in 8 large Dutch hospitals.

Patients receive either a fixed dose of 40 cc of PCC, or a variable dose based
on INR on presentation, body weight and target INR.

Both dosing strategies are used in routine clinical practice. There is no
burden for the individual patient regarding the choice of strategy. The risks
and/or benefits are related to clinical outcome: a lower fixed dose might be
less effective, while the higher variable dose might have a higher risk of
side-effects. Given the data already available, these risks are small.
A delayed consent procedure is used, as it is unacceptable to lose valuable
time before the start of treatment. This makes it impossible for patients to
decline randomization, and therefore poses a burden on patients. Patients can
still refuse to participate in the study.
Most of the benefit from the study is applicable to future similar patients.
However, patients who present with bleeding on VKA are at increased risk of
rebleeding, so a proportion of participants might benefit themselves.