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Prothrombin Complex Concentrate Safer Than Fresh
Frozen Plasma for Intracranial Hemorrhage Related to
Vitamin K Antagonists
For patients who experience intracranial
hemorrhage related to vitamin K antagonists (VKA-ICH), hematoma expansion
can be a major cause of mortality. The
optimal method for normalizing the international normalized ratio (INR) to a safe
range, however, is unclear.
In a multicenter, prospective, openlabel, randomized trial, researchers, led by
Thorsten Steiner, MD, from the Department of Neurology at Klinikum Frankfurt
Höchst in Germany, compared the safety
and efficacy of two methods of hemostatic
management, fresh frozen plasma (FFP)
and prothrombin complex concentrate
(PCC). Results of the study were published
in Lancet Neurology.
“Our trial is the first randomized
controlled trial to compare anticoagulation reversal with FFP or PCC in patients
with ICH specifically,” Dr. Steiner and
colleagues explained. “In the absence of
evidence from randomized controlled trials of VKA-ICH, treatment guidelines recommend using PCC or FFP on the basis
of plausibility, or [they] refrain [entirely]
from making any recommendations.”
Results from this study, however,
suggest that four-factor PCC might be superior to FFP for faster INR normalization
and for controlling hematoma expansion.
The trial included 50 adult patients
with VKA-ICH (intracerebral or subdural) that was diagnosed by cerebral computed tomography (CT) scans within 12
hours of symptom onset who also had an
INR of at least 2.0. Patients were excluded
if they had:
• traumatic or secondary ICH
• concurrent acute ischemic events
• congestive heart failure
• thrombotic events within the past 30
days
Patients were randomized 1:1 to receive
either of the following treatments within
one hour of initial cerebral CT scan:
• 20 mL/kg of intravenous (IV) FFP
(after blood group typing or by using
AB group plasma supplied by local
transfusion units; n=23)
ASHClinicalNews.org
• 30 IU/kg of IV four-factor PCC
(n=27)
p values reported), received subsequent
PCC because the INR was not normalized
at three hours.
The researchers also found that hematoma expansion at three hours was higher
in the FFP cohort compared with the PCC
cohort (adjusted difference = 16.9 mL;
95% CI 2.5-31.3; p=0.023).
The trial was halted early on February
6, 2015, due to safety concerns and because
of the significant differences in hematoma
expansion between the treatment groups.
“Since this termination was unplanned,
effect of treatment on hematoma expansion might have been biased away from the
null,” the authors wrote.
A total of 43 serious adverse events
(AEs) were reported in 26 patients (20 FFP
vs. 23 PCC). Six serious AEs were associated with FFP (hematoma expansion,
n=4; anaphylactic reaction, n=1; ischemic
stroke, n=1), and two were related to PCC
(ischemic stroke, n=1; pulmonary embolism, n=1).
Death or hematoma expansion of
>15 percent above baseline at three hours
occurred in 73 percent of the FFP group
(n=16) compared with 58 percent in the
PCC grou