Prothrombin complex concentrate administration for bleeding associated with non-vitamin K antagonist oral anticoagulants: The SAMURAI-NVAF study.
BACKGROUND
Antidotes appropriate for non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are not yet in widespread clinical use. Efficacy of prothrombin complex concentrate (PCC) in NOAC-associated bleeding remains unclarified.


METHODS
Ten NOAC users (4 women, median 74years old) who developed major bleeding and received PCC were prospectively enrolled. Eight single-center NOAC users (0 women, median 74years old) with intracerebral hemorrhage, who over the same period did not receive PCC, were studied for comparison.


RESULTS
Of the 10 PCC-treated patients, 8 developed intracerebral hemorrhage, 1 developed subdural hematoma, and another developed gastrointestinal bleeding. The median size of intracerebral hemorrhage was 8mL, relatively lower than the reported size for patients without NOACs. Patients received a median of 1000IU or 16IU/kg of PCC. Before and 1h after PCC administration, the median PT-INR changed from 1.41 to 1.09 (p<0.05) and median aPTT changed from 35.4 to 38.0s (p=0.39). Five patients developed intracranial hematoma expansion and 4 required surgical hematoma evacuation. No symptomatic thrombotic events occurred in either group, no participants died, and 2 participants from each group were independent.


CONCLUSIONS
Ten NOAC users developed major bleeding and were given relatively low doses of PCC. The effect of PCC on early cessation of bleeding was unclear, while the therapy did not trigger thromboembolic complications.
Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita-city, Osaka 565-8565, Japan. Electronic address: sohei-y@ncvc.go.jp.
Sohei
S
Yoshimura
Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita-city, Osaka 565-8565, Japan.
Shoichiro
S
Sato
Department of Neurology, Kobe City Medical Center General Hospital, 2-1-1, Minatojimaminamimachi, Chuo-ku, Kobe-city, Hyogo 650-0047, Japan.
Kenichi
K
Todo
Department of Neurology and Cerebrovascular Medicine, NHO Kyushu Medical Center, 1-8-1, Jigyohama, Chuo-ku, Fukuoka-city, Fukuoka 810-8563, Japan.
Yasushi
Y
Okada
Department of Stroke Neurology, Kohnan Hospital, 4-20-1, Nagamachiinami, Taihaku-ku, Sendai-city, Miyagi 982-8523, Japan.
Eisuke
E
Furui
Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita-city, Osaka 565-8565, Japan.
Takayuki
T
Matsuki
Department of Neurology, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita-city, Osaka 565-8565, Japan.
Hiroshi
H
Yamagami
Division of Stroke Care Unit, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita-city, Osaka 565-8565, Japan.
Masatoshi
M
Koga
Departments of Neurosurgery, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita-city, Osaka 565-8565, Japan.
Jun C
JC
Takahashi
Department of Neurology, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita-city, Osaka 565-8565, Japan.
Kazuyuki
K
Nagatsuka
Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita-city, Osaka 565-8565, Japan.
Shoji
S
Arihiro
Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita-city, Osaka 565-8565, Japan.
Kazunori
K
Toyoda
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology*; D006801:Humans; D008297:Male; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy; D016896:Treatment Outcome
D000925:Anticoagulants; D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates
Atrial fibrillation; Intracerebral hemorrhage; Major bleeding; Non-vitamin K antagonist oral anticoagulants; Prothrombin complex concentrate; Stroke