Sohei Yoshimura1, Shoichiro Sato2, Kenichi Todo3, Yasushi Okada4, Eisuke Furui5, Takayuki Matsuki2, Hiroshi Yamagami6, Masatoshi Koga7, Jun C Takahashi8, Kazuyuki Nagatsuka6, Shoji Arihiro2, Kazunori Toyoda2. 1. 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. 2. Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita-city, Osaka 565-8565, Japan. 3. Department of Neurology, Kobe City Medical Center General Hospital, 2-1-1, Minatojimaminamimachi, Chuo-ku, Kobe-city, Hyogo 650-0047, Japan. 4. Department of Neurology and Cerebrovascular Medicine, NHO Kyushu Medical Center, 1-8-1, Jigyohama, Chuo-ku, Fukuoka-city, Fukuoka 810-8563, Japan. 5. Department of Stroke Neurology, Kohnan Hospital, 4-20-1, Nagamachiinami, Taihaku-ku, Sendai-city, Miyagi 982-8523, Japan. 6. Department of Neurology, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita-city, Osaka 565-8565, Japan. 7. Division of Stroke Care Unit, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita-city, Osaka 565-8565, Japan. 8. Departments of Neurosurgery, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita-city, Osaka 565-8565, Japan.
Abstract
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.
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.
Authors: Daniel M Witt; Robby Nieuwlaat; Nathan P Clark; Jack Ansell; Anne Holbrook; Jane Skov; Nadine Shehab; Juliet Mock; Tarra Myers; Francesco Dentali; Mark A Crowther; Arnav Agarwal; Meha Bhatt; Rasha Khatib; John J Riva; Yuan Zhang; Gordon Guyatt Journal: Blood Adv Date: 2018-11-27