Hemostatic therapy in experimental intracerebral hemorrhage associated with Rivaroxaban

• Verfasst von: Zhou, Wei [VerfasserIn]
• Verfasst von: Zorn, Markus [VerfasserIn]
• Verfasst von: Nawroth, Peter Paul [VerfasserIn]
• Verfasst von: Veltkamp, Roland [VerfasserIn]
• Titel: Hemostatic therapy in experimental intracerebral hemorrhage associated with Rivaroxaban
• Verf.angabe: Wei Zhou, Markus Zorn, Peter Nawroth, Ulf Bütehorn, Elisabeth Perzborn, Stefan Heitmeier, and Roland Veltkamp
• E-Jahr: 2013
• Jahr: 22 Jan 2013
• Umfang: 8 S.
• Teil: volume:44
• Teil: year:2013
• Teil: number:3
• Teil: pages:771-778
• Teil: extent:8
• Fussnoten: Gesehen am 28.07.2021
• Titel Quelle: Enthalten in: Stroke
• Ort Quelle: New York, NY : Association, 1970
• Jahr Quelle: 2013
• Band/Heft Quelle: 44(2013), 3, Seite 771-778
• ISSN Quelle: 1524-4628
• DOI: doi:10.1161/STROKEAHA.112.675231
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: anticoagulation
• Sach-SW: factor VIIa
• Sach-SW: fresh frozen plasma
• Sach-SW: prothrombin complex concentrate
• Sach-SW: stroke
• K10plus-PPN: 1764766059

Abstract

Background and Purpose— - - Rivaroxaban has recently been approved for stroke prevention in atrial fibrillation. However, lack of an effective antidote represents a major concern in the event of intracerebral hemorrhage (ICH). The aims of the present study were to establish a murine model of ICH associated with rivaroxaban, and to examine the effectiveness of different hemostatic factors in preventing excess hematoma expansion. - - Methods— - - In C57BL/6 mice receiving 10 or 30 mg/kg rivaroxaban by gastric gavage, plasma concentration, prothrombin time, and coagulation factor activities were measured repeatedly. Thirty minutes after inducing ICH by intrastriatal collagenase-injection, mice received an intravenous injection of either saline, prothrombin complex concentrate (100 U/kg), murine fresh frozen plasma (200 μL), or recombinant human Factor VIIa (1 mg/kg). ICH volume was quantified on brain cryosections and using hemoglobin spectrophotometry 24 hours later. - - Results— - - Rivaroxaban in 30 mg/kg dose substantially increased the hematoma volume in ICH induced by 0.060 U collagenase. Prothrombin complex concentrate, fresh frozen plasma, or Factor VIIa prevented excess hematoma expansion caused by anticoagulation. Prevention of hematoma expansion by prothrombin complex concentrate was dose-dependent. None of the 3 agents completely corrected the prolonged prothrombin time, although they restored the activities of deficient FII and X. - - Conclusions— - - Prothrombin complex concentrate, Factor VIIa, and fresh frozen plasma prevent excess intracerebral hematoma expansion in a murine ICH model associated with rivaroxaban. The efficacy and safety of this reversal strategy must be further evaluated in clinical studies.