Prothrombin Complex Concentrate for Major Bleeding on Factor Xa Inhibitors: A Prospective Cohort Study

Sam Schulman; Peter L. Gross; Bruce Ritchie; Susan Nahirniak; Yulia Lin; Lani Lieberman; Marc Carrier; Mark A. Crowther; Indy Ghosh; Alejandro Lazo-Langner; Michelle Zondag; On Behalf of the Study Investigators

doi:10.1055/s-0038-1636541

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2018; 118(05): 842-851
DOI: 10.1055/s-0038-1636541

Coagulation and Fibrinolysis

Schattauer GmbH Stuttgart

Prothrombin Complex Concentrate for Major Bleeding on Factor Xa Inhibitors: A Prospective Cohort Study

Sam Schulman

¹Department of Medicine, McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada

²Department of Hematology, Karolinska Institutet, Stockholm, Sweden

,

Peter L. Gross

¹Department of Medicine, McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada

,

Bruce Ritchie

³Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

,

Susan Nahirniak

⁴Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada

,

Yulia Lin

⁵Department of Clinical Pathology, Sunnybrook Health Sciences Centre, University of Toronto, Ontario, Canada

,

Lani Lieberman

⁶Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada

,

Marc Carrier

⁷Department of Clinical Pathology, University Health Network, University of Toronto, Toronto, Ontario, Canada

,

Mark A. Crowther

¹Department of Medicine, McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada

,

Indy Ghosh

⁸Department of Medicine, The Ottawa Hospital Research Institute at the University of Ottawa, Ottawa, Ontario, Canada

,

Alejandro Lazo-Langner

⁹Department of Emergency Medicine, Trillium Hospital, Mississauga, Ontario, Canada

,

Michelle Zondag

¹⁰Department of Medicine, Western University, London, Ontario, Canada

,

On Behalf of the Study Investigators

› Institutsangaben

Abstract

Oral factor Xa inhibitors are increasingly used for anticoagulation, but there is no approved reversal agent. Prothrombin complex concentrate (PCC) for the management of Xa-inhibitor–associated bleeding has been described in small case series and one cohort study. Patients on apixaban or rivaroxaban, suffering a major bleed, were treated at nine Canadian hospitals as per existing hospital protocol with a fixed dose of PCC 2,000 units and subsequently recruited for a 30-day follow-up. The treating physician evaluated the haemostatic effectiveness as observed during the first day as good, moderate or poor/none, using an assessment guide. Safety outcomes were thromboembolism or death. We recruited 66 patients with major bleeding who were treated with PCC and who were receiving rivaroxaban (56%) or apixaban (44%). The effectiveness was assessed as good in 65% (95% confidence interval [CI], 53–77), moderate in 20% (95% CI, 10–30) and poor/none in 15% (95% CI, 6–24). For the 36 patients with intracranial haemorrhage, the corresponding ratings were 67, 17 and 17%, and for 16 patients with gastrointestinal bleeding they were 69, 12 and 19%, respectively. There were nine deaths (14%) by 30 days, and five (8%) major thromboembolic events. In a post hoc analysis, according to International Society on Thrombosis and Haemostasis criteria, reversal was effective in 68% and ineffective in 32%. For major bleeding associated with oral Xa inhibitors, PCC may have a beneficial effect. The risk of thromboembolism after reversal of anticoagulation in patients with a prothrombotic background has to be taken into account.

Keywords

antagonists and inhibitors - haemorrhage - atrial fibrillation - rivaroxaban - apixaban

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