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, Table of Contents

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

Authors

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

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

Full Text

References

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