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

Thromb Haemost. 2018 May;118(5):842-851. doi: 10.1055/s-0038-1636541. Epub 2018 Mar 21.

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.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Blood Coagulation Factors / adverse effects
  • Blood Coagulation Factors / therapeutic use*
  • Canada
  • Coagulants / adverse effects
  • Coagulants / therapeutic use*
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / adverse effects*
  • Female
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / diagnosis
  • Gastrointestinal Hemorrhage / drug therapy*
  • Gastrointestinal Hemorrhage / mortality
  • Hemostasis / drug effects
  • Humans
  • Intracranial Hemorrhages / chemically induced
  • Intracranial Hemorrhages / diagnosis
  • Intracranial Hemorrhages / drug therapy*
  • Intracranial Hemorrhages / mortality
  • Male
  • Prospective Studies
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects*
  • Pyridones / administration & dosage
  • Pyridones / adverse effects*
  • Risk Factors
  • Rivaroxaban / administration & dosage
  • Rivaroxaban / adverse effects*
  • Thromboembolism / etiology
  • Time Factors
  • Treatment Outcome

Substances

  • Blood Coagulation Factors
  • Coagulants
  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • prothrombin complex concentrates
  • apixaban
  • Rivaroxaban