Differences between activities of coagulation factors after one month of therapy with different direct oral anticoagulant in pulmonary embolism patients

J Clin Pharm Ther. 2019 Apr;44(2):236-242. doi: 10.1111/jcpt.12776. Epub 2018 Nov 8.

Abstract

What is known and objective: Direct oral anticoagulants (DOACs) are frequently used for the treatment of pulmonary embolism (PE), but both clinical and laboratory data comparing their efficacy and safety are conflicting. This study investigated and compared the impact of three DOACs (apixaban, rivaroxaban and dabigatran) on coagulation cascade in acute PE patients.

Methods: After the initial treatment, acute PE patients were randomly allocated to one of three groups, and treatment continued using one of the three DOACs. Following 1 month of treatment, the activity of factors II, VII and VIII, as well as protein C, antithrombin, D-dimer and fibrinogen, were measured, and the values were compared between the groups.

Results and discussion: One hundred consecutive PE patients were included. The mean values for the activity of factors II and VII and protein C were higher in patients on apixaban than in patients on rivaroxaban (1.45 ± 1.12 (IU/mL) vs 1.13 ± 0.92 (IU/mL), P < 0.001; 1.24 ± 1.10 (IU/mL) vs 1.05 ± 0.98 (IU/mL), P = 0.024 and 1.15 ± 0.62 vs 1.02 ± 0.68 (IU/mL), P = 0.019, respectively). The mean of factor II activity and the median of factor VIII activity were also significantly higher in patients on apixaban than in patients on dabigatran (1.45 ± 1.12 vs 1.20 ± 0.96 (IU/mL), P = 0.003 and 2.9 (2.0-4.0) vs 2.1 (1.5-2.7) (IU/mL), P = 0.001, respectively). No difference was noticed in D-dimer concentrations, or in the activity of the other factors measured. Additionally, no difference was noticed between the rivaroxaban and dabigatran groups.

What is new and conclusion: Apixaban had a significantly higher thrombin activity, above the laboratory determined normal range, compared to patients on rivaroxaban and dabigatran. This higher thrombin activity in patients on apixaban may contribute to a better haemostatic response during the therapy or increased prothrombotic state after therapy interruption.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Administration, Oral
  • Adult
  • Aged
  • Anticoagulants / administration & dosage
  • Anticoagulants / adverse effects
  • Anticoagulants / pharmacology
  • Blood Coagulation Factors / metabolism
  • Dabigatran / administration & dosage*
  • Dabigatran / adverse effects
  • Dabigatran / pharmacology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Embolism / drug therapy*
  • Pyrazoles / administration & dosage*
  • Pyrazoles / adverse effects
  • Pyrazoles / pharmacology
  • Pyridones / administration & dosage*
  • Pyridones / adverse effects
  • Pyridones / pharmacology
  • Rivaroxaban / administration & dosage*
  • Rivaroxaban / adverse effects
  • Rivaroxaban / pharmacology
  • Thrombin / metabolism
  • Treatment Outcome

Substances

  • Anticoagulants
  • Blood Coagulation Factors
  • Pyrazoles
  • Pyridones
  • apixaban
  • Rivaroxaban
  • Thrombin
  • Dabigatran