Photo by Juan D. Alfonso
A new study indicates that coagulation tests are an unreliable means for measuring the risk of internal bleeding in patients taking the factor Xa inhibitors rivaroxaban and apixaban.
For most patients who experienced internal bleeding in this study, results of coagulation tests were normal.
Prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratios (INRs) were elevated in a minority of patients treated with rivaroxaban and none of the patients treated with apixaban.
Henry Spiller, of the Central Ohio Poison Center at Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues conducted this retrospective study and reported the results in Annals of Emergency Medicine.
The study included data on 223 patients from more than 800 hospitals and 8 regional poison centers covering 9 states. The patients’ mean age was 60, and 56% were female. Nine percent of patients (n=20) were children younger than 12.
Eighty-nine percent of patients had taken rivaroxaban (n=198), and 11% had taken apixaban (n=25). The mean dose of rivaroxaban (reported in 182 patients) was 64.5 mg (range, 15 mg to 1200 mg). And the mean dose of apixaban (reported in 21 patients) was 9.6 mg (range, 2.5 mg to 20 mg).
For rivaroxaban, PT was measured in 49 patients (25%) and elevated in 7. PTT was measured in 49 patients (25%) and elevated in 5. And INR was measured in 61 patients (31%) and elevated in 13.
For apixaban, PT and PTT were both measured in 6 patients (24%) and elevated in none. INR was measured in 5 patients (20%) and elevated in none.
Cases of bleeding
Bleeding was reported in 15 patients (7%)—11 on rivaroxaban and 4 on apixaban. The sites of bleeding were gastrointestinal (n=8), oral (n=2), nose (n=1), bruising (n=1), urine (n=1), and subdural (n=1).
All bleeds occurred in adults who were taking the anticoagulants long-term. Twelve bleeds were considered adverse drug reactions, 2 were therapeutic error, and the reason was unknown in 1 case.
Coagulation test results were normal in most patients with bleeding. PT and PTT were both normal in 5 of 6 patients tested (83%), and INR was normal in 5 of 9 patients tested (55%).
PT and PTT were elevated in 1 of 4 patients treated with rivaroxaban and none of the patients treated with apixaban. The INR was elevated in 5 of 8 patients treated with rivaroxaban and none of the patients treated with apixaban.
The researchers said these results suggest that, without specific clarification of methodology and reagent use, PT, PTT, and INR may not reliably predict the risk of bleeding after rivaroxaban or apixaban ingestion.
“One way to overcome the variation in these tests is to use anti-factor Xa chromogenic assays to measure Xa plasma concentrations,” Spiller said.
“However, these are not widely available, and a potential drawback with measuring anti-factor Xa concentrations and plasma rivaroxaban and apixaban concentrations is that the turnaround time for results may be too long to guide a treatment plan.”
