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Tests Used to Measure Internal Bleeding May Not Be Reliable, Study Finds

Authors recommend anti-factor Xa chromogenic assays

A recent study has determined that while internal bleeding may be uncommon as a result of taking blood thinners, such as rivaroxaban (Xarelto) and apixaban (Eliquis), the normal coagulation tests physicians use to check for the adverse effects of bleeding may not be reliable.

The study, published online in the Annals of Emergency Medicine, found that in cases reported to poison centers, the routine laboratory tests used to monitor patients for clotting factors, such as the prothrombin time (PT), the partial thromboplastin time (PTT), and the international normalized ratio (INR), which are commonly ordered to help diagnose internal bleeding, may be elevated in a few cases, but appear to be unreliable for measuring the risk of internal bleeding in patients.

“Blood thinners are helpful drugs, and we do not want people to stop taking them,” said co-author Dr. Henry Spiller. “We may need to get better about how we monitor patients on these drugs.”

The retrospective study collected data from more than 800 hospitals and eight regional poison centers in nine states. Of the 223 patients involved in the study, bleeding was reported in 15 patients (7%). The sites of bleeding included gastrointestinal (8), oral (2), nose (1), bruising (1), urine (1), and subdural (1). Coagulation tests were normal in most patients with bleeding (PT, 83%; PTT, 83%; and INR, 55%).

The PT was shown to be elevated in volunteer studies with rivaroxaban and also in individuals with massive overdose. However, results of the PT after the use of blood thinners varied with different components. The effects of medications on the PTT are short lived and vary based on the reagents used. In patients with bleeding, the PT and the PTT were elevated in one of four subjects tested with rivaroxaban and in no subjects tested with apixaban. In the single case with a measured serum rivaroxaban concentration, the PT was recorded as 126.3 seconds. Without specific clarification of the methods and reagents used, the PT and the PTT may not reliably predict the risk of bleeding after rivaroxaban or apixaban ingestion, the authors concluded.

Measurement of the INR with rivaroxaban has been questioned because that variable does not correct for variations in the PT based on which reagent was used. The INR was elevated in 21% of patients tested with rivaroxaban and in no patients tested with apixaban. In patients with bleeding, the INR was elevated in five of eight patients tested with rivaroxaban but in none tested with apixaban. Without clarification of the methods and reagents use, the INR may also be an unreliable test after rivaroxaban or apixaban ingestion, the authors stated. The use of activated clotting time also appears to be insensitive after Xa inhibitor use.

“One way to overcome the variation in these tests is to use anti-factor Xa chromogenic assays to measure Xa plasma concentrations; however, these are not widely available,” Spiller remarked “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.”

Sources: Nationwide Children’s Hospital; August 21, 2015; and AEM; August 19, 2015.


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