Red cell exchange removes apixaban in patients with sickle cell disease

Many patients with sickle cell disease undergo red cell exchange (RCE) and are anticoagulated with apixaban for treatment and/or prevention of venous thromboembolism. Prior studies have demonstrated that apixaban can bind to red blood cells (RBCs). However, the effect of RCE on apixaban levels is unknown. We aimed to determine if RCE alters patient plasma apixaban levels.

Plasma apixaban levels in patients were examined before/after RCE. Apixaban in the RCE collection bag and the hematocrit of the collection bag were quantified. The ability of washed RBCs from healthy donors or from patients on apixaban to inhibit FXa activity was determined using a chromogenic Direct Xa Inhibitor kit.

Seven patients underwent 72 RCE. Plasma apixaban levels declined significantly after RCE (mean decline in apixaban level 68.1 ± 20.7%, p < 0.0001). Apixaban was present in the plasma/supernatant of all RCE collection bags tested. The percent decline in patient plasma apixaban levels after RCE was weakly correlated with the hematocrit of the RCE collection bag (r = 0.36, p = ns). Incubation of FXa with RBCs from patients on apixaban resulted in significantly less FXa activity compared to RBCs from healthy donors (mean Xa activity [A405 nm] of healthy RBC 0.79 ± 1.8 vs. apixaban RBC 0.54 ± 0.22, p = 0.005).

We provide the first description of apixaban removal with RCE. Removal of apixaban is occurring via removal of incidental plasma and of RBC-bound drug and can result in undetectable drug levels in this high-risk population.