Patterns of DOAC interference in hemostasis/thrombosis assays
| Expected change . | Assays . | Notes . |
|---|---|---|
| Clotting time prolongation | • aPTT (dabigatran > direct Xa inhibitors) • PT (rivaroxaban > edoxaban > apixaban) • Thrombin time (dabigatran) | Effects on clotting times are reagent dependent. aPTT and PT mixing tests are expected to show incomplete correction in the presence of DOACs. |
| False increase | • Clot-based protein C activity • Clot-based protein S activity • Antithrombin activity (in factor IIa–based assays with dabigatran, in factor Xa–based assays with direct Xa inhibitors) • Activated protein C resistance ratio | False increase in protein C, protein S, and antithrombin activities may result in misdiagnosis of a patient with true deficiency as normal. Falsely elevated activated protein C resistance ratio may result in misdiagnosis of a patient with factor V Leiden mutation as normal. |
| False decrease | • aPTT-based factor assays (VIII, IX, XI, XII) • PT-based factor assays (II, V, VII, X) | Dilutions in factor assays may show nonspecific inhibitor effect. |
| False positive (or potentially false negative) | • LA assays | Includes aPTT- and DRVVT-based assays, among other clotting time-based LA assays; effects are drug and reagent dependent. |
| No change | • Clauss fibrinogen activity (for most reagents, rare methods show false decrease in presence of high concentrations of dabigatran) • D-dimer • Chromogenic protein C activity • Free and total protein S antigen • Anticardiolipin, anti-β2GP1 ELISAs • von Willebrand activity and antigen assays • DNA-based assays (eg, factor V Leiden mutation, prothrombin G20210A mutation) |
| Expected change . | Assays . | Notes . |
|---|---|---|
| Clotting time prolongation | • aPTT (dabigatran > direct Xa inhibitors) • PT (rivaroxaban > edoxaban > apixaban) • Thrombin time (dabigatran) | Effects on clotting times are reagent dependent. aPTT and PT mixing tests are expected to show incomplete correction in the presence of DOACs. |
| False increase | • Clot-based protein C activity • Clot-based protein S activity • Antithrombin activity (in factor IIa–based assays with dabigatran, in factor Xa–based assays with direct Xa inhibitors) • Activated protein C resistance ratio | False increase in protein C, protein S, and antithrombin activities may result in misdiagnosis of a patient with true deficiency as normal. Falsely elevated activated protein C resistance ratio may result in misdiagnosis of a patient with factor V Leiden mutation as normal. |
| False decrease | • aPTT-based factor assays (VIII, IX, XI, XII) • PT-based factor assays (II, V, VII, X) | Dilutions in factor assays may show nonspecific inhibitor effect. |
| False positive (or potentially false negative) | • LA assays | Includes aPTT- and DRVVT-based assays, among other clotting time-based LA assays; effects are drug and reagent dependent. |
| No change | • Clauss fibrinogen activity (for most reagents, rare methods show false decrease in presence of high concentrations of dabigatran) • D-dimer • Chromogenic protein C activity • Free and total protein S antigen • Anticardiolipin, anti-β2GP1 ELISAs • von Willebrand activity and antigen assays • DNA-based assays (eg, factor V Leiden mutation, prothrombin G20210A mutation) |