Direct oral anticoagulants are becoming increasingly important for stroke prophylaxis in atrial fibrillation or therapy and recurrence prophylaxis after venous thromboembolism. In practice, a few tips should be followed when dealing with this new group of substances.
The special feature of DOAKs is the fact that – unlike vitamin K antagonists – they do not interfere with the synthesis of clotting factors, but interact directly with them. Moreover, they bind not only free but also clot-bound target molecules. The coagulation factors can then no longer be active as proteases. Factor Xa inhibitors inhibit factor Xa, preventing the conversion of prothrombin to thrombin. The thrombin inhibitors inhibit thrombin (factor II).
Due to their shorter half-life and fewer interactions, they are much easier to control and therefore generally do not require regular monitoring of coagulation parameters. If a measurement is nevertheless taken, the maximum level is measured two to four hours after ingestion to check for adequate absorption of the preparation. Measuring the valley level just before the next dose is predictive of bleeding risk.
Coagulation monitoring
The effect of DOAK use on prothrombin time (PTZ), activated partial thromboplastin time (aPTT), and thrombin time (TC) depends on individual DOAK behavior, dosage, and time of last use, as well as the sensitivity of the test reagent. Only semi-quantitative statements can be made with the global coagulation tests: If the thromboplastin time (Quick/INR) is within the normal range when taking a factor Xa inhibitor, a clinically relevant residual effect is unlikely. When taking a thrombin inhibitor, an aPTT >80 s in the valley level indicates an increased risk of bleeding; a TC within the normal range indicates no clinically relevant effect. Monitoring of direct factor Xa inhibitors is performed using anti-Xa assays with compound-specific calibrators. Modified thrombin time (TC) is available for the management of direct thrombin inhibitors.
Beware of pharmacokinetic interactions
With regard to pharmacokinetic interactions, the focus is on cytochrome P450-type enzymes and the transport protein P-glycoprotein (P-gp). Inhibition leads to potentiation of the effect with the consequence of a higher bleeding tendency. Accordingly, caution is advised, especially with HIV protease inhibitors. However, concomitant administration of anticoagulants should also be avoided with certain immunosuppressants, calcium antagonists and SSRIs.
Induction of cytochrome P450 enzymes may result in attenuation of effect and an associated increased risk of thrombosis. When taking certain anticonvulsants, glucocorticoids, antibiotics or St. John’s wort, anticoagulation should therefore be monitored regularly and the dose adjusted according to the specialist information – if the drug cannot be dispensed with.
HAUSARZT PRAXIS 2019; 14(6): 39
CARDIOVASC 2019; 18(5): 24
