Monday, July 14, 2014

Effects of target specific (novel) oral anticoagulants on the coag assays

Quantitative monitoring or TSOACs is not available in most community hospitals nor is it necessary. Nevertheless some knowledge of the qualitative effects of these agents on commonly used assays may come in handy to assess for “drug on board” or to get some idea of excessive effect and bleeding risk. The information below was taken from this resource.

For dabigatran, the aPTT may provide a qualitative assessment of dabigatran level and activity. The relation between dabigatran and the aPTT is curvilinear (Figure 3).12 Nevertheless, the sensitivity of the different aPTT reagents varies greatly. In patients receiving chronic therapy with dabigatran 150 mg twice daily (bid), the median peak aPTT was approximately two-fold that of control. Twelve hours after the last dose, the median aPTT was 1.5-fold that of control, with less than 10% of patients exhibiting two-fold increases. Therefore, if the aPTT level at trough (i.e. 12–24 h after ingestion) still exceeds two times the upper limit of normal, this may be associated with a higher risk of bleeding, and may warrant caution especially in patients with bleeding risk factors.12
Dabigatran has little effect on the PT and INR at clinically relevant plasma concentrations, resulting in a very flat response curve...
Factor Xa-inhibitors demonstrate a concentration-dependent prolongation of the PT. Nevertheless the effect on the PT depends both on the assay and on the FXa inhibitor. For rivaroxaban, the PT may provide some quantitative information, even though the sensitivity of the different PT reagents varies greatly (Figure 4). If Neoplastin Plus or Neoplastin is used as thromboplastin reagent, the PT is influenced in a dose-dependent manner with a close correlation to plasma concentrations.16 Neoplastin Plus is also more sensitive than Neoplastin.14 Assay-specific calibrators and calibration curves can be made (Figure 4). There are currently no such data available for edoxaban and apixaban. Importantly, the INR (and certainly a point-of-care determined INR) is completely unreliable for the evaluation of FXa inhibitory activity.

Finally it should be noted that the TSOACs can interfere with thrombophilia tests.

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