Global assays and the management of oral anticoagulation

Abstract

Coagulation tests range from global or overall tests to assays specific to individual clotting factors and their inhibitors. Whether a particular test is influenced by an oral anticoagulant depends on the principle of the test and the type of oral anticoagulant. Knowledge on coagulation tests applicable in monitoring status and reversal of oral anticoagulation is a prerequisite when studying potential reversal agents or when managing anticoagulation in a clinical setting. Specialty tests based on the measurement of residual activated factor X (Xa) or thrombin activity, e.g., are highly effective for determining the concentration of the new generation direct factor Xa- and thrombin inhibitors, but these tests are unsuitable for the assessment of anticoagulation reversal by non-specific prohemostatic agents like prothrombin complex concentrate (PCC) and recombinant factor VIIa (FVIIa). Global coagulation assays, in this respect, seem more appropriate. This review evaluates the current status on the applicability of the global coagulation assays PT, APTT, thrombin generation and thromboelastography in the management of oral anticoagulation by vitamin K antagonists and the direct factor Xa and thrombin inhibitors. Although all global tests are influenced by both types of anticoagulants, not all tests are useful for monitoring anticoagulation and reversal thereof. Many (pre)analytical conditions are of influence on the assay readout, including the oral anticoagulant itself, the concentration of assay reagents and the presence of other elements like platelets and blood cells. Assay standardization, therefore, remains an issue of importance.

Rivaroxaban pharmacodynamics in healthy volunteers evaluated with thrombin generation and the active protein C system: Modeling and assessing interindividual variability

“…The normalization of TG parameter values with those of reference plasmas did not affect results (not shown) . Our ex vivo findings reinforce those obtained in vitro using normal plasma spiked with rivaroxaban and 1‐picomolar to 20‐picomolar TF concentrations . Interestingly, we obtained PD mirror‐inverted time profiles to PK time profiles for both temporal parameters (lag time and time to peak), markedly for peak height and to a lesser extent for ETP, with peak height consistently more affected than ETP in agreement with previous findings .…”

“…We determined there were no substantial differences in results from the ST‐Genesia system versus the extensively documented CAT system . We tested 47 DRIVING samples covering a wide range of rivaroxaban concentrations on both ST‐Genesia systems using STG‐ThromboScreen without TM and the CAT using PPP‐reagent (5‐picomolar TF) (Stago).…”

“…Moreover, prothrombin time sensitivity varies widely across reagents. [ 4,8,11,[23][24][25] In addition, prothrombin time is only reflective of the initiation phase of coagulation. Other assays based on viscoelastometry have also been shown to be poorly sensitive to FXa inhibitors.…”

Therapeutic monitoring of rivaroxaban in dogs using thromboelastography and prothrombin time

“…Thromboelastography (TEG) is a viscoelastic hemostatic assay that measures the global viscoelastic properties of whole blood clot formation . In a previous study, TEG using different strong activators was used to monitor unfractionated heparin treatment in dogs .…”

“…In a previous study, TEG using different strong activators was used to monitor unfractionated heparin treatment in dogs . Evaluating the effect of rivaroxaban in blood using TEG appears promising but may yield variable results with different activators.…”