Effect of argatroban on laboratory measurement of fibrinogen activity in ex vivo samples – Potential for errors in clinical decision‐making

Abstract

Argatroban is a direct thrombin inhibitor (DTI) that is available as an alternate anticoagulant for patients with heparin-induced thrombocytopaenia (HIT), 1 and has also been used to anticoagulate patients with COVID-19 related thrombosis 2 and vaccine-induced immune thrombocytopenia and thrombosis (VITT). 3 Argatroban can interfere with many coagulation assays, as can other DTIs, 4 by binding avidly to thrombin that may be formed in the assay, or to thrombin that is used to generate a clot, for example in thrombin time and fibrinogen activity assays. A recent publication from the UK National External Quality Assessment Scheme for Blood Coagulation (UK NEQAS BC) 5 has demonstrated significant interfer-

International council for standardisation in haematology recommendations on fibrinogen assays, thrombin clotting time and related tests in the investigation of bleeding disorders

“…[18][19][20][21][22][23] The degree of influence of these inhibitors varies depending on the reagents and system used, for example, the thrombin concentration or buffer composition; typically, reagents containing a lower concentration of thrombin (35 NIHU/mL), or without plasma dilution (<1/10), are more affected by DTIs than those with higher thrombin (100 NIHU/mL), resulting in FBG underestimation. [23][24][25] When using a high concentration thrombin reagent or a high dilution rate (≥1/10) for the test plasma, DTIs at therapeutic concentrations have little impact on the test results. 20,[23][24][25] Pre-treatment of plasma samples with DOAC adsorbent tablets has been shown to remove the effect of therapeutic dabigatran levels on Clauss FBG assays.…”

“…[23][24][25] When using a high concentration thrombin reagent or a high dilution rate (≥1/10) for the test plasma, DTIs at therapeutic concentrations have little impact on the test results. 20,[23][24][25] Pre-treatment of plasma samples with DOAC adsorbent tablets has been shown to remove the effect of therapeutic dabigatran levels on Clauss FBG assays. 26 High levels of fibrin/fibrinogen-degradation products have also been shown…”