Effect of direct thrombin inhibitors on laboratory measurement of fibrinogen: Potential for errors in clinical decision‐making

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

“…To our knowledge this is the first study to examine the relationship between argatroban levels from ex vivo samples and multiple fibrinogen activity and antigen assays. We support the recommendations of UK NEQAS BC that laboratories take steps to consider their choice of reagents and Clauss fibrinogen results reporting 5 in light of these findings. We suggest that a similar study be performed in samples from patients receiving bivalirudin to confirm the findings in spiked samples 8 and the strong suspicion that Clauss fibrinogen assays using lowthrombin reagents may be affected in this group.…”

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

“…On the other hand, DTIs, for example, bivalirudin, argatroban, and dabigatran, can greatly affect the assay results in a manner that is usually dependent on their concentration in the test plasma. [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.…”

“…[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…”

“…However, assays should be performed with caution in samples collected from patients receiving high levels of UFH (e.g., cardiopulmonary bypass), or for samples collected from UFH‐contaminated venous or arterial blood access devices/lines, due to the risk of false low results. On the other hand, DTIs, for example, bivalirudin, argatroban, and dabigatran, can greatly affect the assay results in a manner that is usually dependent on their concentration in the test plasma 18–23 . 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 23–25 .…”