Discrepancy between international normalized ratio measurements in a heterozygous carrier of F10:p.Gly244Arg with recurrent venous thromboembolism: a case report

Abstract

Background: The international normalized ratio (INR) is designed to monitor vitamin K antagonist (VKA) treatment. Before patients start a self-managing VKA program, parallel measurements are conducted to compare point-of-care testing (POCT) INR with venous INR samples. Previously, genetic variants in F7 have shown discrepancies in INR measurements when thromboplastins from different species were used. It is unknown whether genetic variants in F10 affect INR measured with thromboplastins from different species. Key Clinical Question: Does F10:p.Gly244Arg heterozygosity affects the INR when measured using rabbit compared with human thromboplastin? Clinical Approach: A patient self-managing warfarin treatment had a recurrent venous thromboembolism during VKA treatment. The POCT therapeutic range was low (ie, 1.6-2.4) based on parallel measurements of POCT INR (human thromboplastin) and venous INR (rabbit thromboplastin). Subsequently, it was noted that the patient had a spontaneous increase in INR (1.3), and the patient was found to be a heterozygous carrier of F10:p.Gly244Arg. Conclusion: Genetic variants in F10 may also interfere with INR or prothrombin time measurements when different thromboplastins are used. This case illustrates that discrepancies in INR measurements with different thromboplastins should prompt consideration of genetic variants in F10 and F7 to ensure sufficient anticoagulant VKA treatment.