Russel Roberts, BCCCP, PharmD
Clinical Manager (Cardiology, Critical Care and Transplant Services)
Massachusetts General Hospital
Boston, Massachusetts, United States
Disclosure information not submitted.
Christine Ryan, MD
Clinical Fellow in Hematology/Oncology
Massachusetts General Hospital
Boston, Massachusetts, United States
Disclosure information not submitted.
Kelly Newman, PharmD, BCCCP
Advanced Clinical Pharmacist
Massachusetts General Hospital
Boston, Massachusetts, United States
Disclosure information not submitted.
Galit Frydman, DVM, ScD
Massachusetts General Hospital
Cambridge
Disclosure information not submitted.
Rachel Rosovsky, MD, MPH
Assistant Professor of Medicine
Massachusetts General Hospital
Boston, Massachusetts, United States
Disclosure information not submitted.
Title: Novel Monitoring and Dose Adjustment of Argatroban to Maintain Therapeutic Anticoagulation
Introduction: In patients with unreliable activated partial thromboplastin time (aPTT) measurements who require anticoagulation with a direct thrombin inhibitor (DTI), the only reliable alternative measurement at present is a dilute thrombin time (dTT). However, this assay is not always readily available, which limits accurate real-time dose adjustments necessary to maintain therapeutic anticoagulation.
Description: A 57-year-old woman with a history of antiphospholipid antibody syndrome, heparin-induced thrombocytopenia, and multiple prior deep venous thromboses and pulmonary emboli was admitted with COVID-19 pneumonia and intubated due to hypoxic respiratory failure. Argatroban was initiated in place of her home medication warfarin. This patient had a prolonged aPTT value at baseline and overnight dTT assay measurements were limited at our institution. To overcome this challenge, a multidisciplinary team of hematology and pharmacy clinicians created a modified aPTT algorithm. By measuring aPTT and dTT simultaneously from patient plasma samples, a patient-specific aPTT target range was derived and argatroban dosing was titrated accordingly. Subsequent aPTT values in the modified target range corresponded to therapeutic dTT values, indicating therapeutic anticoagulation was successfully achieved and maintained. Patient plasma samples were also evaluated retrospectively using a novel point-of-care (POC) coagulation test to detect and quantify the effect of argatroban. A Clotting Time Score (CTS) was derived for each sample tested. Comparison of CTS and dTT values demonstrated moderate positive correlation between test results. All CTS results accurately reflected if argatroban dosing achieved an appropriate level of anticoagulation.
Discussion: Therapeutic anticoagulation with a DTI in a patient with unreliable aPTT measurements is challenging but can be achieved with use of a modified aPTT scale, which in our case study was retrospectively confirmed by corresponding dTT measurements. Early validation of a novel test that could offer a rapid, POC alternative to dTT when dTT measurements are necessary but not readily available is promising. Such a technology could dramatically improve rapid accurate titration of DTIs to maintain therapeutic anticoagulation.