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.
Jarone Lee, MD, MPH, FCCM
Assistant Professor of Medicine
Massachusetts General Hospital, United States
Disclosure information not submitted.
Barry Berger, MD
Chief Medical Officer
Coagulo Medical Technologies, Inc., United States
Disclosure information not submitted.
Dimitrios Papageorgiou, PhD
Engineer/Researcher
Coagulo Medical Technologies, Inc., United States
Disclosure information not submitted.
Ryan Mize, BS
Clinical Laboratory Supervisor
Massachusetts General Hospital, United States
Disclosure information not submitted.
Jonathan Stefely, MD, PhD
Clinical Fellow in Pathology
Massachusetts General Hospital, United States
Disclosure information not submitted.
Bianca Christensen, MD, MPH
Clinical Fellow in Pathology
Massachusetts General Hospital, United States
Disclosure information not submitted.
Jensyn Cone Sullivan, MD
Clinical Fellow
Massachusetts General Hospital, United States
Disclosure information not submitted.
Gabriella Montgomery, BS
Medical Technologist
Massachusetts General Hospital, United States
Disclosure information not submitted.
John Barranco, BS
Medical Technologist
Massachusetts General Hospital, United States
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Venkataraghavan Ramamoorthy
Baptist Health South Florida
Coral Gables, Florida
Disclosure information not submitted.
Michael Laposata, MD, PhD
Professor and Chairman
University of Texas Medical Branch, United States
Disclosure information not submitted.
Elizabeth Van Cott, MD
Professor of Pathology
Massachusetts General Hospital, United States
Disclosure information not submitted.
Title: Novel Coagulation Test Successfully Detects Anticoagulation Resistance in Patients With COVID-19
Introduction: Severe COVID-19 has been associated with aberrant coagulation factor activities, particularly in patients with a thrombotic event (TE). Management of anticoagulant is critical in the care of hospitalized patients with COVID-19. This study evaluates a point-of-care (POC), functional, clot-time-based coagulation test to detect the anticoagulant effect of therapeutic unfractionated heparin (UFH) in hospitalized SARS-CoV-2-positive patients who developed a TE.
Methods: An IRB-approved analysis of 36 citrated plasma specimens from 26 SARS-CoV-2-positive patients and 10 matched negative controls was performed. A Clotting Time Score (CTS), a measure of factor-specific inhibition (i.e. anticoagulant activity), was derived for each patient. CTS results were compared with traditional coagulation tests. Five UFH COVID-19 samples with low CTS scores (< 10) were spiked with uniform dosing of UFH, low molecular weight heparin (LMWH), apixaban, or argatroban and retested to assess anticoagulation response.
Results: The CTS detected sub-therapeutic UFH anticoagulation levels more frequently in COVID-19 cases compared with controls (76% vs. 17%). Prothrombin Times, activated Partial Thromboplastin Times, anti-Xa levels, and antithrombin activity did not correlate with each other or with the CTS in the COVID-19 samples. CTS correlated with both FV and Factor X activity (R²=0.49, Spearman R=-0.68), which form the prothrombinase complex. The CTS was 88% sensitive and 67% specific for the occurrence of TEs in patients on UFH. CTS demonstrated a consistent anticoagulant response only to argatroban (100%) compared with other anticoagulants (60%).
Conclusions: The CTS, generated using a novel, low-volume, rapid POC coagulation test is a strong indicator of the therapeutic effect of UFH anticoagulation in COVID-19 patients and may provide a predictive measure of TEs potentially occurring from anticoagulation resistance.