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BACKGROUND:. In patients who require systemic anticoagulation, a reliable monitoring method is required to ensure anticoagulation is maintained within the correct therapeutic window and patients are treated appropriately. When titrating direct thrombin inhibitors (DTIs), dilute thrombin time (dTT) measurements have been demonstrated to be more reliable and accurate than activated partial thromboplastin time (aPTT) measurements and thus often the preferred DTI assessment. However, a clinical need arises when both dTT measurements are not readily available and aPTT measurements are unreliable. CASE SUMMARY:. 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. However, the patient had a prolonged aPTT value at baseline and overnight dTT assay measurements were limited at our institution. A multidisciplinary team of hematology and pharmacy clinicians created a modified patient-specific aPTT target range 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 blood samples were additionally evaluated retrospectively using an investigational novel point-of-care test that detected and quantified the argatroban anticoagulant effect. CONCLUSIONS:. Therapeutic anticoagulation with a DTI in a patient with unreliable aPTT measurements can be achieved with use of a modified patient-specific aPTT target range. Early validation of an investigational rapid testing alternative for DTI monitoring is promising.

OBJECTIVES:. Bivalirudin, an IV direct thrombin inhibitor, and unfractionated heparin (UFH) are frequently used anticoagulants in the pediatric critical care setting. An accurate, specific, point-of-care test to quantify and detect anticoagulation resistance is not currently available. This study evaluates the ability of a rapid (< 10 min), micro-volume (< 50 uL) coagulation test to detect and quantify the anticoagulation effect of bivalirudin and UFH using a functional, clot time endpoint in pediatric critical care patients. DESIGN:. Single-site retrospective laboratory sample analysis and chart review. SETTING:. A 105-bed pediatric and cardiac ICUs delivering extracorporeal membrane oxygenation. SUBJECTS:. Forty-one citrated, frozen, biobanked plasma specimens comprising 21 with bivalirudin and 20 with UFH from 15 anticoagulated pediatric patients were analyzed. Thirteen patients were on extracorporeal membrane oxygenation, one had a submassive pulmonary embolism, and one was on a left ventricular assist device. INTERVENTIONS:. None. MEASUREMENT AND MAIN RESULTS:. A Clotting Time Score (CTS) was derived on each sample. The CTS detected patients that had developed a pathologic clotting event with 100% sensitivity and 82% specificity compared with prothrombin time with 25% sensitivity/76% specificity and activated partial thromboplastin time with 0% sensitivity/0% specificity. Additionally, the CTS detected subtherapeutic anticoagulation in response to UFH in patients that were clinically determined to be UFH resistant requiring alternative anticoagulation with bivalirudin. CONCLUSIONS:. The CTS appears to be a clinically valuable indicator of coagulation status in patients treated with either UFH or bivalirudin. Results outside of the therapeutic range due to inadequate dosing or anticoagulation resistance appeared to be associated with clot formation. CTS testing may reduce the risk of anticoagulation-related complications via the rapid identification of patients at high risk for pathologic thrombotic events.

Severe acute respiratory syndrome coronavirus 2 infection (COVID-19) is known to induce severe inflammation and activation of the coagulation system, resulting in a prothrombotic state. Although inflammatory conditions and organ-specific diseases have been shown to be strong determinants of morbidity and mortality in patients with COVID-19, it is unclear whether preexisting differences in coagulation impact the severity of COVID-19. African Americans have higher rates of COVID-19 infection and disease-related morbidity and mortality. Moreover, African Americans are known to be at a higher risk for thrombotic events due to both biological and socioeconomic factors. In this review, we explore whether differences in baseline coagulation status and medical management of coagulation play an important role in COVID-19 disease severity and contribute to racial disparity trends within COVID-19.