Laboratory and Clinical Monitoring of Direct Acting Oral Anticoagulants: What Clinicians Need to Know

Abstract

The direct acting oral anticoagulants (DOACs), including dabigatran, rivaroxaban, apixaban, and edoxaban, have favorable pharmacokinetic and pharmacodynamic properties and equal or superior efficacy and an improved safety profile compared with warfarin. Noted shortcomings with DOACs are shorter half-lives requiring stricter adherence, lack of standardized laboratory monitoring, lack of anticoagulation reversal agents, and loss of routine coagulation monitoring leading to fewer patient-clinician interactions. This review addresses many of these limitations including monitoring of DOACs for efficacy and toxicity, an assessment of selected qualitative and quantitative tests, and development of monitoring strategies for special populations. Coagulation monitoring is generally recommended only in overdose situations, but once standardized assays are readily available, they could be helpful to ensure efficacy, assess bleeding, and aid in drug selection in a number of other patient scenarios. Coagulation tests that may provide qualitative assessment include activated partial thromboplastin time, prothrombin time, and thrombin time. Methods with potential utility for quantitative assessment of DOACs include plasma drug concentrations, ecarin clotting time, dilute thrombin time, and antifactor Xa concentrations. Noncoagulation laboratory monitoring should include serum creatinine, liver function tests, and complete blood counts. Clinical monitoring of the DOAC-treated patient should include routine assessment of adherence, bleeding risks, and drug interactions. Frequency of monitoring should be 1-3 months after initiation and then at least every 6 months, with more frequent follow-up (i.e., 3 months) based on patient specific characteristics such as age, renal impairment, hepatic impairment, and concomitant drug therapy. The authors provide a practical tool to assist in DOAC monitoring and recommend that pharmacists collaborate with physicians in selecting appropriate patients and tailoring patient-specific monitoring plans.

Evaluation of global laboratory methods and establishing on‐therapy ranges for monitoring apixaban and rivaroxaban: Experience at a single institution

“…The present study was conducted at a single institution to establish on‐therapy ranges for conventional coagulation assays using anti‐factor Xa chromogenic assay results. PT was less sensitive to apixaban than rivaroxaban and could be within the reference range in patients with clinically relevant situations . Only PT (%) results were well correlated with plasma apixaban levels, whereas both PT (sec) and PT (%) results were well correlated with plasma rivaroxaban levels.…”

“…PT was less sensitive to apixaban than rivaroxaban and could be within the reference range in patients with clinically relevant situations. 22,23 Only PT (%) results were well correlated with plasma apixaban levels, whereas both PT (sec) and PT (%) results were well correlated with plasma rivaroxaban levels. However, PT does not always predictably reflect the anticoagulant activity of rivaroxaban, and the sensitivity of PT to rivaroxaban depends on the laboratory reagents used.…”

Fases Pré-Analítica, Analítica E Pós-Analítica No Monitoramento Laboratorial Da Anticoagulação Com Antagonistas Da Vitamina K

“…O fator tecidual está presente nesse reagente, sendo composto por uma fração proteica e outra de fosfolipídios que mimetizam in vivo a função do fator 3 plaquetário, no que concerne à ativação de fatores que se combinam a fosfolipídios de membrana 15,16 . A expressão dos resultados do TP pode ser realizada das seguintes formas 15,16 : a) Tempo pelo método de Quick, em segundos; b) Percentual de atividade em relação a um plasma normal (no qual foi considerada uma atividade de 100%), sendo necessário tangenciar uma curva de atividade utilizando um pool de plasmas normais obtidos e titulados com salina fisiológica (0,9%); c) Coeficiente Internacional Normatizado (CIN). Os valores de referência dos parâmetros desses ensaios estão apresentados a seguir 17 : a) Tempo de protrombina (Quick) -10-14 segundos; b) Atividade (%) -70-100%; c) CIN -1,0-1,08 em pessoas hígidas e 2,0-3,5 em pacientes submetidos à terapêutica com AVK.…”

“…A sensibilidade do reagente é inversamente proporcional ao valor de ISI. Na grande maioria, situase entre 1,0-2,0, sendo que quanto mais próximo de 1,0, mais sensível é o reagente utilizado 15,16 .…”

“…Se este ensaio apresentar resultado normal, é indicativo da presença de inibidores. Se, porventura, não regularizar, conclui-se provavelmente tratar-se de uma coagulopatia 15,16,34 . A etapa analítica corresponde à fase do processo laboratorial que pode ser regulada pelo controle interno de qualidade (CIQ) e pela avaliação externa da qualidade (AEQ) ou pelos ensaios de proficiência.…”