Direct oral anticoagulant (DOAC) interference in hemostasis assays

Direct oral anticoagulants (DOACs) are a group of direct coagulation factor inhibitors including both direct thrombin inhibitors and direct factor Xa inhibitors. These medications may cause hemostasis assay interference by falsely increasing or decreasing measured values, depending on the analyte. Considering the potential for DOAC interference in a variety of hemostasis assays is essential to avoid erroneous interpretation of results. Preanalytic strategies to avoid DOAC interference include selecting alternatives to clot-based hemostasis assays in patients taking DOACs when possible and sample collection timed when the patient is off anticoagulant therapy or at the expected drug trough. Clinical laboratories may also provide educational materials that clearly describe possible interferences from DOAC, develop testing algorithms to aid in detection of DOAC in submitted samples, use DOAC-neutralizing agents to remove DOACs before continuing with testing, and write interpretive comments that explain the effects of DOAC interference in hemostasis tests. Using a combination of the described strategies will aid physicians and laboratorians in correctly interpreting hemostasis and thrombosis laboratory tests in the presence of DOACs.

Direct oral anticoagulants; a review for the non-specialist

Thrombin inhibitors and direct factor Xa inhibitors represent a major breakthrough in the field of anticoagulation pharmacotherapy. These novel agents have replaced warfarin as the oral anticoagulant of choice in certain indications, as they possess equal or superior efficacy and better safety profiles. They have a quick onset of action, predictable pharmacokinetic properties and minimal drug and food interactions. So they do not require frequent blood monitoring and dose adjustments as with warfarin. Considering all the advantages, there seems to be a rapid increase in the number of patients who are started on these novel anticoagulants. In this review, we highlight the pharmacology of these direct oral anticoagulants and the evidence-based indications for their use. We aim to provide a clinical overview for the non-specialist who may be called upon to manage a patient who is currently on one of these novel anticoagulants.

Efficacy and safety of direct oral anticoagulants with diabetes and nonvalvular atrial fibrillation: a systematic review and meta-analysis

Background Diabetes Mellitus (DM) is an independent risk factor for stroke and atrial fibrillation (AF). Therefore, the risk/benefit profile of the direct oral anticoagulants (DOAC) is of clinical interest. Purpose To compare efficacy and safety outcomes of DOAC for nonvalvular AF in patients with DM versus without DM. Methods We systematically searched PubMed, Embase and Cochrane databases, in January 2020, for interventional studies comparing DOAC efficacy and safety in patients with AF and diabetes versus without diabetes. Results Four randomized clinical trials were included, providing a total of 63987 patients, 18860 with DM and 45127 without DM. In terms of efficacy, our meta-analysis revealed a similar rate of stroke/systemic embolism (pooled OR 1.02 [0.79, 1.31], P=0.87, I2=83%), stroke (pooled OR 1.98 [0.68, 1.40], P=0.90, I2=90%) and all-cause mortality (pooled OR 1.18 [0.97, 1.43], P=0.10, I2=87%), albeit with a significant heterogeneity. However, in direct factor Xa inhibitors sub analysis, diabetic patients had a lower trend of systemic embolism/stroke (pooled OR 0.90 [0.79, 1.02], P=0.09, I2=18%), significantly lower stroke rate (pooled OR 0.82 [0.73, 0.93], P<0.01, I2=0%), but a higher all-cause mortality (pooled OR 1.08 [1.00, 1.16], P<0.01, I2=0%). In terms of safety, the diabetic patients receiving DOAC had higher rates of major bleeding events (pooled OR 1.28 [1.14, 1.45], P<0.01, I2=50%), although with significant heterogeneity. Direct factor Xa inhibitors sub analysis also revealed a higher rate of major bleeding events (pooled OR 1.22 [1.08, 1.38], P<0.01, I2=24%), but a similar intracranial bleeding events (pooled OR 1.03 [0.86, 1.24], P=0.72, I2=0%). Conclusion Our pooled analysis suggests that diabetic patients on DOAC have an higher bleeding risk on DOAC, although with a superior embolic protection. FUNDunding Acknowledgement Type of funding sources: None. Systemic Embolism/Stroke in DM vs. NonDM

Anticoagulation is the Answer in Treating Non-Critical COVID-19 Patients

All autopsy studies demonstrated widespread thrombosis and alveolar-capillary microthrombi as the cause of death among patients with COVID-19. The autopsy studies are the gold standard for diagnostic accuracy and therapeutic strategies for any clinical scenario. The author initially observed that patients already taking therapeutic dose oral direct factor Xa inhibitors for an unrelated reason, have significantly better survival rates than those not taking any anticoagulants. This influenced the author to conduct a retrospective chart review of the Jackson Hospital (Alabama) hospitalized patients to evaluate the effect of variable doses of anticoagulation among COVID-19 patients. The study found that serum inflammatory bio-marker D-Dimer trends are associated with changes in oxygen requirement among patients with COVID-19 if patients present at an early stage and titration of Enoxaparin (anticoagulation) dose based on D-Dimer trends leads to increased patient survival.

Laboratory assessment of the compliance to direct oral anticoagulants

Введение. Для пролонгированной профилактики тромбозов после операций, при фибрилляции предсердий, терапии тромбозов глубоких вен и/или тромбоэмболии легочной артерии широко используются прямые пероральные антикоагулянтные препараты (ПОАК). Считается, что ПОАК лишены недостатков, присущих антагонистам витамина К (АВК) и обладают предсказуемыми фармакокинетическими и фармакодинамическими эффектами и следовательно не требуют рутинного лабораторного контроля для коррекции и подбора дозы препарата. Отдельного внимания, на наш взгляд, заслуживает вопрос приверженности к терапии ПОАК. Цель исследования: оценка приверженности к терапии прямыми пероральными ингибиторами фактора Ха путем определения концентрации ПОАК в плазме крови пациентов. Материалы и методы. Выполнено проспективное клинико-лабораторное исследование, включены 50 пациентов с продленной антитромботической терапией ПОАК. Для оценки приверженности к терапии проведено определение пиковой концентрации прямых ингибиторов фактора Ха хромогенным методом. Результаты. До 10% пациентов в реальной клинической практике не принимали назначенную антитромботическую терапию и скрыли этот факт от врача. Таким образом, с помощью определения концентрации прямых ингибиторов фактора Ха хромогенным методом можно выявить отсутствие приверженности к терапии ПОАК. Заключение. Для определения приверженности к антикоагулянтной терапии прямыми ингибиторами фактора Ха возможно использование метода оценки концентрации ПОАК в плазме крови, что позволяет оценить приверженность пациента к данному виду терапии и, как следствие, эффективность и безопасность продленной антитромботической терапии. Background. For prolonged prophylaxis of thrombosis after surgery, of atrial fibrillation, therapy of deep vein thrombosis and/or pulmonary embolism, direct oral anticoagulants (DOACs) are widely used. It is believed that DOACs lack the deficiencies inherent in antagonists of vitamin K (AVK), have predictable pharmacokinetic and pharmacodynamic effects, and therefore do notrequire routine laboratory monitoring to adjust and select the dose of the drug. We pay special attention to the issue of adherence to DOACs therapy. Objectives: to assess compliance to therapy with direct oral factor Xa inhibitors by determining plasma DOACs concentration. Patients/Methods. A prospective clinical and laboratory study was performed, 50 patients with prolonged antithrombotic therapy by DOACs were included. To assess compliance to therapy, the peak concentration of direct factor Xa inhibitors was determined by the chromogenic method. Results. In real clinical practice up to 10% of patients did not take the prescribed antithrombotic therapy and hid this fact from the doctor. Thus, by determining the concentration of direct factor Xa inhibitors by the chromogenic method, it is possible to identify a lack of compliance to therapy. Conclusions. Determination of plasma DOACs concentration allows assessing the patient’s adherence to anticoagulant therapy with direct factor Xa inhibitors and the efficacy and safety of prolonged antithrombotic therapy.