Apixaban trough concentrations in atrial fibrillation patients with reduced renal function.

Introduction: The direct factor Xa inhibitor apixaban is partially eliminated by the kidneys but is still prescribed at fixed doses without therapeutic drug monitoring across varying levels of renal function. If apixaban accumulates due to renal impairment, this may translate into safety concerns, e.g.

Apixaban plasma concentrations in patients with obesity.

Purpose: Routine therapeutic drug monitoring of apixaban is currently not recommended but may however be warranted in some situations and for some patient groups to provide better and safer treatment. Due to limited data on apixaban concentrations in different subpopulations, it is still unclear which group of patients could possibly gain from monitoring. The purpose of this study was to examine apixaban exposure in patients with obesity compared with normal-weight patients.

Rapid Detection of Apixaban by a ROTEM-Based Approach and Reversibility with Andexanet Alfa or DOAC-Stop.

 A rapid test to detect apixaban treatment would be useful in acute situations such as major bleeding, urgent surgery, or in acute thrombosis.  This article aims to study if the viscoelastic test rotational thromboelastometry (ROTEM) can rapidly detect apixaban in whole blood using modified triggers based on factor Xa (FXa) or Russell viper venom (RVV).  ROTEM clotting time (CT) was measured in samples from 40 patients on apixaban treatment, and in vitro in samples spiked with apixaban (20-500 ng/mL).

Effects of direct oral anticoagulants on lupus anticoagulant assays in a real-life setting.

Laboratory diagnosis of lupus anticoagulant (LA) is based on prolongation in at least one coagulation assay (diluted Russell's viper venom time - dRVVT or activated partial thromboplastin time - aPTT), which normalises after addition of phospholipids. Both assays may be influenced by anticoagulants and therefore LA should not be tested during warfarin or heparin treatment. It has been shown (primarily in vitro) that direct oral anticoagulants (DOACs - dabigatran [DAB], rivaroxaban [RIV] and apixaban [API]) may also influence LA testing.

Whole blood coagulation assays ROTEM and T-TAS to monitor dabigatran treatment.

Background: A rapid and reliable assessment of the dabigatran effect is desirable in dabigatran treated patients with uncontrolled bleeding or before acute surgery.

Objective: To evaluate how the viscoelastic point-of-care test Rotational thromboelastometry (ROTEM) and Total Thrombus-formation system (T-TAS), which studies thrombus formation under flowing conditions, correlate with dabigatran concentrations in patients with atrial fibrillation (AF).

Method: ROTEM using the reagents In-tem, Ex-tem, Fib-tem or low tissue factor concentration (TF), and T-TAS with the AR-chip (shear rate 600s, representing flow in large arteries) were investigated in whole blood samples.

Usefulness of Health Registers for detection of bleeding events in outcome studies.

Administrative and claims databases are attractive for safety studies of anticoagulant and antithrombotic drugs. However, the validity of such data is often uncertain. It was our aim to assess the usefulness of the Swedish administrative health databases for detection of major bleeding events.

Clinical evaluation of laboratory methods to monitor exposure of rivaroxaban at trough and peak in patients with atrial fibrillation.

Purpose: The one-dose daily regime of rivaroxaban could cause a pronounced variability in concentration and effect of which a deeper knowledge is warranted. This study aimed to evaluate the typical exposure range and effect of the direct factor Xa (FXa)-inhibitor rivaroxaban in a cohort of well-characterized patients with atrial fibrillation (AF).

Methods: Seventy-one AF patients (72 ± 8 years, 55 % men) were treated with rivaroxaban 15 mg/20 mg (n = 10/61) OD.

Clinical evaluation of laboratory methods to monitor apixaban treatment in patients with atrial fibrillation.

Introduction: The direct factor-Xa inhibitor apixaban is approved e.g. for the prevention of stroke in patients with atrial fibrillation (AF).

Benefit of anticoagulation unlikely in patients with atrial fibrillation and a CHA2DS2-VASc score of 1.

Background: Patients with atrial fibrillation (AF) and ≥1 point on the stroke risk scheme CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) are considered at increased risk for future stroke, but the risk associated with a score of 1 differs markedly between studies.

Objectives: The goal of this study was to assess AF-related stroke risk among patients with a score of 1 on the CHA2DS2-VASc.

Methods: We conducted this retrospective study of 140,420 patients with AF in Swedish nationwide health registries on the basis of varying definitions of "stroke events.

On the monitoring of dabigatran treatment in "real life" patients with atrial fibrillation.

Introduction: The oral direct thrombin inhibitor dabigatran is increasingly used to prevent thromboembolic stroke in patients with atrial fibrillation (AF). Routine laboratory monitoring is currently not recommended, but measurements of dabigatran and/or its effect are desirable in certain situations. We studied dabigatran exposure and compared different tests for monitoring of dabigatran in a real-life cohort of AF patients.

Adherence to warfarin treatment among patients with atrial fibrillation.

Background: Treatment with warfarin greatly reduces the risk of stroke related to atrial fibrillation, but will not be effective unless patients adhere to treatment. Lack of fixed dosing makes it difficult to objectively estimate adherence to treatment from prescription data.

Objective: To evaluate two methods that assess adherence to warfarin from prescription data.

Evaluation of coagulation assays versus LC-MS/MS for determinations of dabigatran concentrations in plasma.

Background: Dabigatran is an oral direct thrombin inhibitor for which routine laboratory monitoring is currently not recommended. However, there are situations in which measurements of the drug and its effect are desirable. We therefore compared and validated different coagulation methods for assessments of dabigatran in clinical samples in relation to measurements of plasma dabigatran, without the purpose of establishing effective and safe concentrations of dabigatran in plasma.

Platelet-derived microparticles during and after acute coronary syndrome.

As microparticles are shedded upon platelet activation, and may be used to assess platelet function, we measured plasma concentrations of platelet-derived microparticles (PMPs) during and after an acute coronary syndrome (ACS). Fifty-one patients with ACS were investigated at admission, within 24 hours (before coronary angiography), and six months later. Sixty-one sex- and age-matched healthy controls were investigated once.

Is fibrin formation and thrombin generation increased during and after an acute coronary syndrome?

Introduction And Methods: In order to study coagulation and fibrinolysis in acute coronary syndrome (ACS) we used a recently developed assay, called OH-index, which provides simultaneous measurements of fibrin formation and fibrinolysis (fibrin degradation) in the patients' plasma. We also investigated thrombin generation using the calibrated automated thrombogram (CAT), and assessed thrombin generation in vivo by measuring F1+2 plasma concentrations. In addition, to better characterize the patients we also assessed markers of inflammation and endothelial function.

ADAMTS13 and von Willebrand factor concentrations in patients with diabetes mellitus.

The von Willebrand factor (VWF) is elevated in patients with diabetes mellitus and degraded by a metalloprotease, ADAMTS13. We hypothesized that this elevation is due to a decreased function of ADAMTS13. Thus, we investigated ADAMTS13 in patients with diabetes mellitus without and with peripheral artery occlusive disease (PAOD).

Can both EDTA and citrate plasma samples be used in measurements of fibrinogen and C-reactive protein concentrations?

Background: Fibrinogen and C-reactive protein (CRP) concentrations are predictors of outcome in the atherosclerotic patient. It is important in risk stratification that these quantities are measured reproducibly in routine and research.

Method: In the present study, we compare measurements of fibrinogen and high-sensitivity CRP in EDTA and citrate plasma samples (n=150) using nephelometric immunoassays.

A global assay of haemostasis which uses recombinant tissue factor and tissue-type plasminogen activator to measure the rate of fibrin formation and fibrin degradation in plasma.

The global assay of Overall Haemostasis Potential we previously described has been refined. The coagulation cascade in platelet-poor plasma is triggered by adding a minimal dose of recombinant tissue factor together with purified phospholipids and calcium; fibrinolysis is initiated by adding recombinant tissue type-plasminogen activator in a concentration similar to what can be obtained during thrombolysis. Numerical differentials of optical densities reflecting rates of fibrin formation and degradation are calculated by a new software, and the Coagulation Profile (Cp) and the Fibrinolysis Profile (Fp) are determined.

Comparison of two immunochemical assays for measuring thrombin-activatable fibrinolysis inhibitor concentration with a functional assay in patients with acute coronary syndrome.

TAFI was measured as relative activity concentration (Pefakit) and antigen concentration (Haemochrom and Asserachrom) both acutely and during convalescence in patients suffering from acute coronary syndrome, and in a group of healthy controls. There was a rather weak but significant correlation between the activity and antigen concentrations. The results obtained by the Haemochrom method, assumed to measure the concentrations of all forms of TAFI, were lower than those by the Asserachrom method although the latter is assumed to only measure the pro-TAFI concentration.