Efficacy of a point of care international normalised ratio device for monitoring of patients on vitamin K antagonists in the inpatient and ambulatory setting

Abstract Robust evidence remains scarce in guiding best practice in the prevention and treatment of venous thromboembolism in patients living with cancer. Recommendations from major consensus guidelines are largely based on extrapolated data from trials performed mostly in noncancer patients, observational studies and registries, studies using surrogate outcomes, and underpowered randomized controlled trials. Nonetheless, a personalized approach based on individual risk assessment is uniformly recommended for inpatient and outpatient thromboprophylaxis and there is consensus that anticoagulant prophylaxis is warranted in selected patients with a high risk of thrombosis. Prediction tools for estimating the risk of thrombosis in the hospital setting have not been validated, but the use of prophylaxis in the ambulatory setting in those with a high Khorana score is under active investigation. Symptomatic and incidental thrombosis should be treated with anticoagulant therapy, but little is known about the optimal duration. Pharmacologic options for prophylaxis and treatment are still restricted to unfractionated heparin, low molecular weight heparin, and vitamin K antagonists because there is currently insufficient evidence to support the use of target-specific, non-vitamin K-antagonist oral anticoagulants. Although these agents offer practical advantages over traditional anticoagulants, potential drug interaction with chemotherapeutic agents, gastrointestinal problems, hepatic and renal impairment, and the lack of rapid reversal agents are important limitations that may reduce the efficacy and safety of these drugs in patients with active cancer. Clinicians and patients are encouraged to participate in clinical trials to advance the care of patients with cancer-associated thrombosis.

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Differential inhibition of thrombin generation by vitamin K antagonists alone and associated with low-molecular-weight heparin

Thrombosis and Haemostasis ◽

10.1160/th08-10-0653 ◽

2009 ◽

Vol 102 (07) ◽

pp. 42-48 ◽

Cited By ~ 12

Author(s):

Grigoris T. Gerotziafas ◽

Charlotte Dupont ◽

Alex C. Spyropoulos ◽

Mohamed Hatmi ◽

Meyer M. Samama ◽

...

Keyword(s):

Molecular Weight ◽

Vitamin K ◽

Low Molecular Weight Heparin ◽

Thrombin Generation ◽

Vitamin K Antagonists ◽

Low Molecular Weight ◽

Plasma Samples ◽

Thrombin Generation Assay ◽

International Normalised Ratio ◽

Inhibition Of Thrombin

SummaryVitamin K antagonists (VKA) treatment starts with co-administration of low-molecular-weight heparin (LMWH). The anticoagulation induced by the two drugs is still not well determined. In the present study we used thrombin generation assay to evaluate the hypo-coagulation induced by treatment with VKA and by the combination of VKA with LMWH. Tissue factor triggered thrombin generation in platelet-poor plasma was assessed in samples from 15 healthy volunteers, 97 samples from patients treated with VKA and 41 samples from patients receiving enoxaparin and VKA. Patients were classified according to international normalised ratio (INR) level (<2, 2–3 and >3).In plasma samples from patients treated with VKA having INR 2–3 the inhibition of thrombin generation reached 50% compared to controls. In samples with INR>3 this inhibition was 80%. In samples from patients receiving both LMWH and VKA, thrombin generation was significantly decreased compared to the controls and VKA group. In samples with an INR 2–3 obtained from patients treated with LMWH and VKA, the inhibition of thrombin generation was similar to that observed in samples with an INR>3 obtained from VKA treated patients. Thrombin generation assay is sensitive to detect the global the anticoagulant effect produced by the association of LMWH and VKA. For equal INR dual anticoagulant treatment induces significantly more profound inhibition of thrombin generation compared to treatment with VKA alone. The clinical relevance of this observation merits to be studied in prospective studies in patients with defined indications of anticoagulant therapy.

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Development of a clinical prediction model for an international normalised ratio ≥ 4·5 in hospitalised patients using vitamin K antagonists

British Journal of Haematology ◽

10.1111/bjh.15161 ◽

2018 ◽

Vol 181 (1) ◽

pp. 102-110

Author(s):

Albert R. Dreijer ◽

Joseph S. Biedermann ◽

Jeroen Diepstraten ◽

Anouk D. Lindemans ◽

Marieke J. H. A. Kruip ◽

...

Keyword(s):

Prediction Model ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Clinical Prediction ◽

Clinical Prediction Model ◽

Hospitalised Patients ◽

International Normalised Ratio

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Point-of-care testing and INR within-subject variation in patients receiving a constant dose of vitamin K antagonist

Thrombosis and Haemostasis ◽

10.1160/th15-02-0128 ◽

2015 ◽

Vol 114 (12) ◽

pp. 1260-1267

Author(s):

Joseph S. Biedermann ◽

Marieke J. H. A. Kruip ◽

A. M. H. P. van den Besselaar

Keyword(s):

Blood Coagulation ◽

Vitamin K ◽

Whole Blood ◽

Point Of Care ◽

Vitamin K Antagonists ◽

Professional Staff ◽

Self Testing ◽

Target Intensity ◽

Constant Dose ◽

Coaguchek Xs

SummaryMany patients treated with vitamin K antagonists (VKA) determine their INR using point-of-care (POC) whole blood coagulation monitors. The primary aim of the present study was to assess the INR within-subject variation in self-testing patients receiving a constant dose of VKA. The second aim of the study was to derive INR imprecision goals for whole blood coagulation monitors. Analytical performance goals for INR measurement can be derived from the average biological within-subject variation. Fifty-six Thrombosis Centres in the Netherlands were invited to select self-testing patients who were receiving a constant dose of either acenocoumarol or phenprocoumon for at least six consecutive INR measurements. In each patient, the coefficient of variation (CV) of INRs was calculated. One Thrombosis Centre selected regular patients being monitored with a POC device by professional staff. Sixteen Dutch Thrombosis Centres provided results for 322 selected patients, all using the CoaguChek XS. The median within-subject CV in patients receiving acenocoumarol (10.2 %) was significantly higher than the median CV in patients receiving phenprocoumon (8.6 %) (p = 0.001). The median CV in low-target intensity acenocoumarol self-testing patients (10.4 %) was similar to the median CV in regular patients monitored by professional staff (10.2 %). Desirable INR analytical imprecision goals for POC monitoring with CoaguChek XS in patients receiving either low-target intensity acenocoumarol or phenprocoumon were 5.1 % and 4.3 %, respectively. The approximate average value for the imprecision of the CoaguChek XS, i. e. 4 %, is in agreement with these goals.

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Impact of point-of-care international normalized ratio monitoring on quality of treatment with vitamin K antagonists in non-self-monitoring patients: a cohort study: reply

Journal of Thrombosis and Haemostasis ◽

10.1111/jth.13485 ◽

2016 ◽

Vol 14 (11) ◽

pp. 2312-2314 ◽

Cited By ~ 1

Author(s):

J. S. Biedermann ◽

A. M. van den Besselaar ◽

F. W. Leebeek ◽

M. J. Kruip

Keyword(s):

Cohort Study ◽

Vitamin K ◽

Point Of Care ◽

Vitamin K Antagonists ◽

International Normalized Ratio ◽

Self Monitoring ◽

Quality Of Treatment

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Point-of-care testing: is it a paradox in international normalised ratio measurements?

Journal of Medical Laboratory Science & Technology of South Africa ◽

10.36303/jmlstsa.2020.2.2.52 ◽

2020 ◽

pp. 109-113

Author(s):

W Maule

Keyword(s):

Clinical Laboratory ◽

Point Of Care ◽

Vitamin K Antagonists ◽

Anticoagulation Therapy ◽

Brand Names ◽

Point Of Care Testing ◽

Oral Anticoagulation Therapy ◽

International Normalised Ratio ◽

Control Programmes ◽

Support Mechanisms

Point-of-care testing (POCT) in haemostasis has shown a steady state increase in the range of tests available with an exponential increase in the number of tests that are performed annually. The most commonly performed test remains the out of hospital measurement of the international normalised ratio (INR). The INR is used to monitor oral anticoagulation therapy (OAT) with vitamin K antagonists. Such drugs include some of the following: warfarin (Coumadin®), phenprocoumon (Marcumar®) and acenocoumarol (Sintrom®, also sold as other brand names). Contrary to laboratory testing, POCT is often performed by general practitioners (GPs), nurses, pharmacists, patients and other healthcare professionals. In many cases these individuals do not have access to the same support mechanisms that exist in the clinical laboratory regarding strict quality control programmes. When an INR test is performed in the clinical laboratory, it has to be accredited, monitored and inspected. Accreditation is also advisable and part of these requirements is to be involved in external quality assessment (EQA). In the case of POCT haemostasis assays, EQA programmes do exist, however these programmes are still relatively few in number. Over the last decade there has been a significant increase in the scope of POCT, particularly in the field of haemostasis. This brief review summarises POCT in haemostasis, highlighting some of its benefits, challenges and future perspectives, especially with regard to the measurement of the INR.

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Abstract 164: Specific Point-of-Care Testing of Coagulation in Patients Treated With Non-Vitamin K Antagonist Oral Anticoagulants Part I (SPOCT-NOAC I)

Stroke ◽

10.1161/str.47.suppl_1.164 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Florian Härtig ◽

Andreas Peter ◽

Charlotte Spencer ◽

Matthias Ebner ◽

Christine S Zürn ◽

...

Keyword(s):

Vitamin K ◽

Point Of Care ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Rapid Assessment ◽

Plasma Concentrations ◽

Vitamin K Antagonist ◽

Point Of Care Testing ◽

Blood Samples ◽

First Time

Introduction: Non-vitamin K antagonist oral anticoagulants (NOAC) are increasingly replacing vitamin K antagonists for prevention of thromboembolism in atrial fibrillation (AF) and venous thrombosis. Ischemic stroke rate in NOAC-treated AF-patients is 1-2% per year. Subsequently, stroke physicians face a growing number of NOAC-treated patients with acute stroke. Rapid assessment of coagulation in NOAC-treated patients is vital prior to thrombolysis, but existing point-of-care testing (POCT) is suboptimal. For the first time we evaluate NOAC-specific POCT. Hypothesis: Ecarin clotting time (ECT)- and anti-Xa activity-POCT accurately predict plasma concentrations of dabigatran and apixaban/edoxaban/rivaroxaban. Methods: 80 patients receiving first NOAC-dose and 80 already on NOAC-treatment will be enrolled (N=40 for each NOAC). Subjects receiving other anticoagulants will be excluded. 6 blood samples will be collected from each patient: before drug intake, 30min, 1, 2, and 8h after intake, and before next dose. NOAC-concentrations will be measured by mass spectrometry. Results (preliminary): Until now 138 blood samples of 23 dabigatran-treated patients were analyzed. Dabigatran-concentrations ranged from 0-371ng/mL. ECT-POCT ranged from 20-219s. Pearson’s correlation coefficient showed strong correlation for ECT-POCT and dabigatran-concentrations (r=0.94, p<0.001). Dabigatran-concentrations >50ng/mL (threshold for thrombolysis according to expert recommendation) were detected by ECT-POCT (>50s) with 100% sensitivity and 82% specificity. Baseline-samples not containing any dabigatran yielded normal ECT-POCT. Conclusions: This is the first study evaluating NOAC-specific POCT. Preliminary results show excellent correlation for ECT-POCT and dabigatran; relevant dabigatran-concentrations were detected in 100%. More pioneering results on NOAC-specific POCT will be presented.

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Point-of-care monitoring of vitamin K-antagonists: validation of CoaguChek XS test strips with International Standard thromboplastin

Journal of Clinical Pathology ◽

10.1136/jclinpath-2012-200934 ◽

2012 ◽

Vol 65 (11) ◽

pp. 1031-1035 ◽

Cited By ~ 10

Author(s):

Anton M H P van den Besselaar ◽

Nathalie C V Péquériaux ◽

Marij Ebben ◽

Joke van der Feest ◽

Kerst de Jong ◽

...

Keyword(s):

The Netherlands ◽

Vitamin K ◽

Point Of Care ◽

Vitamin K Antagonists ◽

Capillary Blood ◽

Blood Samples ◽

Test Strips ◽

International Standard ◽

The Mean ◽

Coaguchek Xs

AimsMany patients treated with vitamin K-antagonists (VKA) use point-of-care (POC) whole blood coagulometers for self-testing. The majority of patients in the Netherlands use one type of POC coagulometer, that is, the CoaguChek XS. Each new lot of test strips for the CoaguChek XS is validated by a group of collaborating thrombosis centres. We assessed the International Normalised Ratio (INR) differences between each of 51 new lots of test strips and the International Standard for thromboplastin rTF/95 or its successor rTF/09.MethodsEach year, a particular lot of CoaguChek XS test strips was used as reference lot. The reference lot was validated by comparison to the International Standard, yielding a relationship between the reference lot INR and International Standard INR. Successive lots of test strips were compared to the reference lot by three centres using 19–29 capillary blood samples obtained from VKA-treated patients. Each patient provided two blood drops from the same finger prick, one for the reference lot strip and one for the new lot.ResultsThe mean INR differences between each lot and the International Standard varied between −8% and +4%. The mean absolute values of the relative differences varied between 2.4% and 8.1%. There were small but clinically unimportant differences in INR between the first and second drop of blood.ConclusionsAccuracy of CoaguChek XS INR determinations can be assessed by a group of collaborating centres using a limited number of capillary blood samples. As the mean INR differences with the International Standard were smaller than 10%, the lots were approved for use by the Netherlands Thrombosis Services.

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