Are Capillary Whole Blood Coagulation Monitors Suitable for the Control of Oral Anticoagulant Treatment by the International Normalized Ratio?

1993 ◽  
Vol 70 (06) ◽  
pp. 0921-0924 ◽  
Author(s):  
Armando Tripodi ◽  
Arnaldo A Arbini ◽  
Veena Chantarangkul ◽  
Donato Bettega ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Whole Blood ◽  
Oral Anticoagulant ◽  
Oral Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Regression Line ◽  
International Normalized Ratio ◽  
Rabbit Brain ◽  
Sensitivity Index ◽  
Calibration Model ◽  
Oral Anticoagulant Treatment

SummaryThe 512 Coagulation Monitor is a portable coagulation photometer that uses disposable cartridges containing a lyophilized rabbit brain thromboplastin to measure the PT for capillary whole blood. It has been proposed as a suitable system for patient self monitoring at home, but its performance has never been thoroughly assessed for results expressed as International Normalized Ratio (INR). In particular, there is no available information about the adequacy of the WHO calibration model with the Monitor. The aims of the study were to determine the International Sensitivity Index (ISI) against the secondary International Reference Preparation for rabbit thromboplastin and to assess the precision of the INR. The study demonstrates that the Monitor can be calibrated with the WHO model, because log-transformed PTs for patients stabilized on oral anticoagulants and normal individuals are linearly related and because the same orthogonal regression line describes patient and normal data points adequately. However, the ISI calculated in this study (2.715) is higher than that adopted by the manufacturer (2.036). The between-assay reproducibility of the Monitor is acceptable (CV = 9.7%) with results expressed in seconds, but become unacceptably poor when the results are converted into INR (CV = 18.8%) because of the high ISI value of the thromboplastin used. We think that the Monitor might be suitable for monitoring oral anticoagulant therapy if the manufacturer would provide a more sensitive thromboplastin in the cartridges.

Determination of the International Sensitivity Index of a New Near-Patient Testing Device to Monitor Oral Anticoagulant Therapy

1997 ◽  
Vol 78 (02) ◽  
pp. 855-858 ◽  
Author(s):  
Armando Tripodi ◽  
Veena Chantarangkul ◽  
Marigrazia Clerici ◽  
Barbara Negri ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Linear Relationship ◽  
Whole Blood ◽  
Oral Anticoagulant ◽  
Oral Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Calibration Model ◽  
Testing Device ◽  
Data Points ◽  
Near Patient Testing

SummaryA key issue for the reliable use of new devices for the laboratory control of oral anticoagulant therapy with the INR is their conformity to the calibration model. In the past, their adequacy has mostly been assessed empirically without reference to the calibration model and the use of International Reference Preparations (IRP) for thromboplastin. In this study we reviewed the requirements to be fulfilled and applied them to the calibration of a new near-patient testing device (TAS, Cardiovascular Diagnostics) which uses thromboplastin-containing test cards for determination of the INR. On each of 10 working days citrat- ed whole blood and plasma samples were obtained from 2 healthy subjects and 6 patients on oral anticoagulants. PT testing on whole blood and plasma was done with the TAS and parallel testing for plasma by the manual technique with the IRP CRM 149S. Conformity to the calibration model was judged satisfactory if the following requirements were met: (i) there was a linear relationship between paired log-PTs (TAS vs CRM 149S); (ii) the regression line drawn through patients data points, passed through those of normals; (iii) the precision of the calibration expressed as the CV of the slope was <3%. A good linear relationship was observed for calibration plots for plasma and whole blood (r = 0.98). Regression lines drawn through patients data points, passed through those of normals. The CVs of the slope were in both cases 2.2% and the ISIs were 0.965 and 1.000 for whole blood and plasma. In conclusion, our study shows that near-patient testing devices can be considered reliable tools to measure INR in patients on oral anticoagulants and provides guidelines for their evaluation.

Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects

Blood ◽  
2004 ◽  
Vol 104 (9) ◽  
pp. 2682-2689 ◽  
Author(s):  
Leon J. Schurgers ◽  
Martin J. Shearer ◽  
Karly Hamulyák ◽  
Elisabeth Stöcklin ◽  
Cees Vermeer
Keyword(s):  
Vitamin K ◽  
Dose Response ◽  
Oral Anticoagulant ◽  
Oral Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
International Normalized Ratio ◽  
Dietary Vitamin ◽  
Undercarboxylated Osteocalcin ◽  
Vitamin K1 ◽  
Oral Anticoagulant Treatment

Abstract Oral anticoagulants exert their effect by blocking the utilization of vitamin K, yet little is known about competitive aspects of their interaction with dietary vitamin K. We carried out systematic dose-response studies in healthy volunteers who had been stably anticoagulated and maintained on their individualized doses for 13 weeks. First, we studied the response to weekly incremental doses (50 μg-500 μg) of vitamin K1 supplements (K1) taken daily for 7 days. The threshold K1 dose causing a statistically significant lowering of the INR was 150 μg/day. In 25% of the participants the INR change was regarded as clinically relevant at a vitamin K intake of 150 μg/day. Circulating undercarboxylated osteocalcin did not decrease until 300 μg K1/day compared with 100 μg K1/day for undercarboxylated FII, suggesting differential antidotal effects on bone and hepatic γ-carboxylation. Next, we tested the response to vitamin K-rich food items. The short-lived response after meals of spinach and broccoli suggested an inefficient bioavailability from these 2 sources. We conclude that short-term variability in intake of K1 is less important to fluctuations in the international normalized ratio (INR) than has been commonly assumed and that food supplements providing 100 μg/day of vitamin K1 do not significantly interfere with oral anticoagulant therapy. (Blood. 2004;104:2682-2689)

Multi-Center Study of Thromboplastin Calibration Precision – Influence of Reagent Species, Composition, and International Sensitivity Index (ISI)

1993 ◽  
Vol 69 (01) ◽  
pp. 035-040 ◽  
Author(s):  
A M H P van den Besselaar ◽  
R M Bertina
Keyword(s):  
Oral Anticoagulants ◽  
International Normalized Ratio ◽  
The Other ◽  
World Health ◽  
Rabbit Brain ◽  
Sensitivity Index ◽  
Bovine Plasma ◽  
Significant Difference ◽  
The Mean ◽  
International Sensitivity Index

SummaryFour thromboplastin reagents were tested by 18 laboratories in Europe, North-America, and Australasia, according to a detailed protocol. One thromboplastin was the International Reference Preparation for ox brain thromboplastin combined with adsorbed bovine plasma (coded OBT/79), and the second was a certified reference material for rabbit brain thromboplastin, plain (coded CRM 149R). The other two thromboplastin reagents were another rabbit plain brain thromboplastin (RP) with a lower ISI than CRM 149R and a rabbit brain thromboplastin combined with adsorbed bovine plasma (RC). Calibration of the latter two reagents was performed according to methods recommended by the World Health Organization (W. H. O.).The purpose of this study was to answer the following questions: 1) Is the calibration of the RC reagent more precise against the bovine/combined (OBT/79) than against the rabbit/plain reagent (CRM 149R)? 2) Is the precision of calibration influenced by the magnitude of the International Sensitivity Index (ISI)?The lowest inter-laboratory variation of ISI was observed in the calibration of the rabbit/plain reagent (RP) against the other rabbit/plain reagent (CRM 149R) (CV 1.6%). The highest interlaboratory variation was obtained in the calibration of rabbit/plain (RP) against bovine/combined (OBT/79) (CV 5.1%). In the calibration of the rabbit/combined (RC) reagent, there was no difference in precision between OBT/79 (CV 4.3%) and CRM 149R (CV 4.2%). Furthermore, there was no significant difference in the precision of the ISI of RC obtained with CRM 149R (ISI = 1.343) and the rabbit/plain (RP) reagent with ISI = 1.14. In conclusion, the calibration of RC could be performed with similar precision with either OBT/79 or CRM 149R, or RP.The mean ISI values calculated with OBT/79 and CRM 149R were practically identical, indicating that there is no bias in the ISI of these reference preparations and that these reference preparations have been stable since their original calibration studies in 1979 and 1987, respectively.International Normalized Ratio (INR) equivalents were calculated for a lyophilized control plasma derived from patients treated with oral anticoagulants. There were small but significant differences in the mean INR equivalents between the bovine and rabbit thromboplastins. There were no differences in the interlaboratory variation of the INR equivalents, when the four thromboplastins were compared.

Rebound Phenomenon After Discontinuation Of Oral Anticoagulant Therapy?

1981 ◽  
Author(s):  
J Harenberg ◽  
R Haas ◽  
R Zimmermann
Keyword(s):  
Anticoagulant Therapy ◽  
Oral Anticoagulant ◽  
Oral Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
In Vitro Release ◽  
Oral Anticoagulant Treatment ◽  
Thrombin Activity ◽  
Rebound Phenomenon

Duration and discontinuation of oral anticoagulant therapy in the prophylaxis of recurrent thrombembolic diseases is often discussed. After stopping of the therapy an elevated incidence of rethromboses are observed. Therefore we determined fibrinopeptide A (FPA) as the most sensitive parameter of thrombin activity in vivo in patients treated with phenprocoumon in order to get information on the effectivity of the oral anticoagulant therapy and on the rebound phenomenon after discontinuation of the treatment.In 136 outpatients a significant relation between FPA and the effectivity of the anticoagulant therapy was observed: 2.7 ng/ml plasma (mean, thrombotest values < 5%), 3.5 ng/ml (5%-15%) and 4.1 ng/ml (>15%, p < 0.01). Normal FPA were 1.4ng/ml. In 11 patients with low FPA the oral anticoagulants were discontinued. FPA was determined in weekly intervalls. Within four weeks a continous increase of FPA from 1.6 ng/ml (median) to 3.8 ng/ml was observed. After eight weeks FPA was 8.2 ng/ ml (p < 0.05). The in vitro release of FPA after 10 min incubation of blood increased from 3.4ng/ml to 72 ng/ml after eight weeks (p < 0.05, normal release up to 5 ng/ml).The data indicate the clinical relevance and the different therapeutic implications of the determination of FPA in patients treated with phenprocoumon. They further give the first criterion, which outlines the effectivity of an oral anticoagulation therapy by reducing the thrombin activity in vivo. They give some evidence for a rebound like phenomenon after discontinuation of the oral anticoagulant treatment.

Oral Anticoagulant Therapy Control: Evidence that INR Expression Improves the Inter-Laboratory Comparability of Results - The Bologna Oral Anticoagulant Control Exercise

1987 ◽  
Vol 58 (03) ◽  
pp. 905-910 ◽  
Author(s):  
G Palareti ◽  
S Coccheri ◽  
M Poggi ◽  
M Bonetti ◽  
V Cervi ◽  
...  
Keyword(s):  
Anticoagulant Therapy ◽  
Oral Anticoagulant ◽  
Oral Anticoagulant Therapy ◽  
Normal Subjects ◽  
International Normalized Ratio ◽  
Sensitivity Index ◽  
Therapy Control ◽  
Educational Value ◽  
International Reference ◽  
Interlaboratory Variability

SummaryThe aims of the present study were: l) interlaboratory normalization of prothrombin time (PT) testing for anticoagulant therapy control through calibration of customary thromboplastins against international reference materials, and 2) “on field” validation of the advantages offered by expression of results as International Normalized Ratio (INR) as opposedto percentage activity. PT tests were carried out over 8 days on the same normal subjects (16) and patients on oral an ticoagulants (48) in the 9 laboratories of the Bologna area. The use of customary thromboplastins and coagulometers was maintained in all labs throughout the study. The main results were: 1) the interlaboratory CV of the prothrombin ratios obtained for each sample with all customary thromboplastins (5 different brands) was 15%, but was reduced to levels of 5.8 to 8.9 when using constant thromboplastin brands and batches; 2) the International Sensitivity Index (ISI) values obtained in the different labs were only slightly influenced by the use of different coagulometers; 3) comparable ISI values were obtained through direct calibration with the international reference material and through intermediate calibration with a locally selected standard; 4) use of INR values instead of percentage activity greatly reduced interlaboratory variability and significantly improved uniformity of anticoagulation level measurements. thus reducing the possibility of erroneous prescriptions. The Bologna exercise is therefore of educational value for laboratory and community doctors of the area in understanding and accepting the INR system.

Management of Oral Anticoagulant-associated Intracerebral Hemorrhage

2018 ◽  
Vol 1 (2) ◽  
pp. 114-125
Author(s):  
Corina Epple ◽  
Thorsten Steiner
Keyword(s):  
Vitamin K ◽  
Oral Anticoagulant ◽  
Anticoagulant Activity ◽  
Oral Anticoagulant Therapy ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Clinical Problem ◽  
International Normalized Ratio ◽  
Bleeding Management ◽  
Number Of Patients

Introduction: Oral anticoagulant-associated intracerebral hemorrhages (OAC-ICHs) account for nearly 20% of all ICH and are associated with high mortality. The number of patients with an indication for oral anticoagulant therapy (OAT) is increasing with the aging population; therefore, despite the improved safety profile of non-vitamin K oral anticoagulants (NOACs), the number of patients with OAC-ICH will increase. OAT was simplified with the introduction of NOACs, which are easy to handle and show a favorable risk-benefit profile. The rate of ICH is lower than for vitamin K antagonists (VKA) and routine coagulation testing is not required. Nevertheless, OAC-ICH does occur and is still a devastating disease, thus representing the most feared complication in OAT, irrespective of treatment with VKA or NOAC. Purpose: The aim of this article is to address the clinical problem of bleeding management in patients with ICH due to OAC and will consider anticoagulation with NOAC and VKA. Recommendations: Restoring coagulation as soon as possible is the main goal and, therefore, knowledge of the actual coagulation status is essential. In VKA-associated ICH, the international normalized ratio (INR) should be lowered to below 1.3. However, laboratory measurement of anticoagulant activity in NOAC patients is more complex, rendering OAC-ICH treatment more complicated. The best assays are specialized and not widely available, whereas more accessible tests such as prothrombin time and activated partial thromboplastin time have important limitations. For VKA-ICH, prothrombin complex concentrate (PCC) should be administered to reverse the INR. For dabigatran-related ICH, 5 g idarucizumab should be administered. For factor Xa inhibitors, PCC is recommended in the absence of andexanet alfa as soon as an OAC-related ICH evolves. Resuming OAC after ICH should be considered, depending on risk factors and a risk-benefit evaluation.

scholarly journals Use of Lyophilized Calibrant Plasmas for Simplified International Normalized Ratio Determination with a Human Tissue Factor Thromboplastin Reagent Derived from Cultured Human Cells

2003 ◽  
Vol 49 (12) ◽  
pp. 2006-2011 ◽  
Author(s):  
Anton M H P van den Besselaar ◽  
Wim P M Houdijk
Keyword(s):  
Tissue Factor ◽  
Human Tissue ◽  
Oral Anticoagulants ◽  
Regression Line ◽  
Reference Method ◽  
International Normalized Ratio ◽  
Human Cells ◽  
Sensitivity Index ◽  
Cultured Human Cells ◽  
The Mean

Abstract Background: For monitoring of treatment with oral anticoagulants, the clotting time obtained in the prothrombin time (PT) test is transformed to the International Normalized Ratio (INR) with use of a system-specific International Sensitivity Index (ISI). The calibrant plasma procedure (CPP) is an alternative approach to INR calculation based on the use of a set of lyophilized plasmas with assigned INRs. Methods: With the CPP, a linear relationship is established between log(PT) and log(INR), using orthogonal regression. CPP was validated for Simplastin HTF, a new human tissue factor reagent derived from cultured human cells. CPP precision was assessed as the CV of the slope of the regression line. The accuracy of the CPP was determined by comparing the INR obtained with the CPP with that obtained with the established ISI-based reference method. INRs of the calibrants were assigned by different routes: by manufacturer (consensus labeling) or by use of Simplastin HTF or International Reference Preparations (IRPs; rTF/95 or RBT/90). Results: The mean CV of the CPP regression slope ranged from 1.0% (Simplastin HTF reagent-specific INR) to 2.4% (INR assigned with rTF/95). INRs calculated with the CPP were similar to those obtained with the reference method, but when the routes for assigning INRs to the calibrant plasmas were compared, the mean difference in INR between CPP and the reference method was smaller with Simplastin HTF reagent-specific values. In several (but not all) cases, this difference was significant (P &lt;0.05, t-test). Conclusion: CPP can be used for local INR determination, but better precision and accuracy are obtained with reagent-specific INRs compared with INR assignment by consensus labeling or IRP.

Validity of International Normalized Ratio in Expressing Prothrombin Times in Anticoagulated and Nonanticoagulated Patients

1996 ◽  
Vol 2 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Rasheed Alshameeri ◽  
Eberhard F. Mammen ◽  
Christa Paisley ◽  
Christine Perry
Keyword(s):  
Human Placenta ◽  
Oral Anticoagulant ◽  
High Sensitivity ◽  
International Normalized Ratio ◽  
Rabbit Brain ◽  
Sensitivity Index ◽  
Normal Range ◽  
Normal Ranges ◽  
Highly Sensitive ◽  
International Sensitivity Index

We investigated the effect of four thrombo plastins with different International Sensitivity Index (ISI) values on prothrombin times (PTs), expressed as International Normalized Ratios (INRs), of 30 normal plasmas, 30 patients on stable oral anticoagulant (OA) therapy, and 30 patients with prolonged PTs for reasons other than OA therapy. Normal ranges became signifi cantly longer when three thromboplastins of rabbit brain origin were used—the lower the ISI, the wider the normal range. The human placenta-derived thromboplastin had a range similar to the values obtained with the most insen sitive rabbit reagent. Significantly different INR values were noted when normal plasmas and plasmas of patients with prolonged PTs not due to OA therapy were tested. This was not the case when specimens from patients on OAs were tested. When PT values from 212 consecutive ly selected patients were tested with the least sensitive rabbit reagent (ISI 2.477) and the most sensitive human placenta reagent (ISI 1.06), significantly more "abnor mal" PTs were identified with the high-sensitivity throm boplastin. The data indicate that special attention has to be paid to "normal" ranges when thromboplastins with low ISI replace less sensitive reagents, that INR should not be used to express PT in patients not on stable OA therapy, and that with the routine use of highly sensitive reagents (low ISI) more abnormal patients are identified.

Rabbit Polyclonal Antibodies Against the Calcium-Dependent Conformation of Factor IX and Their Application in Solid Phase Immunoradiometric Assays

1986 ◽  
Vol 55 (01) ◽  
pp. 122-128 ◽  
Author(s):  
S R Poort ◽  
I K van der Linden ◽  
C Krommenhoek-van Es ◽  
E Briët ◽  
R M Bertina
Keyword(s):  
Oral Anticoagulant ◽  
Conformational Transition ◽  
Solid Phase ◽  
Oral Anticoagulant Therapy ◽  
Oral Anticoagulants ◽  
Polyclonal Antiserum ◽  
Factor Ix ◽  
Hemophilia B ◽  
Oral Anticoagulant Treatment ◽  
Human Factor Ix

SummaryTwo subpopulations of antibodies were isolated from rabbit polyclonal antiserum directed against human factor IX: one against the Ca(II)-dependent conformation of factor IX and one against the Ca(II)-independent conformation of factor IX. The two subpopulations were used for the development of immunoradiometric assays (IRMA’s) for factor IX: Ca(II)Ag and factor IX: NonCa(II)Ag respectively. Ranges for the concentration of factor IX:Ca(II)Ag and factor IX: NonCa(II)Ag were established in plasmas of healthy volunteers, patients treated with oral anticoagulants and hemophilia B patients. In the group of patients using oral anticoagulant therapy a progressively reduced ratio of factor IX:Ca(II)Ag to factor IX: NonCa(II)Ag was observed with increasing intensity of oral anticoagulant treatment. Variant factor IX molecules from hemophilia B patients . (CRM-, CRMRed and CRM+) with a defective Ca(II) binding or defective conformational transition induced by Ca(II) binding, were identified. These defects are absent in variant factor IX molecules from one hemophilia Bm patient and from patients with hemophilia B Leyden.

Sign in / Sign up

Export Citation Format

Share Document