Mechanized amidolytic technique for determination of factor X and factor-X antigen, and its application to patients being treated with oral anticoagulants.

1980 ◽  
Vol 26 (7) ◽  
pp. 885-890 ◽  
Author(s):  
E M van Wijk ◽  
L H Kahlé ◽  
J W ten Cate
Keyword(s):  
Oral Anticoagulant ◽  
Oral Anticoagulants ◽  
Neutralization Assay ◽  
Factor X ◽  
Extrinsic Pathway ◽  
Oral Anticoagulant Treatment ◽  
Chromogenic Assay ◽  
Russell’S Viper ◽  
The One

Abstract We describe a mechanized chromogenic assay for factor X, the results of which correlate well with those for the one-stage clotting assays for factor X in which it is activated either via the extrinsic pathway by thromboplastin or directly by Russell's viper venom. We purified human factor X and raised monospecific antibodies to it in rabbits. We used our chromogenic assay for factor X to develop a factor-X-inhibitor neutralization assay for determination of factor-X antigen. Patients receiving oral anticoagulant treatment had significantly different factor-X activities after activation via thromboplastin or with Russell's viper venom. The concentration of factor-X antigen, although decreased, significantly exceeded factor-X clotting activity or chromogenic activity in this group of patients. Results of the chromogenic assay for factor X correlated well with results of "Thrombotest," a clotting test introduced by Owren (Lancet ii: 754, 1959) to control anticoagulant therapy. For patients taking oral anticoagulant drugs, the therapeutic range by our assay is 180 to 300 units/L.

Mechanized amidolytic technique for determination of factor X and factor-X antigen, and its application to patients being treated with oral anticoagulants.

1980 ◽  
Vol 26 (7) ◽  
pp. 885-890
Author(s):  
E M van Wijk ◽  
L H Kahlé ◽  
J W ten Cate
Keyword(s):  
Oral Anticoagulant ◽  
Oral Anticoagulants ◽  
Neutralization Assay ◽  
Factor X ◽  
Extrinsic Pathway ◽  
Oral Anticoagulant Treatment ◽  
Chromogenic Assay ◽  
Russell’S Viper ◽  
The One

Abstract We describe a mechanized chromogenic assay for factor X, the results of which correlate well with those for the one-stage clotting assays for factor X in which it is activated either via the extrinsic pathway by thromboplastin or directly by Russell's viper venom. We purified human factor X and raised monospecific antibodies to it in rabbits. We used our chromogenic assay for factor X to develop a factor-X-inhibitor neutralization assay for determination of factor-X antigen. Patients receiving oral anticoagulant treatment had significantly different factor-X activities after activation via thromboplastin or with Russell's viper venom. The concentration of factor-X antigen, although decreased, significantly exceeded factor-X clotting activity or chromogenic activity in this group of patients. Results of the chromogenic assay for factor X correlated well with results of "Thrombotest," a clotting test introduced by Owren (Lancet ii: 754, 1959) to control anticoagulant therapy. For patients taking oral anticoagulant drugs, the therapeutic range by our assay is 180 to 300 units/L.

Control of Oral Anticoagulation in Patients with the Antiphospholipid Syndrome – Influence of the Lupus Anticoagulant on International Normalized Ratio

1998 ◽  
Vol 80 (07) ◽  
pp. 99-103 ◽  
Author(s):  
Le Querrec ◽  
B. Delahousse ◽  
C. Caron ◽  
L. Houbouyan ◽  
B. Boutière ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Oral Anticoagulant ◽  
International Normalized Ratio ◽  
Factor X ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
Average Value ◽  
Significant Difference ◽  
Patient Groups

SummaryThe recommended therapeutic range of International Normalized Ratio (INR) for oral anticoagulant treatment in patients with the antiphospholipid syndrome remains controversial. As a part of this controversy, it has been suggested that lupus anticoagulants (LA) could interfere with the determination of prothrombin time, thus questioning the validity of monitoring the treatment of these patients using INR. To clarify this point, we compared the values of INR obtained in the plasmas of two groups of patients, one without LA (n = 47), and the other with LA (n = 43). INR were determined using 8 different thromboplastin reagents on the same automated coagulation instrument. Chromogenic factor X, which is supposed to be insensitive to the presence of LA, was also measured. The results are the following: provided INR was calculated using calibrated reference plasmas, there was no significant difference between INR values obtained with the 8 reagents, both in the non-LA and in the LA groups (CV: 5.9 and 6.7%, respectively). Closer examination revealed that INR results obtained with one reagent (the recombinant thromboplastin Innovin) diverged from those of the 7 others, leading to an overestimation of INR, to a very large extent in some instances. However this effect was restricted to a subset of the patient population with LA (6 out of 43). Finally, the relationship between INR (average value obtained using the 8 reagents) and factor X was identical in non-LA and in LA patient groups. We conclude that, provided the reagents which display the LA interference are identified and excluded for this purpose, the INR system is valid for monitoring oral anticoagulant treatment in patients with LA.

PROTEIN C RESPONSE TO INDUCTION AND WITHDRAWAL OF ORAL ANTICOAGULANT TREATMENT

1987 ◽  
Author(s):  
K P Schofield ◽  
J M Thomson ◽  
L Poller
Keyword(s):  
Oral Anticoagulant ◽  
Protein C ◽  
Oral Anticoagulants ◽  
Factor Vii ◽  
Factor X ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
Rate Of Increase ◽  
Long Term Treatment

Protein C (PC) activity and antigen levels have been related to clotting activities of factors VII and X during the induction and withdrawal periods of oral anticoagulant treatment. Both factor VII and PC activities fell rapidly during a gradual induction regime of nicoumalone in six consecutive patients but factor VII showed a more rapid and much more marked depression than PC. In contrast reductions in factor X were much slower. PC antigen although depressed rapidly at the initiation of treatment did not subsequently fall to the same degree as PC activity, The ratio of activity to antigen became progressively smaller.In six further serial patients discontinued from long-term treatment with nicoumalone (mean duration 12-6 months) there was a reversal of the pattern, but with two important differences. Firstly, there was evidence of an excessive rise (“rebound”) of factor VII compared with the steady state levels in these patients; and secondly there was an unexpectedly slow return of PC activity and antigen to normal levels after the oral anticoagulant was withdrawn (levels were still below normal on day 4). Factor X also showed a slow rate of increase, similar to PC activity recovery. These observations lend support to gradual withdrawal of oral anticoagulants after a period of long-term administration. The results suggest that after discontinuation of long-term oral anticoagulants patients may have increased coagulability up to four days.

An Assessment Of An Amidolytic Assay For Factor VII In The Laboratory Control Of Oral Anticoagulants

1981 ◽  
Author(s):  
A Bodzenta ◽  
Jean M Thomson ◽  
Z S Latallo
Keyword(s):  
Prothrombin Time ◽  
Oral Anticoagulant ◽  
Oral Anticoagulants ◽  
Factor Vii ◽  
Limiting Factor ◽  
Factor X ◽  
Present Evidence ◽  
Chromogenic Assay ◽  
Better Than

An amidolytic assay for factor VII, modified from the method of Seligsohn et al (1978), has been compared with the results of the prothrombin time using British Comparative Thromboplastin, Thronbotest and a clotting assay for factor VII. In ‘long-term’ oral anticoagulant administration agreement with the conventional methods was good and better than in our previous study when amidolytic assays for factors II and X respectively were studied (Latallo et al 1981). The method appeared to be reasonably specific for factor VII.On the present evidence the chromogenic assay for factor VII offers a limited but apparently dependable guide to dosage but it is elaborate to perform and difficult to standardise. The main limiting factor for its routine application is the need to prepare a purified factor X extract.

A Comparison of a Moderate with Moderate-high Intensity Oral Anticoagulant Treatment in Patients with Mechanical Heart Valve Prostheses

1997 ◽  
Vol 77 (05) ◽  
pp. 0839-0844 ◽  
Author(s):  
Vittorio Pengo ◽  
Fabio Barbero ◽  
Alberto Banzato ◽  
Elisabetta Garelli ◽  
Franco Noventa ◽  
...  
Keyword(s):  
Heart Valve ◽  
High Intensity ◽  
Oral Anticoagulant ◽  
Oral Anticoagulants ◽  
Mechanical Heart Valve ◽  
Moderate Intensity ◽  
Minor Bleeding ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
Valve Prostheses

SummaryBackground. The long-term administration of oral anticoagulants to patients with mechanical heart valve prostheses is generally accepted. However, the appropriate intensity of oral anticoagulant treatment in these patients is still controversial.Methods and Results. From March 1991 to March 1994, patients referred to the Padova Thrombosis Center who had undergone mechanical heart valve substitution at least 6 months earlier were randomly assigned to receive oral anticoagulants at moderate intensity (target INR = 3) or moderate-high intensity (target INR = 4). Principal end points were major bleeding, thromboembolism and vascular death. Minor bleeding was a secondary end-point.A total of 104 patients were assigned to the target 3 group and 101 to the target 4 group; they were followed for from 1.5 years to up 4.5 years (mean, 3 years). Principal end-points occurred in 13 patients in the target 3 group (4 per 100 patient-years) and in 20 patients in the target 4 group (6.9 per 100 patient-years). Major hemorrhagic events occurred in 15 patients, 4 in the target 3 group (1.2 per 100 patient-years) and 11 in the target 4 group (3.8 per 100 patient-years) (p = 0.019). The 12 recorded episodes of thromboembolism, 4 of which consisted of a visual deficit, were all transient ischemic attacks, 6 in the target 3 group (1.8 per 100 patient-years) and 6 in the target 4 group (2.1 per 100 patient- years). There were 3 vascular deaths in each group (0.9 and 1 per 100 patient-years for target 3 and target 4 groups, respectively). Minor bleeding episodes occurred 85 times (26 per 100 patient-years) in the target 3 group and 123 times (43 per 100 patient-years) in the target 4 group (p = 0.001).Conclusions. Mechanical heart valve patients on anticoagulant treatment who had been operated on at least 6 months earlier experienced fewer bleeding complications when maintained on a moderate intensity regimen (target INR = 3) than those on a moderate-high intensity regimen (target INR = 4). The number of thromboembolic events and vascular deaths did not differ between the two groups.

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.

P4745Concomitant oral anticoagulant and antidepressant therapy in patients with atrial fibrillation and risk of stroke and bleeding: a population based cohort study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J J Komen ◽  
P Hjemdahl ◽  
A K Mantel - Teeuwisse ◽  
O H Klungel ◽  
B Wettermark ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Propensity Score ◽  
Oral Anticoagulant ◽  
Cox Regression ◽  
Oral Anticoagulants ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
Increased Risk ◽  
Antidepressant Use

Abstract Background Anticoagulation treatment reduces the risk of stroke but increases the risk of bleeding in atrial fibrillation (AF) patients. Antidepressants use is associated with increased risk for stroke and bleeds. Objective To assess the association between antidepressant use in AF patients with oral anticoagulants and bleeding and stroke risk. Methods All AF patients newly prescribed with an oral anticoagulant in the Stockholm Healthcare database (n=2.3 million inhabitants) from July 2011 until 2016 were included and followed for one year or shorter if they stopped claiming oral anticoagulant treatment or had an outcome of interest. Outcomes were severe bleeds and strokes, requiring acute hospital care. During follow-up, patients were considered exposed to antidepressant after claiming a prescription for the duration of the prescription. With a time-varying Cox regression, we assessed the association between antidepressant use and strokes and bleeds, adjusting for confounders (i.e., age, sex, comorbidities, comedication, and year of inclusion). In addition, we performed a propensity score matched analysis to test the robustness of our findings. Results Of the 30,595 patients included after claiming a prescription for a NOAC (n=13,506) or warfarin (n=17,089), 4 303 claimed a prescription for an antidepressant during follow-up. A total of 712 severe bleeds and 551 strokes were recorded in the cohort. Concomitant oral anticoagulant and antidepressant use was associated with increased rates of severe bleeds (4.7 vs 2.7 per 100 person-years) compared to oral anticoagulant treatment without antidepressant use (aHR 1.42, 95% CI: 1.12–1.80), but not significantly associated with increased stroke rates (3.5 vs 2.1 per 100 person-years, aHR 1.23, 95% CI: 0.93–1.62). No significant differences were observed between different oral anticoagulant classes (i.e., warfarin or NOAC) or different antidepressant classes (i.e., SSRI, TCA, or other antidepressant). Additional propensity-score matched analyses yielded similar results but showed a significantly increased risk for stroke (HR: 1.47, 95% CI: 1.08–2.02). Incidence rates of strokes and bleeds Conclusion Concomitant use of an oral anticoagulant and an antidepressant, irrespective of type, is associated with an increased bleeding risk. Increased awareness and a critical consideration for the need of an antidepressant is recommended in this population. Acknowledgement/Funding Swedish Heart Lung Foundation

THE THROMBOTIC COMPLICATIONS OF TWO GROUPS OF PATIENTS WITH DIFFERENT INR THERAPEUTIC RANGES. THE NECESSITY OF INTENSE ORAL ANTICOAGULANT TREATMENT

1987 ◽  
Author(s):  
Ir Kontopoulou-Griva ◽  
J Spiliotopoulou ◽  
L Digenopoulou ◽  
J Georgopoulos
Keyword(s):  
High Risk ◽  
Oral Anticoagulant ◽  
Heart Valves ◽  
Oral Anticoagulants ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
Daily Dose ◽  
Group A ◽  
Thrombotic Complications ◽  
Group B

One of the reasons why oral anticoagulants fell into disrepute is the absence of internationally acceptable standarised procedures for controlling the level of anticoagulation. This deplorable situation resulted in over and under coagulation and uncertainty in the therapeutic range. The International Normalised Ratio (INR) can safely be applied in patients on oral anticoagulants.We present two Groups of patients under long term anti coagulation, mainly because of prosthetic heart valves that have recently been added to our outpatients clinic. These patients were till then attended by two cardiologists with different attitudes on the intensity of the anticoagulant treatment. The thromboplastin reagent used is that of ox origin and the results are expressed on INR.The Group A with 32 patients had at the time that we started attending them an INR x = 1,80 ± 0,48 and a daily dose of acenocoumarol x = 1,65 ± 0,51.The Group B with 49 patients had an INR x = 2,75 ± 0,51 and a daily dose of acenocoumarol x = 2,52 ± 1,53.Seven patients of the Group A referred thrombotic complications, while three patients of the Group B referred transiant thrombotic complications.The statistical analysis with the t-test of the INR between the two Groups is p<0,001 while that of the thrombotic complication with the x2 is p<0,05.The introduction of the INR and the acceptance by the medical people of the necessity of the intense oral anticoagulant treatment especially on high risk patients with mechanical heart valves as is the majority of the presented patients, will minimize the thromboembolic complications without high risk of bleeding.

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.

The Determination of Factor X Using an Automated Amidolytic Technique

1979 ◽  
Author(s):  
E.M. van Wijk ◽  
L.H. Kahlé ◽  
J.W. ten Cate
Keyword(s):  
Antithrombin Iii ◽  
Oral Anticoagulant Therapy ◽  
Close Correlation ◽  
Bleeding Disorders ◽  
Factor X ◽  
Amidolytic Activity ◽  
One Stage ◽  
Automated Method ◽  
The One

An automated method for the determination of factor X has been developed using a procoagulant fraction from Russell’s Viper Venom (RW), which activates FX within 4 minutes at pH 8.6, resulting in a Xa activity that is assayed using the chromogenic substrate S 2222. The amidolytic activity generated by sufficient RW is proportional to the FX level of the plasma and is not influenced by antithrombin III within the time studied. By using polybrene, the influence of heparin (up to 10 U/ml) can be eliminated. The method has been adapted for performance automatically on an Automated Kinetic Enzyme and Substrate analyser (Vitatron), Comparison of FX activities of 30 normals and 41 patients with bleeding disorders revealed a close correlation of this method with the one stage clotting assay using thromboplastin (r=0.93). Values obtained in a group of 83 patients on oral anticoagulant therapy showed good correlation (r=0.87) but tended to be about 8% higher compared to the one stage method. No significant differences were found when RW was used in the clotting assay (r-0.91). The values obtained by the amidolytic assay correlated well with thrombotest (r=0.87).

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