A High Factor II/Factor X Functional Ratio Is Not a Useful Predictor of the FII G20210A Gene Mutation in Thromboembolic Patients Undergoing Oral Anticoagulant Treatment

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.

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The Inhibitor of Prothrombin Conversion in Plasma of Patients on Oral Anticoagulant Treatment

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650178 ◽

1981 ◽

Vol 45 (03) ◽

pp. 237-241 ◽

Cited By ~ 13

Author(s):

R M Bertina ◽

M E J Westhoek-Kuipers ◽

G H J Alderkamp

Keyword(s):

Vitamin K ◽

Spectrophotometric Assay ◽

Factor Ix ◽

Factor Vii ◽

Factor X ◽

Dilution Curve ◽

Anticoagulant Treatment ◽

Oral Anticoagulant Treatment ◽

Coagulation Assays ◽

Factor Ii

SummaryPooled plasma of patients under stable oral anticoagulation has been analysed with respect to the presence of the vitamin-K dependent factors (factors II, VII, IX and X). Of all factors 1.5-2 times more antigen than procoagulant activity was present. The concentration of factors II, X (measured spectrophotometrically) and VII is about 0.25 U/ml while factor IX is slightly higher. Coagulation assays of factor X always gave lower values than the spectrophotometric assay. This discrepancy was not influenced by the removal of either factor II-factor VII- or factor IX antigen. However, when the factor X antigen was replaced by normal factor X, all factor X assays gave identical results, indicating that PIVKA X is responsible for these discrepancies. Using the technic of the Thrombotest-dilution curve it was shown that PIVKA X is the factor that causes the abnormal prolongation of ox-brain prothrombin time in these plasmas.

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PROTEIN C RESPONSE TO INDUCTION AND WITHDRAWAL OF ORAL ANTICOAGULANT TREATMENT

10.1055/s-0038-1643273 ◽

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.

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Ex vivo evidence that effective inhibition of prothrombin activation follows reduction of plasma factor II in patients starting oral anticoagulant treatment

Thrombosis Research ◽

10.1016/0049-3848(92)90472-m ◽

1992 ◽

Vol 65 ◽

pp. S79

Keyword(s):

Oral Anticoagulant ◽

Ex Vivo ◽

Anticoagulant Treatment ◽

Oral Anticoagulant Treatment ◽

Factor Ii ◽

Plasma Factor ◽

Effective Inhibition ◽

Prothrombin Activation

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Oral Anticoagulant Treatment with and without Aspirin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642729 ◽

1995 ◽

Vol 74 (01) ◽

pp. 506-510 ◽

Cited By ~ 11

Author(s):

Raul Altman ◽

Jorge Rouvier ◽

Enrique Gurfinkel

Keyword(s):

Oral Anticoagulant ◽

Anticoagulant Treatment ◽

Oral Anticoagulant Treatment

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656064 ◽

1997 ◽

Vol 77 (05) ◽

pp. 0839-0844 ◽

Cited By ~ 34

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.

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