Kinetic Study Of Factor X (FX) : Potential Value For The Initiation Of Oral Anticoagulant Treatment

1981 ◽  
Author(s):  
J N Fiessinger ◽  
M Aiach ◽  
C Nussas ◽  
L Capron
Keyword(s):  
Exponential Decay ◽  
Regression Line ◽  
Heparin Therapy ◽  
Term Treatment ◽  
Factor Vii ◽  
Factor X ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
Significant Linear Correlation ◽  
Long Term Treatment

FX has been claimed to be of clinical relevance in monitoring long term treatment with anticoagulants. The aim of this investigation was to study the behaviour of FX at the beginning of the treatment.Seventeen patients under heparin therapy received a daily dose of 3 mg of Acenocoumarol. Blood samples were obtained at 1, 2, 4, 6, 8 days (Dθ - 8), after starting the treatment. Heparin was stopped when prothrombin time (PT) was less than 40 per cent of normal value. FX was evaluated using an automated amidolytic method. Factor VII (FVII) and PT were measured in a clotting assay.The disappearance of FX from plasma could be fitted to an exponential decay pattern during 6 days in 17 patients, 8 days in 11 patients. Concerning FVII, the exponential decay was limited to the first 2 days, then a stable level was reached. The decrease rates of FVII and FX during the first two days were correlated (r = 0,76). The regression line In (FX) = f (D) calculated from D0, D1, D2 could be used for predicting FX concentration at or D8. A highly significant linear correlation existed between the observed and predicted levels (D8 : r = 0,97) (D6 : r = 0,92).These results suggest that FX amidolytic assay could be useful for monitoring the initiation of anticoagulant treatment. The decrease rate of FX could be a valuable guide for an early determination of the maintenance dose of anticoagulant.

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.

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

1981 ◽  
Vol 45 (03) ◽  
pp. 237-241 ◽  
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.

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.

Long Term Treatment with Anticoagulants in Coronary Artery Disease

1958 ◽  
Vol 02 (05/06) ◽  
pp. 492-504 ◽  
Author(s):  
P. A Owren
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Angina Pectoris ◽  
Term Treatment ◽  
Anticoagulant Treatment ◽  
Long Term Treatment ◽  
Artery Disease ◽  
Treatment Improvement ◽  
Annual Mortality

Summary347 patients with angina pectoris and 222 patients who had survived an attack of myocardial infarction for at least 8 weeks have been under long-term treatment with dicumarol or phenylindanedione. The annual mortality-rate was reduced to 5% in both groups. Patients with angina pectoris show improvement in 47.7% of the cases, if the disease is not older than 1 year before the start of treatment. Improvement was found in only 25% of the cases when the disease was older than 4 years. It was clearly evidenced that anticoagulant treatment of angina pectoris is only useful when the disease is not older than 2 to 3 years before starting treatment.

COAGULATION, FIBRINOLYSIS AND PLATELET FUNCTION DURING COUMARIN THERAPY

1987 ◽  
Author(s):  
D A Taberner ◽  
J M Thomson ◽  
L Poller
Keyword(s):  
Factor Viii ◽  
Protein C ◽  
T Test ◽  
Factor Vii ◽  
Factor V ◽  
Factor X ◽  
Complex Activity ◽  
Oral Anticoagulant Treatment ◽  
Protein C Activity ◽  
Paired T Test

The inactivation of factors VIII:C, V:C and fast acting TPA inhibitor by activated Protein C indicates that oral anticoagulation is more than simple reduction of prothrombin complex activity. To investigate these changes, six patients were studied after stopping oral anticoagulant treatment. Protein C activity and C antigen, Factors VIII:C, VIII:vWFAg, V:C, V:Ag, X:C, VII:C, fibrinogen and TPA activity were measured during long-term nicoumalone therapy (duration of therapy 8-96 months, mean 28 months), and after discontinuation on days 2, 4, 8, 10, 15, 30 and 42.The INR on the last day of therapy ranged between 2.0 - 3.3, (mean 2.6). Protein C activity and antigen and factor X became normal by day 8; factor II by day 10. Factor VII activity peaked on day 8, falling to resting levels by day 30. Factor VIII parameters remained high throughout, whereas Factor V antigen showed no significant change. Factor V activity was not quantifiable untill day 8 because of non-parallelism (? PIVKA effect), but was higher on day 8 than day 42 (p < 0.002 paired “t” test) . The higher levels of factor V activity could be protein C dependent, but the high factor VIII appears unrelated. Fibrinogen levels were higher on coumarin treatment (p < 0.05 paired “t” test) and took 30 days to fall to resting level. The effect of Protein C on TPA inhibitor would be expected to increase the activity of TPA, but this activity remained unchanged. Raised fibrinogen levels did not, therefore, appear to be mediated by the effect of protein C on fibrinolysis. Fibrinogen levels in plasma influence ADP induced platelet aggregation which is known to be increased in patients receiving coumarin drugs. In conclusion, patients on coumarin treatment, in addition to showing a reduction in protein C activity, also have higher fibrinogen levels and increased platelet aggregability all of which may be undesirable.

Studies On PIVKA-VII

1981 ◽  
Author(s):  
G Mariani ◽  
G Avvisati ◽  
D Romoli ◽  
M G Mazzucconi ◽  
F Mandelli
Keyword(s):  
Vitamin K ◽  
Therapeutic Range ◽  
Sharp Increase ◽  
Oral Anticoagulants ◽  
Barium Chloride ◽  
Term Treatment ◽  
Factor Vii ◽  
Long Term Treatment ◽  
Two Parameters

The factor VII related antigen (Pivka-VII) in 25 random patients under long term treatment with oral anticoagulants was studied. All the patients had Thrombotest levels well within the therapeutic range (3 to 11%) and had been receiving the drugs for at least 4 months. Factor VII activity (VII: C) mean levels were 8.7 u/dl(sem 0.78) and factor VII antigen (VII: Ag) mean levels were 30.7 u/dl(sem 1.99), (ratio Pivka/Activity 4.04). Barium chloride adsorbed the same mean amount of factor VII: C and factor VII: Ag (8.7 u/dl and 8.0 u/dl respectively). After exposure to cold in 4/25 subjects the “cold activation” phenomenon became evident, characterised by an increase of factor VII: C levels and immodified VII : Ag levels. In the remaining 21 patients, mean VII : C as well as VII: Ag levels did not show modifications (8.5 u/dl and 30.7 u/dl respectively). Moreover, three normal volunteers received three different oral anticoagulants ( Acenocoumarin, Coumarin and Ethyl-Biscomacetate). A sharp increase of factor VII:C levels was observed in all the three subjects (from 30 to 50%), a few hours after the beginning of the treatments, followed by consensual decrease of the two properties related to factor VII that reached the nadir after 48 hours. The vitamin K administration was followed by a rapid and consenual increase of the two parameters.

Behaviour of Factors II, VII, IX, and X during Long-Term Treatment with Coumarin

1963 ◽  
Vol 09 (01) ◽  
pp. 074-089 ◽  
Author(s):  
E. A Loeliger ◽  
B van der Esch ◽  
M. J Mattern ◽  
A. S. A den Brabander
Keyword(s):  
Prothrombin Time ◽  
Coagulation Factors ◽  
Term Treatment ◽  
Factor Ix ◽  
Separate Determination ◽  
Factor X ◽  
Warfarin Sodium ◽  
Long Term Treatment ◽  
Significant Difference

SummaryDuring long-term treatment with the long-acting coumarin derivative phenprocoumarol (marcoumar) no statistically significant difference in the depression of the activity of coagulation factors II, VII, IX, and X was found. The shorter-acting anticoagulants acenocoumarol (sintrom), warfarin sodium (coumadin), and dicoumarol, possibly lower factor IX somewhat less and factor X somewhat more than they do factors II and VII.A 2.5-fold prolongation of the “prothrombin” time (using Owren 5 s human brain thromboplastin) and the same prolongation of the thrombotest time appear to correspond with a depression of all four factors from 100% down to approximately 20’%, the normal standard being a mixed population with a mean age of 29 years.Separate determination of one of the four coagulation factors concerned is pointless; “prothrombin” time estimation, and more specifically thrombotest, still remain the most reliable methods for controlling the anti-vitamin K action of anticoagulants during long-term treatment.

scholarly journals 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

2000 ◽  
Vol 46 (6) ◽  
pp. 886-887
Author(s):  
Angel José González Ordóñez ◽  
José Manuel Fernández Carreira ◽  
María Victoria Alvarez ◽  
Leoncio Martín Sánchez ◽  
Jesús María Medina Rodríguez ◽  
...  
Keyword(s):  
Gene Mutation ◽  
Oral Anticoagulant ◽  
Factor X ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
Factor Ii

CLOTTING FACTOR DEPENDENCY OF PROTHROMBINASE ACTIVITY IN DICOUMAROL PLASMA. THE IMPORTANCE OF A FACTOR IX DEPENDENT PATHWAY IN EXTRINSIC COAGULATION

1987 ◽  
Author(s):  
Ma Xi ◽  
S Béguin ◽  
H C Hemker ◽  
P P Devilée
Keyword(s):  
Thrombin Generation ◽  
Factor Ix ◽  
Factor Vii ◽  
Coagulation System ◽  
Clotting Factor ◽  
Factor X ◽  
Oral Anticoagulant Treatment ◽  
Anticoagulated Patients ◽  
Dependent Pathway ◽  
Prothrombinase Activity

We determined the generation of prothrombinase activity in plasma using a mathematical analysis of the thrombin generation curve (H. C. Hemker, G. M. Willems, S. Béguin. Thromb. Haemostas. 56, 9-17, 1986).Addition of the purified factor VII, IX or X to plasma from deeply anticoagulated patients (<15% level >10%) did not influence the rate and amount of prothrombinase formed. Only the amount of prothrombin in the starting plasma determined the course of thrombin generation. Adding increasing amounts of purified human clotting factor preparations to deficient plasmas showed that the treshold concentration under which factor VII, and IX start to have an effect on prothrombinase activity are 5% or lower. For factor X it is lower than 10%.From this it can be concluded that only the changes in prothrombin level must be held responsible for the anti thrombotic effect of oral anticoagulation. These conclusions are not modified if different types and concentrations of thromboplastin are used.We were able to show that at dilutions of human brain thromboplastin higher than 1:50, a factor IX and factor VIII dependent pathway plays an increasingly important role. This directly demonstrates the Josso pathway. The concentration of factor IX necessary for full activity is again <5%.We conclude that the antithrombotic effect of oral anticoagulant treatment, if it is mediated via the coagulation system, works via modification of the prothrombin level only.

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