RESPONSE OF PROTEIN C AND PROTEIN S INHIBITORS IN LONG-TERM ORAL ANTICOAGULANT THERAPY

1987 ◽  
Author(s):  
M Mukhlova Montiel ◽  
H Bussey
Keyword(s):  
Anticoagulant Therapy ◽  
Oral Anticoagulant ◽  
Protein C ◽  
Oral Anticoagulant Therapy ◽  
Anticoagulation Therapy ◽  
Protein S ◽  
Factor Vii ◽  
Control Group ◽  
Statistical Regression

Protein C (PC) and its coenzyme Protein S (PS) are physiologic inhibitors of activated factors Va and Villa. Deficiency of either one of these inhibitors has been associated with venous thrombosis. Their activity is dependent on vitamin K for hepatic gamma carboxylation and it is depressed during oral anticoagulant therapy. Because rebound thrombosis complicates cessation of anticoagulant therapy, we investigated the response of PC and PS during long term oral anti coagulation. The study encompassed 30 patients ranging between 26 and 76 years of age, who have received therapeutic doses of coumadin from 15 days to more than 8 years. The conditions for which treatment was initiated were deep vein thrombosis, cerebral vascular accidents and cardiac valve replacements.Factor VII and X activity was assayed by one step routine clotting assays. PC antigen (ag), total PSag and free PSag were assayed by Laurel 1 Rocket electroimmunodiffusion method. The measurement of the free PS was carried out after precipitation of C4b-binding protein with polyethylene glycol. PC activity was measured by clotting assay using PC deficient plasma to which was added patient plasma as a source of PC. Control group of 30 individuals in similar age group were assayed parallel with the patient samples. Compared with the control group the coumadin-treated patients showed substantial decrease of all factors studied. Statistical regression analysis of the coumadin group showed a significant increase in PS free (p = 0.014)during long term anti coagulation, while all of the other variables did not change significantly.PCag and total PSag were decreased and their activities, as expected, were more severely affected. The ratio of PC activity to PCag averages 0.39 (normal >0.80) and free PS represented only 27% of the total PSag (normal about 40%). The inhibitors' persistent activity parallels that of the depression of Factors VII and X and there appears to be a balanced coagulation-inhibi-tion system. If PC and PS play a role in rebound thrombosis after a prolonged anticoagulation therapy, the changes may occur after discontinuation of medication.

ACUTE INTERRUPTION OF ORAL ANTICOAGULANT THERAPY: A THROMBOTIC RISK?

1987 ◽  
Author(s):  
J Rouvier ◽  
H Vidal ◽  
J Gallino ◽  
M Boccia ◽  
A Scazziota ◽  
...  
Keyword(s):  
Anticoagulant Therapy ◽  
Vitamin K ◽  
Oral Anticoagulant ◽  
Protein C ◽  
Oral Anticoagulant Therapy ◽  
Factor Vii ◽  
Factor X ◽  
Functional Protein ◽  
Thrombotic Risk ◽  
Factor Ii

It is still on discussion how oral anticoagulant therapy must be interrupted. A progressive diminution of drug intake have been proposed in order to avoid a MreboundM of vitamin K-dependent procoagulant factors. At the present, it is well known that coumarin drugs affect not only the biologic activity of factors II, VII, IX and X but also Protein C (PC), an inhibitor of coagulation kinetics, and their cofactor Protein S. With the aim to determine the recovery level of PC in relation with the others vitamin K-dependent factors, the effect of suppression of anticoagulant therapy in patients under chronic treatment with acenocoumarin was studied.Quick time, functional factors II, VII, X (one stage methods), functional PC (Francis method) and immunological Factor II and Protein C (Laurell) were determined before and 36 hours after suspension of acenocoumarin administration.Results showed that: 1) Recovery levels of functional Protein C (increased from 28.55% ±2.57 to 72.64% ±5.9) were significantly higer than functional Factor II (22.09% ±2.34 to 30.73% ±8.64), Factor VII (22.55% ±2.01 to 40.73% ±4.85) and Factor X (23.27% ±2.66 to 39.18% ±3.19). Statistical analysis (Newmann-Keuls test) showed at least a p<0.01 between PC increase and factors II, VII or X increment.2) No significant differences were seen between immunological levels of Factor II before and after suspension of acenocoumarin.3) Levels of immunological PC in patients under anticoagulant therapy were higer than functional PC. After acenocoumarin suppression, not correlation was seen between immunological and functional Protein C recovery.It is concluded that acute suppression of acenocoumarin does not induce a thrombotic tendency because the recuperation of functional Protein C is more important than factors II, VII and X recovery.

scholarly journals Plasma levels of protein C and vitamin K-dependent coagulation factors in patients on long-term oral anticoagulant therapy.

1986 ◽  
Vol 149 (4) ◽  
pp. 351-357 ◽  
Author(s):  
HOYU TAKAHASHI ◽  
MASAHARU HANANO ◽  
SENJI HAYASHI ◽  
YUTAKA ARAI ◽  
NORIKO YOSHINO ◽  
...  
Keyword(s):  
Anticoagulant Therapy ◽  
Vitamin K ◽  
Plasma Levels ◽  
Oral Anticoagulant ◽  
Protein C ◽  
Oral Anticoagulant Therapy ◽  
Coagulation Factors

Behavior of protein S during long-term oral anticoagulant therapy

1988 ◽  
Vol 51 (3) ◽  
pp. 241-249 ◽  
Author(s):  
Hoyu Takahashi ◽  
Ken Wada ◽  
Senji Hayashi ◽  
Masaharu Hanano ◽  
Wataru Tatewaki ◽  
...  
Keyword(s):  
Anticoagulant Therapy ◽  
Oral Anticoagulant ◽  
Oral Anticoagulant Therapy ◽  
Protein S

Controlled Trial of the Sequential Use of Streptokinase and Ancrod in the Treatment of Deep Vein Thrombosis of Lower Limb

1977 ◽  
Vol 37 (02) ◽  
pp. 222-232 ◽  
Author(s):  
D. A Tibbutt ◽  
C. N Chesterman ◽  
E. W Williams ◽  
T Faulkner ◽  
A. A Sharp
Keyword(s):  
Deep Vein Thrombosis ◽  
Clinical Improvement ◽  
Anticoagulant Therapy ◽  
Lower Limb ◽  
Oral Anticoagulant ◽  
Controlled Trial ◽  
Oral Anticoagulant Therapy ◽  
Control Group ◽  
Vein Thrombosis ◽  
Deep Vein

SummaryTreatment with streptokinase (‘Kabikinase’) was given to 26 patients with venographically confirmed deep vein thrombosis extending into the popliteal vein or above. Treatment was continued for 4 days and the patients were allocated randomly to oral anticoagulant therapy or a course of treatment with ancrod (‘Arvin’) for 6 days followed by oral anticoagulant therapy. The degree of thrombolysis as judged by further venographic examination at 10 days was not significantly different between the 2 groups. The majority of patients showed clinical improvement but there was no appreciable difference between the groups at 3 and 6 months. Haemorrhagic complications were a more serious problem during the period of treatment with ancrod than during the equivalent period in the control group.

Long-Term Outcomes in Patients Undergoing Coronary Stenting on Dual Oral Antiplatelet Treatment Requiring Oral Anticoagulant Therapy

2008 ◽  
Vol 102 (12) ◽  
pp. 1618-1623 ◽  
Author(s):  
Roberta Rossini ◽  
Giuseppe Musumeci ◽  
Corrado Lettieri ◽  
Maria Molfese ◽  
Laurian Mihalcsik ◽  
...  
Keyword(s):  
Anticoagulant Therapy ◽  
Oral Anticoagulant ◽  
Oral Anticoagulant Therapy ◽  
Coronary Stenting ◽  
Long Term Outcomes ◽  
Antiplatelet Treatment

scholarly journals Compliance with and awareness about long-term oral anticoagulant therapy among Saudi patients in a University Hospital, Riyadh, Saudi Arabia

2016 ◽  
Vol 7 (1) ◽  
pp. 10 ◽  
Author(s):  
NervanaM. K Bayoumy ◽  
ShehanahFahad Al-Omair ◽  
NorahAhmed Musallam ◽  
NoraYazid Al-Deghaither ◽  
NoufAbdulwahab Al-Sadoun
Keyword(s):  
Saudi Arabia ◽  
Anticoagulant Therapy ◽  
Oral Anticoagulant ◽  
Oral Anticoagulant Therapy ◽  
University Hospital ◽  
Saudi Patients

Bleeding complications to long-term oral anticoagulant therapy

1994 ◽  
Vol 1 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Annette Lemche Gull�v ◽  
Birgitte Gade Koefoed ◽  
Palle Petersen
Keyword(s):  
Anticoagulant Therapy ◽  
Oral Anticoagulant ◽  
Oral Anticoagulant Therapy ◽  
Bleeding Complications

Inhibition of Activated Protein C Anticoagulant Activity by Prothrombin

Blood ◽  
1999 ◽  
Vol 94 (11) ◽  
pp. 3839-3846 ◽  
Author(s):  
Mikhail D. Smirnov ◽  
Omid Safa ◽  
Naomi L. Esmon ◽  
Charles T. Esmon
Keyword(s):  
Anticoagulant Therapy ◽  
Oral Anticoagulant ◽  
Protein C ◽  
Anticoagulant Activity ◽  
Oral Anticoagulant Therapy ◽  
Membrane Surface ◽  
Activated Protein C ◽  
Significant Risk ◽  
Thrombotic Risk ◽  
Factor Va

Abstract In this study, we test the hypothesis that prothrombin levels may modulate activated protein C (APC) anticoagulant activity. Prothrombin in purified systems or plasma dramatically inhibited the ability of APC to inactivate factor Va and to anticoagulate plasma. This was not due solely to competition for binding to the membrane surface, as prothrombin also inhibited factor Va inactivation by APC in the absence of a membrane surface. Compared with normal factor Va, inactivation of factor Va Leiden by APC was much less sensitive to prothrombin inhibition. This may account for the observation that the Leiden mutation has less of an effect on plasma-based clotting assays than would be predicted from the purified system. Reduction of protein C levels to 20% of normal constitutes a significant risk of thrombosis, yet these levels are observed in neonates and patients on oral anticoagulant therapy. In both situations, the correspondingly low prothrombin levels would result in an increased effectiveness of the remaining functional APC of ≈5-fold. Thus, while the protein C activation system is impaired by the reduction in protein C levels, the APC that is formed is a more effective anticoagulant, allowing protein C levels to be reduced without significant thrombotic risk. In situations where prothrombin is high and protein C levels are low, as in early stages of oral anticoagulant therapy, the reduction in protein C would result only in impaired function of the anticoagulant system, possibly explaining the tendency for warfarin-induced skin necrosis.

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