Immunoradiometric Assay for the Calcium-Stabilized Conformation of Human Protein S

1987 ◽  
Vol 58 (04) ◽  
pp. 0998-1004 ◽  
Author(s):  
S R Poort ◽  
P P Deutz-Terlouw ◽  
A van Wijngaarden ◽  
R M Bertina
Keyword(s):  
Lower Limit ◽  
Anticoagulant Therapy ◽  
Oral Anticoagulant ◽  
Limit Of Detection ◽  
Solid Phase ◽  
Oral Anticoagulant Therapy ◽  
Protein S ◽  
Human Protein ◽  
Type I ◽  
Oral Anticoagulant Treatment

SummaryRabbit polyclonal anti-protein S serum was fractionated with immobilized human protein S to establish solid-phase immunoradiometric assays recognizing Ca(II)-dependent and NonCa(II)-dependent epitopes of human protein S. The two assays were specific for PS:Ca(II)Ag and PS:NonCa(II)Ag and highly sensitive with a lower limit of detection of about 2.5 ng/ml.PS:Ca(II)Ag and PS:NonCa(II)Ag levels were measured in immunopurified protein S, thrombin-modified protein S and chy-motrypsin-cleaved protein S. Only in chymotrypsin-cleaved protein S an important discrepancy between the two antigen levels was observed.Ranges for the concentration of PS:Ca(II)Ag and PS:NonCa(II)Ag and their ratio were established in plasma of healthy individuals (0.92 ± 0.13 U/ml, 0.98 ± 0.21 U/ml, 0.96 ± 0.17, respectively). In a group of patients using oral anticoagulant therapy the ratio PS:Ca(II) Ag/PS : NonCa(II)Ag decreased at increasing intensity of anticoagulation suggesting the presence of sub- and noncarboxylated protein S molecules.In plasma of patients with a hereditary type I protein S deficiency PS:Ca(II)Ag and PS:NonCa(II) Ag were reduced to the same extent: mean ratio 1.02 ± 0.12 in the group not on oral anticoagulant treatment and 0.94 ± 0.10 in the group on oral anticoagulant therapy. Analysis of patients with a history of unexplained thrombo-embolic disease did not reveal individual patients with a PS:Ca(II)Ag/PS:NonCa(II)Ag ratio below the lower limit of the normal range (mean ratio 1.05 ± 0.17), suggesting that the frequency of genetic protein S variants with defects in the Ca(II)-stabilized conformation is very low.

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 association between atrial fibrillation and pulmonary embolism

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Svennberg ◽  
L Friberg
Keyword(s):  
Atrial Fibrillation ◽  
Pulmonary Embolism ◽  
Risk Factor ◽  
Anticoagulant Therapy ◽  
Oral Anticoagulant ◽  
Oral Anticoagulant Therapy ◽  
Funding Source ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
Increased Risk

Abstract Background and objectives Previous studies have suggested that atrial fibrillation is a risk factor for pulmonary embolism. Oral anticoagulant therapy is the mainstay of treatment for atrial fibrillation and pulmonary embolism. We wanted to investigate if atrial fibrillation remained associated with the development of pulmonary embolism if oral anticoagulant treatment was accounted for. Method In this retrospective registry study a random sample of 20% of the adult Swedish population comprising approximately 1.5 million individuals were included during 2010–2017 in a cohort analysis. The endpoint was acute pulmonary embolism. In the cohort study, patients were analysed according to oral anticoagulant treatment and presence of atrial fibrillation at baseline. Results The group with atrial fibrillation was &gt;25 years older than the group without and had almost three times higher incidence of pulmonary embolism (2.91 vs 1.09 /1000 year at risk, p&lt;0.001). Individuals with atrial fibrillation on oral anticoagulant therapy had a lower risk of pulmonary embolism in multi-variable analysis (HR 0.59, CI 0.45–0.77). In the unadjusted analysis participants with atrial fibrillation without oral anticoagulant therapy showed an increased risk of pulmonary embolism (HR 3.33, CI 3.05–3.63). However, after multi-variable adjustment this association disappeared (HR 0.98, CI 0.89–1.07). In the entire atrial fibrillation cohort, no association was seen with the development of pulmonary embolism after multi-variable adjustment (HR 0.92, CI 0.84–1.01). The higher rate of pulmonary embolism among patients with atrial fibrillation can be fully explained by differences in age and co-morbidity. Conclusion Atrial fibrillation does not appear to be a clinically relevant risk factor for pulmonary embolism. Oral anticoagulant therapy protects against the development of pulmonary embolism in patients with atrial fibrillation. Associations with pulmonary embolism Funding Acknowledgement Type of funding source: Other. Main funding source(s): The main author has received funding from Stockholm County Council (Clinical postdoctorial appointment)

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

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.

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.

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