Protein C Deficiency in a Dutch Family with Thrombotic Disease

1982 ◽  
Vol 48 (01) ◽  
pp. 001-005 ◽  
Author(s):  
R M Bertina ◽  
A W Broekmans ◽  
I K van der Linden ◽  
K Mertens
Keyword(s):  
Protein C ◽  
Quantitative Estimation ◽  
Factor X ◽  
Protein C Deficiency ◽  
Oral Anticoagulant Treatment ◽  
Thrombotic Disease ◽  
Normal Ranges ◽  
Factor Ii ◽  
History Of ◽  
Dutch Family

SummaryA rabbit antibody against human protein C was used for the quantitative estimation of protein C in plasma. In healthy individuals protein C antigen ranged from 0.65-1.45 U/ml. Plasma protein C antigen was found to be independent of either age or sex. Under influence of oral anticoagulant treatment the protein C antigen concentration decreased to 0.47 U/ml (at low intensity treatment) or 0.33 U/ml (at high intensity treatment). Using normal ranges of protein C and protein C/factor II and protein C/factor X ratios criteria were developed for the assessment of protein C deficiency. In a Dutch family with a history of thrombotic disease two members were found to have an isolated protein C deficiency, while a third one is suspected of protein C deficiency. In one case it was possible to confirm the diagnosis of suspected protein C deficiency during temporary withdrawal of the anticoagulant therapy.

scholarly journals Plasma protein S deficiency in familial thrombotic disease

Blood ◽  
1984 ◽  
Vol 64 (6) ◽  
pp. 1297-1300 ◽  
Author(s):  
HP Schwarz ◽  
M Fischer ◽  
P Hopmeier ◽  
MA Batard ◽  
JH Griffin
Keyword(s):  
Plasma Protein ◽  
Protein C ◽  
Anticoagulant Activity ◽  
Oral Anticoagulant Therapy ◽  
Activated Protein C ◽  
Protein S ◽  
Factor X ◽  
Protein C Deficiency ◽  
Thrombotic Disease ◽  
Disease Protein

Abstract A family with a history of severe recurrent venous thromboembolic disease was studied to determine if a plasma protein deficiency could account for observed disease. Protein S levels in plasma were determined immunologically using the Laurell rocket technique. The propositus, his mother, his aunt, and his cousin who were clinically affected had 17% to 65% of the control levels of protein S antigen (normal range, 71% to 147%). Since three of these patients were receiving oral anticoagulant therapy, the ratios of protein S to prothrombin, factor X, and protein C in these patients were compared with values for a group of orally anticoagulated controls. These results suggested that protein S is half-normal in all family members with thrombotic disease. Other proteins known to be associated with familial thrombotic disease, including antithrombin III, plasminogen, fibrinogen, and protein C, were normal. Because plasma protein S serves as a cofactor for the anticoagulant activity of activated protein C and because protein C deficiency is associated with recurrent thrombotic disease, it is suggested that recurrent thrombotic disease in this family is the result of an inherited deficiency of protein S.

Protein C Deficiency in Two Austrian Families

1983 ◽  
Vol 50 (04) ◽  
pp. 810-813 ◽  
Author(s):  
I Pabinger-Fasching ◽  
R M Bertina ◽  
K Lechner ◽  
H Niessner ◽  
Ch Korninger
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Autosomal Dominant ◽  
Antigen Concentration ◽  
Protein C Deficiency ◽  
Oral Anticoagulant Treatment ◽  
Vein Thrombosis ◽  
History Of ◽  
Anticoagulated Patients ◽  
Thrombotic Tendency

SummaryProtein C antigen was determined by Laurell rocket immunelectrophoresis in 225 patients with a history of venous thrombosis. Among these patients two females with protein C deficiency were detected. Additional studies in the families of the protein C deficient patients revealed further 7 family members with protein C deficiency. In 8 not anticoagulated patients with protein C deficiency the protein C ranged from 36 to 62% (median: 45%). In one patient on oral anticoagulant treatment protein C antigen concentration was < 10%, FII and F X were 65 and 50%, respectively. The pattern of inheritance was consistent with autosomal dominant inheritance. 5 of the 9 protein C deficient patients had severe thrombotic tendency characterized by recurrent deep venous thrombosis (n = 4), pulmonary embolism (n = 1), probable mesenteric vein thrombosis (n = 1) and superficial thrombophlebitis (n = 2). All protein C deficient patients without thrombosis were less than 17 years old.

Severe Protein C Deficiency in Congenital Thrombotic Disease – Description of an Immunoenzymological Assay for Protein C Determination

1985 ◽  
Vol 53 (03) ◽  
pp. 293-296 ◽  
Author(s):  
J Soria ◽  
C Soria ◽  
M Samama ◽  
G Nicolas ◽  
W Kisiel
Keyword(s):  
Protein C ◽  
Quantitative Assay ◽  
Sensitive Assay ◽  
Protein C Deficiency ◽  
Thrombotic Disease ◽  
Routine Investigation ◽  
Disease Protein ◽  
History Of ◽  
Immunoenzymatic Assay

SummaryAn immunoenzymatic assay (ELISA) is described for the quantitative assay of protein C in plasma. This technique allows a safe, reliable, and sensitive assay of protein C, and is easily used for routine investigation. Using this technique, a protein C deficiency (0.16 U/ml) was discovered in a 16 year old patient with a history of very severe thrombotic disease. Protein C deficiency was also discovered in his mother (0.62 U/ml) and father (0.50 U/ml). We therefore suggest that this case could represent a homozygous deficiency of protein C.

scholarly journals Plasma protein S deficiency in familial thrombotic disease

Blood ◽  
1984 ◽  
Vol 64 (6) ◽  
pp. 1297-1300 ◽  
Author(s):  
HP Schwarz ◽  
M Fischer ◽  
P Hopmeier ◽  
MA Batard ◽  
JH Griffin
Keyword(s):  
Plasma Protein ◽  
Protein C ◽  
Anticoagulant Activity ◽  
Oral Anticoagulant Therapy ◽  
Activated Protein C ◽  
Protein S ◽  
Factor X ◽  
Protein C Deficiency ◽  
Thrombotic Disease ◽  
Disease Protein

A family with a history of severe recurrent venous thromboembolic disease was studied to determine if a plasma protein deficiency could account for observed disease. Protein S levels in plasma were determined immunologically using the Laurell rocket technique. The propositus, his mother, his aunt, and his cousin who were clinically affected had 17% to 65% of the control levels of protein S antigen (normal range, 71% to 147%). Since three of these patients were receiving oral anticoagulant therapy, the ratios of protein S to prothrombin, factor X, and protein C in these patients were compared with values for a group of orally anticoagulated controls. These results suggested that protein S is half-normal in all family members with thrombotic disease. Other proteins known to be associated with familial thrombotic disease, including antithrombin III, plasminogen, fibrinogen, and protein C, were normal. Because plasma protein S serves as a cofactor for the anticoagulant activity of activated protein C and because protein C deficiency is associated with recurrent thrombotic disease, it is suggested that recurrent thrombotic disease in this family is the result of an inherited deficiency of protein S.

Plasma Levels of Protein S, Protein C, and Factor X: Effects of Sex, Hormonal State and Age

1995 ◽  
Vol 74 (05) ◽  
pp. 1271-1275 ◽  
Author(s):  
C M A Henkens ◽  
V J J Bom ◽  
W van der Schaaf ◽  
P M Pelsma ◽  
C Th Smit Sibinga ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Postmenopausal Women ◽  
Protein C ◽  
Blood Donors ◽  
Premenopausal Women ◽  
Protein S ◽  
The Other ◽  
Factor X ◽  
Normal Ranges

SummaryWe measured total and free protein S (PS), protein C (PC) and factor X (FX) in 393 healthy blood donors to assess differences in relation to sex, hormonal state and age. All measured proteins were lower in women as compared to men, as were levels in premenopausal women as compared to postmenopausal women. Multiple regression analysis showed that both age and subgroup (men, pre- and postmenopausal women) were of significance for the levels of total and free PS and PC, the subgroup effect being caused by the differences between the premenopausal women and the other groups. This indicates a role of sex-hormones, most likely estrogens, in the regulation of levels of pro- and anticoagulant factors under physiologic conditions. These differences should be taken into account in daily clinical practice and may necessitate different normal ranges for men, pre- and postmenopausal women.

The Influence of Insulin, ß-Estradiol, Dexamethasone and Thyroid Hormone on the Secretion of Coagulant and Anticoagulant Proteins by HepG2 Cells

1995 ◽  
Vol 74 (02) ◽  
pp. 686-692 ◽  
Author(s):  
René W L M Niessen ◽  
Birgit A Pfaffendorf ◽  
Augueste Sturk ◽  
Roy J Lamping ◽  
Marianne C L Schaap ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Protein C ◽  
Protein Production ◽  
Culture Medium ◽  
Protein S ◽  
Cell Protein ◽  
Hepatoma Cell Line ◽  
Factor X ◽  
Factor Ii ◽  
At Iii

SummaryAs a basis for regulatory studies on the influence of hormones on (anti)coagulant protein production by hepatocytes, we examined the amounts of the plasma proteins antithrombin III (AT III), protein C, protein S, factor II, factor X, fibrinogen, and prealbumin produced by the hepatoma cell line HepG2, into the culture medium, in the absence and presence of insulin, β-estradiol, dexamethasone and thyroid hormone. Without hormones these cells produced large amounts of fibrinogen (2,452 ± 501 ng/mg cell protein), AT III (447 ± 16 ng/mg cell protein) and factor II (464 ± 31 ng/mg cell protein) and only small amounts of protein C (50 ± 7 ng/mg cell protein) and factor X (55 ± 5 ng/mg cell protein). Thyroid hormone had a slight but significant effect on the enrichment in the culture medium of the anticoagulant protein AT III (1.34-fold) but not on protein C (0.96-fold) and protein S (0.91-fold). This hormone also significantly increased the amounts of the coagulant proteins factor II (1.28-fold), factor X (1.45-fold) and fibrinogen (2.17-fold). Insulin had an overall stimulating effect on the amounts of all the proteins that were investigated. Neither dexamethasone nor ß-estradiol administration did substantially change the amounts of these proteins.We conclude that the HepG2 cell is a useful tool to study the hormonal regulation of the production of (anti)coagulant proteins. We studied the overall process of protein production, i.e., the amounts of proteins produced into the culture medium. Detailed studies have to be performed to establish the specific hormonal effects on the underlying processes, e.g., transcription, translation, cellular processing and transport, and secretion.

C0045 Protein c deficiency in a family with a history of childhood thrombosis

2012 ◽  
Vol 130 ◽  
pp. S131
Author(s):  
Anicee Danaee ◽  
Jayanthi Alamelu ◽  
David Bevan
Keyword(s):  
Protein C ◽  
Protein C Deficiency ◽  
History Of Childhood ◽  
History Of

PROTEIN C, PROTEIN S AND THE FIBRINOLYTIC SYSTEM IN PATIENTS WITH A HISTORY OF THROMBOSIS

1987 ◽  
Author(s):  
J Malm ◽  
M Laurell ◽  
I M Nilsson ◽  
B Dahlbäck
Keyword(s):  
Plasminogen Activator ◽  
Fibrinolytic Activity ◽  
Protein C ◽  
Protein S ◽  
Protein S Deficiency ◽  
Functional Protein ◽  
Protein C Deficiency ◽  
S Deficiency ◽  
Tissue Plasminogen ◽  
History Of

Consecutive patients with a history of thrombo-embolic disease (n = 241, 109 males, 132 females, mean age 46 y), referred to the Coagulation Laboratory during an 18 month period, were analysed for defects in their coagulation and fibrinolytic systems. The diagnosis of thrombosis had been verified with phlebography and that of pulmonary embolus with scintigraphy or angiography. Retinal venous thrombosis was found in 15 of the patients. In 15 cases the thrombotic episodes occurred postoperatively, in 15 during pregnancy, in 12 during the postpartum period and in 20 during use of oral contraceptives. In the remaining cases no clinical riskfactors were identified.The concentration of protein C zymogen was measured with an immunoradiometric assay. Functional protein C was determined with a clotting inhibition assay. Protein C deficiency was found in 8 cases. Two of these had a functional protein C deficiency with normal zymogen levels. The concentration of total, as well as free (not in complex with C4b-binding protein), protein S was determined with a radioimmunoassay. Two cases of protein S deficiency were detected. Three patients with antithrombin III deficiency and two with plasminogen deficiency were found.The fibrinolytic activity after venous occlusion was analysed in 216 patients. Decreased levels were found in 32 %. The concentration of tissue plasminogen activator inhibitor (PAI) was measured in 110 patients and found to be increased in 65 % of the cases. In 99 patients both the fibrinolytic activity and the PAI concentration were measured. A combination of decreased fibrinolytic activity and increased levels of PAI was found in 44 cases. The concentration of tissue plasminogen activator antigen was decreased in 22 % of 105 cases analysed.Thus, in this material of patients with thrombo-embolic disease, abnormalities were found in 47 %. Defects in the fibrinolytic system were the most common findings. Protein C or protein S deficiency was diagnosed in less than 5 % of the cases.

Hereditary Protein C-Deficiency: Laboratory Values in Transmitters and Guidelines for the Diagnostic Procedure Report on a Study of the SSC Subcommittee on Protein C and Protein S

1992 ◽  
Vol 68 (04) ◽  
pp. 470-474 ◽  
Author(s):  
I Pabinger ◽  
C F Allaart ◽  
J Hermans ◽  
E Briët ◽  
R M Bertina ◽  
...  
Keyword(s):  
Protein C ◽  
Protein S ◽  
Pedigree Analysis ◽  
Control Group ◽  
Factor X ◽  
Likelihood Ratios ◽  
Protein C Deficiency ◽  
Statistical Procedures ◽  
Genetically Determined ◽  
Protein C Activity

SummaryA multicenter study on protein C-antigen and -activity values was carried out in transmitter patients with hereditary protein C deficiency (diagnosis established by pedigree analysis) and in normal controls in order to (1) establish the range of protein C levels in genetically determined heterozygotes and (2) to evaluate the usefulness of statistical procedures to discriminate between protein C deficient patients and controls. In transmitters absolute protein C activity values ranged from 19 to 82% and antigen values from 22 to 88.5%. Most transmitter patients could clearly be differentiated from the control group. However, in some transmitter patients values of protein C were within the range of the control group. The discrimination between transmitters and controls could be improved by statistical procedures. Using tolerance ellipses the overlapping area of the two groups was smallest when (factor II antigen + factor X antigen)/2 was plotted against protein C antigen. To specify the degree of uncertainty likelihood ratios were calculated to obtain the posterior probability for an individual for being deficient or not. In quadratic discriminant analysis the best discrimination between transmitters and controls was obtained using protein C activity versus factor X antigen and protein C antigen versus factor X antigen. Based on these analysis an equation was derived, which allows the calculation of the likelihood ratio favouring deficiency or non-deficiency in an individual.

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