Hereditary Protein S Deficiency and Venous Thrombo-Embolism

1985 ◽  
Vol 53 (02) ◽  
pp. 273-277 ◽  
Author(s):  
A W Broekmans ◽  
R M Bertina ◽  
J Reinalda-Poot ◽  
L Engesser ◽  
H P Muller ◽  
...  
Keyword(s):  
Total Protein ◽  
Oral Anticoagulant ◽  
Anticoagulant Activity ◽  
Coagulation Factor ◽  
Protein S ◽  
Protein S Deficiency ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
S Deficiency ◽  
The Mean

SummaryProtein S, a vitamin K-dependent coagulation factor, is involved in the regulation of the anticoagulant activity of activated protein C.Using an immunoradiometric assay for total protein S in plasma we identified 14 patients (7 male and 7 female) in three unrelated Dutch families as fulfilling the criteria for an isolated protein S deficiency. In 9 patients who were not receiving oral anticoagulant treatment the mean total protein S antigen concentration was 0.50 ± 0.08 U/ml (± S.D.) and the calculated free protein S concentration was 0.15 ± 0.01 U/ml (± S.D.). In the five patients who were on oral anticoagulant treatment the mean total protein S antigen was 0.23 ± 0.05 U/ml (± S.D.).Seven of the 14 patients had a history of venous thromboembolism occurring at a mean age of 25 years and often without an apparent cause. Protein S deficiency is inherited as an autosomal dominant trait.

A Mutation in the Protein S Pseudogene Is Linked to Protein S Deficiency in a Thrombophilic Family

1989 ◽  
Vol 62 (03) ◽  
pp. 897-901 ◽  
Author(s):  
Hans K Ploos van Amstel ◽  
Pieter H Reitsma ◽  
Karly Hamulyák ◽  
Christine E M de Die-Smulders ◽  
Pier M Mannucci ◽  
...  
Keyword(s):  
Total Protein ◽  
Protein S ◽  
Southern Analysis ◽  
Type I ◽  
Protein S Deficiency ◽  
S Deficiency ◽  
The Family ◽  
Dna Pattern ◽  
Deficiency Type ◽  
S Genes

SummaryProbands from 15 unrelated families with hereditary protein S deficiency type I, that is having a plasma total protein S concentration fifty percent of normal, were screened for abnormalities in their protein S genes by Southern analysis. Two probands were found to have a deviating DNA pattern with the restriction enzyme Mspl. In the two patients the alteration concerned the disappearance of a Mspl restriction site, CCGG, giving rise to an additional hybridizing Mspl fragment.Analysis of relatives of both probands showed that in one family the mutation does not co-segregate with the phenotype of reduced plasma protein S. In the family of the other proband, however, complete linkage between the mutated gene pattern and the reduced total protein S concentration was found: 12 heterozygous relatives showed the additional Mspl fragment but none of the investigated 26 normal members of the family. The mutation is shown to reside in the PSβ gene, the inactive protein S gene. The cause of type I protein S deficiency, a defect PSα gene has escaped detection by Southern analysis. No recombination has occurred between the PSα gene and the PSβ gene in 23 informative meioses. This suggests that the two protein S genes, located near the centromere of chromosome 3, are within 4 centiMorgan of each other.

Protein S mRNA in Patients with Protein S Deficiency

1995 ◽  
Vol 73 (05) ◽  
pp. 746-749 ◽  
Author(s):  
E Sacchi ◽  
M Pinotti ◽  
G Marchetti ◽  
G Merati ◽  
L Tagliabue ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Total Protein ◽  
Restriction Analysis ◽  
Protein S ◽  
Type I ◽  
Protein S Deficiency ◽  
Phenotypic Analysis ◽  
S Deficiency ◽  
Deficiency Type ◽  
S Genes

SummaryA protein S gene polymorphism, detectable by restriction analysis (BstXI) of amplified exonic sequences (exon 15), was studied in seven Italian families with protein S deficiency. In the 17 individuals heterozygous for the polymorphism the study was extended to platelet mRNA through reverse transcription, amplification and densitometric analysis. mRNA produced by the putative defective protein S genes was absent in three families and reduced to a different extent (as expressed by altered allelic ratios) in four families. The allelic ratios helped to distinguish total protein S deficiency (type I) from free protein S deficiency (type IIa) in families with equivocal phenotypes. This study indicates that the study of platelet mRNA, in association with phenotypic analysis based upon protein S assays in plasma, helps to classify patients with protein S deficiency.

scholarly journals Protein S for Portal Vein Thrombosis in Cirrhotic Patients Waiting for Liver Transplantation

2020 ◽  
Vol 9 (4) ◽  
pp. 1181
Author(s):  
Hao-Chien Hung ◽  
Jin-Chiao Lee ◽  
Chih-Hsien Cheng ◽  
Yu-Chao Wang ◽  
Tsung-Han Wu ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Risk Factor ◽  
Portal Vein ◽  
Independent Risk Factor ◽  
Protein S ◽  
Protein S Deficiency ◽  
Term Survival ◽  
S Deficiency ◽  
Cirrhotic Patients ◽  
The Mean

Portal vein thrombus (PVT) is a challenge in liver transplantation. How PVT develops in cirrhotic patients who already have coagulopathy is unclear. This study aimed to investigate possible contributing factors to PVT in cirrhotic patients. A total of 349 cirrhotic patients who waited liver transplantation were included in this study and 48 of them had PVT. For all the patients, the mean age was 53.5 ± 9.0 year old, and 75.9% of the patients were male. There were 233 (66.8%) patients who had either hepatitis B or C. The mean Model For End-Stage Liver Disease (MELD) score was 16.4 ± 7.5. Eighteen of 48 patients with PVT and 145 of 301 patients without PVT received liver transplantation. Multivariate analysis showed that low protein S level (hazard ratio = 2.46, p = 0.017) was the only independent risk factor for PVT development. Protein S deficiency also demonstrated prognostic value on short-term survival, not only for cirrhotic patients awaiting liver transplantation (69.9% versus 84.1% at 1 year survival, p = 0.012), but also for the patients having liver transplantation (70.4% versus 84.8% at 1 year survival, p = 0.047). In conclusion, protein S level was an independent risk factor for PVT development in decompensated cirrhotic patients, and protein S deficiency was also a prognostic factor for the patients waiting for liver transplantation.

scholarly journals Familial protein S deficiency with a variant protein S molecule in plasma and platelets

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 213-221 ◽  
Author(s):  
HP Schwarz ◽  
MJ Heeb ◽  
R Lottenberg ◽  
H Roberts ◽  
JH Griffin
Keyword(s):  
Gene Expression ◽  
Family Member ◽  
Anticoagulant Activity ◽  
Oral Anticoagulants ◽  
Protein S ◽  
The Other ◽  
Protein S Deficiency ◽  
Functional Protein ◽  
S Deficiency ◽  
Variant Protein

Abstract A protein S deficient family presenting a variant protein S molecule in plasma and platelets is described. The propositus, age 20, and two brothers suffered from venous thrombotic disease. The propositus, the only family member studied while taking oral anticoagulants, had a protein S antigen (ag) level of 17% and undetectable activity. As demonstrated by immunoblotting both the propositus and one clinically affected brother (42% ag, 7% activity) presented variant protein S molecules of 65,000 molecular weight (mol wt) while the other clinically affected brother (64% ag, 11% activity) had only protein S with normal electrophoretic mobility of 70,000 mol wt. The mother had normal protein S levels (93% ag, 100% activity) but had both normal and variant protein S molecules and based on her functional protein S data a normal anticoagulant activity of the variant molecule is suggested. One asymptomatic but protein S deficient sister (68% ag, 9% activity) as well as the asymptomatic protein S deficient father (59% ag, 10% activity) had only protein S molecules of 70,000 mol wt. The variant protein S bound to C4b-binding protein in plasma, and differed from normal protein S in carbohydrate content. Platelets of each family member contained the same immunoblotting pattern of normal and variant protein S forms as found in plasma, consistent with the hypothesis that protein S gene expression involves codominant expression of two alleles that is similar in cells that control the synthesis of both platelet and plasma forms of protein S.

ANTICOAGULANT AND ANTIGENIC LEVELS OF PROTEIN C AND PROTEIN S IN PATIENTS ON STABILIZED ORAL ANTICOAGULANT TREATMENT

1987 ◽  
Author(s):  
A D'Angelo ◽  
F Gilardoni ◽  
M P Seveso ◽  
P Poli ◽  
R Quintavalle ◽  
...  
Keyword(s):  
Vitamin K ◽  
Oral Anticoagulant ◽  
Protein C ◽  
Protein S ◽  
Reference Interval ◽  
Factor Ix ◽  
Activity Levels ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
Congenital Deficiency

Isolated deficiencies of protein C and protein S, two vitamin K-dependent plasma proteins, constitute about 70% of the congenital abnormalities of blood coagulation observed in patients with recurrent venous thrombosis beLow the age of 40. The laboratory diagnosis of congenital deficiency of these proteins represents a major problem since a large proportion of patients are on oral anticoagulation (OA) at the time the deficiencies are suspected.Under these circumstances the availability of a reference interval obtained in patients on stabilized OA has proven useful.Functional (C) and antigenic levels (Ag) of protein C, protein S, factor IX and II were estimated in 136 patients on stabilized OA, subdivided according to the degree of anticoagulation (Internatio nal Normalized Ratio, INR).The results indicate that with increasing anticoagulation the activity levels of all the vitamin K-dependent factors decrease to a greater extent than the corresponding antigenic levels. At variance with the other factors, total protein S antigen levels are only moderately reduced by OA with protein S anticoagulant activi ty comparing well to factor IX clotting activity. These data suggest the possibility of identifying both quantitative and qualita tive deficiencies of protein C and protein S in patients on oral anticoagulant treatment.

Hormonal State rather than Age Influences Cut-off Values of Protein S: Reevaluation of the Thrombotic Risk Associated with Protein S Deficiency

1999 ◽  
Vol 82 (09) ◽  
pp. 1093-1096 ◽  
Author(s):  
G. Liberti ◽  
R. M. Bertina ◽  
F. R. Rosendaal
Keyword(s):  
Total Protein ◽  
Protein S ◽  
Independent Effect ◽  
Healthy Population ◽  
Reference Ranges ◽  
Protein S Deficiency ◽  
Thrombotic Risk ◽  
Free Protein ◽  
S Deficiency ◽  
Menopausal State

SummaryOf the well known risk factors for thrombosis protein S deficiency is one of the most difficult to diagnose with certainty. Reliable estimates for the prevalence of protein S deficiency in the general population are not available and the risk of thrombosis is a controversial issue. It has been shown that levels of protein S fluctuate over time. However the determinants of low levels of protein S in the healthy population are not clear. Therefore, we evaluated the influence of sex, age and hormonal state on the antigen levels of protein S in 474 healthy control subjects of the Leiden Thrombophilia Study (LETS). In univariate analysis, sex, age, oral contraceptive (OC) use and post-menopausal state all influenced protein S antigen levels. In a multivariate model for the whole sample only menopausal state and OC use had still an effect on the levels of total protein S and only menopausal state had an independent effect on the values of free protein S. On the basis of this analysis we established different cut-off levels for these subgroups and we re-evaluated in the Leiden Thrombophilia Study the risk of thrombosis for individuals with low protein S using these different reference ranges. With these specific cut-off points, we did not observe an increase in the risk of thrombosis in patients deficient of total protein S (OR 1.2, 95% CI 0.5-2.9) or free protein S (OR 1.3, 95% CI 0.5-3.5). When men and women were analyzed separately, the risk in women was 1.5 (95% CI 0.4-5.4) and 2.4 (95% CI 0.6-9.2) for total and free protein S deficiencies, respectively; and there was no increase in thrombotic risk for men. We conclude that it may be helpful to apply separate cut-off levels in the assessment of protein S levels. This does not, however explain the differences between our results and those of others in the estimate of thrombotic risk of protein S deficiency.

scholarly journals A Rare Case of Portal Vein Thrombosis due to Protein S deficiency in a patient with Decompensated Cryptogenic CLD with Portal Hypertension, Completely Recanalized by Single Oral Anticoagulant-Rivaroxaban

2020 ◽  
pp. 29-37
Author(s):  
Richmond Ronald Gomes
Keyword(s):  
Portal Hypertension ◽  
Liver Disease ◽  
Portal Vein ◽  
Portal Vein Thrombosis ◽  
Oral Anticoagulant ◽  
Protein S ◽  
Protein S Deficiency ◽  
Vein Thrombosis ◽  
S Deficiency ◽  
Hepatic Portal

Venous thromboembolic diseases are a group of heterogeneous diseases with different clinical forms and prognosis. Abdominal venous thrombosis may present either as Budd-Chiari syndrome (BCS) caused by hepatic vein or proximal inferior vena cava (IVC) obstruction or as an extra hepatic portal obstruction (EHPVO) caused by Portal vein thrombosis or mesenteric vein thrombosis. Portal vein thrombosis (PVT) is a rare form of venous thrombosis that affects the hepatic portal vein flow, which can lead to portal hypertension. Treatment of PVT includes anticoagulants, thrombolysis, and insertion of shunts, bypass surgery, and liver transplantation. Single anticoagulation therapy can be associated with a reduction in new thrombotic episodes. Here we experienced a 23 year old young lady with history of recent intrauterine death (IUD) diagnosed as PVT provoked by protein S deficiency with newly diagnosed decompensated cryptogenic chronic liver disease with portal hypertension. PVT was completely recanalized with single oral anticoagulant therapy rivaroxaban as initial low molecular weight heparin, enoxaparin administration caused reversible pancytopenia and there is a concern for bleeding and regular monitoring of INR with warfarin in this patient. Keywords: Portal vein thrombosis; Chronic liver disease; Protein S deficiency; Oral anticoagulant; Portal hypertension; Thrombolysis

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