scholarly journals Recommendations for clinical laboratory testing for protein S deficiency: Communication from the SSC committee plasma coagulation inhibitors of the ISTH

2021 ◽  
Vol 19 (1) ◽  
pp. 68-74
Author(s):  
Richard A. Marlar ◽  
Jana N. Gausman ◽  
Hiroko Tsuda ◽  
Marian A. Rollins‐Raval ◽  
Herm Jan M. Brinkman
Keyword(s):  
Laboratory Testing ◽  
Clinical Laboratory ◽  
Protein S ◽  
Protein S Deficiency ◽  
Plasma Coagulation ◽  
S Deficiency ◽  
Coagulation Inhibitors ◽  
Clinical Laboratory Testing

The Frequency of Type I Heterozygous Protein S and Protein C Deficiency in 141 Unrelated Young Patients with Venous Thrombosis

1988 ◽  
Vol 59 (01) ◽  
pp. 018-022 ◽  
Author(s):  
C L Gladson ◽  
I Scharrer ◽  
V Hach ◽  
K H Beck ◽  
J H Griffin
Keyword(s):  
Venous Thrombosis ◽  
Protein C ◽  
Antithrombin Iii ◽  
Young Patients ◽  
Protein S ◽  
Type I ◽  
Protein S Deficiency ◽  
Protein C Deficiency ◽  
Low Protein ◽  
S Deficiency

SummaryThe frequency of heterozygous protein C and protein S deficiency, detected by measuring total plasma antigen, in a group (n = 141) of young unrelated patients (<45 years old) with venous thrombotic disease was studied and compared to that of antithrombin III, fibrinogen, and plasminogen deficiencies. Among 91 patients not receiving oral anticoagulants, six had low protein S antigen levels and one had a low protein C antigen level. Among 50 patients receiving oral anticoagulant therapy, abnormally low ratios of protein S or C to other vitamin K-dependent factors were presented by one patient for protein S and five for protein C. Thus, heterozygous Type I protein S deficiency appeared in seven of 141 patients (5%) and heterozygous Type I protein C deficiency in six of 141 patients (4%). Eleven of thirteen deficient patients had recurrent venous thrombosis. In this group of 141 patients, 1% had an identifiable fibrinogen abnormality, 2% a plasminogen abnormality, and 3% an antithrombin III deficiency. Thus, among the known plasma protein deficiencies associated with venous thrombosis, protein S and protein C. deficiencies (9%) emerge as the leading identifiable associated abnormalities.

Severe Arterial Cerebral Thrombosis in a Patient with Protein S Deficiency (Moderately Reduced Total and Markedly Reduced Free Protein S): A Family Study

1989 ◽  
Vol 61 (01) ◽  
pp. 144-147 ◽  
Author(s):  
A Girolami ◽  
P Simioni ◽  
A R Lazzaro ◽  
I Cordiano
Keyword(s):  
Arterial Thrombosis ◽  
Protein C ◽  
Protein S ◽  
Protein S Deficiency ◽  
Protein C Deficiency ◽  
Free Protein ◽  
Her Family ◽  
S Deficiency ◽  
Increased Risk ◽  
Patient Reported

SummaryDeficiency of protein S has been associated with an increased risk of thrombotic disease as already shown for protein C deficiency. Deficiencies of any of these two proteins predispose to venous thrombosis but have been only rarely associated with arterial thrombosis.In this study we describe a case of severe cerebral arterial thrombosis in a 44-year old woman with protein S deficiency. The defect was characterized by moderately reduced levels of total and markedly reduced levels of free protein S. C4b-bp level was normal. Protein C, AT III and routine coagulation tests were within the normal limits.In her family two other members showed the same defect. All the affected members had venous thrombotic manifestations, two of them at a relatively young age. No other risk factors for thrombotic episodes were present in the family members. The patient reported was treated with ASA and dipyridamole and so far there were no relapses.

The Relationship between Plasma Microparticles, Protein S and Anticardiolipin Antibodies in Patients with Human Immunodeficiency Virus Infection

1996 ◽  
Vol 76 (01) ◽  
pp. 038-045 ◽  
Author(s):  
Jean-Christophe Gris ◽  
Pierre Toulon ◽  
Sophie Brun ◽  
Claude Maugard ◽  
Christian Sarlat ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Anticardiolipin Antibody ◽  
Protein S ◽  
Anticardiolipin Antibodies ◽  
Protein S Deficiency ◽  
Free Protein ◽  
Precipitation Technique ◽  
S Deficiency ◽  
Immunodeficiency Virus ◽  
Antibody Titers

SummaryThe high prevalence of free protein S deficiency in human immunodeficiency virus (HlV)-infected patients is poorly understood. We studied 38 HIV seropositive patients. Free protein S antigen values assayed using the polyethylene-glycol precipitation technique (PEG-fS) were statistically lower in patients than in controls. These values using a specific monoclonal antibody-based ELISA (MoAb-fS) and the values of protein S activity (S-act) were not statistically different between patients and controls. C4b-binding protein values were not different from control values. In patients, PEG-fS values were lower than MoAb-fS values. Ten patients had a PEG-fS deficiency, 4 patients had a MoAb-fS deficiency and 8 had a S-act deficiency. Protein S activity and MoAb-fS were lower in clinical groups with poor prognosis and in patients with AIDS but PEG-fS was not. A trend for reduced S-act/MoAb-fS ratios was observed in patients. PEG-fS was negatively correlated with anticardiolipin antibody titers whereas MoAb-fS was not. The plasma of PEG-fS deficient HIV-patients contained high amounts of flow cytometry detectable microparticles which were depleted from plasma by PEG precipitation. The microparticles were partly CD42b and CD4 positive but CD8 negative. These microparticles were labelled by an anti free protein S monoclonal antibody. The observed differences between MoAb-fS and PEG-fS values were correlated with the amount of detectable plasma microparticles, just like the differences between MoAb-fS and S-act. Plasma microparticles correlated with anticardiolipin antibody titers.In summary, free protein S antigen in HIV infected patients is underestimated when the PEG precipitation technique is used due to the presence of elevated levels of microparticles that bind protein S. The activity of free protein S is also impaired by high levels of microparticles. The prevalence of free protein S deficiency in HIV positive patients is lower than previously published (4/38, -10%) and is correlated with poor prognosis. By implication, use of a PEG precipitation technique might give artefactually low free protein S antigen values in other patient groups if high numbers of microparticles are present. In HIV patients, high titers of anticardiolipin antibodies are associated with high concentrations of cell-derived plasma microparticles.

Factor V Leiden: An Additional Risk Factor for Thrombosis in Protein S Deficient Families?

1995 ◽  
Vol 74 (02) ◽  
pp. 580-583 ◽  
Author(s):  
B P C Koeleman ◽  
D van Rumpt ◽  
K Hamulyák ◽  
P H Reitsma ◽  
R M Bertina
Keyword(s):  
Protein C ◽  
Normal Population ◽  
Factor V Leiden ◽  
Protein S ◽  
Reliable Estimate ◽  
Additional Risk Factor ◽  
Protein S Deficiency ◽  
S Deficiency ◽  
High Prevalence ◽  
Fv Leiden

SummaryWe recently reported a high prevalence of the FV Leiden mutation (R506Q, responsible for Activated Protein C resistance) among symptomatic protein C deficient probands (19%), and the involvement of the FV Leiden mutation in the expression of thrombophilia in six protein C deficient families. Here, we report the results of a similar study in protein S deficient probands and families. Among 16 symptomatic protein S deficient probands the prevalence of the FV Leiden mutation was high (38%). This high prevalence is significantly different from that in the normal population, and is probably caused by the selection of probands for familial thrombosis and protein S deficiency. In 4 families, the segregation of the FV Leiden mutation and the protein S deficiency could be studied. In sibships where both abnormalities were segregating, the percentage of symptomatic individuals with both abnormalities was 80%. Three of the seven subjects with only the FV Leiden mutation, and two out of the three subjects with only protein S deficiency had developed thrombosis. These results indicate that in the families presented here the combination of the FV Leiden mutation and the protein S deficiency is associated with a high risk for thrombosis. A reliable estimate of the penetrance of the single defects is not possible, because the number of individuals with a single defect is too low.

Elevated Levels of Prothrombin Activation Fragment 1+2 in Plasma from Patients with Heterozygous Arg506 to Gin Mutation in the Factor V Gene (APC-Resistance) and/or Inherited Protein S Deficiency

1996 ◽  
Vol 75 (02) ◽  
pp. 270-274 ◽  
Author(s):  
Benget Zöller ◽  
Johan Holm ◽  
Peter Svensson ◽  
Björn Dahlbäck
Keyword(s):  
Plasma Concentration ◽  
Protein C ◽  
Protein S ◽  
Factor V ◽  
Protein S Deficiency ◽  
Apc Resistance ◽  
S Deficiency ◽  
Increased Risk ◽  
Factor V Gene ◽  
V Gene

SummaryInherited resistance to activated protein C (APC-resistance), caused by a point mutation in the factor V gene leading to replacement of Arg(R)506 with a Gin (Q), and inherited protein S deficiency are associated with functional impairment of the protein C anticoagulant system, yielding lifelong hypercoagulability and increased risk of thrombosis. APC-resistance is often an additional genetic risk factor in thrombosis-prone protein S deficient families. The plasma concentration of prothrombin fragment 1+2 (F1+2), which is a marker of hyper-coagulable states, was measured in 205 members of 34 thrombosis-prone families harbouring the Arg506 to Gin mutation (APC-resistance) and/or inherited protein S deficiency. The plasma concentration of F1+2 was significantly higher both in 38 individuals carrying the FV:Q506 mutation in heterozygous state (1.7 ± 0.7 nM; mean ± SD) and in 48 protein S deficient cases (1.9 ± 0.9 nM), than in 100 unaffected relatives (1.3 ±0.5 nM). Warfarin therapy decreased the F1+2 levels, even in those four patients who had combined defects (0.5 ± 0.3 nM). Our results agree with the hypothesis that individuals with APC-resistance or protein S deficiency have an imbalance between pro- and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state.

Autoimmune Protein S Deficiency and Deep Vein Thrombosis after Chickenpox

1996 ◽  
Vol 75 (01) ◽  
pp. 212-213 ◽  
Author(s):  
Flora Peyvandi ◽  
Elena Faioni ◽  
Gian Alessandro Moroni ◽  
Alberto Rosti ◽  
Luigi Leo ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Protein S ◽  
Protein S Deficiency ◽  
Vein Thrombosis ◽  
S Deficiency ◽  
Deep Vein

Arterial Thrombosis and Protein S Deficiency

1989 ◽  
Vol 62 (03) ◽  
pp. 1040-1040 ◽  
Author(s):  
P Sié ◽  
B Boneu ◽  
R Biermé ◽  
M L Wiesel ◽  
L Grunebaum ◽  
...  
Keyword(s):  
Arterial Thrombosis ◽  
Protein S ◽  
Protein S Deficiency ◽  
S Deficiency

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.

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