Decreased Free Protein S Levels in Polycythemia Vera

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.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650519 ◽

1996 ◽

Vol 76 (01) ◽

pp. 038-045 ◽

Cited By ~ 24

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.

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Free Protein S Deficiency Is a Risk Factor for Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665408 ◽

1997 ◽

Vol 78 (05) ◽

pp. 1343-1346 ◽

Cited By ~ 54

Author(s):

Elena M Faioni ◽

Carla Valsecchi ◽

Alessandra Palla ◽

Emanuela Taioli ◽

Cristina Razzari ◽

...

Keyword(s):

Risk Factor ◽

Relative Risk ◽

Venous Thrombosis ◽

Protein S ◽

Unexpected Finding ◽

Reference Ranges ◽

Protein S Deficiency ◽

Men And Women ◽

Free Protein ◽

S Deficiency

SummaryA recent study suggests that protein S deficiency is not a risk factor for venous thrombosis. Since this unexpected finding would have important clinical implications if confirmed, we performed a case-control study with the aim to determine the prevalence of protein S deficiency in patients with thrombosis and in healthy individuals taken from the general population and the relative risk of thrombosis in protein S-deficient patients. Free protein S concentration was measured in 327 consecutive patients with at least one venous thrombotic episode and in 317 age- and sex-matched control individuals. Different normal reference ranges were obtained and adopted for men and women. Protein S deficiency was found in 3.1% (95% Cl: 1.5-5.2) of patients and in 1.3% of controls (95% Cl: 0.3-2.8). Ten patients and 4 control subjects had protein S deficiency, which determined a relative risk of thrombosis (sex- and age-adjusted odds ratio) of 2.4 (95% Cl: 0.8-7.9). When men and women were analyzed separately, the risk was 5.0 (95% CI: 0.6-43.6) and 1.6 (95% Cl: 0.4-6.7) respectively. PS-deficient men had more thrombotic episodes than women and later in life. Multivariate analysis established that sex was an independent determinant of the number of episodes, as was age, while PS deficiency was not. However sex and PS deficiency status were both determinants of age at first thrombotic episode.

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THU0178 Circulating free protein S levels may be linked to cardiovascular events and venous thrombosis in SLE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2012-eular.2143 ◽

2013 ◽

Vol 71 (Suppl 3) ◽

pp. 215.3-216

Author(s):

G.J. Silverman ◽

J. Jung ◽

E. Akhter ◽

M. Petri ◽

C. Gronwall

Keyword(s):

Venous Thrombosis ◽

Cardiovascular Events ◽

Protein S ◽

Free Protein

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Protein S deficiency in men with long-term human immunodeficiency virus infection [see comments]

Blood ◽

10.1182/blood.v81.7.1801.1801 ◽

1993 ◽

Vol 81 (7) ◽

pp. 1801-1807 ◽

Cited By ~ 96

Author(s):

CP Stahl ◽

CS Wideman ◽

TJ Spira ◽

EC Haff ◽

GJ Hixon ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Pneumocystis Carinii ◽

Anticardiolipin Antibody ◽

Protein S ◽

Protein S Deficiency ◽

Free Protein ◽

Long Term Study ◽

S Deficiency ◽

Immunodeficiency Virus

Abstract Decreases in protein S levels have recently been reported in some human immunodeficiency virus (HIV)-infected patients. To examine predisposing factors, 25 men randomly selected from a long-term study of HIV- infected patients were studied. The minimum mean duration of HIV seropositivity in this group was 106.6 months (range 15 to 143 months). No patients were anticoagulated at the time of the study. Three of the 25 randomly selected patients gave a history of thrombosis, in each instance occurring after the onset of HIV positivity. Two of the 3 patients with thrombosis had more than one episode. Coagulation studies showed that 3 of 3 (100%) of the patients with thrombosis and 16 of 22 (72.7%) of those without previous thrombosis had decreased free protein S. Mean-free and total protein S levels were statistically lower for HIV-infected patients with and without previous thrombosis compared with healthy male controls. C4b-binding protein was not increased in study patients with decreased protein S levels. Decreases in protein S levels did not correlate with CD4+ cell levels, CDC class, p24 antigen positivity, zidovudine (AZT) use, or Pneumocystis carinii prophylaxis. The duration of disease statistically correlated with decreases in protein S levels (r = .37, P < .05). A linear correlation existed between increasing IgG anticardiolipin antibody levels and decreasing free protein S antigen (r = .67, P < .005). This study shows that protein S deficiency is common in long-term HIV-infected patients and is caused by a decrease in the free protein, rather than by changes in the bound complex. The data suggest that protein S deficiency is not correlated with HIV disease severity but may predispose patients to thromboembolic complications.

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Sagittal sinus thrombosis associated with transient free protein S deficiency after l-asparaginase treatment: case report and review of the literature

Clinical Neurology and Neurosurgery ◽

10.1016/s0303-8467(99)00076-1 ◽

2000 ◽

Vol 102 (1) ◽

pp. 33-36 ◽

Cited By ~ 10

Author(s):

Jae-Hong Lee ◽

Sang-We Kim ◽

Jong Sung Kim

Keyword(s):

Case Report ◽

Sinus Thrombosis ◽

Protein S ◽

Protein S Deficiency ◽

Review Of The Literature ◽

Free Protein ◽

Sagittal Sinus ◽

S Deficiency ◽

Sagittal Sinus Thrombosis

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Assessment of protein C antigen, free protein S, and protein C activity in pregnancy: A cross-sectional study of pregnant Nigerian women

International Journal of Medicine and Health Development ◽

10.4103/ijmh.ijmh_21_20 ◽

2021 ◽

Vol 26 (2) ◽

pp. 118

Author(s):

TheresaUkamaka Nwagha ◽

HelenChioma Okoye ◽

AngelaOgechukwu Ugwu ◽

LisaIfenyinwa Eweputanna ◽

EmmanuelOnyebuchi Ugwu

Keyword(s):

Protein C ◽

Protein S ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional ◽

Nigerian Women ◽

Free Protein ◽

Protein C Activity ◽

In Pregnancy

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Free Protein S Activity Actual to Control Ratio Measurement

10.32388/pdt00u ◽

2020 ◽

Author(s):

Keyword(s):

Protein S ◽

Ratio Measurement ◽

Free Protein ◽

Protein S Activity

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The Ser460Pro mutation in recombinant protein S Heerlen does not affect its APC-cofactor and APC-independent anticoagulant activities

Thrombosis and Haemostasis ◽

10.1160/th04-02-0082 ◽

2004 ◽

Vol 91 (06) ◽

pp. 1105-1114 ◽

Cited By ~ 11

Author(s):

Rory Koenen ◽

Lucio Gomes ◽

Guido Tans ◽

Jan Rosing ◽

Tilman Hackeng

Keyword(s):

Recombinant Protein ◽

Vitamin K ◽

Dissociation Constants ◽

Anticoagulant Activity ◽

Protein S ◽

Wild Type ◽

Free Protein ◽

Increased Risk ◽

Plasma Factor ◽

Thrombotic Complications

SummaryProtein S is a vitamin K-dependent plasma protein that functions as an APC-cofactor, but also exhibits anticoagulant activity in the absence of APC. The Heerlen polymorphism of protein S is characterized by a Ser460Pro substitution and lacks glycosylation at Asn458. It is associated with decreased protein S levels due to selective deficiency of free protein S Heerlen.To understand the lack of thrombotic complications associated with the protein S Heerlen mutation, we compared recombinant protein S Heerlen, wild type (wt) protein S and plasmaderived protein S. wt-Protein S and protein S Heerlen each bound 1:1 to C4BP with dissociation constants of 0.27 and 0.33 nM, respectively. Both wt-protein S and protein S Heerlen, either free or in complex with C4BP, were equally active as prothrombinase inhibitors in the absence of APC. All three protein S preparations stimulated APC-catalyzed inactivation of normal FVa, FVa Leiden and FVIIIa to the same extent. If extrapolated to plasma, it is not likely that the decreased free protein S levels in carriers of the protein S Heerlen mutation are compensated by an increased anticoagulant activity of protein S Heerlen-C4BP complexes. It is possible that an unrecognized plasma factor selectively enhances the anticoagulant activity of protein S Heerlen. If not, the reduction of free protein S levels in heterozygous protein S Heerlen-carriers combined with (low) normal total protein S levels apparently minimally affects the total anticoagulant activity of protein S (APC-cofactor and APC-independent activity) and hence is not associated with increased risk of venous thrombosis.

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