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

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1801-1807 ◽  
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.

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

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1801-1807
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

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.

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.

Acquired protein S deficiency in children infected with human immunodeficiency virus

1996 ◽  
Vol 15 (2) ◽  
pp. 106-111 ◽  
Author(s):  
ROBERT W. SUGERMAN ◽  
JOSEPH A. CHURCH ◽  
JONATHAN C. GOLDSMITH ◽  
GORDON E. ENS
Keyword(s):  
Human Immunodeficiency Virus ◽  
Protein S ◽  
Protein S Deficiency ◽  
S Deficiency ◽  
Immunodeficiency Virus

Protein S Deficiency and Lower-Extremity Arterial Thrombosis

2007 ◽  
Vol 97 (2) ◽  
pp. 151-155 ◽  
Author(s):  
Krista A. Archer ◽  
Thomas Lembo ◽  
Jonathan A. Haber
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Healthy Woman ◽  
Protein S ◽  
Protein S Deficiency ◽  
S Deficiency ◽  
Immunodeficiency Virus ◽  
The Right

A 42-year-old woman presented to the emergency department with progressive painful discoloration of the digits of her right foot and symptoms previously diagnosed as neuroma. She was admitted to the hospital for dorsalis pedis arterial occlusion and ischemic foot pain. Despite attempts to restore perfusion to the right leg, ischemia of the right foot persisted and progressed to digital gangrene. The patient subsequently required right transmetatarsal amputation and eventually below-the-knee amputation. After extensive inpatient vascular and hematologic work-up of this otherwise healthy woman, test results revealed that she had protein S deficiency, hepatitis C, and human immunodeficiency virus type 1. In addition to describing this patient’s evaluation and treatment, we review protein S deficiency, including its correlation with human immunodeficiency virus type 1 infection and laboratory diagnosis. This case promotes awareness of protein S deficiency and serves as a reminder to the physician treating patients with vascular compromise and a history of human immunodeficiency virus type 1 to include protein S deficiency in the differential diagnosis. (J Am Podiatr Med Assoc 97(2): 151–155, 2007)

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.

Free Protein S Deficiency Is a Risk Factor for Venous Thrombosis

1997 ◽  
Vol 78 (05) ◽  
pp. 1343-1346 ◽  
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.

FAMILIAL TYPE I PROTEIN S DEFICIENCY ASSOCIATED WITH SEVERE VENOUS THROMBOSIS. A STUDY OF FIVE CASES

1987 ◽  
Author(s):  
C Boyer-Neumann ◽  
M Wolf ◽  
J Amiral ◽  
A M Guyager ◽  
D Meyer ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Plasma Protein ◽  
Active Form ◽  
Vena Cava ◽  
Protein S ◽  
Immunological Methods ◽  
Type I ◽  
Protein S Deficiency ◽  
Free Protein ◽  
S Deficiency

Protein S deficiency has been demonstrated in 5 members from the same family with a history of severe recurrent venous thrombosis over three generations. The propositus, a 16 year old female, had a first spontaneous thrombotic episode at age 15. Phlebography revealed a total obstruction of her left ilio-femoral vein with an extension to the vena cava. She was treated with heparin followed by oral anticoagulant therapy. The four other affected members (mother, aunts and uncle of the propositus) had also presented recurrent thrombosis with onset at a young age. The grandfather, not tested, had died from massive pulmonary embolism at age 54. The immunological assay of protein S was performed in plasma by Laurell, using a monospecific antiserum to human protein S, or by an ELISA, using a kit from Diagnostica Stago (Asserachrom Protein S). In order to separate free protein S, the functionally active form, from protein S complexed with C4-binding protein, plasma was adsorbed with 3.75 % polyethyleneglycol (PEG 6000). Following PEG precipitation, the levels of free protein S antigen remaining in the supernatant were quantitated by the usual immunological methods. In addition, two-dimensional immunoelectrophoresis (DDIE) also provided information on the distribution of both forms. In plasma protein S levels were decreased (40 to 55 % of the normal range) in two untreated patients and lower levels (17 to 20 96) were observed in the three others, including the propositus, who were under dicoumarol therapy. In PEG treated-plasma, protein S was undetectable (less than 5 %) in all patients, indicating a lack of free protein S. This was confirmed by DDIE : whereas protein S migrated as two distinct peaks, corresponding to free and complexed protein S in normal plasma, only a single peak of complexed protein S was observed in all affected patients. These results clearly demonstrate a total lack of free protein S which appears to be responsible for the thromboembolic disorder in this family as there was no deficiency of the other plasma inhibitors (antithrombin III, heparin cofactor II and protein C). According to the classification recently proposed by Comp et al., this family belongs to type I protein S deficiency, with an autosomal dominant mode of inheritance.

Genetic analysis, phenotypic diagnosis, and risk of venous thrombosis in families with inherited deficiencies of protein S

Blood ◽  
2000 ◽  
Vol 95 (6) ◽  
pp. 1935-1941 ◽  
Author(s):  
Michael Makris ◽  
Michael Leach ◽  
Nick J. Beauchamp ◽  
Martina E. Daly ◽  
Peter C. Cooper ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Protein S ◽  
Structural Defects ◽  
Protein S Deficiency ◽  
Gene Defect ◽  
Thrombotic Risk ◽  
Free Protein ◽  
First Degree Relatives ◽  
S Deficiency ◽  
Increased Risk

Abstract Protein S deficiency is a recognized risk factor for venous thrombosis. Of all the inherited thrombophilic conditions, it remains the most difficult to diagnose because of phenotypic variability, which can lead to inconclusive results. We have overcome this problem by studying a cohort of patients from a single center where the diagnosis was confirmed at the genetic level. Twenty-eight index patients with protein S deficiency and a PROS1 gene defect were studied, together with 109 first-degree relatives. To avoid selection bias, we confined analysis of total and free protein S levels and thrombotic risk to the patients' relatives. In this group of relatives, a low free protein S level was the most reliable predictor of a PROS1gene defect (sensitivity 97.7%, specificity 100%). First-degree relatives with a PROS1 gene defect had a 5.0-fold higher risk of thrombosis (95% confidence interval, 1.5-16.8) than those with a normal PROS1 gene and no other recognized thrombophilic defect. Although pregnancy/puerperium and immobility/trauma were important precipitating factors for thrombosis, almost half of the events were spontaneous. Relatives with splice-site or major structural defects in the PROS1 gene were more likely to have had a thrombotic event and had significantly lower total and free protein S levels than those relatives having missense mutations. We conclude that persons withPROS1 gene defects and protein S deficiency are at increased risk of thrombosis and that free protein S estimation offers the most reliable way of diagnosing the deficiency.

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