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Biomedical subjects

P C Comp

Publications and source records attributed to P C Comp.

At least 55 records · Page 3Linked to original sources
PubMed1990

Superior sagittal sinus thrombosis in a patient with protein S deficiency.

A 30-year-old man presented with sagittal sinus thrombosis. He had a history of multiple thrombotic events since adolescence, and his father had had a similar history. Laboratory studies revealed the complete absence of free protein S in his plasma. Protein S deficiency, an autosomal dominant disorder, is an identifiable cause of cerebral thrombosis. The literature and our experience with this case suggest that long-term anticoagulant therapy may prevent thrombotic episodes in patients with this disorder.

Adult↗
PubMed1988

Acquired deficiencies of protein S. Protein S activity during oral anticoagulation, in liver disease, and in disseminated intravascular coagulation.

Protein S is a vitamin K-dependent plasma protein which serves as the cofactor for activated protein C. Protein S circulates in both an active, free form and in an inactive complex with C4b-binding protein. To elucidate the role of protein S in disease states and during oral anticoagulation, we developed a functional assay for protein S that permits evaluation of the distribution of protein S between free and bound forms and permits determination of the specific activity of the free protein S. In liver disease, free protein S antigen is moderately reduced and the free protein S has significantly reduced specific activity. In disseminated intravascular coagulation, reduced protein S activity occurs due to a redistribution of protein S to the inactive bound form. During warfarin anticoagulation, reduction of free protein S antigen and the appearance of forms with abnormal electrophoretic mobility significantly decrease protein S activity. After the initiation of warfarin, the apparent half-life of protein S is 42.5 h. In patients with thromboembolic disease, transient protein S deficiency occurs due to redistribution to the complexed form. Caution should be exercised in diagnosing protein S deficiency in such patients by use of functional assays.

Adult↗
PubMed1987

Anticoagulation proteins C and S.

Proteins C and S are two vitamin K-dependent plasma proteins that work in concert as a natural anticoagulant system. Activated protein C is the proteolytic component of the complex and protein S serves as an activated protein C binding protein that is essential for assembly of the anticoagulant complex on cell surfaces. The anticoagulant activity is expressed through the selective inactivation of Factors Va and VIIIa. Many patients deficient in proteins C and S have been described and have an associated thrombotic tendency, but not all heterozygous protein C and S deficient individuals experience thrombotic complications. Multiple mechanisms and/or drugs can lead to acquired deficiencies of these proteins: oral anticoagulation, liver disease, DIC and in the case of protein S, lupus erythematosus, nephrotic syndrome, pregnancy and certain hormones. The anticoagulant activity of protein C decreases rapidly after administration of warfarin (i.e., with a time course similar to Factor VII). This rapid decrease may lead to a transient imbalance and contribute to coumarin induced skin necrosis. Protein S antigen levels do not decrease as rapidly, but protein S functional levels are often low in patients with an acute thrombus. The discrepancy between antigen and function results from elevations in C4b-binding protein, which complexes reversibly with protein S. Unlike free protein S, the complex does not function in the anticoagulant pathway. The available information all suggest that deficiency of protein C and protein S should be considered a risk factor contributing to recurrent thrombotic disease and that the function of these proteins is altered by many common clinical conditions which have associated an increased risk of thrombosis.

Anticoagulants↗
PubMed1987

Protein S deficiency occurs in the nephrotic syndrome.

Protein S activity may be compromised in patients with the nephrotic syndrome and contribute to a thrombotic diathesis. Protein S is found in two forms in plasma as free and functionally active protein S, and complexed to C4b-binding protein. When compared with controls, patients with nephrotic syndrome had reduced functional levels of protein S (69% +/- 27% [SD], p less than 0.001) despite having elevated levels of total protein S antigen (139% +/- 42%, p less than 0.001). Decreased protein S activity was caused by significant reductions in free (active) protein S levels (90% +/- 38%, p less than 0.05) due to the selective urinary loss of free protein S and elevation of C4b-binding protein levels (170% +/- 52%, p less than 0.001) that favors complex formation; and in the specific activity of the circulating free protein S (0.76; p less than 0.001). Along with this reduction in specific activity, we noted the abnormal electrophoretic mobility of the protein S in the presence of calcium ions. We conclude that acquired protein S deficiency occurs in the nephrotic syndrome and may be a risk factor for the development of the thromboembolic complications.

Blood Coagulation↗
PubMed1987

Oral contraceptives and gender affect protein S status.

Protein S is a plasma protein that serves as a cofactor for the anticoagulant effects of activated protein C. Congenital protein S deficiency is often associated with thromboembolic disease. During pregnancy a decrease in the functional and antigenic levels of protein S occurs; this change in protein S status may contribute to the thromboembolic complications that sometimes occur during pregnancy. In certain patients, oral contraceptive use has also been associated with thrombotic complications. In this study, protein S status was determined in 21 women taking oral contraceptives and compared with that of 21 women not taking oral contraceptives and that of 21 men. The results show that women taking oral contraceptives have significantly lower total protein S (24.3 +/- 3.6 micrograms/mL; mean +/- SD) than women not taking oral contraceptives (28.6 +/- 3.9 micrograms/mL) (P less than .005). Men had significantly higher protein S levels (30.9 +/- 3.9 micrograms/mL, P less than .01) than age-matched women not taking oral contraceptives. In plasma, an equilibrium exists between free (functionally active) protein S and protein S complexed to C4b-binding protein, which is functionally inactive. The mean levels of C4b-binding protein were essentially the same among the three groups, but the levels of free protein S were significantly different and reflected different total protein S antigen levels. Additionally, we found that inflammation significantly elevated C4b-binding protein levels and could result in a further significant decrease in free protein S levels. These data indicate that plasma protein S levels are significantly affected by hormonal status and inflammation.

Adolescent↗
PubMed1987

Analysis of protein C and protein S in disease states.

Protein C and protein S are two vitamin K dependent plasma proteins which function in concert to serve as a natural anticoagulant. Deficiencies of both proteins are associated with thrombotic disease. Assay procedures employing monoclonal antibodies are discussed and compared to previous assay procedures. The assays are effective in patients undergoing heparin or oral anticoagulant therapy and are not influenced by inhibitory factors generated during intravascular coagulation. These assays should aid in our understanding of the role of protein C and protein S in thrombotic disease.

Antibodies, Monoclonal↗
PubMed1987

Protein C, isolation and potential use in prevention of thrombosis.

Protein C and protein S serve as natural anticoagulants. Deficiencies of these proteins are often associated with recurrent deep vein thrombosis and coumarin induced skin necrosis. These two proteins function by selectively inactivating factors Va and VIIIa, two of the "cofactors" of blood coagulation. Hence, inhibition of coagulation by this pathway complements the better known inhibition mediated by the antithrombin III-heparin system. These observations suggest that protein C and/or activated protein C may prove useful in controlling thrombosis and/or DIC. We have developed a Ca2+ dependent monoclonal antibody which allows the rapid isolation of human protein C. This rapid isolation has allowed us to demonstrate that activated protein C can protect baboons from the lethal effects of E. coli/endotoxin and that protein C supplementation can minimize fibrinogen consumption following tissue factor infusion into dogs.

Animals↗
PubMed1986

Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states.

Protein C is a natural vitamin K-dependent plasma anticoagulant, deficiencies of which have been found in patients with recurrent thrombosis and warfarin-induced skin necrosis. To appreciate more fully the role of protein C in disease states and during oral anticoagulation, a new functional assay for protein C involving adsorption of plasma protein C on a Ca+2-dependent monoclonal antibody, elution, quantitative activation, and assessment of plasma anticoagulant activity, has been developed. When oral anticoagulation is initiated, the anticoagulant activity of protein C decreases to a greater extent than either the amidolytic or immunologic levels. During stabilized warfarin treatment, there is no correlation between either amidolytic or antigenic levels and the functional protein C activity, suggesting that measurement of protein C anticoagulant activity may be necessary to reflect adequately the anticoagulant protection afforded by this protein. In contrast, there was a strong correlation between anticoagulant and amidolytic and immunologic levels in liver failure and disseminated intravascular coagulation. Two patients with thromboembolic disease have been identified who exhibit a marked decrease in anticoagulant activity, but who have normal immunologic and amidolytic levels. Thus, this assay permits assessment of protein C in individuals who have received anticoagulant treatment and identification of a new class of protein C-deficient individuals.

Adult↗
PubMed1986

An abnormal plasma distribution of protein S occurs in functional protein S deficiency.

Protein S is a natural anticoagulant present in the plasma that serves as a cofactor for activated protein C. Patients deficient in protein S are subject to recurrent venous thrombotic disease. Protein S deficiency differs from other plasma protein deficiencies in that deficient patients often have normal or only mildly reduced levels of protein S in their plasma as detected by conventional immunologic methods but have markedly reduced functional protein S levels. This apparent discrepancy is due to the presence of two forms of protein S in plasma. The protein S is present free and in a complex with C4b-binding protein. The free form is functionally active, whereas the bound form is not. Examination by crossed immunoelectrophoresis of 31 functionally protein S-deficient individuals from seven families reveals that 29 of the 31 have all or most of their protein S complexed to C4b-binding protein with little or no free protein and have correspondingly low levels of protein S functional activity (type I deficiency). Two related protein S-deficient individuals show a different type of distribution with little or no protein S, either bound or free (type II deficiency). The detection and classification of protein S-deficient individuals requires the application of both a functional assay and an assessment of protein S distribution between bound and free forms.

Carrier Proteins↗
PubMed1986

Functional and immunologic protein S levels are decreased during pregnancy.

Protein S, is a natural anticoagulant protein which serves as a cofactor for activated protein C. During pregnancy and in the postpartum period, functional protein S levels are significantly reduced (38% +/- 17.3%, mean +/- 1 SD) when compared to nonpregnant females (97% +/- 31.6%) (P less than 0.001). In plasma an equilibrium exists between functionally active free protein S and protein S complexed with C4b-binding protein, which is functionally inactive. As a result of this equilibrium either a decreased level of total protein S antigen or an elevation of C4b-binding protein could lead to reduced protein S activity. C4b-binding protein levels measured by enzyme-linked immunoassay are not significantly different in pregnant women versus nonpregnant controls (103.5% +/- 21.2% v 100% +/- 16.9%). However, during pregnancy and in the postpartum period, total protein S levels are reduced (68% +/- 10.7%) compared to nonpregnant controls (100% +/- 17.0%). This difference is significant at P less than 0.001. These data demonstrated that the reduction in protein S activity observed during pregnancy is a result of reduced total protein S antigen.

Carrier Proteins↗
PubMed1984

Recurrent venous thromboembolism in patients with a partial deficiency of protein S.

Protein S is an antithrombotic plasma protein that serves as a cofactor for another plasma protein, activated protein C. Protein S is required for the expression of the anticoagulant effect of activated protein C, which inhibits blood clotting at the levels of factors V and VIII in the blood-clotting cascade. We postulated that patients deficient in protein S would have inadequate regulatory control of the clotting cascade and would be prone to thrombotic disease in a manner similar to that of patients congenitally deficient in protein C. To determine whether protein S deficiency is associated with recurrent thrombosis, we developed a functional assay for the plasma protein. With this assay, the protein S activity of normal persons ranges from 63 to 160 per cent. Using this test, we have now identified six unrelated persons with severe recurrent venous thrombosis who were deficient in protein S, with levels between 15 and 37 per cent while they were not receiving warfarin therapy. Our data suggest that the determination of protein S levels will be useful in the evaluation of patients with recurrent thrombosis.

Adult↗