Biomedical subjects

S Vigano-D'Angelo

Publications and source records attributed to S Vigano-D'Angelo.

6 recordsLinked to original sources

PubMed1996

Potential failure of the International Normalized Ratio (INR) System in the monitoring of oral anticoagulation in patients with lupus anticoagulants.

Patients with antiphospholipid antibody syndrome (APS) experience a higher rate of recurrence of thrombosis than the general population of patients with thrombotic disease. Based on a retrospective analysis, it has been suggested that patients with APS should be kept on prolonged anticoagulation aiming at international normalised ratio (INR) values > 3.0. To evaluate whether the requirement for more intense anticoagulation depends on the variable sensitivity of thromboplastin reagents to the influence of aPLA, we monitored oral anticoagulant treatment in 10 patients with persistent lupus anticoagulants (LA) and venous thromboembolic disease using two thromboplastin reagents: Pro-IL-Complex (Instrumentation Laboratory, combined) and Recombiplastin (Ortho, recombinant). Acenocoumarol dosage was always assigned based on INR values obtained with the combined thromboplastin using diluted (1:20) test plasma, aiming at an INR interval of 2.0 to 3.0. Single INR determinations with both reagents were obtained throughout the study period for 110 aPLA-free patients on stable oral anticoagulation. Using the manufacturer's instrument-certified international sensitivity index (ISI) values, INR obtained with the recombinant reagent were significantly higher than those obtained with the combined reagent in LA-positive patients, but they were lower in LA-negative patients. After correction for local ISI calibration in LA-negative patients, INR values of 3.1 and 4.6 with Recombiplastin corresponded, respectively, to INR values of 2.0 and 3.0 with Pro-IL-Complex. These results indicate the thromboplastin-dependency of INR values in patients with LA, thereby questioning the validity of the INR system for the monitoring of oral anticoagulant treatment in these patients.

Administration, Oral↗

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 C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon.

Gram-negative septicemia elicits multiple abnormalities of the coagulation system. Although products of coagulation can lead to clot formation, thereby potentiating organ damage, recent work has shown that low concentrations of thrombin can protect animals from the shock state. Because these amounts of thrombin also lead to formation in vivo of the anticoagulant enzyme, activated protein C, we examined the role of protein C in modulation of Escherichia coli shock in baboons. First, we infused activated protein C and lethal concentrations of E. coli organisms, which prevented the coagulopathic, hepatotoxic, and lethal effects of E. coli. Second, using an antibody to protein C we blocked protein C activation in vivo to determine if this influenced the response to lethal and sublethal concentrations of E. coli organisms. Under these conditions the response to lethal concentrations of E. coli organisms was made more severe and the response to sublethal concentrations of E. coli was made lethal. The coagulopathic, hepatotoxic, and lethal responses in this latter case were prevented by infusion of exogenous protein C.

Alanine Transaminase↗

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

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↗