Download PDF
Thromb Haemost 1989; 61(03): 474-478
DOI: 10.1055/s-0038-1646617
Original Article
Schattauer GmbH Stuttgart

Functional and Immunologic Protein S in Normal Pregnant Women and in Full-Term Newborns

José A Fernández
1   The Research Center, Hospital “La Fe”, Valencia, Spain
,
Amparo Estellés
1   The Research Center, Hospital “La Fe”, Valencia, Spain
,
Juan Gilabert
2   The Department of Obstetrics and Gynecology, Hospital “La Fe”, Valencia, Spain
,
Francisco España
1   The Research Center, Hospital “La Fe”, Valencia, Spain
,
Justo Aznar
3   The Department of Clinical Pathology, Hospital “La Fe”, Valencia, Spain
› Author Affiliations
Further Information

Publication History

Received 01 July 1988

Accepted after revision 02 February 1989

Publication Date:
24 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Total and free protein S antigen and C4b-binding protein (C4bp) were determined by rocket immuno-electrophoresis, and functional protein S was assayed by a coagulation method, throughout pregnancy and normal puerperium and in a group of normal full-term newborns (FTN). The functional protein S assay is based on a modification of the APTT, using a mixture of test sample, protein S deficient plasma, activated protein C, phospholipids and calcium. This protein S functional assay is specific for protein S since the APTT prolongation by normal plasma was abolished by incubation of plasma with monospecific, rabbit antiprotein S IgG. The ratios of functional protein S/free protein S antigen in healthy men (n = 13) and women (n = 14) were 1.0 ± 0.13 (mean ± SD) and 1.03 ± 0.20, respectively. During pregnancy there is a decrease in functional protein S and a progressive decrease in total and free protein S antigen, with a functional/free protein S ratio of 0.75 ± 0.28 in the third trimester of pregnancy (n = 16). In early puerperium the functional protein S level was lower than the free protein S antigen level (ratio about 0.5). In the FTN group, the free protein S level was 39% and protein S activity was about 70% that of adults, with a functional/free protein S ratio of 1.84 ± 0.31. C4bp values were 23.5 ± 10.3% in the FTN group, and crossed immunoelectrophoresis showed that in this group the major protein S peak corresponded to free protein S. These results indicate that both in early puerperium and in FTN group, free protein S antigen may not be an adequate parameter for estimating of functional protein S activity. The decrease in functional protein S activity during early puerperium may be connected with the risk of developing thrombotic episodes during the postpartum period.

Keywords

Protein S - Pregnancy - Full-term newborn - C4bp
 

  • References

  • 1 DiScipio RG, Hermodson MA, Yates SG, Davie EW. A comparison of human prothrombin, factor IX (Christmas Factor), factor X (Stuart Factor), and protein S. Biochemistry 1977; 16: 698-706
    CrossrefPubMedSearch in Google Scholar
  • 2 Walker FJ. Regulation of activated protein C by a new protein: A possible function for bovine protein S. J Biol Chem 1980; 255: 5521-5524
    PubMedSearch in Google Scholar
  • 3 Dahlback B. Purification of human C4b-binding protein and formation of its complex with vitamin K-dependent protein S. Biochem J 1983; 209: 847-856
    CrossrefPubMedSearch in Google Scholar
  • 4 Comp PC, Nixon RR, Cooper MR, Esmon CT. Familial protein S deficiency is associated with recurrent thrombosis. J Clin Invest 1984; 74: 2082-2088
    CrossrefPubMedSearch in Google Scholar
  • 5 Comp PC, Esmon CT. Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 1984; 311: 1525-1528
    CrossrefPubMedSearch in Google Scholar
  • 6 Engesser L, Broekmans AW, Briet E, Brommer EJ P, Bertina RM. Hereditary protein S deficiency: Clinical manifestations. Ann Intern Med 1987; 106: 677-682
    CrossrefPubMedSearch in Google Scholar
  • 7 Gladson CL, Scharrer I, Hach V, Beck KH, Griffin JH. The frequency of type I heterozygous protein S and protein C deficiency in 141 unrelated young patients with venous thrombosis. Thromb Haemostas 1988; 59: 18-22
    PubMedSearch in Google Scholar
  • 8 Bertina RM. In: Biotechnology in Clinical Medicine. Congenital Deficiencies of Protein C and Protein S. Albertini A, Lenfant C, Paoletti R. eds Raven Press Ltd; New York: 1987. pp 175-182
  • 9 Bertina RM. Hereditary protein S deficiency. Haemostasis 1985; 15: 241-246
    PubMedSearch in Google Scholar
  • 10 Francis Jr RB, Patch MJ, Comp PC. A simplified protein S activity assay. Blood 1987; 70 Suppl (Suppl. 01) 1463 abst
    PubMedSearch in Google Scholar
  • 11 van de Waart P, Preissner KT, Bechtold JR, Miiller-Berghaus G. A functional test for protein S activity in plasma. Thromb Res 1987; 48: 427-437
    CrossrefPubMedSearch in Google Scholar
  • 12 Suzuki K, Nishioka J. Plasma protein S activity measured using protac, a snake venom derived activator of protein C. Thromb Res 1988; 49: 241-251
    CrossrefPubMedSearch in Google Scholar
  • 13 Schwarz HP, Heeb MJ, Lämmle B, Berrettini M, Griffin JH. Quantitative immunoblotting of plasma and platelet protein S. Thromb Haemostast 1986; 56: 382-386
    PubMedSearch in Google Scholar
  • 14 Fair DS, Revak DJ. Quantitation of human protein S in the plasma of normal and warfarin-treated individuals by radioimmunoassay. Thromb Res 1984; 36: 527-535
    CrossrefPubMedSearch in Google Scholar
  • 15 Comp PC, Doray D, Patton D, Esmon CT. An abnormal plasma distribution of protein S occurs in functional protein S deficiency. Blood 1986; 67: 504-508
    PubMedSearch in Google Scholar
  • 16 Friedman KD, Marlar RA, Gill JC, Endres-Brooks J, Montgomery RR. Protein S deficiency in patients with lupus anticoagulant. Blood 1986; 68 Suppl (Suppl. 01) 1210 Abstr
    PubMedSearch in Google Scholar
  • 17 Vigano-d’Angelo S, d’Angelo A, Kaufmann Jr CE, Sholer C, Esmon CT, Comp PC. Protein S deficiency occurs in the nephrotic syndrome. Ann Intern Med 1987; 107: 42-47
    CrossrefPubMedSearch in Google Scholar
  • 18 Bertina RM. Report of the Subcommittee on Protein C and Protein S. 1987. XIth International Congress on Thrombosis and Haemostasis. Brussels; Belgium:
  • 19 Schwarz HP, Muntean W, Watzke H, Richter B, Griffin JH. Low total protein S antigen but high protein S activity due to decreased C4b-binding protein in neonates. Blood 1988; 71: 562-565
    PubMedSearch in Google Scholar
  • 20 Moalic P, Gruel Y, Body G, Foloppe P, Dalahousse B, Leroy J. Levels and plasma distribution of free and C4b-BP-bound protein S in human fetuses and full-term newborns. Thromb Res 1988; 49: 471-480
    CrossrefPubMedSearch in Google Scholar
  • 21 Malm J, Bennhagen R, Holmberg L, Dahlbäck B. Plasma concentrations of C4b-binding protein and vitamin K-dependent protein S in term and preterm infants: low levels of protein S-C4b-binding protein complexes. Br J Haematol 1988; 68: 445-449
    CrossrefPubMedSearch in Google Scholar
  • 22 Comp PC, Thumau GR, Welsh J, Esmon CT. Functional and immunologic protein S levels are decreased during pregnancy. Blood 1986; 68: 881-885
    PubMedSearch in Google Scholar
  • 23 Gruel Y, Moalic P, Durouchet E, Guerois C, Delahousse B, Leroy J. Levels of total and free protein S during normal and pathological pregnancy and in post-partum. Thromb Haemostas 1987; 58: 404 Abstr
    PubMedSearch in Google Scholar
  • 24 Malm J, Laurell M, Dahlbäck B. Changes in the plasma levels of vitamin K-dependent protein C and S and of C4b-binding protein during pregnancy and oral contraception. Br J Haematol 1988; 68: 437-443
    CrossrefPubMedSearch in Google Scholar
  • 25 Scharfstein J, Ferreira A, Gigli I, Nussenzweig V. Human C4-binding protein. I. Isolation and characterization. J Exp Med 1978; 148: 207-222
    CrossrefPubMedSearch in Google Scholar
  • 26 Gilabert J, Fernández JA, Espaňa F, Aznar J, Estellés A. Physiological coagulation inhibitors (protein S, protein C and antithrombin III) in several preeclampsia states and in users of oral contraceptives. Thromb Res 1988; 49: 319-329
    CrossrefPubMedSearch in Google Scholar
  • 27 Espaňa F, Estellés A, Aznar J, Gilabert J. Assay of protein C in human plasma: Comparison of amidolytic, coagulation, and immunochemical assays. Thromb Res 1986; 44: 771-782
    CrossrefPubMedSearch in Google Scholar
  • 28 Laurell CB, McKay EJ. Electroimmuno-assay. In: Methods in Enzymology, Vol 73, pt B. Colowick SP, Kaplan NO. eds Academic; Orlando, F L: 1981. pp 339-369
    Search in Google Scholar
  • 29 Ganrot PO. Crossed immunoelectrophoresis. Scand J Clin Lab Invest 1972; 29 Suppl (Suppl. 124) 39-47
    CrossrefPubMedSearch in Google Scholar
  • 30 Boerger LM, Morris P, Thumau GR, Esmon C T. Oral contraceptives and gender influence protein S status. Blood 1987; 69: 692-694
    PubMedSearch in Google Scholar
  • 31 Melissari E, Kakkar VV. The effects of oestrogen administration on the plasma free protein S and C4bp-binding protein. Thromb Res 1988; 49: 489-495
    CrossrefPubMedSearch in Google Scholar
  • 32 Rose PG, Essig GF, Vaccaro PS, Brandt JT. Protein S deficiency in pregnancy. Am J Obstet Gynecol 1986; 155: 140-141
    CrossrefPubMedSearch in Google Scholar
  • 33 Mitchell CA, Salem HH. The inhibition of the anticoagulant activity of protein S by prothrombin. Blood 1987; 70 Suppl (Suppl. 01) 1480
    PubMedSearch in Google Scholar
  • 34 Polack B, Pouzol P, Amiral J, Kolodie L. Protein C level at birth. Thromb Haemostas 1984; 52: 188-190
    PubMedSearch in Google Scholar