Protein S levels during Normal Pregnancy Options

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This is in reference to my earlier post about Diagnosis of PSD during Pregnancy. Apart from the article which was posted by James earlier, I also found following references on Protein S levels during normal Pregnancy which I thought may be of interest:

Paper 1

http://www.ncbi.nlm.nih.gov/entrez/query.f...l=pubmed_docsum

Am J Obstet Gynecol. 1995 Jan;172(1 Pt 1):147-50. Changes in protein C and protein S levels in normal pregnancy. Faught W, Garner P, Jones G, Ivey B.

Department of Obstetrics and Gynecology, University of Ottawa, Ontario, Canada.

OBJECTIVE: The objective of the study was to determine the normal changes in the plasma concentrations of protein C and protein S that occur during each trimester of pregnancy. STUDY DESIGN: The study was a prospective cross-sectional study of 91 normal pregnant women who had plasma concentrations of protein C and protein S measured during the first, second, and third trimesters. RESULTS: There was no statistically significant change in antigenic or functional protein C levels during normal pregnancy. Total protein S levels also remained unchanged. Free protein S levels fell significantly from first to second trimesters (0.45 U/ml mean to 0.26 U/ml mean, p < 0.001), but no further fall occurred during the third trimester. CONCLUSIONS: The second-trimester fall in free protein S levels is a physiologic pregnancy adaptation. Women with a thromboembolic event appearing for the first time during pregnancy should have investigations for protein S deficiency delayed until the postpartum period, to avoid misdiagnosis and treatment.

(MY NOTE: Detilaed study of the paper indicated the patients who were in second trimester were in 26-28 weeks which is begining of third trimester, so the abstract is slightly mis leading in that respect. Also the range of levels reported in the table were as follows:

Protein S free Potein S total
8-16 weeks 0.43 +/- 0.09 0.89 +/- 0.14
26-28 wks 0.26 +/- 0.07 0.81 +/- 0.13
36-38 wks 0.25 +/- 0.05 0.86 +/- 0.15

If any one wants the complete paper I would be happy to fax the same to you)

Paper 2

http://www.ncbi.nlm.nih.gov/entrez/query.f...l=pubmed_docsum

Am J Obstet Gynecol. 1996 Sep;175(3 Pt 1):657-60. Comparison of protein S functional and antigenic assays in normal pregnancy. Lefkowitz JB, Clarke SH, Barbour LA.

Department of Pathology, University of Colorado Health Sciences Center, Denver 80262, USA.

OBJECTIVE: Our purpose was to determine the effect of pregnancy on the protein S functional assay (clot based), which is used to screen for all subtypes of protein S deficiency states, and to compare its behavior in pregnancy with antigenic assays. STUDY DESIGN: This was a cross-sectional study of 37 normal pregnant women without thromboembolic risks who were tested by both functional and antigenic protein S assays during the first, second, and third trimesters. RESULTS: Mean protein S functional levels decline strikingly from the first to the third trimester, all 10 third-trimester patients had functional protein S levels well below the lower limit of the reference range. In contrast, only 3 of 10 third-trimester and none of the second-trimester patients had free protein S antigenic levels below the reference range. CONCLUSIONS: The protein S functional assay should not be used in pregnancy to screen for the subtypes of protein S deficiency; misdiagnosis and inappropriate treatment could result.

( MY NOTE: I got the entire article from my library and that has a table which shows:

Protein S free antigen level:
non-pregnant 0.5-1.5, in 1st trimester 0.8-1.33 , 2nd trimester 0.65-1.03, 3rd trimester 0.45-0.64

Protein S functional activity :
non-pregnant 0.62-1.42, in 1st trimester 0.57-0.95 , 2nd trimester 0.42-0.68, 3rd trimester 0.16-0.42

Protein S total antigen level:
non-pregnant 0.7-1.34, in 1st trimester 0.77-1.15, 2nd trimester 0.65-0.101, 3rd trimester 0.58-0.80

If any one wants the complete paper I would be happy to fax the same to you)


Paper3:

Original Spanish Version

http://www.scielo.cl/scielo.php?script=sci...&lng=en&nrm=iso

Google Translated Version

http://translate.google.com/translate?hl=e...hl%3Den%26lr%3D

Abstract:

Free protein S (PS) in normal pregnancy: A comparison between two analytical methods
Patricia Fardella B, Mauro Parra C, Guillermo Conte L, Claudio Flores P, Hernán Muñoz S, Lilian Soto S, Marianela Cuneo Va, Carmen Mallea Pa, María Beatriz Retamales Mb, Sofía Peña Rb, Constanza Ojeda Hb.

Sección Hematología y Unidad de Medicina Fetal del Departamento de Ginecología y Obstetricia, Hospital Clínico de la Universidad de Chile. Laboratorio de Hematología, Clínica Alemana. Santiago, Chile.
aTecnólogo Médico.
bEstudiante, Facultad de Medicina de la Universidad de Chile.

Dirección para correspondencia
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Background: Pregnancy is a physiological hypercoagulable state with an increased incidence of thromboembolic phenomena. There is an increase in the concentrations of most clotting factors, a decrease in concentration of some of the natural anticoagulants and reduced fibrinolytic activity. Changes in PS levels have also been reported. Aim: To establish referral range values of functional PS and free PS antigen, during the second (2nd T) and third trimester (3rd T) of normal gestation. Patients and methods: Forty one normal pregnant women were included in our study, 20 during the 2nd T (22-24 weeks) and 21 during the 3rd T (29-38 weeks). Functional PS was measured by a clot based test and free PS antigen by ELISA. Results: Free PS Antigen was 65.8±18.3% during the 2nd T and 62.3±16.5% during the 3rd T. The figures for normal controls were 106±6.5%. Functional PS was 43.8±13.3 and 25.9±14.6% during the 2nd T and 3rd T, respectively. The figures for normal controls were 97±24% (p <0.001 compared with pregnant women). Free PS antigen did not change from the 2nd to the 3rd T (p=NS), however functional PS fell significantly from the 2nd to the 3rd T (p <0.001) and was significantly lower than free PS antigen in both trimesters (p <0.001). Conclusions: Pregnancy is associated to a decrease in PS. This abnormality is more pronounced for functional PS than free PS antigen and functional PS falls progressively during pregnancy. These assays should not be used to screen for PS deficiency during pregnancy because they could lead to a misdiagnosis.

(Key Words: Pregnancy trimesters; Protein S; Protein S deficiency)


Paper 4

http://www.ncbi.nlm.nih.gov/entrez/query.f...l=pubmed_docsum

Aust N Z J Obstet Gynaecol. 2000 Nov;40(4):448-50. Changes in the plasma activities of protein C and protein S during pregnancy. Oruc S, Saruc M, Koyuncu FM, Ozdemir E. Department of Obstetrics and Gynecology, Celal Bayar University Medical School, Manisa, Turkey.

The objective of the study was to determine the changes in the plasma activities of protein C and protein S that occur during normal pregnancy In this prospective cross-sectional study, plasma activities of protein C and protein S were measured in 32 normal pregnant women in the first, second and third trimester and 6 weeks after delivery There was a significant fall in protein C and protein S activities during normal pregnancy compared with the post-puerperal period. The activities of protein C and protein S also gradually decreased throughout pregnancy (p < 0.01). Increasing plasma volume during normal pregnancy and its dilutional effect might play some role in the low activities of protein S observed. The normal falls in protein S and protein C activities make it difficult to diagnose protein S and C deficiency during pregnancy. Based on our findings, if a woman has a thromboembolic event during pregnancy, testing for a definitive diagnosis of protein C or protein S deficiency or functional failure should be delayed until at least 6 weeks postpartum.

(My Note: I was not able to get the full text version of this article but if any one can - it should report the levels detected by them)