Protein C and Antithrombin III Activities in Healthy
Nigerian Women
Imoru
Momodu, Fiekumo Igbida Buseri
Imoru
Momodu, Department of
Haematology, Aminu Kano Teaching Hospital, P.M.B. 3452, Kano, Kano State,
Nigeria
Fiekumo
Igbida Buseri, Department of Medica Laboratory Science, Faculty of Basic Medical
Sciences, Niger Delta University, Wilberforce Island, Bayelsa State, Nigeria
Correspondence to: Imoru Momodu, Department of
Haematology, Aminu Kano Teaching Hospital, P.M.B. 3452, Kano, Kano State, Nigeria
Email: imorumomodu67@yahoo.com
Telephone: +2348033174997
Received: January 2,
2015
Revised: January 27, 2015
Accepted: January 28, 2015
Published online: April 30, 2015
ABSTRACT
Aim: In order to
ensure that thrombin generation is limited and localised to prevent thrombosis
after minor injury, coagulation inhibitors play a vital role. The study
assessed protein C and antithrombin III levels in pregnant women in Kano,
North-Western Nigeria.
Materials and methods: A total of two-hundred and fifty apparently healthy
subjects (150 pregnant and 100 non-pregnant women), aged 17-40 years were
recruited for the study in Aminu Kano Teaching Hospital, Kano between August
2010 and October 2011. Blood samples collected were analysed for Protein C and
antithrombin III activities using standard laboratory procedures.
Results: There was significantly lower value of
proteins C activity in pregnant women compared to non-pregnant women (P<0.05)
while the values of antithrombin III in pregnant and non-pregnant women showed
no statistically significant difference (P>0.05). Different and
fluctuated values of Protein C activities and antithrombin III activities with
regard to first, second and third trimesters respectively, showed no
significant differences (P>0.05). Maternal age and parity had no
significant influences on protein C and antithrombin III activities.
Conclusion: Pregnancy is
associated with significantly lower value of protein C activity while antithrombin
level remained stable and unchanged. Gestational age, maternal age and parity
showed no influences in protein C and antithrombin III activities. It is
recommended that protein C activity be assessed in pregnant women to avoid
thromboembolism.
© 2015 ACT. All
rights reserved.
Key words: Protein C; Antithrombin III; Activities; Healthy
Nigerian women
Imoru M, Buseri FI. Protein C and
Antithrombin III Activities in Healthy Nigerian Women. International
Journal of Hematology Research 2015; 1(1): 20-23 Available from: URL:
http://www.ghrnet.org/index.php/ijhr/article/view/1007
INTRODUCTION
In order to ensure that thrombin generation is limited and localised to
prevent thrombosis after minor injury, coagulation inhibitors play a vital role[1,2].
The natural coagulation inhibitors can be of endothelial or hepatic group,
based on their synthetic sites[1].
Antithrombin
III, heparin, heparin co-factor II, antitrypsin and tissue-factor pathway
inhibitor (TFPI) are inhibitors of serine proteases of the coagulation cascade
such as thrombin, Xa and TF-VIIa[2]. Antithrombin III accounts for
about 60% of plasma anticoagulant activities and it plays its inhibitory role
by not only complexing with thrombin but also by inhibiting the clotting factors
XIIa, XIa, IXa and Xa in the presence of heparin sulphate on the endothelial
cell surface[2-5].
Protein C, TM
(thrombomodulin), protein S, C4b binding protein and APC (activated protein C)
inhibitor are all components of the protein C system[2]. Activation
of this system occurs when thrombomodulin binds to thrombin to form activated
protein C (APC) which rapidly degrades factors VIIIa and Va on the phospholipid
surface of activated platelets and prevents the appropriate tenase and
prothrombinase complexes, a reaction that increases 10-20 folds when protein C
combines with its co-factor protein S[6-9].
Antithrombin
concentration varies with race, age, sex and methodology used[10,11].
Conflicting reports have been made on the levels of antithrombin III in
pregnancy as reduced activity was documented by earlier author[12],
increased activity was reported by During et al[13] while
majority of the studies reported no significant changes[14-16].
Earlier researcher documented reduced protein C activity during pregnancy[17]
while other studies showed stable and unchanged levels of protein C during
pregnancy[18-20].
The study was
to determine protein C and antithrombin III levels in pregnancy as extremely
scanty information on these naturally occurring anticoagulants is available in
Nigeria.
Materials
and methods
A total of two-hundred and fifty apparently healthy subjects (150
pregnant and non-pregnant women), aged 17-40 years were recruited for this
study in Aminu Kano Teaching Hospital (AKTH), Kano between August 2010 and
October 2011. Ethical approval and consent were obtained from the ethical
committee of AKTH, Kano and the subjects respectively. Pregnant and
non-pregnant women with histories of recurrent miscarriages, liver disease,
renal disease, diabetes and hypertension and non-pregnant women who are on oral
contraceptives were excluded from the study.
4.5 mL of
venous blood sample was collected from each subject and mixed with 0.5 mL of
32.0 g/L trisodium citrate solution in the plain container. Blood samples in
the citrated containers were centrifuged at 2,500 g for 15 minutes and the
plasma separated into plastic containers for the determination of protein C and
antithrombin III activities.
Protein C and
antithrombin III activities were assayed according to the instructions of
TEChron kits with reference numbers C1100-012 and C1000-010 respectively,
manufactured in Germany and the clotting times determined using Cormay KG
coagulometer manufactured in Poland.
Statistical
analysis
The mean values and standard deviations of the parameters in the pregnant
and non-pregnant women were assessed using student’s t-test while the
differences with regard to gestation period, maternal age and parity were
assessed using one-way analysis of variance (ANOVA). P-value of ≤0.05 was considered significant.
RESULTS
Table 1 shows protein C and antithrombin III levels in pregnant and
non-pregnant women. Pregnant women showed significantly lower value of protein
C activity (55.4±29.0%) compared to non-pregnant women (86.0±32.7%) (P<0.05)
while the values of antithrombin III in pregnant and non-pregnant women showed
no statistically significant difference (P>0.05).
Changes in
protein C and antithrombin III activities with gestation period (trimester) are
summarised in table 2. Different and fluctuated values of protein C activities
(52.9±28.4%, 60.0±31.4% and 51.3±26.1%) and antithrombin III activities
(85.58±14.88%, 79.64±19.73% and 85.34±12.01%) with regard to first, second and
third trimesters respectively, showed no statistically significant differences
(P>0.05).
Table 3 indicates the effects of
maternal age on protein C and antithrombin III activities. Different values of
protein C activities (61.4±35.0%, 53.7±30.0%, 60.3±26.9% and 45.2±23.1%) and
antithrombin III activities (78.34±22.96%, 82.7±15.26%, 85.37±13.47% and
74.81±18.14%) with regard to age-groups 17-22 years, 23-28 years, 29-34 years
and 35-40 years respectively, showed no statistically significant differences (P>0.05).
Table 4 shows
parity influences on protein C and antithrombin III activities in pregnant
women. The levels of protein C (55.9±26.2%, 57.2±36.1% and 54.3±23.9%) and
antithrombin III (78.07±20.94%, 79.42±17.36% and 84.98±13.17%) with regard to
parity of 0, 1-2 and ≥3 respectively, showed no
statistically significant differences (P>0.05).
DISCUSSIONS
Deficiencies of naturally occurring anticoagulant proteins such as
antithrombin III, protein C and protein S produce favourable medium for
thrombus generation which has been linked to thromboembolic disease[21,22].
This study has
shown significantly lower value of protein C activity in pregnant women
compared to the control subjects. This is in line with the previous authors[17,23,24]
but disagrees with other researchers who reported no significant change[6,25].
Inconsistent reports of protein C levels during pregnancy by various authors
might be associated with different sensitivities and specificities of protein C
reagents used, and assay techniques employed. The study further showed the
stability of protein C levels within the gestation period which is consistent
with other studies[6,26,27], however, protein C deficiency has been associated with venous
thromboembolism[28,29]. Maternal age and parity had no significant
effects on protein C activity within the period of pregnancy but showed
significance when compared to non-pregnant status. However, maternal age of
35-40 years showed the least protein C level which could make an advanced
maternal age a risk factor to thrombosis.
This study has
further demonstrated that antithrombin III level showed no significant
difference in pregnant women. This finding agrees with the majority of the
earlier studies[6,13,15] but disagrees with the significantly lower
value reported by Essien[12] probably due to the variation of
sensitivities and specificities of antithrombin III reagents used. This study
has further confirmed the earlier studies that gestational age had no effect on
antithrombin III activity[6,27]. Maternal age and parity showed no
influences on antihrombin III level during pregnancy in this study. However,
variation in antithrombin III levels in pregnancy as reported by various
authors[6,12,13] could be associated with methodology employed, poor
storage of citrated plasma and reagents and sample size.
In conclusion,
pregnancy is associated with significantly lower value of protein C activity
while antithrombin III level showed no significant difference. Gestational age,
maternal age and parity showed no influences on protein C and antithrombin III
activities. It is recommended that protein C activity be assessed amongst other
routine tests for pregnant women since its deficiency has been linked to
thromboembolism.
CONFLICT OF INTERESTS
The author has no conflicts of interest to declare.
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Peer reviewers: Mohamed Radhi,
Department Of Pediatrics, Children’s Mercy Hospital, 2401 Gillham Road, Kansas
City, Missouri, 64108, USA; Wei Zhang, MD & PhD, Professor, Department of
pharmacology, Institutes for Advanced Interdisciplinary Research, EAST CHINA
NORMAL UNIVERSITY, No. 3663 North ZhongShan Road, Shanghai, China.
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