
RISK FACTORS OF VENOUS THROMBOEMBOLISM
IN SUDANESE PREGNANT WOMEN Abdalhabib EK, Alfeel A, Ali EI, Ibrahim IK, Mobarki AA, Dobie G, Hamali HA, Saboor M, *Corresponding Author: Dr. Muhammad Saboor, Department of Medical Laboratory Technology,
Faculty of Applied Medical Science, Jazan University, Jazan, Saudi Arabia. Tel.: +966-54-495-9029.
E-mail: msaboor@ jazanu.edu.sa page: 49
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DISCUSSION
Hemostasis is a delicate balance between procoagulant
and anticoagulant factors that maintains blood flow
within the blood vessels. Abnormal bleeding tendency or
thrombosis occurs when the level of any of the pro coagulant
factors and/or anticoagulants is in excess, deficient, or
functionally abnormal. Protein C, PS, and AT are the most
important natural anticoagulants. Factor V and prothrombin
(factor II) are pivotal in the coagulation cascade. Thrombin
also plays a crucial role in the conversion of fibrinogen
into fibrin and factor XIII into XIIIa to form a stable clot.
Simultaneously, thrombin forms a complex with thrombomodulin
that activates PC in the presence of PS. The
activated PC inhibits the activated coagulation factors V and
VIII, thereby limiting the clot formation [11]. Deficiency of
PC or PS results in increased susceptibility to thrombosis.
Antithrombin inactivates the activated coagulation factors
XI, IX, X and II. Single-nucleotide polymorphism of the
FVL gene results in the development of FVL. It renders
FVL resistant to the activated PC, thereby decreasing the
anticoagulant function of PC and predisposition to thrombus
formation [12]. The prothrombin G20210A mutation
of the prothrombin gene exhibits increased synthesis and
functional capability of prothrombin, favoring thrombosis [4]. Thus, evaluation of the risk factors, frequency of FVL
G1691A, prothrombin G20210A, and deficiency of the
most common natural anticoagulants in pregnancy, is essential
for better management of patients with VTE and to
avoid any untoward clinical manifestations. In this study,
approximately 81.3% of the cases exhibited an association
with VTE risk factors. The most frequent risk factors associated
with VTE were contraceptive use, high BMI, and
termination. These findings correlate well with those of
previous studies [13-16]. Meanwhile, 10.1% of the cases
had a family history of VTE. History of hypertension, surgery,
renal diseases, and immobility were comparatively
rare clinical manifestations in patients with VTE.
In this study, the frequency of the FVL G1691A heterozygous
mutation (G/A) was 3.5%, whereas that of the
homozygous mutation (A/A) was 0.5% [OR = 17.71, 95%
confidence interval (9%% CI): = 1.015-309.05], which is
consistent with the results of previous studies [17,18]. The
rate of the FVL G1691A polymorphism is almost similar
in various pregnancy-associated clinical manifestations
[19]. In a group of Sudanese women with preeclampsia,
the frequency of such polymorphism was found to be 9.6%
[20]. Moreover, only one (0.5%, OR = 0.332, 95% CI: =
0.013-8.191) case was heterozygous (G/A) for prothrombin
G20210A polymorphism. These findings are consistent
with some studies but in contrast with others. However, a
recent study did not detect this mutation in a selected group
of pregnant women [20]. In another study conducted in
Sudan, the prevalence of prothrombin G20210A mutation
was reported as 3.0%, which is higher than that observed
in this study [17]. Other researchers have also reported a
high prevalence of prothrombin G20210A heterozygous
mutations in pregnant women with DVT or PE [19]. By
reviewing the ODs, it is evident that although statistically
insignificant, patients with VTE were more susceptible to
carry the FVL G1691A polymorphism than controls. According
to the clinical presentation, of 156 patients with
DVT, seven (4.49%) had the heterozygous FVL G1691A
(G/A) polymorphism and one of 20 patients with pulmonary
thromboembolism had a homozygous (A/A) polymorphism.
These data suggest that among the VTE cases, FVL
G1691A polymorphism was the most common finding in
patients with DVT, which was consistent with other studies
that reported a high prevalence of this polymorphism
in patients with DVT [16,19,21-24]. Only one case had a
heterozygous prothrombin G202210A mutation, representing
0.5% of the study population, in contrast with other
studies that reported a slightly high prevalence [19,25].
The results of this study showed that AT deficiency was the
most common finding in patients with DVT. The rates of
PC and PS deficiencies were slightly lower than the rate of
AT deficiency. These findings suggest that AT deficiency is
more commonly associated with DVT than FVL G1691A
polymorphism and PC and PS deficiencies among patients
with VTE. Similarly, AT deficiency was the most common
finding in patients with PE and venous thrombosis
of the upper limb. The correlation analysis disclosed a
statistically significant (p <0.05) association with age (r
= –0.122), contraceptive use (r = 0.189), and termination
(r = 0.274). The FVL G1691A polymorphism and PC and
PS deficiencies also demonstrated strong correlation with
contraceptive use, high BMI, age and termination. These
findings are consistent with those of previous studies [4-6].
In conclusion, among the VTE cases, FVL G1691A
polymorphism and PC, PS, and AT deficiencies were the
most common findings in patients presenting with DVT.
The AT deficiency was more common in the study population
than PC and PS deficiencies. Contraceptive use,
high BMI, and termination correlated strongly with FVL
G1691A polymorphism and PC and PS deficiencies in
patients with VTE. Major limitation of the study was no
follow-up of the pregnant patients with VTE to observe
the effect of FVL G1691A polymorphism and low levels of
PC, PS and AT on the outcome of pregnancy. We intend to
conduct further studies to explore the role of these factors
in the pregnancy outcome.
Authors’ Contributions. E.K. Abdalhabib, A. Alfeel,
EI Ali and I.K. Ibrahim designed the study, analyzed the
results and collected the samples and performed DNA
purification; M. Saboor, A.A. Mobarki, G. Dobie and H.A.
Hamali wrote, revised, and reviewed the manuscript.
Declaration of Interest. The authors report no conflicts
of interest. The authors alone are responsible for the
content and writing of this article.
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