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

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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