1. Relevance

Varicose veins are a significant problem in obstetrics and gynecology, especially among pregnant women. With the increasing frequency of this disease, it is necessary not only to study its pathogenesis and clinical manifestations, but also to develop optimal approaches to its prevention and treatment.

There is a lot of information about the increasing incidence of varicose veins in the world community. According to phlebologists, in recent decades, cases of varicose veins (VV) of the internal organs and pelvic organs have been increasing [6]. As is known, VV of the genitals is an expansion of the veins of the external and internal genital organs (labia majora and minora, vagina, appendages of the uterus and uterus), which, according to some authors, is classified as an atypical form of venous disease [5,15]. According to the international epidemiological study of the Vein Consult program, which included 99,359 patients from different countries, the prevalence of varicose veins of the legs reaches 51.9-70.18%, depending on the region [3,12]. According to a study by Vuylsteke M.E., age and female gender are correlated with more severe clinical manifestations of the disease (p<0.001). Patients who regularly exercise and do not have a family history of this pathology are included in the lower CEAP classification for chronic venous diseases, group C. This study also provides information on the relationship of the degree of varicose veins with a high body mass index, lack of regular physical activity, the number of pregnancies, hereditary predisposition and the age of the patients [12]. According to the studies of Novikov B.N. (2011), 70-90% of women associate the appearance of varicose veins with pregnancy. This scientist's research is confirmed by both international and domestic scientists, but pregnancy cannot be a direct cause of varicose changes [10]. The development of advanced technologies in modern medicine has introduced many methods for diagnosing varicose veins. With the help of modern technologies, innovative methods for diagnosing varicose veins of the legs and pelvis have been introduced, and there are methods that provide high accuracy and safety for patients, including pregnant women. However, they are aimed at diagnosing the disease after it has developed.

A 2021 study (Trombos Research), a 2023 study found that thrombodynamics is 30% more accurate than D-dimer in predicting thrombosis in pregnant women [11]. In the work of Smith J.R. et al. (2022), the method was successfully used to monitor anticoagulant therapy in patients with varicose veins [14]. In this regard, finding adequate diagnostic methods that are able to identify the risk of developing varicose veins and maintain the stability of hemodynamic parameters is a very important task.

The purpose of the study management of pregnant women with various manifestations of varicose veins in the city of Samarkand.

2. Research Materials and Methods

This research was conducted on the basis of the Samarkand branch of the Republican Specialized Scientific and Practical Center for Maternal and Child Health and the maternity complex of the Multidisciplinary Clinic of the Samarkand State Medical University. 132 pregnant women were selected to participate in the study. The main group was formed by pregnant women with varicose veins (n=99), who were divided into three subgroups depending on the manifestation of varicose veins: group 1 included 33 pregnant women with varicose veins of the legs, group 2 included 33 pregnant women with varicose veins of the pelvis, and group 3 included 33 pregnant women with varicose veins of both the legs and the pelvis. The clinical and laboratory control group included 33 practically healthy pregnant women.

Examination and treatment were carried out in accordance with the standards of medical care, as new methods for diagnosis, thrombodynamic blood analysis and methods for determining the prothrombin G2021OA, antithrombin III, Leiden factor V mutation were used.

The working principle of the thrombodynamic analysis is as follows: a coagulation activator (usually tissue factor) is added to a blood plasma sample. The blood is placed in a special chamber with a two-dimensional cavity modeled (imitation of blood vessels). The process of fibrin clot formation is recorded in real time using a fluorescence microscope or optical sensors. We study this analysis based on such indicators as the thrombus growth rate, the delay in its development, the initial growth rate, the steady-state growth rate of the thrombus, the thrombus volume after 30 minutes, the thrombus density, and the time of spontaneous thrombus formation.

From instrumental methods, an ECG was performed according to the standard, and Dopplerography of the pelvic organs and leg vessels was performed using UTT, as well as the state of the fetus and feto-placental system was studied. According to the results of a comprehensive examination, a decision was made on the need for VC therapy and prevention of thrombosis and thromboembolism.

Variational and statistical processing of the study results was carried out using the Statistica 6.0 program with the determination of the main variability indicators: mean values (M), errors of the mean value (m), standard deviation (p). The reliability of the results was determined using the Student t-test. The difference between two mean values is considered significant if the p-parameter is less than 0.05. The level of confidence was at least 95%. The correlation between the indicators was calculated using the Excel 2010 spreadsheet.

3. Research Results and Discussion

All pregnant women studied were of active reproductive age, i.e. from 19 to 44 years. The average age was 27±0.7 in the main group and 26.2±0.5 in the control group.

Analysis of the social status of women in the main group showed that in group 1, 45.45% of women were employees, of which 27.27% were workers requiring heavy labor, 24.24% were unemployed (housewives), 30.3% were students, and in group 2, 35.35% were employees, workers - 18.18%, housewives - 42.42% and students - 4.05%. It is seen that the prevalence of varicose veins in the legs is more pronounced in workers with heavy labor and students. In the third group of women, workers accounted for 54.54%, housewives for 21.21%, and students for 24.24%. Women in the control group did not differ significantly from the previous two groups in terms of social status (p>0.05).

The main and control groups were compared according to the main parameters, including social status, menstrual and reproductive history, obstetric and gynecological condition, somatic diseases, contraceptive methods used, etc.

The average number of pregnancies was 2.8±0.2 in the main group of women, and the number of births was 2.4±0.2. The average gestational age in the main group was 30.3 ± 1.0 weeks. According to statistical data, the average BMI varied from 17 to 35, but averaged 28.4 ± 0.4. High BMI values were more common in women of group 3, who had mixed forms of varicose veins.

Analysis of complaints showed that the most common symptom in women of the main group was the presence of a feeling of heaviness and pain in the legs, which was noted by 83.83% of women in group 2 and 100% in groups 1 and 3. Subjective symptoms in the form of heaviness in the legs, dilation and pain in the area of varicose veins were noted in 100% of women in all subgroups of the main group.

The CEAP classification of varicose veins in pregnant women was carried out. 30 women in the control group were assigned to category C0, and 3 women in the control group to category C1. Pregnant women in the main group were divided into categories from C1 to C5. In group 1, telangiectasias and venous plexuses (C1) were detected in 12.12%, in group 2 - in 15.15%, and in group 3 - in 9.09%. Category C5, i.e., trophic ulcers, occurred in 15.15% and 21.21% of representatives of groups 1 and 3, respectively.

Figure 1. Group 1 patient in category C-5 (E.F. case history No. 116/533)

Figure 2. Group 3 patient of category C-5 (D.K. case history No. 180)

Figure 3

When evaluating the results of the coagulogram, such indicators as APTT (in seconds), fibrinogen (g/l), D-dimer (ng/ml), and antithrombin III (%) were evaluated (Table 1).

Table 1. Coagulogram results

If we analyze these data in subgroups, the mixed form of VC had the most pronounced abnormalities: Fibrinogen: 5.1 ± 0.8 g / l. D-dimer: 750 ± 170 ng / ml. Group 2 of VV showed moderate hypercoagulability: D-dimer: 610 ± 130 ng / ml. In our study, we used an innovative laboratory method of thrombodynamics, which allows us to assess the dynamics of thrombus formation in conditions as close as possible to physiological conditions. Unlike traditional analyzes (APTT, INR), it provides information about the speed, strength and spatial distribution of the thrombus, which is especially important for patients at risk of thrombosis. Thrombodynamic analysis was performed in the multidisciplinary clinic of SamSMU. The thrombus growth rate in the main group of patients was on average 45.2 ± 5.3 μm/min, which is almost 2 times higher than in the control group (control group 28.1 ± 4.1 μm/min, p<0.001). The mixed form of VV demonstrates the highest growth rate of blood clotting (53.6 μm/min) and the lowest delay (1.5 minutes), which indicates severe hypercoagulability. In the control group, unlike all subgroups of the main group, there was no spontaneous formation of blood clots. Thrombus density was correlated with the severity of the disease, and the maximum values were determined in a mixed pattern.

The study of genetic mutations revealed the following: Factor B (Leiden mutation) was detected in 18.2% (n=18) of the main group, and in 3.0% (n=1) of the control group (p<0.01). Prothrombin G20210A was detected in 12.1% (n=12) of the main group, and was not detected in the control group (p<0.05). Antithrombin III deficiency was detected in 9.1% (n=9) of the main group, and was not detected in the control group (p<0.05). The combination of Leiden mutation + prothrombin G20210A was detected in 6.1% (n=6) of patients, which was associated with an increase in D-dimer to 890 ± 210 ng/ml.

The results obtained are consistent with the studies of Dobrokhotova Y.E. et al. (2020), where hypercoagulability and genetic mutations were the main risk factors for VV in pregnant women. The increase in D-dimer to 750 ng / ml in the mixed form of varicose veins confirms the ACOG data (2020) on the relationship between the severity of varicose veins and thrombotic risk.

Treatment of pregnant women with varicose veins (VV) requires a comprehensive approach that takes into account both the characteristics of the pregnancy and the risks associated with impaired venous blood flow. Below is a detailed algorithm based on current clinical guidelines and the evidence base of our research.

1. Screening - Collection of anamneses with assessment of family history (presence of VV or thrombotic complications in relatives), analysis of previous pregnancies (complications, thrombosis, varicose veins), identification of concomitant diseases (obesity, diabetes mellitus, cardiovascular pathologies). Assessment of symptoms of VV includes analysis of complaints of heaviness in the legs, swelling, a feeling of venous pressure in the legs at night and pain in the pelvic area. The presence of visible telangiectasias or varicose veins and assessment according to the CEAP classification.

Physical examination includes a visual assessment of the condition of the veins in the legs and perineum and genitals. Palpation is necessary to detect varicose veins, pain and tightness. Standard laboratory and instrumental diagnostics include a complete blood count (evaluating hemoglobin levels, platelets), coagulogram analysis with the assessment of APTT, PT / INR, fibrinogen, D-dimer. Ultrasound examination of the pelvis and legs (to exclude diseases of the blood vessels of the pelvic organs).

In the case of varicose veins in the legs - UST Doppler scanning of the legs to assess valve insufficiency, vessel diameter and the presence of reflux. In the case of hypercoagulability according to the coagulogram (D-dimer> 800 ng/ml), a blood test for thrombodynamics.

In the case of varicose veins in the pelvic organs and labia minora - transvaginal ultrasound and Doppler examination to visualize the pelvic vessels, assess their diameter and blood flow. If ultrasound is not informative or thrombosis is suspected, MRI and / or contrast scanning of the pelvic organs is recommended.

In the case of varicose veins in the legs, in the pelvic organs and labia minora - combined ultrasound Dopplerography to assess the vessels of the legs and pelvis. In case of family history or thrombotic complications, in addition to thrombodynamics, genetic analysis for the combination of factor V Leiden mutations, prothrombin G2021OA, thrombin-III is recommended.

Compression stockings (class I-II) are recommended for all pregnant women, which improve venous outflow and reduce the risk of thrombosis. Physical activity in the form of walking, swimming and exercise therapy is recommended to improve blood circulation. It is recommended to avoid prolonged standing / sitting in everyday life, and to maintain an elevated position of the legs during rest.

For the medium-risk group with hypercoagulability (D-dimer> 800 ng / ml), low molecular weight heparins are prescribed in 10-day courses. Control the effectiveness of therapy by monitoring the coagulogram every 4 weeks.

For the high-risk group - in patients with genetic mutations or a history of thrombosis, lifelong anticoagulant therapy, monthly monitoring of thrombodynamics and ultrasound Dopplerography to assess the dynamics of the condition are recommended. It is advisable to consult a phlebologist / hematologist and other relevant specialists for indications for correction of therapy and prevention of complications.

Starting from the second trimester of pregnancy, dynamic monitoring, repeated ultrasound Dopplerography of the veins of the legs and pelvis, and monitoring of the coagulogram (assessment of hypercoagulation) in the second and third trimesters should be carried out. After childbirth, it is recommended to continue compression therapy for 6-8 weeks and monitor D-dimer after 1 month to exclude thrombotic complications. Signs of thrombophlebitis require urgent measures, urgent ultrasound Dopplerography is performed to confirm the diagnosis, therapeutic doses of low molecular weight heparins are prescribed, and hospitalization in an angiosurgical hospital is required. In case of bleeding from varicose veins, it is necessary to immediately apply compression bandages, urgently hospitalize, consult a vascular surgeon or phlebologist. Management of pregnant women with varicose veins requires an individual approach based on risk stratification and modern diagnostic methods. Comprehensive prevention, including compression therapy, anticoagulants, and dynamic monitoring, helps to reduce the risk of thrombotic complications and improve pregnancy outcomes. This algorithm is consistent with ACOG (2023), ESVS (2022) recommendations and complements national clinical protocols.

4. Conclusions

An algorithm for diagnosing and preventing varicose veins in women during pregnancy is proposed, including the tactics of differential treatment and management of pregnant women with varicose veins, taking into account the form and degree of the disease, the presence of complications, if necessary, the identification of polymorphisms of their genes and the appointment of additional therapy.

The use of the algorithm for diagnosing varicose veins in women during pregnancy increases the effectiveness of therapy and treatment outcomes in women with varicose veins and reduces the number of complications of the disease, especially thrombotic complications that can lead to maternal death. The medical effectiveness of the algorithm for diagnosing and preventing varicose veins in women during pregnancy is characterized by a 50% reduction in varicose vein complications. The use of the proposed algorithm has high social effectiveness in terms of preventing the transition of the disease to a complicated form, maintaining reproductive health and improving the quality of life of women, and improving diagnostic and preventive work using primary medical and sanitary services.