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Национальная ассоциация ученых (НАУ) # 66, 2021
МЕДИЦИНСКИЕ НАУКИ
RELATIONSHIP OF HEMOSTASIS AND FREE RADICAL OXIDATION IN PATIENTS
WITH UTERINE CANCER
Gurina Anna Vadimovna
Federal State Budgetary Educational Institution of Higher Education Tyumen State Medical University of the Ministry of Health of the Russian Federation,
Tyumen
Soldatova Ekaterina Aleksandrovna
Candidate of Medical Sciences, obstetrician-gynecologist, Regional Clinical Hospital No. 1, Tyumen
ABSTRACT
In the structure of mortality, oncological problems are of interest to one of the first places, that thrombosis appears as the second most frequent cause of death of cancer patients. Modern literature suggests the activation of the hemostatic system with the development of chronic DIC syndrome in cancer patients. Activation is realized primarily through an external mechanism of blood clotting: through tissue factor (TF) and so-called cancer procoagulants. The tissue factor, which is a complex of apoprotein III with phospholipid, appears as a trigger in this process, forming a complex with F. VII, which includes F. VII is activated, after which F is activated in accordance with the cascade folding scheme. X as part of the ff. TF / VII/Ha / Va and SA2 + complex.
Keywords: selmevitum, antioxidant potential, activation of hemostasis, coagulation.
Various physical, mechanical, and pharmacological agents are used to prevent postoperative venous thrombosis. Some researchers use direct anticoagulants for these purposes, preferring low-molecular-weight heparins, while others use disaggregants, preparations that have the following properties: antihypoxic and stress-protective properties preparations of systemic enzyme therapy, sulfated polysaccharides structurally related to heparins.
Information about the positive effect of antioxidants in the prevention of thrombohemorrhagia caused by effects that initiate hyper-thrombinemia, the relationship of thrombohemorrhagia in neoplasia with hemocoagulation shifts caused by thrombinemia, the absence of contraindications to the use of antioxidant vitamins, their availability and the possibility of outpatient use were the basis for studying the corrective effect of antioxidant vitamins on hemostasis in the surgical treatment of fibroids and cancer uterus. In addition, the nature of hemostatic disorders, especially platelet disorders, cannot be considered sufficiently studied in such operations. Data on the close relationship between hemostasis and confirm the need to study the state of lipid peroxidation in malignant and benign diseases of the uterus.
CONTENT OF THE WORK
Scientific research is of a clinical nature. 104 women were examined, including 20 healthy donors in the second phase of the menstrual cycle and 84 women with uterine cancer or uterine fibroids who received surgical treatment (extirpation of the uterus with appendages).
The criteria for inclusion in the groups are the presence of indications for planned surgical intervention, informed consent of patients for follow-up and surgical intervention, and the implementation of recommendations for treatment and prevention by women in the perioperative period. Exclusion criteria -refusal of examination and implementation of recommendations for treatment in the perioperative period, the presence of severe somatic diseases that are a contraindication to surgical treatment (for patients of group 2, stage IV of the disease). A thematic map was filled out for all women (age, social status, history of life and diseases, results of clinical and laboratory studies). Observations were carried out in the gynecological departments of the Tyumen Regional Oncological Dispensary, maternity hospital No. 3 in Tyumen, and the regional perinatal center in Tyumen.
Table 1.
Distribution of the surveyed women by groups
Characteristics of groups n
1. Healthy women (control group) 20
2. Women suffering from cancer of the uterus who have undergone radical surgical treatment: - comparison group (traditional treatment) - main group (same + selmevitum) 84 39 45
Statistical processing of the obtained data was carried out using the Excel program by the Student method. The analysis of the relationships of the
variables was carried out by the Spearman rank correlation (rs) method.
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RESULTS OF OUR OWN RESEARCH with malignant diseases of the uterus before and after
Clinical characteristics, state of hemostasis, lipid surgical treatment peroxidation and blood antioxidant activity in patients
Table 2.
Localization and stage of malignant neoplasm, n (M±m %)
Diagnosis Comparison group, n = 39 Main group, n = 45
I stage II stage III stage I stage II stage III stage
Cancer of the uterine body 22 (56,4±8,0) 4 (10,9±5,1) 2 (5,1±3,6) 27 (60,0±7,4) 4 (8,9±4,3) 2 (4,4±3,1)
Cervical cancer 9 (23,1±6,8) 2 (5,1±3,6) 0 (0,0) 10 (22,2±6,3) 2 (4,3±3,1) 0 (0,0)
When analyzing the histological conclusions of the study of the surgical macropreparation in patients suffering from cancer of the uterus, who underwent radical surgical treatment, endometrial adenocarcinoma is most often found: 71% in both groups. Squamous cell carcinoma of the cervix was detected in 28.2% and 26.5%. Leiomyosarcoma of the uterus was detected in one case in a patient of the main group.
The patients of the main group also showed an elongation of APTT (by 42%), ART (by 21.7%), an increase in PA (by 150%), INR (by 144%), an increase in fibrinogenemia (by 256%), a high level of RFMC (by 34%) and PDF (by 52.3%), a decrease in AT III (by 32%), and IRP (by 39%) when compared with healthy women. The TT indicators in the patients of the main group did not significantly differ from those in healthy women, in contrast to the patients of the comparison group. An increase in the concentration of RFMC and PDF in the blood plasma of patients with uterine cancer before surgery indicates an increase in thrombinemia.
A significant increase in the content of FG, RFMC, and PDF in women of the comparison group was revealed on the 3rd and 4th days in comparison
with the indicators before the operation (by 38, 27, and 20%, respectively) and with the first days after it (by 45, 28, and 22%). At the same time, the plasminogen reserve index decreased (by 19% in comparison with the indicators before the operation), by 15% (in comparison with the first day). On the 5th-7th day after the operation, the ART lengthened (by 17%) and the INR increased (by 48%). Therefore, hypocoagulemia of consumption (decrease in total blood clotting and acceleration of TFI), which occurred even before the operation and is caused by oncological pathology, is sufficiently completely leveled by heparinotherapy in the postoperative period.
In the study of the platelet component of hemostasis (Table. 4) before the operation, the patients of the comparison group showed a decrease in the number of D (by 36%, p<0.05), an increase in DE (by 28%), C (by 21%), SE (by 50%), APF (by 28%), and BBA (by 180%) relative to healthy women and patients of the main group. In the main group of patients before surgery, the number of TRS (by 46%) and the concentration of PMA (by 39%) and P3 (by 38%) were reduced in comparison with healthy women.
Table 3.
Coagulation hemostasis after surgery in patients with cancer of the uterus on the background __of taking selmevitum (M±m)__
Indicators Before the operation 1st day, 3-4 days, 5-7 days,
n=10 n=10 n=10 n=14
ART, s 71,8±5,7 84,5±6,9 * 66,2±5,2 # 54,5±4,2 *#
APTT, s 57,7±3,3 72,0±4,3 * 61,0±5,9 # 48,2±1,6 *#
TT, s 19,6±1,7 19,4±2,6 18,2±1,7 21,8±1,1
PO 3,5±0,5 1,9±0,2 * 2,2±0,5 * 2,7±0,4 #
MNO 3,9±0,6 2,1±0,3 * 2,4±0,6 * 3,2±0,5 #
FG, g/l 8,9±1,0 5,8±0,8 * 6,0±1,0 * 6,9±0,6 *
RFMC, mg % 4,7±0,7 4,9±0,5 4,9±0,6 6,1±0,3 *#
PDF, mg % 0,84±0,06 0,78±0,04 0,85±0,07 0,84±0,08
AT III, % 64,5±3,5 69,1±3,8 79,6±1,9 *# 58,5±2,9 #
IRP, % 67,1±3,4 64,6±5,9 77,5±2,4 *# 59,2±3,9 *
Note: the * sign indicates that the differences are statistically significant (p<0.05) compared to the indicators before the operation, the # sign indicates the differences with the first days after the operation
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Table 4.
The state of platelet hemostasis after surgery in patients with cancer of the uterus against the background _of traditional treatment (M±m)_
Indicators Before the operation n=13 1st day, n=10 3-4 days, n=10 5-7 days, n=10
TC (x109/l) 225,7±8,7 223,3±11,7 164,6±18,0 *# 185,8±16,2 *#
D, % 29,8±0,8 29,3±1,5 30,3±1,6 32,3±1,2
DE,% 31,9±1,9 31,9±2,8 31,9±2,0 31,0±1,4
S, % 21,8±1,1 23,2±1,1 23,3±0,9 20,5±2,1
SE, % 15,8±0,6 15,6±0,4 14,6±1,0 16,3±1,3
AF, % 68,7±1,5 70,7±1,5 69,7±1,6 67,8±1,2
NSA (per 100 cells) 8,4±1,1 13,4±0,8 * 6,1±1,3 # 8,7±1,3 #
NLA (per 100 cells) 2,8±0,4 2,8±0,7 2,7±0,9 2,6±0,7
NA (per 100 cells) 11,2±1,4 16,2±1,2 * 8,9±2,2 # 11,3±1,9 #
P3, % 43,9±5,0 39,1±5,0 36,4±8,4 38,9±3,2
Note: * - the differences are statistically significant (p<0.05) compared to the indicators before the operation, # - with the first days after the operation
A statistically significant decrease in the number of P (by 18% relative to the level of day 1), an increase in the APF content (by 15%) was detected on 3-4 days after surgery, and did not decrease until 5-7 days (comparison with preoperative indicators). At the same time, NMA decreased by 3 times, NA by 41%, and D
by 22% (in comparison with preoperative values). 5-7 days after surgery continued to grow the number s (68,6%), decreased NMA (45%), NA (106%) and the number of TTS in the peripheral blood (38%) (compared with the level before surgery and 1-me day after it) (tab. 5).
Table 5.
The state of platelet hemostasis after surgery in patients with cancer of the uterus on the background of
Indicators Before the operation n=10 1 st day, n=10 3-4 days, n=10 5-7 days, n=14
P (x109/l) 133,4±10,8 138,1±11,0 113,5±6,2 # 99,8±4,6 *#
D, % 42,3±2,4 35,2±1,7 * 32,9±2,4* 33,53±1,9 *
DE,% 28,0±1,6 28,0±1,7 28,3±1,8 20,6±1,2 *#
S, % 20,4±1,1 23,9±1,1 30,1±3,7 * 34,4±1,7 *#
SA, % 9,3±0,9 12,3±0,9 * 10,7±0,7 11,1±1,0 *
AF, % 58,3±2,7 64,8±1,7 * 67,1±2,4 * 66,5 ±1,9 *
NSA (per 100 cells 5,1±0,6 6,4±1,6 3,5±0,5 2,8±0,8 *
NLA (per 100 cells 1,3±0,3 0,8±0,1 * 0,4±0,2 *# 0,4±0,1 *#
NA (per 100 cells 6,4±0,8 7,2±1,6 3,9±0,5 *# 3,1±0,9 *#
P3, % 27,1±5,0 36,5±4,0 26,6±2,9 # 27,1±1,6 #
Note: the sign * - the differences are significant (p<0.05) in comparison with the indicators before the operation, the sign # - with the first days after the operation
Compared with healthy women before surgery, the activity of antioxidant defense enzymes was significantly increased: G-S-T in patients of the comparison group by 2 times, the main group-by 3.2 times; and the activity of superoxide dismutase (SOD) by 35% and 20% (respectively). The concentration of vitamin E before surgery in patients receiving
traditional treatment and taking selmevitum did not significantly differ from the indicators in healthy women.
In patients of the comparison group with uterine oncopathology on 3-4 days after surgery, there was a decrease in the level of primary POL products (DC by 21%, p<0.05).
Table 6.
The state of LPO and AOP after radical operations in patients with uterine oncopathology on the
Indicators Before the operation , n=16 1 st day, n=15 3-4 days, n=13 5-7 days, n=18
DC, nmol / ml 114,4±6,1 114,3±7,3 102,9±6,8 *# 100,8±3,8 *#
MDA, nmol / ml 15,3±1,3 13,7±0,9 17,1±1,5 *# 16,6±1,0 *#
Vit. E, nmol / ml 4,9±0,3 5,3±0,7 4,4±0,3 3,4±0,3 *#
SOD, y.e.T. 27,5±5,6 43,9±6,6 *# 31,0±6,9 # 34,1±6,7 *#
G-S-T, nmol / (min.l) 940,6±175,1 793,3±125,1 523,2±105,5 *# 675,7±127,9 *
Note: * - the differences are statistically significant (p<0.05) in comparison with the indicators before the operation, # - with the first days after the operation
Национальная ассоциация ученых (НАУ) # 66, 2021
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The women in the comparison group showed a high degree of correlation between the level of sex products and the concentration of FH, IRP, and the number of P. The correlation of DC values with ART, INR, FG, RFMC, NA, and NSA was estimated as a weak degree, and MDA with ART, NSA, and N-as a strong negative one. There was a strong positive relationship between G-S-T and ART and INR, and a strong negative relationship between G-S-T and IRP, G-S-T and the number of P, and an average relationship between G - S-T and RFMC.
In the main group, a high degree of correlation was determined between the level of DC and ART, with the number of P, PMA and N, and DC with INR, FG, and IRP - a weak degree.
There is an average correlation between G-S-T and the values of ART, RFMC, number of P, NSA, and NA, and between G-S-T and INR, IRP, and FG - weak. Comparison of the Spearman rank correlation coefficient (when assessing coagulation hemostasis) in the study groups showed that its values in the women of the main group were higher than in the women of the comparison group.
Thus, our observations indicate the feasibility of using selmevitum during preoperative preparation and postoperative treatment as a means of non-specific correction of hemostatic changes that occur in conditions accompanied by signs of oxidative stress, in particular, after surgical treatment of uterine cancer.
CONCLUSIONS
1.In patients suffering from uterine cancer, lipid peroxidation was accelerated and antioxidant protection was activated (a twofold increase in the level of glutathione-S-transferase) and signs of the development of the "transitional" stage of disseminated intravascular coagulation (elongation of APTT, TT, an increase in PR, INR, RFMC, PDF and fibrinogen levels, a decrease in AT III, IRP, an increase in the number of APF and the number of large aggregates) were found, which persisted after radical surgery for oncopathology of the uterus up to 7 days.
2. Activation of hemostasis in all surgical interventions in patients with uterine cancer is synchronized with the acceleration of LPO and a decrease in the content of vitamin E in red blood cells. The addition of traditional therapy with selmevitum limits the activation of LPO and leads to an increase in the antioxidant potential.
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