The change of hemostasis system in patients with thrombophlebitis of lower extremities deep veins in ozone therapy

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Acute deep vein thrombophlebitis of the lower extremities remains one of the causes of poor outcomes in surgical patients [1, 2].

In recent years, there has been a steady increase in the frequency of thrombotic lesions of veins, which is associated with general aging of the population, an increase in the prevalence of oncological diseases, the increasingly frequent occurrence of hereditary and acquired disorders of the hemostasis system, uncontrolled intake of hormonal agents and an increase in injuries.

In the development of coagulopathic states, an important role is played by oxidized and under-oxidized fatty acids formed during lipid hyperoxidation [3].

Widespread deep vein thrombosis of the lower extremities in the long term leads to the formation of post-thrombophlebitic disease, manifested by chronic venous insufficiency, up to the development of trophic ulcers, which significantly reduces the ability to work and the quality of life of patients [4, 5].

New possibilities in the treatment of acute thrombophlebitis are provided by the use of medical ozone, which has the ability to normalize the hemostasis system and metabolism, which improves microcirculation and rheological properties of blood [2, 6].

The aim of the study was to study changes in the hemostasis system during ozone therapy in patients with acute deep vein thrombophlebitis of the lower extremities.

Materials and methods. The study involved 65 patients treated in the department of vascular surgery of the City Clinical Hospital No. 4 in Saransk with acute deep vein thrombophlebitis of the lower extremities, and 25 apparently healthy individuals without such a disease.

There were 35 women (53.8%) and 30 men (46.2%). At the same time, in the group of patients with thrombophlebitis of the femoral and popliteal veins, women prevailed, and in the group of patients with thrombophlebitis of the leg, on the contrary, men. The average age of women was 55.0 ± 4.5 years, men – 51.0 ± 4.6 years.

Three groups have been formed. The 1st group (n = 25) included practically healthy persons. Patients with acute thrombophlebitis by simple randomization were divided into two groups: group 2 – comparisons (n ​​= 50) – patients with thrombophlebitis of the popliteal vein and veins of the leg – 25, with thrombophlebitis of the femoral and iliac veins – 25, who received traditional treatment : anticoagulants (Heparin in prophylactic doses), antiaggregants (Pentoxifylline), angioprotectors and venotonics (Eskuzan, Detralex, Troxevasin), non-steroidal anti-inflammatory drugs (Indomethacin, Butadion); Group 3 – main (n = 50) – patients with thrombophlebitis of the popliteal and leg veins – 8, with thrombophlebitis of the femoral and iliac veins – 7, who received systemic ozone therapy along with traditional treatment.

Saturation of 200 ml of 0.9% sodium chloride solution with ozone was carried out on a medozons apparatus for 10 min. The outlet ozone concentration was 2500 μg / l. The ozonized sodium chloride solution was administered to the patient intravenously in a stream, once a day, for five days.

In all patients, bleeding time according to Duke, clotting time according to Lee-White, time of recalcification of normal plasma, plasma tolerance to heparin, kaolin and kaolin-cephalin time, prothrombin time using conventional methods, fibrinogen according to Rutberg, as well as the time of Hageman-dependent fibrinolysis upon admission to the clinic (background examination) and after treatment.

Statistical processing of the obtained results was carried out using parametric and nonparametric criteria in the statistical package STADIA 7.0. The results are presented as M ± m, where M is the arithmetic mean, m is the standard error of the arithmetic mean

Results and discussion. 

As the results of the baseline examination showed, in acute thrombophlebitis of the venous bed, hemodynamic disorders occur, leading to changes in the system of hemo- and lymphoid circulation. Moreover, in the femoral and iliac veins, these changes are more pronounced than in the veins of the leg and popliteal (Tables 1, 2).

Thus, the bleeding time in patients with thrombophlebitis of the veins of the leg and popliteal vein in the comparison and main groups during the background examination was statistically significantly less than the same indicator in healthy individuals. 

After traditional treatment, the bleeding time in the comparison group increased 2.3 times, in the main group – 2.5 times (p <0.001) compared with healthy people, which indicates the beneficial effect of ozone therapy on the functional parameters of the blood system.

The clotting times in patients with thrombophlebitis of the leg and popliteal veins also changed during therapy. Thus, upon admission, the clotting time was 1.37 and 1.6 times shorter (p <0.001), respectively, in patients of the comparison group and the main group, in contrast to practically healthy individuals. After the appropriate treatment in the comparison group, it increased 2 times (p <0.001), and mostly – only 1.5 times (p <0.001) relative to the data in practically healthy people (see Table 1).

When determining similar indicators of the coagulation system in patients with thrombophlebitis of the femoral and iliac veins, positive dynamics was also noted against the background of treatment with ozonized saline (see Table 2). 

In this category of patients, the bleeding time when using traditional treatment increased 2.16 times (p <0.001), while when using ozone therapy – 2.23 times (p <0.001). 

The clotting time changed as follows: in the comparison group, upon admission, the indicator was 1.57 times lower (p <0.001) compared with practically healthy individuals, and after treatment it increased 1.6 times (p <0.001). 

In the main group, the clotting time on admission was 1.69 times less than that in healthy individuals (p <0.001), and after ozone therapy it increased 1.7 times (p <0.001).

Studying the change in recalcification time in the group with deep vein thrombophlebitis of the leg and popliteal vein, the same increase was found with both traditional treatment and against the background of ozone therapy – by 1.23 times (p> 0.05 ). However, it should be noted that the range of normal values of the recalcification time is sufficient

Research on dissertation topics

However, it should be noted that the range of normal values ​​of the recalcification time is rather large (from 60 to 120 s), which does not always allow us to draw reasonable conclusions about the effect of treatment on the first phase of blood coagulation. 

In this regard, in recent years, in order to assess the changes in the first phase of blood coagulation, it is customary to use indicators such as kaolin and kaolin-cephalin time. 

The values ​​of kaolin and kaolin-cephalin time changed as follows: in the comparison group – an increase of 1.38 and 1.22 times, respectively, and in the main group – 1.46 and 1.34 times, respectively in relation to similar indicators in practically healthy people (p <0.001) (see Table 2).

In the study of these indicators in patients with thrombophlebitis of the femoral and iliac veins, the following values ​​were obtained: the time of recalcification of normal plasma in the comparison group and the main group after treatment increased by 1.19 and 1.21 times, respectively, relative to the indicators in practically healthy people (p <0.001). 

Kaolin and kaolin-kefalin time after the course of traditional treatment increased by 1.3 and 1.15 times, respectively (p <0.001). In the main group (against the background of the use of ozone therapy), the kaolin time increased by 1.35 times (p <0.001), and the kaolin-cephalin time – by 1.31 times (p <0.001) relative to the indicators in practically healthy people.

Table 1 – Dynamics of hemocoagulation and fibrinolysis indices in patients with thrombophlebitis of the popliteal vein and leg veins (M ± m)

  Indicators  Practically healthy peopleShit groupintrusionsMain group
on admissionafter treatmenton admissionafter treatment
Duke bleeding time, s180.0 ± 4.3150.0 ± 10.7 p <0.001420.0 ± 12.4 p <0.001 p 1 <0.001147.0 ± 12.8 p <0.001452.0 ± 14.4 p <0.001 p 1 <0.001 p 2 <0.05
Coagulation time according to Lee-White, s330.0 ± 5.2240.0 ± 16.0 p <0.001660.0 ± 28.4 p <0.001 p 1 <0.001205.0 ± 21.1 p <0.001513.0 ± 26.0 p <0.001 p 1 <0.001 p 2 <0.05
Recalcification time of conventional plasma, s110.0 ± 8.796.4 ± 4.5 p <0.001135.3 ± 8.1 p <0.001 p 1 <0.00190.0 ± 4.8 p <0.001136.0 ± 5.3 p <0.001 p 1 <0.001 p 2 > 0.05
Plasma Tolerance to heparin, with520.0 ± 4.9460.8 ± 18.3 p <0.001677.8 ± 3.8 p <0.001 p 1 <0.001406.0 ± 17.2 p <0.001698.0 ± 20.2 p <0.001 p 1 <0.001 p 2 <0.05
Kaolin time of conventional plasma, s60.1 ± 2.243.5 ± 2.3 p <0.00183.4 ± 3.1 p <0.001 p 1 <0.00141.5 ± 4.1 p <0.00188.5 ± 2.8 p <0.001 p 1 <0.001 p 2 <0.05
Kaolin-cephalin time, s47.7 ± 1.736.3 ± 1.2 p <0.00158.4 ± 1.8 p <0.001 p <0.00136.9 ± 0.9 p <0.00163.2 ± 1.3 p <0.001 p 1 <0.001 p 2 <0.05
Prothrombin time, s15.4 ± 0.513.1 ± 0.5 p <0.0521.4 ± 0.9 p <0.001 p 1 <0.00115.2 ± 1.0 p> 0.0532.2 ± 0.8 p <0.001 p 1 <0.001 p 2 <0.001
Fibrinogen according to Ruthberg, g / l3.3 ± 0.44.3 ± 0.4 p <0.0014.3 ± 0.3 p <0.05 p 1 > 0.054.2 ± 0.5 p> 0.054.4 ± 0.4 p <0.001 p 1 > 0.05 p 2 > 0.05
Hageman-dependent fibrinolysis, min12.0 ± 0.418.2 ± 0.3 p <0.00115.4 ± 0.6 p <0.05 p 1 <0.0520.5 ± 0.5 p> 0.0514.3 ± 0.6 p <0.001 p 1 <0.001 p 2 > 0.05

Note: p – statistically significant differences with practically healthy persons; p 1 – before and after treatment; p 2 – in the comparison group and the main one after treatment.

Plasma tolerance to heparin in patients with deep vein thrombophlebitis of the leg and popliteal vein against the background of traditionaltreatment increased by 1.3 times (p <0.001), and against the background of ozone therapy – by 1.34 times (p <0.001) relative to the data in practically healthy individuals. 

In patients with thrombophlebitis of the femoral and iliac veins, this indicator increased by 1.17 and 1.25 times (p <0.001), respectively.

The prothrombin time in patients of the comparison group with thrombosis of the veins of the leg and popliteal vein increased 1.38 times, and in thrombosis of the femoral and iliac veins – 1.34 times (p <0.001). In the main group, a similar indicator changed as follows: with thrombosis of the veins of the leg and popliteal vein, there was an increase of 2.13 times (p <0.001), and with thrombosis of the femoral and iliac veins – 1.21 times (p <0.001 ). 

This effect is apparently due to the influence of the ozonized solution on the functional systems of the plasma blood and is associated with the molecular response of bioactive substances in blood plasma [7].

The level of fibrinogen in patients with thrombosis of the popliteal vein and leg veins, as well as thrombosis of the femoral and iliac veins did not significantly change both in the comparison group and in the main group, which, apparently, is due to the protective reaction of the body to injury – the presence of a vein in the thrombus region.

The study of such an indicator as the time of Hageman-dependent fibrinolysis revealed a tendency towards its decrease, and more pronounced against the background of the use of ozone therapy.

 Thus, in patients with acute thrombosis of the popliteal vein and leg veins, this indicator in the comparison group during treatment decreased from 18.2 to 15.4 min (p <0.05), and in the main group – from 20.5 to 14 , 3 min (p <0.001).

Table 2 – Dynamics of hemocoagulation and fibrinolysis indices in patients with thrombophlebitis of the femoral and iliac veins (M ± m)

  Indicators  Practically healthy peopleShit groupintrusionsMain group
on admissionafter treatmenton admissionafter treatment
Bleeding time180.0 ± 4.3120.0 ± 17.0390.0 ± 24.0130.1 ± 14.0402.0 ± 16
according to Duke, withp <0.001p <0.001p <0.001p <0.001
p 1 <0.001p 1 <0.001 p 2 > 0.05
Clotting time330.0 ± 5.2210.0 ± 24.5530.0 ± 26.7195.0 ± 18.2587.0 ± 21.2
according to Lee-White, withp <0.001p <0.001p <0.001p <0.001
p 1 <0.001p 1 <0.001 p 2 <0.05
Recalcification time110.0 ± 8.791.5 ± 3.6131.3 ± 7.480.2 ± 5.1134.0 ± 3.3
conventional plasma, sp <0.001p <0.001p <0.001p <0.001
p 1 <0.001p 1 <0.001 p 2 > 0.05
Plasma Tolerance520.0 ± 4.9430.7 ± 17.4610.3 ± 8.1399.0 ± 18.7650.0 ± 20.2
to heparin, withp <0.001p <0.001p <0.001p <0.001
p 1 <0.001p 1 <0.001 p 2 <0.05
Kaolin time60.1 ± 2.239.4 ± 1.978.3 ± 2.842.1 ± 1.181.0 ± 1.8
conventional plasma, sp <0.001p <0.001p <0.001p <0.001
p 1 <0.001p 1 <0.001 p 2 <0.05
Kaolin-mullet47.7 ± 1.734.5 ± 1.455.1 ± 1.128.1 ± 2.162.0 ± 1.7
time, sp <0.001p <0.001p <0.001p <0.001
p <0.001p 1 <0.001
p 2 <0.05
Prothrombin time, s15.4 ± 0.512.3 ± 0.420.7 ± 0.711.0 ± 0.518.7 ± 0.9
p <0.05p <0.001p <0.001p <0.001
p 1 <0.001p 1 <0.001
p 2 <0.05
Fibrinogen by Rutberg,3.3 ± 0.44.7 ± 0.74.8 ± 0.44.4 ± 0.74.7 ± 0.9
g / lp <0.001p <0.05p> 0.05p <0.05
p 1 > 0.05p 1 > 0.05 p 2 > 0.05
Hageman addicted12.0 ± 0.420.7 ± 0.215.6 ± 0.418.7 ± 0.414.8 ± 0.7
fibrinolysis, minp <0.001p <0.05p> 0.05p <0.001
p 1 <0.05p 1 <0.001 p 2 > 0.05

Note: p – statistically significant differences in values ​​with practically healthy individuals; p 1 – before and after treatment; p 2 – in the comparison group and the main one after treatment.

 In the group of patients with acute thrombosis of the femoral and iliac veins against the background of traditional treatment, it decreased from 20.7 to 15.64 minutes (p <0.05), and with the use of ozone therapy – from 18.7 to 14.8 minutes (p <0.001).

Conclusion. 

The dynamics of indicators characterizing the coagulation and fibrinolytic properties of blood indicates that in patients with deep vein thrombophlebitis of the lower extremities after the use of systemic ozone therapy, there is a more significant shift in hemostasis indicators towards hypocoagulation as compared with patients who received only traditional treatment … 

The revealed changes, apparently, are due to the activation of oxygen-dependent processes in the body under the influence of ozone therapy, both in internal organs and tissues, synthesizing factors of blood coagulation and fibrinolysis, and in the area of ​​venous thrombosis.

Literature

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