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8ACUTE VARICOTROMBOMPHLEBITIS: TREATMENT WITH ORAL SUBTILISINS
Krivoschekov E.
Doctor of Medical Sciences, Professor of the Department of Surgery, IPO FSBEI HE "Samara State Medical University" of the Ministry of Health of the Russian Federation
Poseryaev A.
GUZ "Ulyanovsk Regional Clinical Hospital", Ulyanovsk
Romanov V.
Private institution educational institution of higher education "Medical University" Reaviz ", Samara
El'shin E.
GBUZ Samara Region "Samara City Clinical Hospital No. 8", Samara
Abstract
In this article, the authors write about their experience with the use of the oral fibrinolytic "Thrombovazim" in the conservative treatment of acute ascending varicothrombophlebitis of the lower extremities against the background of the appointment of a direct oral anticoagulant, diosmin preparations, elastic compression of the lower extremities. The comparative results of using this treatment regimen in relation to the therapy of this pathology without prescribing a thrombolytic agent after 3 and 6 months from the start of treatment are presented. The dynamics of recanalization of the venous bed and the dynamics of reduction of clinical manifestations of the disease are analyzed.
Keywords: saphenous vein thrombosis of the treatment, fibrinolytic, direct oral anticoagulant.
Introduction. Varicose veins of the lower extremities is one of the most common diseases from the total number of pathologies of the peripheral vascular bed in the Russian Federation and around the world. [1,5,7] Clinical practice shows that the majority of patients' criticism of this disease is reduced, which leads to a large number of complications. Various complications of varicose veins make up from 0.3% to 8% of the total number of patients who have consulted doctors of the surgical specialty [3,2]. The most dangerous complication of varicose veins is acute ascending varicothrombophlebitis, which occurs in 30-60% of patients with varicose veins [13,17,19]. There is a direct relationship between the size of the venous lesion area and the severity of pain, forcing patients to restrict limb movement. When a thrombus is localized in the basin of the small saphenous vein, local manifestations are less pronounced [4,12,16]. In the absence of proper treatment or late treatment of the patient for medical help, the progression of the thrombotic process leads to the spread into the deep venous system of the lower extremities, as well as to the formation of a floating area of the thrombus, its separation and migration and, as a result, to pulmonary embolism.
The aim of the study is to improve the results of conservative treatment of acute ascending varicothrombophlebitis of the saphenous veins of the lower extremities in terms of preventing the development or decreasing the severity of postthrombophlebitic disease, alleviating symptoms and accelerating recovery.
Materials and methods. This study included 104 patients who underwent inpatient conservative treatment for 7 days in the conditions of the vascular surgery department of the GUZ UOKB for 2018 - 2019. followed by outpatient conservative treatment. The study excluded patients with flotation of the head of a
lower extremities, varicothrombophlebitis, conservative
thrombus in the peri-ostium section, or with a thrombus less than 1 cm from the osteal valve according to ultrasound data, who, according to clinical indications, required surgical intervention at the time of admission to the hospital. The study excluded patients with the presence of a thrombotic process spreading to the deep venous system, pulmonary embolism, clinically significant hemorrhagic complications. The results of the study included complete or significant recanalization of veins affected by the thrombotic process, complete relief of clinical symptoms and restoration of working capacity in the absence of process progression and no complications.
In each patient included in the study group, acute ascending varicothrombophlebitis in the basin of the large or small saphenous vein at the level of the thigh and lower leg was identified and instrumentally confirmed by ultrasound duplex angioscanning, while varicose veins and varicothrombophlebitis with lesions of varices and the trunk of the great saphenous vein were detected in In 88 patients (84.6%), varicothrombophlebitis in the basin of the small saphenous vein was detected in 16 patients (15.4%), which did not require surgical or thrombolytic intervention [17, 16]. The clinical study was of a comparative prospective nature. Women were the overwhelming majority - 91.3% (95) of patients, men - 8.7% (9). The patients' age ranged from 26 to 64 years, averaging 43.2 ± 2.6 years. The duration of the presence of varicose veins in patients ranged from 3 to 18 years, averaging 12 ± 4.2 years. The duration of the course of varicothrombophlebitis ranged from 1 to 6 days, averaging 3 days.
All patients were prescribed basic therapy in accordance with current standards and clinical guidelines: parenteral administration of low molecular weight heparins (Clexane) at a dosage of 1 mg / kg 2 times a day in order to prevent the spread of throm-
bosis to the deep venous system, phlebotonics in therapeutic dosages (Detralex) at a dosage of 1000 mg per day, constant elastic compression of the lower extremities of the 2nd class of compression (elastic stockings or tights) [9], at the outpatient stage, patients were prescribed direct oral anticoagulants (Eliquis 5 mg 2 times a day) for a period of 3 months in order to prevent the spread of the thrombotic process to deep venous system with subsequent transfer according to the results of the control ultrasound scan, which determined the presence of recanalization, progression with spread to the deep venous system and the presence of flotation, to oral antiplatelet agents (Aspirin-Cardio 100 mg once a day) [15]. Transfer of patients to oral antiplatelet agents was carried out in the absence of flotation, the presence of recanalization, and full patency of the deep venous system of the lower extremities.
Before discharge from the hospital, all patients underwent control ultrasound duplex angioscanning of the veins of the lower extremities in order to exclude flotation of the thrombus head, progression of the thrombotic process and its spread to the deep venous system. The patients were re-examined by a vascular surgeon 3 months and 6 months after the first visit. The dynamic examination included a clinical examination, ultrasound duplex angioscanning of the veins of both lower extremities.
The patients were divided into 2 groups, similar in sex, age, degree and level of saphenous veins lesion by thrombotic process. The first study group (comparison group) included 50 (48%) patients, of whom 44 were women (88%), 6 men (12%). The second group (main group) of the study included 54 (52%) patients, 49 women (90.7%), 5 men (9.3%). Patients of the first study group were prescribed only basic therapy according to clinical guidelines (indicated above). The patients of the second group of the study were prescribed basic therapy in combination with the fibrino-lytic drug "Trombovazim" at a dosage of 800 IU 2 times a day for a course of 20 days.
Results. At the inpatient stage, three (2.9%) patients were excluded from the study. In two of them (one from each study group - 2% and 1.9%), according to the results of the control ultrasound scan in the hospital, the progression of thrombosis was revealed in the form of the spread of the thrombotic process to the deep venous system of the limb. And in one (2%) patient of the first group, thromboembolism of small branches of the pulmonary artery was revealed in a hospital setting.
During inpatient treatment, hemorrhagic complications were not detected in any group.
Among the patients of the first group who remained in the study, according to the data of the control ultrasound scan, no recanalization was detected, the relief of clinical symptoms was not observed, however, the absence of flotation and progression of the thrombotic process made it possible to transfer patients to the outpatient stage of treatment. Among the patients of the second group who remained in the study, according to the control ultrasound scan data, recanalization was detected in two patients (3.7%), no
relief of clinical symptoms was observed, however, the absence of flotation and progression of the throm-botic process made it possible to transfer patients to the outpatient stage of treatment.
After 3 months, 82 (78.8%) patients remained under observation, 44 (88%) in the first group, 38 (70.4%) in the second group. The rest of the patients did not show up for the follow-up examination for non-medical reasons.
During the examination, the following parameters were assessed: preservation of subjective manifestations, such as a feeling of discomfort, the presence of a burden; compaction, hyperemia and hyperpig-mentation, the degree of restriction of movements and pain, significantly reducing the ability to work and the quality of life, recanalization in the veins affected by the thrombotic process according to ultrasound angi-oscanning [18], as well as the presence or absence of clinically significant hemorrhagic complications according to anamnesis for the past time.
It should be noted that in the second group of the study there were no hemorrhagic complications after 3 months, recanalization in the veins affected by the thrombotic process occurred in 31.6% of patients, however, complete recanalization was not observed according to ultrasound data. Subjective symptoms, such as local pain and inflammatory changes, such as discomfort in the area of the affected veins, were observed only in 7.9% of patients in the second group, versus 90.9% of patients in the first group of the study. One patient (1.7%) from the first group was excluded from further research as a result of a history of intestinal bleeding, arrested by the cancellation of direct oral anticoagulants, which required additional treatment and examination. After 3 months, all patients, due to the lack of progression of the thrombotic process and according to the Russian clinical guidelines, were transferred from taking direct oral anticoagulants to taking antiplatelet agents (Aspirin-Cardio 100 mg once a day).
After 6 months, 43 (96%) people remained under observation in the first group, 38 (70.4%) patients in the second group. As well as after three months, the degree of recanalization and the presence of clinical symptoms were assessed.
According to the results of the study, in the second group of patients, recanalization to one degree or another occurred in all patients, while complete re-canalization was achieved in 92.1% of patients, compared with 23.3% of patients in the first group who achieved complete recanalization. The duration of the disease and the absence of complete recanalization of the affected veins, the remaining patients developed postthrombophlebitic disease. After 6 months of therapy, complete relief of inflammatory changes in the affected veins and no clinical symptoms were noted, which improved their quality of life. In contrast to the standard treatment regimen, the prescription of Trom-bovazim increased the number of patients with complete and partial recanalization, led to a complete relief of subjective and objective symptoms, which can be considered complete recovery without a transition
to a chronic form of the disease, namely the development of post-thrombophlebitis disease.
Discussion. According to the literature and clinical practice, the process of restoring the patency of the venous bed affected by the thrombotic process actively occurs during the first 6 months after acute venous thrombosis [8]. Therefore, adequate treatment of acute ascending varicothrombophlebitis of the veins of the lower extremities, aimed at early recanalization, relief of pain, inflammatory reaction, reduces the likelihood of developing postthrombophlebitic disease and recurrent venous thrombosis.
The basis of conservative treatment of patients with acute ascending varicothrombophlebitis is anticoagulant and antiplatelet therapy for a sufficiently long period [15].
Thrombovazim is a domestic oral thrombolytic agent containing a highly purified enzyme preparation subtilisin immobilized on polyethylene glycol. It can be effectively used to prevent venous and (or) arterial thrombosis. Thrombovazim reduces swelling and pain, a feeling of heaviness in the limbs, prevents thrombus formation and increases the regression of inflammation. [ten]. At the same time, Thrombovazim does not affect the number of blood platelets, does not lengthen the clotting time and bleeding time, without affecting the parameters of the blood coagulogram. The use of anticoagulants enhances the fibrinolytic effect of Trombovazim without increasing the risk of bleeding.
Our study showed that the appointment of low-molecular-weight heparins in therapeutic dosages to patients from the first day of the disease, followed by a transfer at the outpatient stage of treatment to direct oral anticoagulants, and the subsequent transfer of patients to antiagrenants, allowed to start the processes of restoring the patency of the saphenous veins of the lower extremities. The addition of the direct oral thrombolytic agent Trombovazim to the anticoagulants showed that such a treatment regimen is also quite safe in terms of the development of hemorrhagic complications.
The use of the proposed therapy scheme showed a statistically significant acceleration of recanalization in the veins affected by the thrombotic process. According to the results of the study, the clinically significant period of complete recanalization of the venous bed is from 3 to 6 months during therapy with oral trobolytics from the beginning of therapy for 20 days, which is much faster, namely by 69% in terms of complete recanalization and by 47% in clinical and subjective symptoms compared with the control group of the study using standard therapy. Such a treatment regimen is not only safe, but also significantly more effective clinically [11].
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