Features of the Pathogenesis of Embologenic Venous Thrombosis

The dissertation is devoted to the study of the features of the pathogenesis of embologenic venous thrombosis of the inferior vena cava system — a condition representing high danger in connection with the risk of pulmonary artery thromboembolism. The conditions of formation, structural-functional characteristics, and factors determining the probability of fragmentation and migration of thrombus masses into the pulmonary arteries are investigated. Ultrasonic criteria of thrombus embologenicity are developed, and the role of various pathogenetic factors — including the localization and mobility of the thrombus, its echostructure, and the character of the external contour — in predicting thromboembolic complications is evaluated. Special attention is given to clinical-instrumental diagnostic methods, including ultrasonic duplex scanning, as well as to the development of algorithms for risk assessment and tactics for the prevention of pulmonary artery thromboembolism.

Relevance of the Problem

Acute venous thromboses of the inferior vena cava system represent a serious danger as a potential source of one of the most severe complications, namely pulmonary artery thromboembolism (PAT) [Baluda V.P., Baluda M.V., Goldberg P.L. et al., 1999; Russian Consensus., 2000; Thromboembolism of the Small Circle., 2003; Eftychiou V., 1996; Meignan M., Rosso J., Gauthier H. et al., 2000]. Massive PAT, which develops in 32–45% of patients with acute deep vein thrombosis, occupies the third place in the overall structure of sudden death [Phlebology., 2001; Thromboembolism of the Small Circle., 2003; Eftychiou V., 1996; Meignan M., Rosso J., Gauthier H. et al., 2000]. Venous thromboses of the inferior vena cava system play a key role in thromboembolic disease, since in 90% of cases, thrombi formed in the inferior vena cava system enter the small circulation [Phlebology., 2001; Choen A.T., Edmondson R.A., Phillips M.J. et al., 1996; Ferrari E., Baudouy M., Cerbony P. et al., 1997; Goldhaber S.Z., 1998].

At the same time, it is known that not every phlebothrombosis is complicated by thromboembolism. In connection with this, the question arises: why, in one case, venous thrombosis leads to PAT, while in another case, at the same location of the pathological process, it does not? The concept of embologenic thrombosis is currently quite contradictory. In the opinion of some authors [Phlebology, 2001], an embologenic form should be considered the so-called floating thrombus, which has a single fixation point in its distal portion, while the rest of it is located freely, is not connected with the vessel walls, and is in an intense blood stream. However, according to data from many foreign authors [Pacouret G., Alison D., Pottier J.M. et al., 1997; Raulin S., Raulin C., Greve V., 2001; Patel R.K., Ramasamy K., Goss D., Deane C. et al., 2005], the presence of a floating thrombus even in the proximal portions of the inferior vena cava system does not lead to an increased risk of embolism and does not require the performance of additional procedures for the prevention of pulmonary artery thromboembolism. Some researchers [Patel R.K., Ramasamy K., Goss D., Deane S. et al., 2005] consider that patients with proximal floating thrombi may receive ambulatory treatment, as well as patients with occlusive thromboses. As follows from the above, the problem of embologenic thrombosis requires further investigation, since in clinical practice it is important to know when thrombosis threatens embolism and when this danger is absent.

The main pathogenetic factors of venous thrombosis formation, formulated by R. Virchow approximately 150 years ago [Virchow R, 1856], are today actively studied [Baluda V.P., Baluda M.V., Goldberg A.P. et al., 1999; Phlebology, 2001; Ageno W, Squizzato A, Garcia D. et al., 2006; Prandoni P., 2006]. However, factors predisposing to the development of specifically embologenic forms of thrombosis have not been established to date. In addition, the possibility of reliable diagnosis of floating forms of thrombosis is discussed.

At present, ultrasonic technologies occupy a leading position in the diagnosis of thromboses of the inferior vena cava system [Zubarev A.R., Bogachev V.Yu., Mitykov V.V., 1999; Konstantinova G.D., Zubarev A.R., Gradusov E.G., 2000; Andrews E.J.Jr., Fleischer A.S., 2005]. The sensitivity of ultrasonic methods in the diagnosis of venous thrombosis using modern digital expert-class systems amounts to 97–99% [Kharchenko V.P., Zubarev A.R., Kotlyarov P.M., 2005; Pedersen O.M., Aslaksen A., Vik M.N. et al., 1991; Mostbeck G.H., 2003]. Ultrasonic signs of acute venous thrombosis are well known and described in specialized literature on phlebology and vascular ultrasonography [Phlebology, 2001; Clinical Angiology, 2004; Zwiebel W.J., 1992; Mostbeck G.H., 2003]. At the same time, there are no generally recognized ultrasonic criteria for embologenic and non-embologenic venous thromboses. There are only isolated works in which questions of ultrasonic diagnosis of floating thrombi are considered [Kharchenko V.P., Zubarev A.R., Kotlyarov P.M., 2005; MoBShYeSK O.N., 2003]. Further study of various stages of the course of embologenic deep vein thromboses is required in order to select the optimal tactic for the prevention of pulmonary embolism and the treatment of thrombotic lesions of deep veins.

Thus, on the basis of the above, the problem can be formulated as follows: "Despite the successes of modern medicine achieved in the field of prevention and treatment of venous thromboembolism, the number of embolic complications in acute venous thromboses does not decrease. The lack of a unified opinion regarding the concept of embologenic thrombosis and the existing contradictions in the definition of etiological and pathogenetic factors influencing the probability of fragmentation of thrombus masses and their migration into the pulmonary arteries do not allow sufficiently effective forecasting and prevention of the development of pulmonary artery thromboembolism in patients with thrombosis of the veins of the lower extremities."

The solution of the stated problem was based on the hypothesis that a floating character of the proximal boundary of the thrombus leads to an increased risk of thromboembolic complications. At the same time, factors influencing the probability of fragmentation of thrombus masses and their migration into the pulmonary arteries can be established by the method of ultrasonic angioscanning when investigating the localization of the proximal boundary of thrombosis, the degree of mobility of thrombus masses, echogenicity, and the character of the external contour of the thrombus.

Goal of the Investigation

To study the conditions of formation and structural-functional features of embologenic thrombosis in the inferior vena cava system and, on this basis, to identify pathogenetic factors influencing the probability of fragmentation and migration of thrombus masses into the pulmonary arteries.

Tasks of the Investigation

1. To evaluate the frequency of thromboembolic complications in patients with different types of proximal boundary of thrombosis in the inferior vena cava system.

2. To determine the frequency, risk factors, clinical-anamnestic features, and variants of the course of different types of thrombosis of the inferior vena cava system.

3. To study the features of hemodynamics in the inferior vena cava system at different types of venous thrombosis.

4. To establish ultrasonic features of thromboses of the inferior vena cava system influencing the probability of fragmentation of thrombus masses and their migration into the pulmonary arteries.

5. To compare ultrasonic and morphological characteristics of floating thrombi and to establish factors increasing the embologenicity of the thrombus.

6. To develop an algorithm for evaluating the risk of embolic complications in patients with thrombosis of the inferior vena cava system, taking into account the most significant indicators influencing the probability of fragmentation and migration of thrombus masses into the pulmonary arteries.

7. To study the features of disorders in the hemostasis system in persons with different variants of the course of thrombosis of the inferior vena cava system.

Scientific Novelty

For the first time, key ultrasonic criteria of embologenic thrombosis have been formulated. It has been demonstrated that ultrasonic detection in the area of the proximal boundary of the thrombus of an unfixed mobile fragment with the presence of circumferential parietal blood flow is accompanied by a higher frequency of thromboembolic complications compared with other types of intravascular thrombus formation.

For the first time, it has been established that intravascular thrombosis in lower extremity injuries more often than other risk factors leads to the formation of embologenic (floating) forms of thrombosis. The development of venous thrombosis during pregnancy and the postpartum period is characterized by a higher probability (90% of cases) of the formation of an occlusive proximal boundary. With all other risk factors (surgeries, malignant neoplasms, chronic diseases of the arteries and veins of the lower extremities, use of hormonal preparations, other diseases of a therapeutic profile [IHD, stroke, obesity, etc.]), the frequency of formation of various types of thrombosis is the same.

It has been established that the course of venous thrombosis against the background of prolonged immobilization leads to a greater number of embolic complications compared with patients in whom the disease proceeds during a usual mode of motor activity.

For the first time, it has been shown that the probability of fragmentation and migration of the thrombus increases with proximal location (above the femoral vein) of the thrombus, pronounced mobility of thrombus masses, heterogeneous echostructure, and the presence of an irregular external contour of the thrombus.

Features of local phlebodynamics in thrombosis of the deep veins of the lower extremities have been identified. It has been found that thrombotic occlusion at the level of the superficial femoral vein is accompanied by compensation of venous outflow from the extremity with a significant increase in the proportion of blood flow through the subcutaneous venous network.

New scientific data have been obtained regarding the correspondence of ultrasonic and morphological characteristics of floating thrombi. It has been established that different degrees of maturity of fibrin forming a floating thrombus manifest themselves by a characteristic ultrasonic picture upon ultrasonic investigation and are accompanied by an increased risk of its fragmentation.

The ultrasonic effect of a hyperechoic structure in the periphery of the thrombus corresponds morphologically to deposits of "mature" fibrin with signs of organization, which limit the probability of detachment of thrombus masses.

Practical Significance

High efficiency of ultrasonic angioscanning in the differential diagnosis of acute venous thrombosis has been demonstrated. It has been established that deep vein thrombosis of the lower extremities is the cause of acute asymmetric edema in no more than half of the cases. In the remaining cases, the edematous syndrome is associated with other causes, the most frequent of which are osteoarticular pathology, secondary lymphedema, hematomas, prolonged compression syndrome, edema due to circulatory insufficiency, kidney and liver diseases.

A comprehensive ultrasonic technology for investigation of the proximal boundary of venous thrombosis has been developed and implemented, with established ultrasonic criteria of embologenic thrombosis.

An algorithm for evaluating the probability of embolic complications in the presence of venous thrombosis with a floating character of the proximal boundary of the thrombus has been developed.

A methodology for dynamic ultrasonic monitoring of the course of venous thrombosis has been implemented, which has made it possible to increase the efficiency of treatment of acute deep vein thrombosis due to timely detection of progression of the pathological process and correction of the conducted therapy.

An optimal period for temporary endovascular prevention of PAT has been developed, taking into account the established duration of fixation of floating thrombi. Ultrasonic criteria of thrombosis and embolism in the area of the caval filter have been developed.

Positions for Defense

1. The number of embolic complications in thrombosis of the inferior vena cava system depends on the type of proximal boundary of the thrombus. Thrombosis with a floating apex is accompanied by a higher frequency of thromboembolic complications compared with other types of intravascular thrombus formation.

2. Venous thrombosis against the background of prolonged immobilization more often leads to a non-occlusive and floating character of intravascular thrombus formation compared with other risk factors, which is accompanied by a higher frequency of embolic complications.

3. Ultrasonic criteria of increased risk of embolic complications are thrombus location proximal to the femoral vein, heterogeneous structure, irregular external contour, and pronounced mobility of thrombus masses.

4. Different degrees of fibrin maturity forming a floating thrombus manifest themselves by a characteristic ultrasonic picture upon ultrasonic investigation and are accompanied by an increased risk of its fragmentation. The ultrasonic effect of a hyperechoic structure in the periphery of the thrombus corresponds morphologically to deposits of "mature" fibrin with signs of organization and limits the probability of detachment of thrombus masses.