Optimization of the Methodology for Prevention of Thrombotic Complications Using Low-Molecular-Weight Heparins in Surgical Patients in the Early Postoperative Period

The dissertation is devoted to the optimization of the methodology for the prevention of thrombotic complications in surgical patients using low-molecular-weight heparins during the early postoperative period. The research is based on a comprehensive study of the effect of heparin-class preparations (enoxaparin, dalteparin, unfractionated heparin) on the functional state of the microcirculation bed using ultrasonic Dopplerography. The study characterized the clinico-laboratory data of 67 patients of surgical and traumatological-orthopedic profile, including 19 surgical interventions for endoprosthetic hip replacement. It has been demonstrated that low-molecular-weight heparins possess not only an anticoagulant but also a profibrinolytic effect, influencing microhemodynamics by increasing blood flow velocity, improving the elastic properties of microvessels, and reducing peripheral resistance. A modified scheme for the prophylactic administration of low-molecular-weight heparins has been developed, which allows a reduction in intraoperative blood loss and hemorrhagic discharge from drains in the early postoperative period without loss of thromboprophylaxis effectiveness.

Relevance of the Problem

Deep vein thrombosis (DVT) of the lower extremities and the associated pulmonary artery embolism (PAE) are frequent and dangerous complications affecting many patients of surgical and traumatological profile (5; 17; 34; 206).

In contrast to superficial vein thrombophlebitis, the disease is detected in only one out of eight patients with a verified diagnosis of DVT (18; 54; 78).

Recovered DVT does not pass without a trace. In the majority of patients, post-thrombotic disease of the affected extremity develops. It may manifest after 5–15 years and is registered in approximately 25 % of patients who have suffered extensive thrombosis of the veins of the leg, in 46 % of patients with damage to the vessels of the leg and thigh, and in 90–98 % of patients after iliofemoral thrombosis (132; 206). One third of patients with this consequence of DVT are forced to change their job or become disabled (9).

In 21–34 % of persons who have suffered DVT, a recurrence of the disease develops, which in 15 % of observations leads to such a grave complication as embolism of the branches and trunk of the pulmonary artery, whereas in patients who have not suffered deep vein thrombosis of the lower extremities, PAE develops extremely rarely or is not encountered at all (55; 61; 128).

DVT of the lower extremities constitutes a large proportion among patients in the postoperative and post-traumatic periods. Among patients who have undergone various surgical interventions on thoracic or abdominal organs, deep vein thrombosis of the lower extremities develops in approximately 30 % of cases. The highest incidence of DVT of the lower extremities is observed in the population of patients who have undergone orthopedic interventions on the knee and hip joints (60–70 %) (5; 17; 153; 210).

The development of postoperative TFB is associated with blood stasis and hypertension in the veins of the lower extremities, a state of increased readiness for thrombus formation inherent to the organism under conditions of «surgical aggression» (32; 144; 157), depression of fibrinolytic activity; both overall and the fibrinolytic activity of the venous wall itself (7; 96; 100):

The number of patients with thromboembolic complications of the primary disease is growing from year to year. In Germany, 10,000, and in the United States — 50,000 and more fatal outcomes from PAE are registered annually (36; 112). N.N. Alexandrov et al. (1) emphasize that the true dimensions of the postoperative «embolic epidemic» are difficult to imagine, since often only cases of fatal outcomes are registered.

The most widespread application for prevention and treatment of TFB at present is ordinary (unfractionated) heparin; low-molecular-weight (fractionated) heparins (24; 38; 184).

The literature contains data that low-molecular-weight heparins exert not only an anticoagulant effect, but also possess a profibrinolytic effect mediated by increasing plasminogen activation with the help of tissue plasminogen activator (98; 101; 152).

However, the schemes currently proposed for the administration of heparin-class preparations have characteristic disadvantages, primarily the probability of hemorrhagic complications (6; 7; 67; 83; 114; 201).

At present, the effect of low-molecular-weight heparins on the state of the microcirculation bed and its individual components is insufficiently studied. Investigation of this mechanism may introduce substantial corrections into the known schemes of low-molecular-weight heparin application, particularly in patients of surgical profile in the pre- and postoperative periods.

Main Objective of the Investigation

Based on the study of the effect of low-molecular-weight heparins on the functional state of the microcirculation bed, to develop an optimal scheme for the application of preparations of this class for the prevention of thrombotic complications in the early postoperative period.

Tasks of the Investigation

1. By means of ultrasonic Dopplerography of the microvascular bed, to determine the nature of the effect of heparin and its low-molecular-weight derivatives on microhemodynamics indicators.

2. To compare the nature of the effect on the microvascular bed of various low-molecular-weight heparins and unfractionated heparin.

3. To study clinico-laboratory data in order to determine intra- and postoperative blood loss in patients receiving heparin prophylaxis of thrombotic complications.

4. Based on the study of microhemodynamics, to develop an optimal scheme for the administration of low-molecular-weight heparins with the aim of preventing thrombotic complications and reducing intraoperative blood loss and blood loss in the early postoperative period.

5. Based on the study of clinico-laboratory data, to demonstrate the effectiveness of the proposed modification of the scheme for the administration of low-molecular-weight heparins.

Scientific Novelty

For the first time, the effect of preparations of the class of low-molecular-weight heparins on the functional state of the microcirculation bed of the patient has been proven.

The advantage of low-molecular-weight heparins over unfractionated heparin in terms of changes in the indicators of the functional state of the microcirculation bed of the operated patient has been demonstrated.

A modification of the prophylactic scheme for the administration of low-molecular-weight heparins has been developed, allowing a reduction in the volume of intraoperative blood loss and a decrease in the amount of hemorrhagic discharge from drains in the early postoperative period.

The effectiveness of the developed modification of the technique for the administration of low-molecular-weight heparins has been proven, both in terms of preventing the development of postoperative complications and in terms of reducing the severity of intraoperative blood loss and tissue bleeding in the early postoperative period.

Practical Significance

For the first time, a modification of the technique for the application of low-molecular-weight heparins in patients of surgical profile has been developed and introduced into clinical practice, taking into account the nature of the changes they induce in the microcirculation bed.

As a result of clinical use of the developed modification of the technique, it was possible to reduce the volume of heparin-associated blood loss in the intra- and postoperative period, the severity of which with the traditional technique of prophylaxis using low-molecular-weight heparins is quite high.

The effect of low-molecular-weight heparins on the state of the microcirculation bed of the patient discovered in the course of the work allows speaking about the possible use of preparations of this class in patients with high and medium risk of developing deep vein thrombosis of the lower extremities not only for the purpose of preventing thrombus formation, but also as a preparation contributing to the improvement of the course of the postoperative period.

Main Propositions for Defence

1. Preparations of the heparin class (enoxaparin, dalteparin, unfractionated heparin), in addition to previously established properties, possess the ability to affect the functional state of the microcirculation bed of the patient, leading to an increase in linear and volumetric velocities of microvascular blood flow, improving the elastic properties of microvessels, and reducing the total peripheral resistance of blood flow in the microcirculation bed.

2. The maximum duration of effect on microhemodynamics is possessed by low-molecular-weight heparins.

3. The use of the traditional scheme for the prevention of thrombotic complications leads to significant blood loss in the intra- and postoperative period, which is associated with the characteristic effect of low-molecular-weight heparins on microhemodynamics and the hemostasis system.

4. In connection with the identified duration of the effect of low-molecular-weight heparins on microhemodynamics, consisting in the enhancement of tissue blood flow, it is expedient to change the time of administration of the preparations to before the beginning of the surgical intervention.

5. The modified scheme for the administration of LMWH does not worsen the results of the prophylactic action of the preparations, and at the same time allows reducing intraoperative blood loss and blood loss in the early postoperative period by normalizing by the time of surgery the indicators of microhemodynamics.

Validation of the Work

The main results of the work were reported and discussed at a meeting of the Academic Council of the Medical Faculty of Saint Petersburg State University in 2001 and 2005. The results were reported at the international conference «Methods of Studying Microcirculation in Clinical Practice» (Saint Petersburg, 2000), at the Russian Phlebological Congress (Rostov-on-Don, 2001), and at the All-Russian Congress of the Association of Surgeons (Moscow, 2002). Nine scientific papers have been published on the topic of the dissertation investigation.

Author's Contribution

In the process of performing the dissertation work, the author supervised 67 patients in the surgical department and the department of traumatology and orthopedics, participated in 19 surgical interventions (endoprosthetic replacement of the hip joint). The author also conducted Dopplerographic investigation of the microvascular bed in all patients included in the first stage of the investigation (120 persons), and analyzed 128 medical histories of patients who underwent endoprosthetic replacement of the hip joint.

Implementation and Introduction of Results

The results of the investigation are used in the educational process at the departments of surgery and hospital surgery of the Medical Faculty of SPbSU and have been introduced into the work of the departments of surgery and traumatology and orthopedics of the Hospital of the Holy Great Martyr George in Saint Petersburg, and the surgical departments of the City Multiprofile Hospital No. 2 in Saint Petersburg.

Methodological recommendations «Prevention of Venous Thromboses and Embolisms Using Low-Molecular-Weight Heparin in Endoprosthetic Replacement of the Hip Joint» have been developed and approved by the All-Russian Scientific and Practical Center of Memory-Shaped Implants on 05.04.2000.

Structure and Volume of the Dissertation

The dissertation is presented on 136 pages of typed text and consists of an introduction, three chapters, a conclusion, conclusions, and practical recommendations. The bibliography includes 317 titles, of which 57 are domestic and 260 are foreign authors. The illustrative material is presented in 25 figures and 15 tables.