RU2737277C1 - Method for prediction of risk of venous thromboembolic complications in severe burn injury - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, namely to laboratory diagnostics, and can be used for prediction of risk of developing venous thromboembolic complications (VTEC) in severe burn injury. Venous blood sampling is performed with subsequent determination of hemostasis parameters. Patient's venous blood sampling is performed on the first post-traumatic day 1 hour after the beginning of the anticoagulant therapy - introduction of unfractionated heparin to obtain thrombocyte-free plasma and subsequent measurement of the Vi (mcm/min) initial clot growth rate. If the value Vi≥66.1 mcm/min, a high risk of developing VTEC is predicted from 1st to 6th day from the moment of injury. If the initial clot growth rate Vi<66.1 mcm/min is obtained, then, from 6 to 8 days after the trauma, the venous blood is re-sampled in the patient at least 4 hours after the last unfractionated heparin introduction and the initial clot Vi growth rate, the clot steady-state growth rate Vs (mcm/min) and the clot density D (con. units) are measured, and Frank index is also estimated. When obtaining the value Vi≥59.2 mcm/min, Vs≥32 mcm/min and D≥32568 (con. units) with the Frank index more than 30 units, high risk of developing VTEC with a severe burn injury is predicted.EFFECT: method enables the early prediction of the risk of developing venous thromboembolic complications in the patients with severe burn injury by evaluating the hemostasis system values, which enables to determine the blood coagulation potential in the patients with severe trauma.1 cl, 1 tbl, 4 ex

Description

The invention relates to clinical medicine, namely to predicting the development of venous thromboembolic complications (VTEC) in patients with severe burn injury on the basis of laboratory methods of blood analysis, and can be used in the treatment of patients with thermal injury for the timely diagnosis of disorders of the hemostatic system and correction of adequate anticoagulant therapy.

State of the art

Disruption of the hemostatic system in severe thermal injury is associated with endothelial damage, release of tissue factor, and the presence of inflammatory cytokines and chemokinins. The damaged vascular endothelium secretes a tissue factor - thromboplastin, the subendothelial, collagen lining of blood vessels is exposed, adhesion and aggregation of platelets occurs on its surface, contact activation of factor XIIa - the internal mechanism of blood coagulation - develops. Platelet aggregation increases sharply under the influence of adrenaline, which is released into the bloodstream as a result of stimulation of the sympathetic-adrenal system under conditions of severe pain stress in severe thermal injury. Ultimately, hyperthrombinemia develops in the body of the victims, the activity of endogenous anticoagulants (AT III, proteins C and S) and XIIa-dependent fibrinolysis decreases, the content of plasmenogen and plasminogen activators decreases. There is a violation of the correlation between the level of fibrinogen and the fibrinolytic activity of the blood. In the blood, the number of damaged erythrocytes increases, which secrete thromboplastin substances and ADP. The latter is an activator of platelet aggregation. The progressive destruction of platelets also contributes to the deepening of the disorder of the blood coagulation system in the victims, leading to thrombocytopenia and thrombocytopathy. Thus, all links of the hemostasis system are involved in the activation cascade, both internal and external mechanisms of blood coagulation are activated [Borisov V.S. Coagulopathy in burn patients (literature review) // V.S. Borisov, A.S. Ermolov / Transfusiology, 2019.- Volume 20.- No. 1.-С. 35-48].

The introduction of active surgical tactics in the treatment of patients with severe thermal trauma, massive intraoperative blood loss, the development of systemic inflammatory response syndrome (SIRS) contribute to the decompensation of the entire hemostatic system during the entire period of burn disease and the development of venous thromboembolic complications.

Taking into account the phasing of changes in the hemostasis system in severe thermal injury, it becomes necessary to recalculate the degree of risk of VTEC on a regular basis in accordance with changes in the clinical picture of the disease, incl. to control and correct the prescribed anticoagulant therapy.

Existing methods for assessing changes in the state of the hemostasis system to determine the risk of thromboembolic disease are aimed at studying fibrinolysis, when tissue plasminogen activator and plasminogen bind to fibrin, forming a triple fibrin-plasminogen complex, which leads to the formation of plasmin, an enzyme that breaks down fibrin into D-dimers ... A patient is at risk of developing thromboembolic disease if the serum D-dimer level is 500 ng / ml or more.

In particular, from the prior art there is a method for in vitro diagnostics of the activation of blood coagulation associated with the risk of thromboembolic disease [RU 2475760C2], based on the determination of the content of soluble fibrin and D-dimers formed during fibrinolysis activated in a blood sample. According to the present invention, a) quantitative analysis of fibrin degradation products contained in the test sample is carried out, including the determination of the content of D-dimers present in the sample and constituting the baseline level of D-dimers; b) processing the sample by incubation with a plasminogen activator with a high affinity for fibrin (PA-sFb), under conditions that ensure the destruction of soluble fibrin contained in the sample, with the formation of degradation products, without destruction of fibrinogen, and determination of the amount of D-dimers contained in the processed sample; c) calculation of the difference between the number of D-dimers determined after activation by the PA-sFb activator in step b) and the content of D-dimers before said activation, determined in step a), while the resulting difference is an indicator of the degree of destruction of soluble destructible fibrin (RFR ); d) comparing the level of D-dimers measured in step a) with the standard cut-off value determined for the specified degradation products, and comparing the level of RFP calculated in step c) with the cut-off value of the norm determined for the RFP; and when the level of D-dimers measured in step a) or the calculated level of RFR determined in step c) exceeds a certain normal value, it is concluded that there is a risk of thromboembolic disease.

However, the determination of the level of D-dimer is possible by a doctor-laboratory assistant only in a modern laboratory. In addition, the definition of D-dimer is not specific for patients with burn injury and its increase was noted in all periods of burn disease [Bedilo NV. Markers of endothelial community-acquired pneumonia // N.V. Bedilo, N.A. Vorobieva / Materials of the XIX All-Russian Scientific and Practical Conference "Consolidation of Science and Practice in Laboratory Medicine" Moscow, March 25-27, 2014 // Laboratory. - 2014 - No. 2 - P.5 .; Klychnikova E.V. The value of d-dimer in diagnosis of thromboembolic complications in burn patients // E.V. Klychnikova, V.S. Borisov, E.V. Tazina, M.Y. Kaplunova, A.S. Bogdanova, T.G. Spiridonova, E. A. Zhirkova / 25th Biennial International Congress on thrombosis, (Venice-Italy, 23-26 May 2018): book of Abstracts.- Italy, 2018.- P.151.- Abs. C0117.].

From the prior art, a method for assessing the hemostasis system using the test "Thrombodynamics" (TD) is known (Lobastov K.V., Dementyeva G.I., etc. Thrombodynamics test, materials of the International Congress "Slavic Venous Forum", Vitebsk (Republic of Belarus ), May 28-29, 2015, p. 122), which reveals the failure of standard pharmacoprophylaxis and predicts the development of venous thromboembolic complications in surgical patients. The method allows in real time to assess the parameters of thrombus formation, to identify the state of hyper-, normo- or hypocoagulation, based on the determination of the rate of growth of the clot - the growth delay time, the initial and stationary growth rate of the clot, as well as the physical characteristics of the clot - its size and density.

However, this study was performed in patients with postoperative colorectal cancer. At the same time, the operation itself lasting more than 60 minutes also belongs to the category of high risk of VTEC development (according to the recommendations).

Closest to the claimed solution is a method for assessing the hemostasis system in burn patients and detecting the state of hypercoagulation based on the use of the test "Thrombodynamics". (NNAndriychenko, VS Borisov, SS Surov, EV Klychnikova., TA Vuimo; "Thrombodynamics test can adequate estimate hemostasis of burn patients and can help to predict thrombotic complications", / 63rd Annual Meeting of the Society of Thrombosis and Haemostasis Research - GTH Dusseldorf Germany 2015., p. 175). It is known that the development of VTEC occurs as a result of the transition of a hypercoagulable (prethrombotic) state to a thrombotic state with the clinical development of VTEC Thus, the Thrombodynamics test allows assessing the hemostasis of burn patients and can be useful in analyzing the state of coagulation in patients with burns and in predicting developing thrombosis. However, in the known method, the time of the test is not determined, which makes it possible to detect the violation in a timely manner, but it is only stated that the patient developed hypercoagulation on the 12th day.

In the claimed method, the prediction of the risk of developing venous thromboembolic complications with high reliability is possible from day 1, given that 19.4% of all VTEC develops in the first 6 days after injury. The use of the test "Thrombodynamics" on the first day and in the period from 6 to 8 days allows you to identify a risk group for the development of VTEC at the earliest stage and during acute burn toxemia and septicotoxemia. Taking into account the fact that in the period from 8 to 14 days there is a peak in the detection of venous thromboembolic complications (23.6% of all VTEC), the identification of risk groups is extremely important for the timely decision-making on changing the treatment tactics of patients with severe burn injury.

A technical problem is the lack of an algorithm for early prediction of the risk of VTEC development in patients with severe burn injury using criteria that allow judging both the state of the hemostasis system and assessing changes in the state of this system as a whole, especially in cases where multidirectional shifts of the studied parameters are observed. which is typical for severe burn injury. All this complicates the timely identification of the pre-thrombotic state of the victim's body.

Disclosure of invention

The technical result is to provide the possibility of early prediction of the risk of developing venous thromboembolic complications (VTEC) in patients with severe burn injury.

The technical result is achieved by implementing a method for predicting the risk of venous thromboembolic complications in patients with severe burn injury, including taking venous blood from a patient on the first day after injury 1 hour after the start of anticoagulant therapy with obtaining plasma free of platelets, and then measuring the initial growth rate clot Vi (μm / min). When Vi ≥ 66.1 μm / min is obtained, it is concluded that there is a high risk of VTEC development in the period from 1 to 6 days from the moment of injury. If a Vi value of <66.1 μm / min is obtained, the Vi parameter is re-measured in the period from 6 to 8 days from the moment of injury on the “tail” of heparin therapy, i.e. the collection of venous blood from the patient is carried out during the period when at least 4 hours have passed since the last injection of unfractionated heparin. In parallel, the following parameters of the "Thrombodynamics" test are measured: stationary clot growth rate V _st (μm / min), clot density D (conventional units), and the Frank index is assessed. In the case of obtaining values Vi ≥ 59.2 μm / min, V _st ≥32 μm / min and D ≥ 32568 (conventional units), with a Frank index> 30 units, with a probability of 92.3%, a conclusion is made about a high risk of development VTEC in patients with thermal injury.

In patients with severe burn injury, a hypercoagulable state is most often revealed, however, not all hypercoagulable states lead to VTEC, therefore, the proposed method is important in managing a patient in order to timely change treatment tactics, if necessary.

The inventive method makes it possible to predict the development of VTEC already in the first day after receiving a burn injury, despite the fact that the standard indicators for assessing the hemostasis system during this period do not show the degree of damage to the hemostasis system, and therefore cannot be used to predict VTEC. Measurement of the initial clot growth rate Vi (μm / min) 1 hour after the administration of a standard dose of UFH makes it possible to assess the response of the hemostasis system in a severely burned person and more accurately predict the degree of its dysfunction, and hence the likelihood of VTEC development. At the same time, venous blood sampling is performed 1 hour after the start of anticoagulant therapy with UFH, i.e. when there is a maximum peak in the concentration of UFH in the patient's blood, which makes it possible to assess the adequacy of the response of the hemostasis system to treatment, and therefore to assess its condition in general. According to the studies, when assessing the diagnostic ability of all parameters of the "Thrombodynamics" test using the ROC analysis, it was revealed that the indicator of the initial clot growth rate Vi (μm / min) showed the highest diagnostic significance. According to the data obtained as a result of research at the N. N.V. Sklifosovsky Research Institute for Emergency Medicine, in the first 6 days after the injury, 19.4% of VTEC develops - these are those thrombosis that arise directly as the body's response to the thermal effect itself. The measured value of Vi shows how the body reacted on the first day to burn injury and allows predicting the early development of such a complication as VTEC in the case of Vi ≥ 66.1 μm / min. Held at the Research Institute of the SP named after N.V. Sklifosovsky research also showed that when obtaining a value of Vi <66.1 μm / min to improve the accuracy of the forecast, it is necessary, in the period from 6 to 8 days, along with the Vi parameter, to additionally measure the stationary clot growth rate V _st (μm / min) and the clot density D (conventional units). It is this complex, measured at a given time interval, which allows predicting the risk of developing venous thromboembolic complications (VTEC) with high reliability and accuracy. Such parameters of the Thrombodyynamics test as the coagulation delay time (Tlag), clot size (CS), the appearance of spontaneous thrombus formation foci (Tsp) during the ROC analysis did not show high significance in predicting the development of VTEC at a later date. Studies have shown that the maximum number of all VTEC falls on the period from 8 to 14 days (23.6%), 19.4% of VTEC falls on the period from 1 to 6 days, and 18.1% from 15 to 21 days.

Because changes in the hemostatic system in severe thermal trauma are of a multidirectional nature, and at different time intervals they can affect various components of the hemostasis system (plasma, fibrinolytic, etc.). It was found that the complex of the listed indicators is diagnostically significant, since allows to reliably assess the state of the victim's hemostasis system.

The implementation of this method is especially relevant in an intensive care unit by a pre-trained doctor (Point-of-care testing technology) in the provision of emergency medical care in an emergency unit.

The listed parameters can be measured, for example, using the laboratory diagnostic system "T-2 thrombodynamics recorder", developed and manufactured by OOO "GemaCor", Russia.

Implementation of the invention

The risk of VTEC development is carried out according to the results of assessing three indicators: the initial rate of clot growth (Vi), stationary clot growth rate (V _st ), clot density D (conventional units), which are measured using the "Thrombodynamics" test based on the study of local triggering coagulation on a flat surface with thromboplastin applied to it - a coagulation activator. Thus, an imitation of damage to the vessel wall and the start of the formation of a thrombus in this place, preventing blood loss, is achieved.

The inventive method can be actively used to determine the coagulation potential of blood in patients with severe trauma. Considering that changes in the hemostasis system are preceded by clinical manifestations of VTEC, predicting the development of this complication using the proposed method is extremely important for the patient's successful recovery.

The method is implemented as follows.

In patients with burns, plasma for analysis is obtained from blood samples prepared in a standard manner in vacuum tubes with 3.8% (0.129 M) sodium citrate (Vacuette tubes) at a blood: citrate ratio of 9: 1.

Then the blood is centrifuged for 15 min at 1600g at room temperature and the upper part (~ 75%) of the obtained plasma (PPP) is taken.

Further, by additional centrifugation of PPP for 5 min at 10000g at room temperature, platelet-free plasma (PFP) is obtained, which is used to measure the parameters of thrombodynamics. In this case, measurements can be carried out using the laboratory diagnostic system "T-2 Thrombodynamics Registrar" (GemaCor LLC, Russia).

To determine the initial clot growth rate (Vi), stationary clot growth rate (V _st ), and clot density D (conventional units), the test PFP sample is mixed with a contact activation inhibitor (supplied with the diagnostic system) to prevent clotting activation during sampling of material, and incubate the sample at 37 ⁰ С for 15 min.

The resulting prepared plasma sample is introduced into the channels of a special measuring cuvette, into which a plate (activator insert) is inserted, the end of which is covered with a coagulation activator (immobilized tissue factor). As soon as the blood plasma comes into contact with the tissue factor, the coagulation process starts, and the growth of a fibrin clot begins from the end of the activator insert. The end of the insert-activator with a fixed tissue factor simulates the site of damage to the blood vessel wall. Coagulation takes place at 37 ⁰ C. The process of the appearance and growth of a fibrin clot from the end of the activator insert in the cuvette channel is recorded by the device in the mode of sequential photography with a digital camera using the dark field method (registration of the light scattering pattern) for 30 minutes (standard time of the study) s frequency of 6 sec / frame. The obtained images are automatically processed by the software of the laboratory diagnostic system "Thrombodynamics Recorder", which calculates the dependence of the clot size on time and calculates the numerical parameters of the spatial dynamics of fibrin clot growth and spontaneous thrombus formation (thrombodynamic parameters), such as clot growth rate, clot growth delay time and a number of others. This allows simultaneous and independent registration of violations at all stages of the process. Each result is the average of two parallel measurements.

A complex of significant parameters was identified as a result of studies of a group of 100 patients admitted through the EMS with varying severity of the condition, but without the use of anticoagulant therapy at the prehospital stage, who, upon admission to the burn center, underwent a study of thrombodynamic parameters (6 indicators), as well as an assessment of the area and the depth of the burn, presence / absence of inhalation trauma, assessment of the hemostasis system using standard tests (activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin activity (PT) according to Quick, fibrinogen according to Clauss). Statistical processing was carried out using the Origin program, version 8.1. It was found that the areas of normal values for various parameters of the test "Thrombodynamics" (TD) were:

- coagulation delay time (delay time of the onset of clot formation after plasma contact with the activator insert) (Tlag), min - 0.3-1.5 min;

- the initial growth rate of the clot (average growth rate of the clot, calculated in the interval 2–6 minutes after the start of clot growth) (Vi), μm / min - 36-56 μm / min;

- stationary clot growth rate (average clot growth rate, calculated in the interval 15–25 minutes after the beginning of clot growth) (V _st ), μm / min - 20-30 μm / min;

- clot size at 30 minutes (size of fibrin clot 30 minutes after plasma contact with an activator insert) (CS), μm - 740-1120 μm

- clot density - an optical indicator equal to the intensity of light scattering by a fibrin clot, proportional to the density of the fibrin network (D), arb. - 15000-32000 conv. units

- registration of the appearance of spontaneous foci of thrombus formation (Tsp), min - absence.

The parameters were measured upon admission of patients to the hospital before the start of anticoagulant therapy, then during the period of burn shock (in 1 day) 1 hour after intravenous fractional administration of unfractionated heparin (UFH) at the peak of its concentration in the blood and then by 6, 7, 8 day (burn disease in the stage of toxemia). 6 indicators of the "Thrombodynamics" test were obtained. All measurements were processed using ROC analysis. This made it possible to identify only those parameters that had the highest predictive value.

Based on the results of the studies, it was revealed that the risk of VTEC development is possible when a set of indicators with the following values is obtained: on the first day when the initial clot growth rate (Vi) is obtained ≥ 66.1 μm / min (from venous blood 1 hour after intravenous administration fractional UFH (at the peak of its concentration); starting from 6 days to 8 days: when obtaining an initial clot growth rate (Vi) ≥ 59.2 μm / min, a stationary clot growth rate (V _st ) ≥32 μm / min and a clot density D ≥ 32568 (conventional units) In this case, with a probability of 92.3% in a victim with severe thermal injury (Frank index> 30 units), burn disease will be complicated by the development of VTEC.

Thus, monitoring the state of the hemostasis system of burn patients by measuring the listed parameters will allow for timely correction of treatment to prevent VTEC in patients with a hypercoagulable state that already exists.

Examples of implementation of the invention

Patients in the prospective study were divided into two groups depending on the development of VTEC: group 1 - with the presence of VTEC in the outcome, group 2 - without the development of this complication. As a result of the research carried out, the results are presented in the table:

Measurement time of TD test parameters, days Parameter Clipping level Area under the curve On the first day, 1 hour after intravenous fractional administration of UFH Vi > 66.1 0.708 On the 6th, 7th and 8th days after admission, at least 4 hours after the last intravenous administration of UFH (on the “tail” of standard heparin therapy) V _st > 32 0.731 Vi > 59.2 0.731 D > 32568 0.779

Below are clinical examples confirming the efficiency of the proposed method.

1. Patient K., 58 years old, male. Was admitted with burns of I-II-III degree. 35% of the body surface (grade III 20%) according to the ICD 10 classification, without the presence of inhalation trauma. IF was 75 units. (20x3 + 15 = 75 units), i.e. thermal injury is referred to as severe burn injury. Upon admission, the patient was admitted to the intensive care unit, where he was prescribed standard pathogenetic and symptomatic therapy, according to the National Clinical Guidelines of 2017, including standard anticoagulant therapy (UFH 5.000 units x 4 times fractionally intravenously). The examination of the patient included an assessment of the objective status, implementation of instrumental and laboratory research methods. The coagulological status of the victim was assessed using a standard coagulogram (activated partial thromboplastin time, APTT (26.4-37.5) sec); the activity of prothrombin according to Quick (70.0-130.0)%); international normalized ratio, INR (0.80-1.20); the level of fibrinogen according to Clauss (1.80-3.50) g / l)). On the first day after the injury, all coagulogram parameters were within the reference values. The results of thrombodynamics indices on the first day after injury, one hour after the start of anticoagulant therapy with UFH were as follows: Vi = 71.5 μm / min, V _st = 41.8 μm / min, D = 27 516 conventional units, Tlag = 0.8 min., CS = 1 607 μm. Taking into account the obtained Vi value, this patient was in the high-risk group for venous thromboembolic complications. As a result, on the 5th day after the injury, the patient was diagnosed with occlusive unilateral DVT using the ultrasound scan of the veins of the lower extremities. Thrombodynamic parameters measured on day 6 were as follows: Vi = 71.7 μm / min., V _st = 34.8 μm / min., D = 32621 arb. units, Tlag = 0.8 min, CS = 1485 μm. On the 30th day, the patient died from pulmonary embolism. Thus, the proposed method has revealed a high risk of VTEC development in the presence of normal indicators of a standard coagulogram.

1. Patient Y., 67 years old, woman. Was admitted with burns of I-II-III degree. 40% of the body surface (III grade 25%) according to the ICD 10 classification, without the presence of inhalation trauma. IF was 90 units. (25x3 + 15 = 90 units), i.e. thermal injury is classified as severe burn injury. Upon admission, the patient was hospitalized in the intensive care unit, where she received standard pathogenetic and symptomatic therapy, including standard anticoagulant therapy (UFH 5.000 units x 4 times fractionally intravenously). The examination of the patient included an assessment of the objective status, implementation of instrumental and laboratory research methods. The coagulological status of the victim was assessed using a standard coagulogram (activated partial thromboplastin time, APTT (26.4-37.5) sec); the activity of prothrombin according to Quick (70.0-130.0)%); international normalized ratio, INR (0.80-1.20); the level of fibrinogen according to Clauss (1.80-3.50) g / l)). On the first day after the injury, all coagulogram parameters were within the reference values. The results of the TD test on the first day after injury one hour after the start of anticoagulant therapy with UFH were as follows: Vi = 70.8 μm / min, V _st = 36.3 μm / min, D = 25055 conventional units, Tlag = 1.2 min. , CS = 1472 μm. Taking into account the obtained Vi value, this patient was in the high risk group for venous thromboembolic complications. Since the victim did not have the opportunity to use mechanical methods of prevention of VTEC (burns of the lower extremities), it was decided to increase the standard anticoagulant therapy with UFH to 25,000 units. per day. The prescribed therapy did not lead to changes in the coagulogram parameters; they remained within normal limits without the presence of laboratory signs of hypercoagulation. The parameters of the Thrombodynamics test, measured on day 6, were as follows: Vi = 62.7 μm / min., V _st = 32.1 μm / min., D = 33391 conv. units, Tlag = 0.8 min, CS = 1311 μm. Thus, even with the correction of anticoagulant therapy, the patient remained at the risk of VTEC development according to the TD test. As a result, DVT was diagnosed on day 56 of the disease. This example demonstrates that the proposed method at an early stage allows to identify patients with a high risk of VTEC in the presence of normal indicators of the standard coagulogram, who really developed VTEC in the long-term period.

3. Patient D., 40 years old male. Was admitted to the hospital with burns of I-II-III degree. 30% of the body surface (III grade 5%) according to the ICD 10 classification, without the presence of inhalation trauma. IF = 40 units. (5x3 + 25 = 40 units). Upon admission, the patient received standard pathogenetic and symptomatic therapy, including standard anticoagulant therapy (UFH 5.000 units x 4 times fractionally intravenously). The examination of the patient included an assessment of the objective status, implementation of instrumental and laboratory research methods. The coagulological status of the victim was assessed using a standard coagulogram (activated partial thromboplastin time, APTT (26.4-37.5) sec); the activity of prothrombin according to Quick (70.0-130.0)%); international normalized ratio, INR (0.80-1.20); the level of fibrinogen according to Clauss (1.80-3.50) g / l)). On the first day after the injury, all coagulogram parameters were within the reference values. The results of thrombodynamics indices on the first day after injury one hour after the start of anticoagulant therapy with UFH were as follows: Vi = 59.5 μm / min., V _st = 30.7 μm / min., D = 32685 conv. units, Tlag = 0.9 min, CS = 1301 μm. Taking into account the obtained Vi value, this patient was not in the high risk group for VTEC. However, taking into account the severity of the victim's condition according to the developed method for assessing the risk of venous thromboembolic complications, the victim underwent a second study of both the standard coagulogram and the thrombodynamic parameters on the 7th day on the “tail” of standard heparin therapy to assess the state of hemostasis. Coagulogram indices were within the reference values. Thrombodynamic parameters against the background of ongoing standard anticoagulant therapy were as follows: Vi = 70 μm / min., V _st = 38.3 μm / min., D = 32899 conv. units, Tlag = 0.8 min, CS = 1536 μm. According to the obtained Vi, V _S and D, the victim fell into the risk group. On the 20th day from the moment of admission of the patient with severe burn injury (Frank index> 30 units), against the background of standard anticoagulant therapy of burn disease, venous thrombosis of OPV of a floating nature was revealed. This example shows that during the entire course of the burn disease, the victim may be in a state of varying degrees of risk of VTEC development. On the first day, an adequate response of the hemostasis system to burn injury was noted; later, in connection with a change in the clinical state, the patient developed decompensation of the hemostasis system, which was promptly detected based on the results of the trmbodynamic parameters. At the same time, the indicators of the standard coagulogram did not show changes in the coagulation status. That is why it is necessary to perform stage 2 to predict the development of WTE.

4. Patient O., 34 years old, male. Was admitted to the hospital with burns of I-II-III degree. 50% of the body surface (III grade 10%) according to the ICD 10 classification, without the presence of inhalation trauma. IF = 70 units. (10x3 + 40 = 70 units). Upon admission, the patient received standard pathogenetic and symptomatic therapy according to, including anticoagulant therapy (UFH 5.000 units x 4 times fractionally intravenously). The examination of the patient included an assessment of the objective status, implementation of instrumental and laboratory research methods. The coagulological status of the victim was assessed using a standard coagulogram (activated partial thromboplastin time, APTT (26.4-37.5) sec); the activity of prothrombin according to Quick (70.0-130.0)%); international normalized ratio, INR (0.80-1.20); the level of fibrinogen according to Clauss (1.80-3.50) g / l)). The results of thrombodynamics indices on the first day were as follows: Vi = 51.7 μm / min., V _st = 29 μm / min., D = 28241 arb. units, Tlag = 0.8 min, CS = 1217 μm. Taking into account the obtained Vi value, this patient was not in the risk group for VTEC. However, according to the claimed method for assessing the risk of VTEC, a repeated study of both coagulological tests and thrombodynamic parameters was performed on the 8th day after injury. The results of the parameters were as follows: Vi = 54.6 μm / min., _Vst = 28.5 μm / min., D = 28136 arb. units, Tlag = 0.8 min, CS = 1194 μm. According to the data obtained, a patient with severe thermal injury (IF = 70 units) was not included in the group of victims with the risk of developing venous thrombosis. As a result of dynamic observation of the victim within 60 days from the moment of injury with the control performance of USDG of the veins of the lower extremities, no venous thromboembolic complications were revealed. This clinical example demonstrates the adequacy of the risk assessment of VTEC in patients with severe thermal injury, based on the claimed method.

Claims (1)

A method for predicting the risk of developing venous thromboembolic complications (VTEC) in severe burn injury, including venous blood sampling with subsequent determination of hemostasis parameters, characterized in that the patient's venous blood is taken on the first day after the injury 1 hour after the start of anticoagulant therapy - the introduction of unfractionated heparin to obtain platelet-free plasma and subsequent measurement of the initial growth rate of the clot Vi (μm / min); when a value of Vi ≥ 66.1 μm / min is obtained, a high risk of VTEC development is predicted from 1 to 6 days from the moment of injury, in case of obtaining a value of the initial growth rate of a clot Vi <66.1 μm / min, then in the period from 6 to 8 days from the moment of injury, the patient's venous blood is re-sampled at least 4 hours after the last injection of unfractionated heparin and the initial clot growth rate Vi, the stationary clot growth rate Vs (μm / min) and the clot density D (conv units) are measured, and the Frank index is also assessed, and when Vi ≥ 59.2 μm / min, Vs ≥32 μm / min and D ≥ 32568 (conv units) with a Frank index of more than 30 units, a high risk of VTEC in severe burn injury is predicted.