RU2513845C1 - Early diagnostic technique for pulmonary artery thromboembolia - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: early diagnosis of pulmonary artery thromboembolia in the presence of the clinical signs of potential pulmonary artery thromboembolia PATE (tachypnea, tachyrhythmia, thoracodynia, bloody expectoration) is ensured by measuring blood serum fibrin D-dimer. If the fibrin D-dimer content is less than 0.5 mg/l, suspended PATE is discarded. If the blood plasma fibrin D-dimer content is 0.5 mg/l and more, an additional enzyme immunoassay is used to measure blood serum interleukin-6, and if the derived concentration is 21.3 pg/ml and more, pulmonary artery thromboembolia is diagnosed.

EFFECT: using the technique enables higher accuracy and information value of diagnosing pulmonary artery thromboembolia.

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Description

The invention relates to medicine and can be used for early diagnosis of pulmonary embolism (pulmonary embolism).

According to published data, pulmonary embolism is one of the leading causes of death in European countries and the United States, along with acute myocardial infarction and cerebrovascular accident and is detected by autopsy in 12-15% of patients [1]. According to the Framingham study (USA), pulmonary embolism is 15.6% of all in-hospital mortality, among them 18% are surgical patients, and 82% are patients with therapeutic pathology [2]. In addition to the high prevalence of pulmonary embolism, it is characterized by significant diagnostic difficulties associated with the non-specificity of clinical symptoms. In general, there is a hypodiagnosis of this disease, despite the introduction into clinical practice of high-tech diagnostic methods, such as ventilation-perfusion lung scintigraphy, computed tomography angiopulmonography, direct angiopulmonography.

To date, laboratory studies in the diagnosis of pulmonary embolism have an auxiliary value. Several methods are known for the diagnosis of pulmonary embolism based on the determination of molecular markers.

One of them is a method of preoperative diagnosis and prevention of hemocoagulation complications (RF Patent No. 2256913, published July 20, 2005). For early diagnosis and prevention of thromboembolism during hip and knee arthroplasty, preoperative determination of antithrombin III level is carried out, sodium thiosulfate is injected intravenously daily at 10 ml, and a cuff test is carried out additionally by blood sampling after applying a tonometer cuff and pumping a pressure equal to systolic, determining in it the level of antithrombin III and in the absence of changes in its level relative to the initial one, preoperative preparation with the introduction of thiosulum is carried out sodium phosphate until the level of antithrombin III increases during a cuff test. This method allows you to monitor and modify the level of antithrombin III. The scope of this method is limited to cases of preparing patients for surgical treatment, and is not acceptable for the diagnosis of pulmonary embolism in other clinical situations.

A known method for the diagnosis of thromboembolism of the lobar pulmonary artery in patients with diseases of the cardiovascular system (RF Patent No. 2256913, published July 20, 2005). The method consists in the fact that immediately after the onset of clinical symptoms of thromboembolism of the lobar pulmonary artery in the patient’s blood serum, the amount of protein-bound oxyproline is determined and, with an increase in its level to 369.78 μmol / L or higher, lobar pulmonary artery thromboembolism is diagnosed. The method provides the possibility of early and accurate diagnosis of thromboembolism of the lobar pulmonary artery with a view to its timely treatment. This method has limitations: it is intended only for patients with diseases of the cardiovascular system with localization of thromboembolism in the lobar pulmonary arteries.

Closest to the proposed method is the determination in the blood of patients with a low or moderate clinical probability of pulmonary embolism, the level of fibrin D-dimer, one of the products of fibrinogen degradation. An increase in concentration of more than 0.5 mg / L indicates a spontaneous activation of fibrinolysis in response to venous thrombosis and is diagnostically significant for pulmonary thromboembolism in the presence of clinical conditions. A normal plasma fibrin D-dimer level (less than 0.5 mg / l) allows rejecting the assumption of pulmonary embolism with an accuracy of more than 90% [3]. However, high values of D-dimer in plasma (more than 0.5 mg / l) are not specific for pulmonary embolism and do not allow to diagnose this disease with confidence. This method has a high negative predictive value, but does not allow to differentiate pulmonary embolism and other diseases and conditions associated with an increase in the level of fibrin D-dimer, for example, with deep vein thrombosis.

It is known that the development of pulmonary embolism is associated with an increase in the level of certain pro-inflammatory cytokines [4, 5, 6].

A new technical task is to increase the accuracy and information content of early diagnosis.

To solve the problem in a method for early diagnosis of pulmonary embolism, which consists in the fact that if the patient has clinical signs of pulmonary embolism, the level of serum fibrin D-dimer is determined; provided that the level of fibrin D-dimer is higher than 0.5 mg / l, serum interleukin-6 is additionally determined using an enzyme-linked immunosorbent assay, and with its content of 21.3 pg / ml and above, pulmonary artery thromboembolism is diagnosed.

The method is as follows.

If the patient has clinical signs indicating the likelihood of pulmonary embolism (tachypnea, tachycardia, chest pain, hemoptysis), the level of serum fibrin D-dimer is determined. If the fibrin D-dimer content is less than 0.5 mg / L, the suspicion of pulmonary embolism is rejected. When the content of fibrin D-dimer is 0.5 mg / L and higher, the level of interleukin-6 in the blood serum is additionally determined using an enzyme-linked immunosorbent assay, and at a concentration of 21.3 pg / ml and above, pulmonary artery thromboembolism is diagnosed.

New is that for the implementation of the method, the level of interleukin-6 in the blood serum is determined and at its concentration of 21.3 pg / ml and higher, pulmonary embolism is diagnosed.

These distinguishing features are not known in the medical and patent literature. Thus, the proposed method meets the criterion of "novelty."

The combination of distinctive features does not follow explicitly for a specialist from the prior art. Thus, the proposed method meets the criterion of "inventive step"

This method has been clinically tested at the clinical base of Khakass State University. N.F. Katanova - Republican Clinical Hospital named after G.-Y. Ryamishevskaya. Thus, this technical solution meets the criteria of the invention "industrially applicable".

The method is based on the analysis of clinical observation data of 33 patients with suspected pulmonary embolism. Spiral computed tomographic angiopulmonography (CT angiopulmonography) was used as a method for verifying the presence of thromboembolism in the pulmonary artery basin. In 19 patients, the diagnosis of pulmonary embolism was confirmed by CT angiopulmonography, in 14 patients it was rejected. All 19 patients with pulmonary embolism, confirmed by CT angiopulmonography, had clinical signs indicating the likelihood of pulmonary embolism (tachypnea (100%), tachycardia (93%), chest pain (53%), hemoptysis (5%)). The level of D-dimer in all patients with pulmonary embolism exceeded the threshold value of 0.5 mg / L. All patients by enzyme immunoassay determined the level of interleukin-6 in the blood serum. The average values of these indicators in the examined patients, depending on the presence of pulmonary embolism, are given in table 1 (Appendix 1). Thus, the threshold level of interleukin-6 was determined for the diagnosis of pulmonary embolism - 21.3 pg / ml.

The proposed method was tested on the analysis of the results of clinical observations in 10 patients with suspected pulmonary embolism. All patients were admitted to the X-ray department with suspected pulmonary embolism. Table 2 presents the results of validation of the proposed method on a group of patients with suspected pulmonary embolism. Verification of the results of the study was carried out using spiral computed tomography when performing indirect angiopulmonography (CT angiopulmonography), which made it possible to visualize the presence of thromboembolism. When using the proposed method for the diagnosis of pulmonary embolism in 6 patients, this disease was established, in 4 patients it was decided that there was no pulmonary embolism. The diagnosis of pulmonary embolism was confirmed in the future (according to CT angiopulmonography) in 5 patients, and in 1 case the diagnosis of pulmonary embolism was rejected. In 4 patients using the proposed method, pulmonary embolism was not diagnosed, with further investigation (CT-angiopulmonography), suspicion of pulmonary embolism was rejected in 3 cases, and in 1 case, direct signs of pulmonary embolism were revealed in the form of thromboembol in the upper lobe pulmonary artery on the right. Thus, when using the new diagnostic method for pulmonary embolism, 5 truly positive, 3 true negative, 1 false positive and 1 false negative results were obtained. Thus, the new method has a fairly high sensitivity (83%), specificity (75%) and accuracy (75%) in the diagnosis of pulmonary embolism.

Example 1. Patient J., 48 years old, medical history No. 110/12, admission date 03/30/11, was admitted to the hospital with complaints of sharply developed shortness of breath, dizziness. When collecting medical history data, the presence of coronary heart disease was detected. Clinically established tachycardia and symptoms of deep vein thrombosis of the leg, at the time of inspection of tachypnea (NPV = 18), tachycardia (heart rate = 108), BP = 95/65. The level of D-dimer 0.67 mg / L.

Diagnosis: pulmonary embolism?

A study according to the proposed method. This patient has anamnestic and clinical signs of pulmonary embolism, a high level of fibrin D-dimer is established - 0.67 mg / l. According to the proposed method, the content of interleukin-6 in the blood serum was additionally determined by enzyme-linked immunosorbent assay. The level of interleukin-6 was 31.4 pg / ml. Since the level of interleukin-6 in the patient's serum exceeded 21.3 pg / ml, a conclusion was made about the presence of pulmonary embolism.

The presence of pulmonary embolism was confirmed by later studies. CT-angiopulmonography was performed on the patient: during CT-angiopulmonography, thromboemboli in the lower lobe artery on the right and thromboemboli in the segmental arteries of the lower lobe on the left were revealed. The patient is prescribed thrombolytic and anticoagulant therapy.

Example 2. Patient E., 51 years old, was sent to an outpatient study to exclude pulmonary embolism. Analysis of medical history revealed the presence of hypertension II tbsp. According to a clinical examination, shortness of breath, tachycardia (heart rate = 105 per minute), respiratory rate of 14 per minute, the level of fibrin D-dimer 0.58 mg / l were revealed.

Diagnosis: pulmonary embolism?

A study according to the proposed method. The patient has some signs of pulmonary embolism (dyspnea, tachycardia). The fibrin D-dimer level corresponded to 0.58 mg / L. According to the proposed method, the level of interleukin-6 in blood serum was additionally determined, which amounted to 13.2 pg / ml. In accordance with the new method, the diagnosis of pulmonary embolism in the patient is rejected, which was confirmed by further observations and studies. According to CT angiopulmonography, the presence of thromboembolism in the small circle is not confirmed, the diagnosis of pulmonary embolism is removed.

The positive effect of the proposed method is confirmed by the results of its use in 10 patients examined for suspected pulmonary embolism.

Thus, the application of the proposed method will improve the accuracy of the diagnosis of pulmonary embolism in the early stages of the disease, which will contribute to a more timely appointment of therapeutic and preventive measures.

Information sources

1. The Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism.//N. Engl. J. Med. - 1997 .-- Vol.337. - P. 657-662.

2. Klochkov N.D. Analysis of lethal outcomes from pulmonary embolism // Vestn. Surgery. - 1994. - No. 5. - S. 101-104.

3. Wells P.S., Anderson D.R., Rodges M. Evaluation of D-dimer in the diagnosis of suspected deepvein thrombosis // N. Engl. J. Med. - 2003 .-- Vol.349. - P. 1227-1235.

4. K.A. Zykov, V.P. Masenko, S.N. Nakonechnikov, I.E. Chazova. Fractalkin - a new marker of cardiovascular disease // Cardiological Bulletin. - 2008. - Volume 3, No. 2. - S. 34-37.

5. Vormittag R, Hsieh K, Kaider A et al .. Interleukin-6 and interleukin-6 promoter polymorphism (-174) G> C in patients with spontaneous venous thromboembolism.//Thromb Haemost. - 2006. - Vol. 95, No. 5. - P.802-806.

6. YANG M., LIU G., SUN Y. et al. Changes ofhomocystiene and interleukin -8 in patients with massive pulmonary embolism before and after thrombolysis therapy // J. Fore. - 2011. - Vol.22, No. 9. - P. 797-798.

application

Table 1. The results of a study of the level of interleukin-6 and interleukin-8 in patients with suspected pulmonary embolism.

Table 2. Validation results of the proposed method in a group of patients with suspected pulmonary embolism.

Table 1 Group Tela No data for pulmonary embolism The level of statistical significance of differences between groups, p Interleukin-6, pg / ml 28.1 (21.3 ÷ 34.3) 13.4 (8.9 ÷ 18.3) 0,046 table 2 A patient The level of interleukin-6 in blood serum, PG / ml The presence of pulmonary embolism, according to the proposed method Conclusion of CT angiopulmonography No. 1 31,2 Tela Tela Number 2 24.5 no Tela Number 3 41.3 Tela Tela Number 4 29.5 Tela Tela Number 5 54,2 Tela Tela Number 6 18.3 no no data for pulmonary embolism Number 7 28.6 Tela no data for pulmonary embolism Number 8 29th Tela Tela Number 9 15,2 no no data for pulmonary embolism Number 10 9.5 no no data for pulmonary embolism

Claims (1)

A method for early diagnosis of pulmonary embolism, which consists in the fact that if the patient has clinical signs indicating the likelihood of pulmonary embolism (tachypnea, tachycardia, chest pain, hemoptysis), the level of serum fibrin D-dimer is determined; if the content of fibrin D-dimer is less than 0.5 mg / l, the suspicion of pulmonary embolism is rejected, and when the content of fibrin D-dimer in serum is 0.5 mg / l and higher, the level of serum interleukin-6 is additionally determined by enzyme immunoassay, and at a concentration of 21.3 pg / ml and above, pulmonary embolism is diagnosed.