RU-2861644-C1 - METHOD FOR PREDICTING SEVERITY OF HAEMORRHAGIC FEVER WITH RENAL SYNDROME BY THROMBOMODULIN INDICATOR

Abstract

FIELD: medicine. SUBSTANCE: invention relates to clinical laboratory diagnostics, pathological physiology, therapy and infectology, and can be used to predict the severity of haemorrhagic fever with renal syndrome (HFRS). Taking a blood sample, determining the quantitative content of a biochemical indicator by enzyme immunoassay. Thrombomodulin is determined as the indicator. When its quantitative content is below 15 ng/ml, a mild course of HFRS is predicted; within the range of 15-22 ng/ml, a moderate course of HFRS is predicted; 23-45 ng/ml – a severe course of HFRS; 46 ng/ml and above – a severe course of HFRS complicated by acute renal failure, with the probability of developing disseminated intravascular coagulation syndrome (DIC syndrome). EFFECT: possibility of increasing the reliability and accuracy of predicting the severity of HFRS, the risk of developing acute renal failure and the probability of DIC syndrome in the early stages of the disease by determining the content of thrombomodulin in the blood of patients, which serves as an indicator of endothelial activity and is one of the markers of endothelial dysfunction in HFRS. 1 cl, 7 ex

Inventors

• Galimova Elmira Fanisovna
• Galimova Saida Shamilevna
• MOCHALOV KONSTANTIN SERGEEVICH
• Galimov Kamil Shamilevich
• GALIMOV SHAMIL NARIMANOVICH

Dates

Publication Date

20260506

Application Date

20250729

Claims (1)

1. A method for predicting the severity of hemorrhagic fever with renal syndrome (HFRS), including blood sampling, determining the quantitative content of a biochemical indicator using enzyme immunoassay, characterized in that thrombomodulin is determined as the indicator and, if its quantitative content is below 15 ng/ml, a mild degree of HFRS is predicted, within the range of 15–22 ng/ml, a moderate degree of HFRS is predicted, 23–45 ng/ml – a severe degree of HFRS, 46 ng/ml and above – a severe degree of HFRS complicated by acute renal failure and with the likelihood of developing disseminated intravascular coagulation syndrome.

Description

The proposed invention relates to medicine, namely to clinical laboratory diagnostics, pathological physiology, therapy and infectology, and can be used to predict the severity of hemorrhagic fever with renal syndrome (HFRS) at an early stage of the disease. HFRS is an acute viral natural focal zoonosis that manifests as capillary toxicosis, hemorrhages, hemodynamic disturbances, and characteristic renal dysfunction such as tubulointerstitial nephropathy, leading to acute renal failure (ARF) and disseminated intravascular coagulation (DIC). Currently, hemorrhagic fever with renal syndrome remains a pressing issue not only due to its widespread prevalence in the Russian Federation but also due to the development of serious complications that impact the course and outcome of the disease. Repeated cycles of intracellular hantavirus replication play a key role in the pathogenesis of HFRS. These cycles lead to increased damage to the endothelial cells of the vascular walls, leading to their detachment from the basement membrane. Altered structure of the vascular lining disrupts endothelial cell production of mediators. This leads to increased vascular permeability, increased thrombogenicity, and impaired vascular tone, all of which contribute to the development of serious complications associated with HFRS. A method for assessing the severity of hemorrhagic fever with renal syndrome is known, which includes determining the content of circulating endothelial cells (CEC) in the peripheral venous blood [patent RU2392858, Bulletin No. 18 dated June 27, 2010]. Moderate HFRS is defined as an increase in the CEC level to 6.4-10.0×10 4 /l. Severe HFRS without complications is defined as an increase in the CEC level to 10.7-14.6×10 4 /l. Severe HFRS with complicated course is defined as an increase in the CEC level to 14.9-21.0×10 4 /l against the background of a pronounced clinical picture. Despite the potential advantages of this method for assessing the severity of HFRS based on the content of CEC in peripheral blood plasma, it has some disadvantages: 1. Limited availability in medical settings. Phase-contrast microscopy is used to determine the number of CECs, which requires expensive, specialized equipment. Light microscopes must be equipped with phase-contrast devices. However, specialized phase-contrast objectives and filters may not be available for all microscope models, and the high cost may limit the acquisition of the required models. 2. The resolution of phase-contrast microscopy does not allow for the distinction of two closely located points, which can lead to false-positive and false-negative results that will not allow for a reliable assessment of the severity of HFRS. 3. The quantitative content of CEC in human blood can vary under the influence of various factors, such as age, gender, comorbidities, and medical interventions, which can complicate interpretation and distort an accurate assessment of the disease. Furthermore, in some cases, CEC levels can change even with successful treatment of HFRS, making it difficult to determine the patient's condition based on this indicator. A known method for the early diagnosis of HFRS involves the simultaneous detection of a specific antigen in urine samples using enzyme-linked immunosorbent assay and the detection of specific antibodies using an indirect fluorescent antibody method [patent RU2061957, published June 10, 1996]. Urine from healthy individuals and patients with other diseases is used as a control. HFRS is diagnosed based on the presence of both antigen and antibodies in urine samples. The disadvantage of this method is: 1. The indirect fluorescent antibody method requires the availability of antiglobulin-specific sera with fluorochromes. Furthermore, a large number of test controls must be run for accurate calibration. 2. Using urine samples from patients with other diseases as a control carries the risk of false-positive and false-negative results due to the presence of antibodies produced by various systemic diseases, metabolic disorders, or medications. Antigen-antibody cross-reactions affect the specificity of the method and may compromise the reliability of the analysis. A method for predicting the severe course of HFRS in the early stages of the disease is known, which includes determining the level of urea and alanine aminotransferase activity in the patient's blood serum, as well as the percentage of T cells with the phenotypes CD3+CD8+CD314+ and CD3+CD8+FoxP3+ among blood lymphocytes (CD45+) [patent RU2790962, Bulletin 7 of 02/28/2023]. Based on these indicators, the prognostic criterion for the severe course of HFRS (PCT HFRS) is calculated using the formula: 2.015+0.072*[ALT]+0.516*[urea]+0.364*[CD3+CD8+CD314+]-0.381*[CD3+CD8+FoxP3+]. If the PCTT values for HFRS are higher than 19, the development of a severe course of HFRS is predicted. The disadvantage of this method is: 1. This forecasting method is very labor-intensive due to the de