RU2851668C1 - Method for predicting risk of spontaneous haematoma development in covid-19 patients - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to surgery, infectious diseases, ultrasound and laboratory diagnostics, and can be used to predict spontaneous haematomas in COVID-19 patients. The extent of lung tissue damage is determined using computed tomography and X-ray imaging; blood samples are taken and the levels of leukocytes, platelets, lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, activated partial thromboplastin time (APTT), prothrombin index (PTI), fibrinogen, D-dimer, and interleukin-6 (IL-6) are measured; determine the presence of comorbidities, gender, age, body mass index (BMI) of the patient, the nature and the need for respiratory support, and assess the presence and severity of multiple organ failure using the SOFA scale. Points are assigned to each of the following signs: degree of lung tissue damage - 1-3 points, where 1 point corresponds to the volume of damage Rg/KT - 0 or the course of acute respiratory viral infection (ARVI), 2 points - Rg/KT - 1-2, 3 points - Rg/KT - 3-4; white blood cell count - 1-2 points, where 1 point corresponds to a white blood cell count (4-9)×10⁹/l, 2 points - less than 4×10⁹/l or more than 9×10⁹/l; platelet count - 0-3 points, where 0 points corresponds to a platelet count of more than 600×10⁹/l, 1 point - (400-599)×10⁹/l, 2 points – (180-399)×10⁹/l, 3 points – less than 180×10⁹/l; LDH level – 0-2 points, where 0 points corresponds to an LDH level of 135-224 U/l, 1 point corresponds to an LDH level of 225-404 U/l, 2 points correspond to an LDH level of more than 405 U/l; CRP level - 0-3 points, where 0 points corresponds to a CRP level of less than 10 mg/l, 1 point corresponds to a CRP level of 10-99 mg/l, 2 points - CRP level 100-199 mg/l, 3 points - CRP level over 200 mg/l; IL-6 level - 0-3 points, where 0 points corresponds to an IL-6 level below 10 pg/mL, 1 point - IL-6 level 10-99 pg/ml, 2 points - IL-6 level 100-199 pg/ml, 3 points - IL-6 level over 200 pg/ml; ferritin level - 1-3 points, where 1 point corresponds to a ferritin level of 10-249 mcg/l, 2 points - a ferritin level of 250-999 mcg/l, 3 points - a ferritin level of more than 1000 mcg/l; APTT level - 1-3 points, where 1 point corresponds to an APTT level of 22-38 s, 2 points - to an APTT level of 39-55 s, 3 points - to an APTT level above 55 s; PTI level - 0-3 points, where 0 points corresponds to a PTI level of 100-140%, 1 point corresponds to a PTI level of 70-99%, 2 points corresponds to a PTI level of 40-69%, and 3 points corresponds to a PTI level of less than 40%; fibrinogen level 0-1 points, where 0 points corresponds to a fibrinogen level of 2-4 g/l, 1 point corresponds to a fibrinogen level of less than 2 g/l and more than 4 g/l; D-dimer level - 0-3 points, where 0 points corresponds to a D-dimer level of less than 400 ng/ml, 1 point corresponds to a D-dimer level of 400-999 ng/ml, 2 points correspond to a D-dimer level of 1000-1500 ng/ml, and 3 points correspond to a D-dimer level of more than 1500 ng/ml. Comorbid background - 0-1 points, where 0 points corresponds to the absence of concomitant diseases, 1 point - to a burdened comorbid background; gender - 1-2 points: male gender corresponds to 1 point, female gender - to 2 points; age - 1-4 points, where 18-44 years old corresponds to 1 point, 45-59 years old corresponds to 2 points, 60-74 years old corresponds to 3 points, and over 75 years old corresponds to 4 points; body mass index - 0-1 points, where a body mass index of 18-25 corresponds to 0 points and a body mass index of less than 18 and more than 25 corresponds to 1 point. Respiratory support - 0-4 points, where 0 points corresponds to no need for respiratory support, 1 point - humidified oxygen insufflation is performed at a flow rate of up to 5 l/min, 2 points - humidified oxygen insufflation is performed at a flow rate of 5-10 l/min and/or transfer to non-invasive ventilation (NIV) is required, 3 points - humidified oxygen insufflation is performed at a flow rate of more than 10 l/min and/or transfer to high-flow oxygenation (HFO) is required, 4 points - transfer to invasive mechanical ventilation (IMV). SOFA score - 1-3 points, where 1 point corresponds to a SOFA level of 0-3 points, 2 points - a SOFA level of 4-6 points, 3 points - a SOFA level of more than 7 points. A score of less than 12 predicts a low risk of spontaneous soft tissue haematomas, a score of 13-21 predicts a moderate risk of spontaneous haematomas, a score of 22-30 predicts a high risk of spontaneous haematomas, and a score of 31 or more predicts a very high risk of spontaneous haematomas.

EFFECT: possibility of improving the accuracy of predicting the development of spontaneous soft tissue haematomas as a complication of COVID-19 by performing laboratory and instrumental examinations, collecting a complete medical history, and assessing respiratory failure within the first 24 hours of the patient's admission to the hospital.

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Description

The invention relates to medicine, in particular to surgery, infectious diseases, ultrasound and laboratory diagnostics, and can be used to predict the development of spontaneous hematomas as a complication of COVID-19.

Soft tissue hematomas develop not only as a result of physical impact, such as trauma or medical procedures, but also as a result of coagulopathies of various origins and anticoagulant therapy. Given the frequent need to prevent thromboembolic complications, the frequent use of heparinization increases the risk of spontaneous hematomas, which can become an aggravating and life-threatening factor in patients with severe underlying diseases and complicated comorbidities.

One of the most well-known scales for predicting the risk of bleeding is HAS-BLED. [Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010 Nov;138(5):1093-100. doi: 10.1378/chest.10-0134. Epub 2010 Mar 18. PMID: 20299623.] This scale includes clinical parameters such as age, arterial hypertension, renal or hepatic dysfunction, and allows for therapy adjustment.

However, this scale may overestimate the risk of bleeding in some patients, which may lead to unnecessary withholding of anticoagulant therapy, particularly in patients at high risk of thromboembolism. It does not include some important factors, such as the use of new oral anticoagulants or comorbidities. Some parameters, such as "propensity to fall" or "INR lability," may be subjective and dependent on physician interpretation. The scale does not take into account the dynamics of the patient's condition and is limited in its applicability to certain patient groups, as it was developed and validated primarily for patients with atrial fibrillation.

There are also known scales for predicting bleeding, which are the primary cause of subdural hematoma development - CRUSADE [Subherwal S, Bach RG, Chen AY, Gage BF, Rao SV, Newby LK, Wang TY, Gibler WB, Ohman EM, Roe MT, Pollack CV Jr, Peterson ED, Alexander KP. Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the ACC/AHA Guidelines) Bleeding Score. Circulation. 2009 Apr 14;119(14): 1873-82. doi: 0.1161/CIRCULATIONAHA.108.828541. Epub 2009 Mar 30. PMID: 19332461; PMCID: PMC3767035.].

The CRUSADE score may lack precision for certain patient groups, such as the elderly or those with multiple comorbidities, as most of the underlying data are based on populations that may not reflect the full diversity of clinical cases. The score also does not take into account factors that may change over time, such as the patient's condition or changes in medication therapy, which may lead to underestimation or overestimation of risk. Another drawback is its limited applicability in non-operative contexts, such as the non-surgical treatment of patients with high cardiovascular risks. Finally, the score requires information on the patient's cardiovascular history, which may be challenging in emergency situations when time is of the essence. Effective preoperative risk assessment requires a multifaceted approach tailored to the individual patient's circumstances.

A method for predicting thrombosis and bleeding in critically ill patients with COVID-19 undergoing ECMO (patent no. 2766350) is known by analyzing the following parameters: the volume of heparinization with unfractionated heparin (IU/kg/hour), determination of the level of activated partial thromboplastin time (APTT/APTT), the level of antithrombin-III activity, the concentration of nitric oxide, the concentration of malondialdehyde, the concentration of angiotensin-converting enzyme-2 (ACE-2) and the total antioxidant status.

The disadvantages of this method include: assessing the risk of bleeding and thrombosis exclusively in critically ill patients treated in intensive care and on extracorporeal membrane oxygenation (ECMO), and the need for complex and expensive equipment and reagents. It should also be noted that the parameters measured are narrowly focused. This method assesses hemostatic disorders only, without taking into account other systemic disorders: it does not adequately assess microcirculation disorders, the severity of tissue ischemia, and necrobiosis.

The closest to the claimed method is the method for determining the prognostic factors for severe hemorrhagic complications in patients with acute promyelocytic leukemia (RU Patent No. 2400750), which is achieved by conducting a laboratory examination, including determining the number of leukocytes, platelets, promyelocytes, APTT levels, prothrombin index (PTI), fibrinogen concentration, soluble fibrin monomer complexes (SFMC) in an ethanol test, fibrin degradation products D-dimer and Amin.

A disadvantage of the prototype method is that only laboratory parameters are considered when stratifying the risk of an adverse disease outcome; patient distribution by gender and age is carried out without taking into account comorbid conditions, which reduces the accuracy and specificity of the diagnosis.

The method also does not assess the dynamics of the above-mentioned parameters; risk stratification is performed once upon detection of leukemia. There is no data on prognosis during chemotherapy treatment. The prototype also does not evaluate the correlation between changes characteristic of different stages of the disease.

The objective of this study is to improve the accuracy of predicting the development of spontaneous soft tissue hematomas as a complication of COVID-19.

The technical result of the stated problem is achieved in that in the method for predicting spontaneous hematomas in patients with COVID-19, including determining the volume of lung tissue damage, the levels of leukocytes, platelets, lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, APTT, PTI, fibrinogen, D-dimer, additionally determining the level of interleukin-6 (IL-6), the presence of a comorbid background, gender, age, body mass index (BMI) of the patient, the nature and need for respiratory support, and also assessing the presence and severity of multiple organ failure, assigning points to each of the following signs: the degree of lung tissue damage - 1-3 points, where 1 point corresponds to the volume of damage Rg / CT - 0 or the course of an acute respiratory viral infection (ARVI), 2 points - Rg / CT - 1-2, 3 points - Rg / CT - 3-4; leukocyte level - 1-2 points, where 1 point corresponds to a leukocyte content of 4 - 9×10 ⁹ /l, 2 points - less than 4×10 ⁹ /l or more than 9×10 ⁹ /l; platelet level - 0-3 points, where 0 point corresponds to a platelet content of more than 600×10 ⁹ /l, 1 point - 400-600×10 ⁹ /l, 2 points - 180-400×10%, 3 points - less than 180×10 ⁹ /l; LDH level - 0-2 points, where 0 points corresponds to an LDH level of 135-225 U/l, 1 point - an LDH level of 225-405 U/l, 2 points - an LDH level of more than 405 U/l; CRP level - 0-3 points, where 0 points corresponds to a CRP level of less than 10 mg/l, 1 point - a CRP level of 10-100 mg/l, 2 points - a CRP level of 100-200 mg/l, 3 points - a CRP level of more than 200 mg/l; IL-6 level - 0-3 points, where 0 points corresponds to an IL-6 level of less than 10 pg/ml, 1 point - an IL-6 level of 10-100 pg/ml, 2 points - an IL-6 level of 100-200 pg/ml, 3 points - an IL-6 level of more than 200 pg/ml; Ferritin level - 1-3 points, where 1 point corresponds to a ferritin level of 10-250 μg/l, 2 points - to a ferritin level of 250-1000 μg/l, 3 points - to a ferritin level of more than 1000 μg/l; APTT level - 1-3 points, where 1 point corresponds to an APTT level of 22-38 s, 2 points - to an APTT level of 39-55 s, 3 points - to an APTT level of more than 55 s; PTI level - 0-3 points, where 0 points corresponds to a PTI level of 100-140%, 1 point - to a PTI level of 70-100%, 2 points - to a PTI level of 40-70%, 3 points - to a PTI level of less than 40%; fibrinogen level 0-1 point, where 0 points corresponds to a fibrinogen level of 2-4 g / l, 1 point - to a fibrinogen level of less than 2 g / l and more than 4 g / l; D-dimer level - 0-3 points, where 0 points corresponds to a D-dimer level of less than 400 ng / ml, 1 point - to a D-dimer level of 400 -1000 ng / ml, 2 points - to a D-dimer level of 1000-1500 ng / ml, 3 points - to a D-dimer level of more than 1500 ng / ml; comorbid background - 0-1 point, where 0 points corresponded to a group of patients without comorbidities, 1 point - to a group of patients with an aggravated comorbid background; gender - 1-2 points, where males are assigned 1 point, females - 2 points; age - 1-4 points, where 18-44 years - 1 point, age 45-59 - 2 points, age 60-74 - 3 points, age over 75 years - 4 points; body mass index - 0-1 points, where body mass index 18-25 - 0 points and body mass index less than 18 and more than 25 - 1 point; implementation of respiratory support - 0-4 points, where 0 points were assigned to the group of patients who did not require respiratory support, 1 point - insufflation with humidified oxygen was performed at a flow rate of up to 5 l/min, 2 points - the flow rate increased to 5-10 l/min and/or a transfer to non-invasive ventilation (NIV) was required, 3 points - the flow rate was more than 10 l/min and/or a transfer to high-flow oxygenation (HFO) was required, 4 points - transfer to invasive ventilation (IVL); SOFA score - 1-3 points, where 1 point corresponds to a SOFA level of 0-3 points, 2 points - a SOFA level of 4-6 points, 3 points - a SOFA level of more than 7 points, and with a score of less than 12, a low risk of developing spontaneous hematomas of soft tissues is predicted, with a score of 13-21, a moderate risk of developing spontaneous hematomas is predicted, with a score of 22-30, a high risk of developing spontaneous hematomas is predicted, and with a score of 31 or more - a very high risk of developing spontaneous hematomas.

Laboratory and instrumental examination, adequate and complete anamnesis, and assessment of respiratory failure within the first 24 hours of the patient's admission to hospital allow for an assessment of the severity of the patient's condition, which improves the accuracy of predicting the development of complications.

Coronavirus infection is characterized by abnormal activation of the immune response, dysregulation of proinflammatory cytokine synthesis (in particular, IL-6) and inflammatory markers (leukocyte levels, CRP, ferritin). Hyperactivation of the immune response leads to the development of ARDS, which in turn reduces blood oxygen saturation and leads to multiple organ failure. Provoked hypoxia leads to thrombosis due to pulmonary arteriolar spasm, which can be assessed by changes in coagulation parameters (APTT, fibrinogen, PTI, D-dimer) and platelet counts. LDH is a multisystem indicator, and elevated levels indicate the development of degenerative-dystrophic changes and acute damage to the lungs, heart, liver, and kidneys.

An elevated BMI indicates the presence of metabolic disorders (diabetes, impaired glucose tolerance, dyslipidemia), which leads to chronic inflammation in the vascular wall, atherosclerotic lesions, ischemia, as well as hemostatic disorders and the development of endotheliopathy. A decreased BMI is also a predisposing factor to the development of hemorrhages due to decreased vitamin and mineral levels, particularly vitamin K and iron levels in the blood.

With age, the risk of developing cardiovascular catastrophes increases due to increased permeability of the vascular wall, a decrease in the functional activity of platelets, a decrease in the volume of absorbed vitamins and microelements, and the accumulation of oxidative stress products.

It is generally accepted that the incidence of hemostatic complications in women and men is approximately equal; however, the influence of hormonal levels can either increase or decrease the risk of developing hemorrhagic complications in women, depending on other associated factors.

Premorbid conditions include respiratory (emphysema, chronic obstructive pulmonary disease, etc.), endocrine (diabetes mellitus, thyroiditis), cardiovascular (generalized atherosclerosis, atrial fibrillation), and hepatorenal (amyloidosis, chronic kidney disease, liver cirrhosis) systems, as predictors of bleeding due to impaired blood clotting, the need for anticoagulants and antiplatelet agents, polypharmacy, degenerative changes in the vascular wall, and impaired microcirculation. The use of mechanical ventilation and intravascular venous insufficiency (IVF) leads to increased intra-alveolar and intracapillary pressure, which, against the background of vascular damage caused by COVID-19, is also a risk factor for the development of spontaneous hematomas.

Each of the indicators is assigned the following points: the degree of lung tissue damage - 1-3 points, the level of leukocytes - 1-2 points, the level of platelets - 0-3 points, the level of LDH - 0-2 points, the level of CRP - 0-3 points, the level of IL-6 - 0-3 points, the level of ferritin - 1-3 points, the level of APTT - 1-3 points, the level of PTI - 0-3 points, the level of fibrinogen 0-1 point, the level of D-dimer - 0-3 points, the implementation of respiratory support 0-3 points, comorbid background - 0-1 point, gender - 1-2 points, age - 1-4 points, BMI - 0-1 point, the implementation of respiratory support - 0-4 points, the SOFA assessment - 1-3 points, and with a total score of less than 12, a low risk of developing spontaneous soft tissue hematomas, with a score of 13-21, a moderate risk of developing spontaneous hematomas is diagnosed, with a score of 22-30, a high risk of developing spontaneous hematomas is diagnosed, and with a score of 31 or more, a very high risk of developing spontaneous hematomas.

Table

Variable 1 Variable options Values
variable Floor Male 1 point Female 2 points Age (according to classification
WHO) 18-44 years old 1 point 45-59 years old 2 points 60-74 years old 3 points Over 75 years old 4 points Premorbid background No concomitant diseases 0 points Concomitant diseases 1 point BMI BMI = 18-25 0 points BMI less than 18
Or BMI over 25 1 point The degree of lung tissue damage (Rg/CT) Rg/CT - 0 or ARVI 1 point Rg/CT - 1-2 degrees 2 points Rg/CT - 3-4 degree 3 points White blood cell count 4-9 x 10 ⁹ /l 1 point Less than 4 x 10 ⁹ /l or
More than 9 x 10 ⁹ /l 2 points Platelet level More than 600 x 10 ^u /l 0 points From 400 to 600 x 10 ⁹ /l 1 point From 180 to 400 x 10 ⁹ /l 2 points

Less than 180 x 10 ⁹ /l 3 points LDH level (U/L) From 135 to 225 U/L 0 points From 225 to 405 U/L 1 point More than 405 U/L 2 points CRV level (mg/L) Less than 10 mg/l 0 points From 10 to 100 mg/l 1 point From 100 to 200 mg/l 2 points More than 200 mg/l 3 points IL-6 level (pg/ml) Less than 10 pg/ml 0 points From 10 to 100 pg/ml 1 point From 100 to 200 pg/ml 2 points More than 200 pg/ml 3 points APTT level (s) 22-38 sec 1 point 39-55 s 2 points More than 55 s 3 points PTI level (%) 100-140% 0 points From 70 to 100% 1 point From 40 to 70% 2 points Less than 40% 3 points Fibrinogen level (g/L) 2-4 g/l 0 points Less than 2 g/l
More than 4 g/l 1 point D-dimer level (ng/ml) Less than 400 ng/ml 0 points From 400 to 1000 ng/ml 1 point More than 1000 ng/ml 2 points Ferritin level (mcg/L) From 10 to 250 mcg/l 1 point From 250 to 1000 mcg/l 2 points More than 1000 mcg/L 3 points SOFA (sequential organ failure assessment) 0-3 points 1 point 4-6 points 2 points More than 7 points 3 points Conducting respiratory
support Not required 0 points Required, up to 5 l/min 1 point Required: 5-10 l/min and/or nivl 2 points Required, more than 10 l/min and/or VPO 3 points artificial ventilation 4 points

The method is as follows: upon admission to the hospital and throughout the course of medical care, laboratory and instrumental monitoring is performed. The frequency of additional examinations depends on the severity of the patient's condition: if the patient is stable, is in the ward, and there is no need for transfer to the intensive care unit, the frequency of examinations is once every 7 days; if the patient is in the intensive care unit, it is once every 3 days. Blood is drawn (clinical and biochemical tests, and a coagulogram), and additional instrumental examinations are performed: CT scan upon admission, X-ray during follow-up, and if there is a sharp deterioration and transport is possible, CT scans are repeated. For COVID-19, stratification according to the SOFA scale is performed daily to assess the presence of organ dysfunction. The degree of respiratory failure and the effectiveness of oxygen support are assessed in the intensive care unit. Upon admission and every 10 days, testing for COVID-19 is performed using the polymerase chain reaction (PCR) method for SARS-CoV-2.

To identify prognostic factors for hematoma development and determine their relationships, Student's t-test and Mann-Whitney tests, as well as correlation analysis using Pearson and Spearman coefficients, were used. The effectiveness of the proposed method was analyzed on 121 patients. Based on the assessment results, 78 patients were classified as having a low risk of spontaneous hematoma development, while 43 patients were classified as having a moderate, high, and very high risk. None of the patients in the low-risk group experienced the complication under study. Spontaneous hematomas developed in 13 patients in the moderate-risk group, 22 in the high-risk group, and 8 in the very-high-risk group.

Example 1. Patient K., 36 years old, was hospitalized at Botkin Hospital, St. Petersburg, on October 15, 2022, seven days after the onset of illness with a preliminary diagnosis of novel coronavirus infection caused by the Covid-19 virus. Complaints upon admission: weakness, fever up to 39°C (102.5°F), and chills. No underlying or concomitant pathology. BMI: 28.2. Chest X-ray upon admission: no recent focal or infiltrative changes. Laboratory: WBC - 6.3×10 ⁹ /l, PLT - 173×10 ⁹ /l, LDH - 186 U/l, CRP - 37.8 mg/l, IL-6 - 5 pg/ml, APTT - 26 s, PTI - 79%, fibrinogen - 2.5 g/l, D-dimer - 321 ng/ml, ferritin - 15 μg/l. Respiratory support was not required. SOFA - 0 points.

Prediction was performed using the proposed method. The total score was 11, indicating a low risk of spontaneous hematoma development.

The patient was prescribed treatment. After 8 days, symptoms regressed, test results returned to normal, and no evidence of spontaneous hematoma development was found. The patient was discharged in satisfactory condition.

Example 2. Patient Zh., 93 years old, was hospitalized in the St. Petersburg State Healthcare Institution "Botkin Hospital" on 12/12/2022, on the 6th day after the onset of the disease with a preliminary diagnosis: Novel coronavirus infection caused by the Covid-19 virus. Complaints upon admission: weakness, fever up to 38, chills, shortness of breath, cough. History: long-term suffering from paroxysmal atrial fibrillation. BMI - 21.9. Chest X-ray on the 1st day after admission: "Ground glass" areas are visualized in the upper and lower lobes of the right lung and the lower lobe of the left lung. Parenchyma involvement up to 20%. X-ray - 1. Increased pulmonary markings. Conclusion: X-ray signs of bilateral polysegmental pneumonia (high probability of Covid-19). Laboratory: WBC - 6.18×10 ⁹ /l, PLT - 251×10 ⁹ /l, LDH - 452 U/l, CRP - 17.18 mg/l, IL-6 - 8 pg/ml, APTT - 27.4 s, PTI - 90%, fibrinogen - 2.8 g/l, D-dimer - 2657 ng/ml, ferritin - 11 μg/l. Respiratory support was not required. SOFA - 1 point.

Prediction was performed using the stated method. The total score was 21, indicating a moderate risk of spontaneous hematoma development.

On the fourth day after admission, the patient complained of a hematoma on her left shoulder. She denied any trauma. A soft tissue ultrasound revealed the hematoma measuring 88 x 42 x 55 mm. Conservative treatment was recommended.

On the 13th day after hospitalization, positive dynamics were observed, including hematoma regression, and a negative PCR test. The patient was discharged for outpatient treatment.

Example 3. Patient A., 67 years old, was hospitalized in the St. Petersburg State Budgetary Healthcare Institution "Mariinsky City Hospital" on February 12, 2021, on the 8th day after the onset of the disease with a preliminary diagnosis: Novel coronavirus infection caused by the Covid-19 virus. Complaints on admission: weakness, fever up to 38.6, chills, shortness of breath, cough. History: coronary artery disease. Hypertension stage III, hypertension stage 3, cardiovascular risk 4. CHF f. class IIa. Type 2 diabetes mellitus. BMI - 31.3. CT on admission: "Ground glass" areas are visualized on both sides with parenchyma involvement up to 70% on the right and up to 60% on the left. Conclusion: CT signs of bilateral polysegmental pneumonia, CT-3 (high probability of Covid-19). Laboratory: WBC - 7.67×10 ⁹ /l, PLT - 96×10 ⁹ /l, LDH - 489 U/l, CRP - 147.6 mg/l, IL-6 - 31.37 pg/ml, APTT - 36.4 s, PTI - 97%, fibrinogen - 3.74 g/l, D-dimer - 478 ng/ml, ferritin - 320.7 μg/l. Respiratory support was not required. SOFA - 9 points.

Prediction was performed using the stated method. The total score was 27, indicating a high risk of spontaneous hematomas.

Five days later, the patient complained of pain in the left abdomen and a soft tissue hematoma in this area. He denied any trauma. A soft tissue ultrasound revealed a circumscribed hematoma on the left anterolateral abdominal wall, measuring 19.3 x 24 cm. Embolization of the left inferior epigastric artery and the deep circumflex iliac artery was performed. The postoperative period was uneventful, with clinical resolution of the hematoma.

After 18 days from the moment of hospitalization, the patient was discharged under outpatient observation of an infectious disease specialist.

Example 4. Patient A., 62 years old, was admitted to the St. Petersburg State Healthcare Institution "Mariinsky City Hospital" on August 26, 2020, on the 10th day after the onset of the disease with a preliminary diagnosis: Novel coronavirus infection caused by the Covid-19 virus. Complaints upon admission: weakness, fever up to 39, chills, shortness of breath, cough with periodic expectoration of thick sputum. History: Chronic glomerulonephritis. CKD stage 5. Bronchial asthma. Gout. Hypothyroidism. Ischemic heart disease. Hypertension stage III, hypertension stage 3, cardiovascular risk 4. Cerebrovascular accident. BMI - 28.6. CT on the 1st day after admission: Areas of "ground glass" are visualized on both scans with parenchyma involvement up to 85% on the right, up to 80% on the left. On the right, the sinus is shadowed. Conclusion: CT signs of bilateral polysegmental pneumonia, CT-4 (high probability of Covid-19). Right-sided hydrothorax. Laboratory tests: WBC - 5.13×10 ⁹ /l, PLT - 118×10 ⁹ /l, LDH - 714 U/l, CRP - 200 mg/l, IL-6 - 101.2 pg/ml, APTT - 46.8 s, PTI - 71%, fibrinogen - 8.66 g/l, D-dimer - 501 ng/ml, ferritin - 2279.6 μg/l. Respiratory support was required with initial transfer to intravenous intubation, then tracheal intubation was performed. SOFA - 10 points.

A prognosis was performed using the proposed method. The total score was 35, indicating a very high risk of spontaneous hematomas. Fifteen days after admission, the patient complained of pain in the left lumbar region. Ultrasound revealed signs of a fluid-filled lesion in the left retroperitoneal space with no evidence of blood flow during color Doppler imaging. A puncture of the left retroperitoneal space was performed under ultrasound guidance, obtaining lysed blood. Under ETN, an incision was made, the retroperitoneal hematoma was drained, and 400 ml of lysed blood was evacuated. Due to the severity of her condition, the patient was treated in the intensive care unit. The postoperative period was characterized by slow healing. She died on the 15th day after surgery.

The proposed method enables stratification of the risk of spontaneous hematoma development at different stages of a patient's hospital stay, assessing the severity of the disease, and its potential outcome. It can be used for dynamic monitoring at different stages of the coronavirus infection, facilitating the assessment of the effectiveness of treatment measures, and promptly adjusting diagnostic and treatment options. The proposed method is highly specific and informative, making it promising for clinical use.

Claims (1)

A method for predicting spontaneous hematomas in patients with COVID-19, including determining the volume of lung tissue damage using computed tomography and radiography; blood sampling and determining the levels of leukocytes, platelets, lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, activated partial thromboplastin time (aPTT), prothrombin index (PTI), fibrinogen, D-dimer and interleukin-6 (IL-6); determination of the presence of a comorbid background, gender, age, body mass index (BMI) of the patient, the nature and need for respiratory support, and also assess the presence and severity of multiple organ failure according to the SOFA scale, characterized by assigning points to each of the following signs: the degree of lung tissue damage - 1-3 points, where 1 point corresponds to the volume of damage Rg / CT - 0 or the course of an acute respiratory viral infection (ARVI), 2 points - Rg / CT - 1-2, 3 points - Rg / CT - 3-4; the level of leukocytes - 1-2 points, where 1 point corresponds to the leukocyte content of (4-9) × 10 ⁹ / l, 2 points - less than 4 × 10 ⁹ / l or more than 9 × 10 ⁹ / l; platelet level - 0-3 points, where 0 point corresponds to a platelet content of more than 600×10 ⁹ /l, 1 point - (400-599)×10 ⁹ /l, 2 points - (180-399)×10 ⁹ /l, 3 points - less than 180×10 ⁹ /l; LDH level - 0-2 points, where 0 points corresponds to an LDH level of 135-224 U/l, 1 point - an LDH level of 225-404 U/l, 2 points - an LDH level of more than 405 U/l; CRP level - 0-3 points, where 0 points corresponds to a CRP level of less than 10 mg/l, 1 point - a CRP level of 10-99 mg/l, 2 points - a CRP level of 100-199 mg/l, 3 points - a CRP level of more than 200 mg/l; IL-6 level - 0-3 points, where 0 points corresponds to an IL-6 level of less than 10 pg/ml, 1 point - an IL-6 level of 10-99 pg/ml, 2 points - an IL-6 level of 100-199 pg/ml, 3 points - an IL-6 level of more than 200 pg/ml; Ferritin level - 1-3 points, where 1 point corresponds to a ferritin level of 10-249 μg/l, 2 points - to a ferritin level of 250-999 μg/l, 3 points - to a ferritin level of more than 1000 μg/l; APTT level - 1-3 points, where 1 point corresponds to an APTT level of 22-38 s, 2 points - to an APTT level of 39-55 s, 3 points - to an APTT level of more than 55 s; PTI level - 0-3 points, where 0 points corresponds to a PTI level of 100-140%, 1 point - to a PTI level of 70-99%, 2 points - to a PTI level of 40-69%, 3 points - to a PTI level of less than 40%; fibrinogen level 0-1 point, where 0 points corresponds to a fibrinogen level of 2-4 g / l, 1 point - to a fibrinogen level of less than 2 g / l and more than 4 g / l; D-dimer level - 0-3 points, where 0 points corresponds to a D-dimer level of less than 400 ng / ml, 1 point - to a D-dimer level of 400-999 ng / ml, 2 points - to a D-dimer level of 1000-1500 ng / ml, 3 points - to a D-dimer level of more than 1500 ng / ml; comorbid background - 0-1 point, where 0 points corresponds to the absence of comorbidities, 1 point - with an aggravated comorbid background; gender - 1-2 points, where male gender corresponds to 1 point, female - 2 points; age - 1-4 points, where 18-44 years - 1 point, age 45-59 - 2 points, age 60-74 - 3 points, age over 75 years - 4 points; body mass index - 0-1 points, where body mass index 18-25 - 0 points and body mass index less than 18 and more than 25 - 1 point; implementation of respiratory support - 0-4 points, where 0 points corresponds to the absence of the need for respiratory support, 1 point - insufflation with humidified oxygen is performed at a flow rate of up to 5 l/min, 2 points - insufflation with humidified oxygen is performed at a flow rate of 5-10 l/min and/or a transfer to non-invasive ventilation (NIVL) is required, 3 points - insufflation with humidified oxygen is performed at a flow rate of more than 10 l/min and/or a transfer to high-flow oxygenation (HFO) is required, 4 points - transfer to invasive ventilation (IVL); SOFA score - 1-3 points, where 1 point corresponds to a SOFA level of 0-3 points, 2 points - a SOFA level of 4-6 points, 3 points - a SOFA level of more than 7 points, and with a score of less than 12, a low risk of developing spontaneous hematomas of soft tissues is predicted, with a score of 13-21, a moderate risk of developing spontaneous hematomas is predicted, with a score of 22-30, a high risk of developing spontaneous hematomas is predicted, and with a score of 31 or more - a very high risk of developing spontaneous hematomas.