RU2623868C1 - Method for prediction of bleeding in newborns with very low or extremely low body weight - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: thromboelastogram indicator is determined in a newborn with a very low and extremely low body weight by a 30-minute lysis of the blood clot (LY30) on day 1-2 of life. The type of respiratory therapy, oxygen concentration in the inspired air (fiO₂) at the time of blood collection is considered and the discriminant function (Y) is calculated by the formula: YY=8,288-0,081×X1-2,553×X2-0,056×X3, where X1 is LY30 in%; X2 is the type of respiratory therapy: nasal CPAP - 1 point, ventilation - 2 points; X3 is fiO₂ concentration in %, and at a value of Y<0, bleeding is predicted.

EFFECT: method provides the ability to predict bleeding in newborns with very low and extremely low body weight with high accuracy, sensitivity and specificity, which allows to determine the tactics of treatment measures in a timely manner.

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Description

The invention relates to medicine, namely to neonatology, and can be used to predict bleeding in premature infants with very low (ONMT) and extremely low body weight (ENMT).

Relevance

To date, determining the state of the blood coagulation system is an important aspect in the diagnosis and prediction of emergency conditions, which is in demand in neonatology. According to Faye B.F. et al. (2013), the prevalence of hemorrhagic syndrome among premature infants is 26.8%, visceral hemorrhages prevail, including pulmonary (34.1%), gastrointestinal (31.7%), skin (26.8%), cerebral (17%) [1].

For preterm infants with ONMT and ENMT, the study of blood coagulation is of great importance, since these children are at risk of serious complications when adapting to extrauterine life, and hemorrhagic disorders, namely bleeding, significantly increase morbidity and mortality in this group [2].

Currently, there is an increased interest in the method of thromboelastography (TEG), the essence of which is an integrated assessment of the state of the entire hemostatic system from the stage of coagulation initiation to its spread, which allows one to evaluate the kinetics of clot formation, its strength, and lysis intensity. In this regard, the prognosis of bleeding in newborns with ONMT and ENMT using TEG, namely its lysis parameter, is relevant.

A known method for predicting hemorrhagic syndrome in hematological patients with thrombocytopenia of less than 20 × 10 ⁹ / l by assessing the patient's condition in points on the scale of assessment of multiple organ dysfunction A.L. Levita et al. (Patent No. 2185089 RU). This scale includes parameters that determine the state of ten major organs and systems of the body: thermoregulation, cardiovascular, respiratory, kidneys, metabolism, liver, coagulopathy, intoxication, central nervous system, gastrointestinal tract. Each system can be in one of four states: norm, compensation, subcompensation and decompensation. With a total score of 120 points or more, a high risk of developing a clinically significant hemorrhagic syndrome is predicted, and with a total score of less than 120 points, a low risk of developing a clinically significant hemorrhagic syndrome (Patent No. 2311638 Russian Federation. A method for predicting hemorrhagic syndrome in hematological patients / Kostin A.I. ., Konstantinova A.S., Levit A.A. // Inventions. Useful models. - 2007. - No. 33).

The disadvantages of the method

1. This method is used only for hematological patients with thrombocytopenia less than 20 × 10 ⁹ / L.

2. This method is time-consuming, since it requires the definition of a clinical laboratory test (blood test with platelet count) in these patients and an assessment of the state of most organs and systems of the body.

A known method for predicting the development of hemorrhagic complications in childbirth according to the hemostatic system in the second half of pregnancy by monitoring the hemostatic system of pregnant women in the second and third trimesters of gestation. In the II trimester, thrombin time and fibrinogen concentration are detected as informative signs of a hemostasiogram. Using the pattern recognition method, the value of the function F is determined by the formula: F = 0.96A-0.042B-2.51, where A is the concentration of fibrinogen, g / l, and B is the thrombin time, s. With an F value greater than 0.31, physiological blood loss is predicted. If F is less than -0.27, pathological blood loss in childbirth is predicted. Then, in the III trimester, the plasma fibrinogen concentration β, the level of D-dimers, the number of platelets and the thromboelastogram parameter K, recorded under conditions of highly contact activation of hemocoagulation, are determined as informative signs. Using the pattern recognition method, the value of the function P is determined by the formula P = -0.89C-0.59D + 0.014E + 0.012G-1.14, where C is the plasma fibrinogen concentration β, g / l, D is the level of D- dimers, ng / ml, E - platelet count, 109 / ml, G - parameter K, mm. With a value of P greater than 0.2, physiological blood loss is predicted. With a P value of less than -0.2, pathological blood loss in childbirth is predicted. The values of F in the range from -0.27 to 0.31, and P from -0.2 to 0.2 are taken as zones of uncertain forecast (RF Patent for invention No. 2156469. Russian Federation. Method for predicting the development of hemorrhagic complications in childbirth according to data of the hemostatic system in the second half of pregnancy / Medvinsky I.D., Yakubovich O.I., Zislin B.D. et al. // Utility models. - 2000. - No. 26).

The disadvantages of the method

1. The forecast requires a long observation time.

2. The method is time-consuming, since the blood is taken to determine the number of platelets, hemostasiograms and TEG.

3. The method is not applicable for newborns.

Closest to the technical solution is a method for predicting intraventricular hemorrhage (IVH) in premature infants by biochemical blood tests of pregnant women admitted to a hospital with the threat of premature birth. In the peripheral blood, the concentration of alpha-1 antitrypsin, malondialdehyde, nitrites is determined, the gestational age, the presence or absence of placental insufficiency are taken into account, and the discriminant function of Y is calculated by the formula. With a value of Y <0 and the realization of the risk of premature birth within 7 days, the occurrence of an IVH in a newborn is predicted (Patent No. 2303782. Russian Federation. A method for predicting intraventricular hemorrhage in premature infants / Kuzmenko G.N., Nazarov SB, Popova I. G. et al. // Utility models. Inventions, 2007. - No. 21. - P. 16). We have chosen this method as the closest analogue, however, it has a number of significant drawbacks.

1. The method allows to predict only high fatty acids.

2. The forecast is carried out during the first seven days of life.

These disadvantages are proposed to eliminate in the present method.

The technical result of the proposed method is the prediction of various bleeding in premature infants with ONMT and ENMT. The technical result is achieved by determining the 1-2-minute life of the newborn indicator of 30-minute lysis of a blood clot (LY30) according to the thromboelastogram (TEG), taking into account the appointment of the type of respiratory therapy of the newborn (CPAP or mechanical ventilation) and determining the concentration of inhaled oxygen at the time of blood collection (fiO ₂ ), with subsequent calculation of the discriminant function (Y), with a value of which is less than zero, bleeding in newborns is predicted with an accuracy of 89%.

The method is as follows.

Within 1-2 days of life, a child receives venous blood in an amount of 340 μl taken from a peripheral vein in a standardized test tube using 3.2% sodium citrate. To interpret the 30-minute lysis of the blood clot (LY30), the study was performed using a TEG 5000 thromboelastograph from Haemoscope Corporation (USA) for 30 minutes in accordance with the instructions for the device. Take into account the type of appointment of respiratory therapy in points and the fiO ₂ indicator - the concentration of oxygen in the inhaled air at the time of blood collection.

Then calculate the discriminant function (Y) according to the formula:

Y = 8.288-0.081 × X1-2.553 × X2-0.056 × X3, where:

X1 - TEG indicator LY30, in percent (%);

X2 - the appointment of respiratory therapy: non-invasive respiratory therapy (nasal CP AR) - 1 point, mechanical ventilation (mechanical ventilation) - 2 points;

X3 is the concentration of fiO ₂ in percent (%).

With a value of Y <0, bleeding is predicted in newborns with ONMT and ENMT.

The novelty of the proposed method lies in the fact that the relationship between the type of respiratory therapy, fiO ₂ and TEG - LY30 for predicting bleeding in premature infants with ONMT and ENMT was traced for the first time.

According to the literature, preterm infants with ONMT and ENMT are difficult to adapt to their prenatal existence, they need intensive treatment, including including respiratory therapy. It has been established that the oxygen concentration in the inhaled mixture (fiO ₂ ) below 60% is considered safe for the child. In the presence of severe concomitant pathology of the premature newborn - intrauterine infection, congenital pneumonia, respiratory distress syndrome, general immaturity of the lungs and heart, critical (up to 100%) oxygen concentrations in the inhaled mixture are used. The fiO ₂ values, due to the toxicity of high oxygen concentrations, can lead to impaired hemostasis, although their use is vital for adequate gas exchange to occur (3).

The use of the method of thromboelastogram (TEG) provides a quick and comprehensive assessment of the state of hemostasis, taking into account the assessment of the functional state of platelets according to the parameters of maximum amplitude (MA) and the intensity of lysis of the clot at 30 minutes (by parameter LY30), which is not available when performing basic baseline hemostasiogram tests (4 ) LY30 is a characteristic of the dissolution of a clot - its lysis at 30 minutes (instructions for the device). The proposed parameter LY30 is calculated automatically by the device.

It is known that a high concentration of oxygen damages the endothelium, while the production of specific proteins — clot lysis regulators — changes, which significantly changes the lytic function of the blood as a whole, and the development of massive hemorrhages depends on the regulation of lysis.

Previously, determination of the duration of mechanical ventilation and fiO ₂ in premature infants was used to assess the severity of respiratory distress syndrome (RDS) (4), TEG parameters, including LY30 in premature infants for a comprehensive assessment of the plasma and cellular components of hemostasis (5). However, the integrated use of the proposed indicators (LY30 parameters according to the TEG data taking into account fiO ₂ indicators) has not been previously carried out. Their use will allow timely prediction of the development of bleeding in premature infants with ONMT and ENMT.

Distinctive features of the method

1. Determination of thromboelastogram index in 30 minutes of blood clot lysis (LY30) in newborns with ENMT and ONMT for 1-2 days of life.

2. Taking into account the type of respiratory therapy in points and the concentration of oxygen in the inhaled air (fiO ₂ ) at the time of taking the blood.

3. The calculation of the discriminant function (Y) according to the formula:

Y = 8.288-0.081 × X1-2.553 × X2-0.056 × X3, where:

X1 - indicator LY30, in%;

X2 - type of respiratory therapy: nasal CPAP - 1 point, mechanical ventilation - 2 points;

X3 is the concentration of fiO ₂ in%.

With a value of Y <0, bleeding is predicted.

The essence of the proposed method is illustrated by the following examples.

Example 1. Baby D. was born from I pregnancy, complicated by preeclampsia and placental abruption, by cesarean section at 30 weeks of gestation. Evaluation on an Apgar scale of 1-3 points, an assessment at birth of respiratory failure according to Downs 6 points, body weight 987 grams. The condition from birth is regarded as extremely severe, the child is depressed, generalized cyanosis, general soft tissue pastiness, muscle atony, shortness of breath up to 70 per minute, marked participation of auxiliary muscles in the act of breathing, auscultation of breathing in the lungs is sharply weakened, crepitating wheezing with both sides. Signs of respiratory failure 3 degrees. Based on the clinical picture and the data of an additional study, the diagnosis was made: respiratory distress syndrome of the newborn (RDSN), respiratory failure (DN) of the 3rd degree, congenital pneumonia, fetal development retardation syndrome (SRO) of the III degree, prematurity 30 weeks. The child was in the neonatal intensive care unit, from the first day respiratory therapy was carried out by the method of mechanical ventilation. On the second day, the blood coagulation system was evaluated by the TEG method - the LY30 indicator was 0%, at the time of blood sampling, the fiO ₂ concentration was 80%. According to the claimed method, the calculation is made according to the formula:

Y = 8.288-0.081 × 0-2.553 × 2-0.056 × 80, where

0, 2, 80 - quantitative characteristics of the claimed parameters - LY30, mechanical ventilation, fiO ₂ .

Y = -1.3, which is less than zero. On the 3rd day, the child against the background of mechanical ventilation developed pulmonary hemorrhage. Clinical diagnosis: congenital bilateral pneumonia with RDSN, complicated by pulmonary hemorrhage, severe anemia. Hypoxic hemorrhagic lesion of the central nervous system, cerebral ischemia of the III degree. Prematurity 30 weeks. ENMT. The forecast for the claimed method was confirmed.

Example 2. Baby C. was born from an IV pregnancy, which was occurring against a background of mixed-type vegetovascular dystonia, chronic pyelonephritis, and placentitis. Delivery by caesarean section at 26 weeks of gestation. Evaluation on the Apgar scale of 2-4 points, an assessment of respiratory failure at birth according to Downs 6 points, body weight 923 grams. The condition from birth is extremely severe, the skin is cyanotic, cyanosis of the nasolabial triangle, muscle hypotension, shortness of breath up to 76 per minute, the participation of auxiliary muscles in the act of breathing, breathing is weakened in the lungs with auscultation, creaking rales on both sides. Based on the clinical picture and data from an additional study, the diagnosis was made: RDSN, congenital pneumonia, respiratory failure of the III degree. The child was on respiratory therapy by mechanical ventilation from birth for 28 hours. According to the claimed method, at the end of 1 day of life, the blood coagulation system was evaluated by the TEG method - the LY30 indicator was 2%, at the time of blood sampling, the fiO ₂ concentration was 50%. According to the claimed method, the calculation is made according to the formula:

Y = 8.288-0.081 × 2-2.553 × 2-0.056 × 50, where

2, 2, 50 - quantitative characteristics of the claimed parameters - LY30, mechanical ventilation, fiO ₂ .

Y = 0.22, which is greater than zero. In a child, the absence of bleeding is predicted. The forecast for the claimed method was confirmed. At 28 hours of age, the child was transferred to non-invasive respiratory therapy (nasal CP AR). On the 7th day of life, the child was transferred to the department of pathology of newborns and premature babies, where he stayed for 6 weeks. Discharged home under the supervision of a local pediatrician.

Example 3. Baby C. was born from an IV pregnancy, which occurred against a background of chronic pyelonephritis, intrauterine infection (IUI). Childbirth at 27 weeks. Evaluation on an Apgar scale of 3-4 points, an assessment of respiratory failure at birth according to Downs 5 points, body weight 980 grams. The condition from birth is serious, cyanosis of the nasolabial triangle, acrocyanosis, muscle hypotension, respiratory rate of 68 per minute, the participation of auxiliary muscles in the act of breathing, with auscultation in the lungs, breathing is weakened, creaking rales on both sides. Taking into account the clinical picture and data from an additional study, the diagnosis was made: RDSN, congenital pneumonia, cerebral ischemia of the 2nd degree, depression syndrome. From birth, respiratory therapy was carried out by the method of mechanical ventilation, 7 hours after birth, the child was transferred to non-invasive respiratory therapy (nasal CPAP - 1 point). At the age of 16 hours of life, the coagulation system of the blood was evaluated by the TEG method according to the claimed method — the LY30 indicator was 1.9%, at the time of blood sampling, the fiO ₂ concentration was 30%. According to the claimed method, the calculation is made according to the formula:

Y = 8.288-0.081 × 1.9-2.553 × 1-0.056 × 30, where

1,9, 1, 30 - quantitative characteristics of the claimed parameters - LY30, CPAP, fiO ₂ .

Y = 3.9, which is greater than zero. In a child, the absence of bleeding is predicted. The forecast for the claimed method was confirmed. On the 9th day, the child was transferred to the pathology department of newborns and premature babies, where he stayed for 6 weeks. Discharged home under the supervision of a local pediatrician.

Example 4. Baby S. was born from III pregnancy, which occurred against the background of placental insufficiency, chronic intrauterine hypoxia of the fetus, burdened with obstetric and gynecological history. The first spontaneous birth at 31 weeks. The Apgar score is 4-5 points, the Downs score for respiratory failure at birth is 4 points, and the body weight is 1490 grams. The condition from birth is regarded as extremely severe, the child is depressed, generalized cyanosis, general soft tissue pastiness, muscle atony, shortness of breath up to 78 per minute, marked participation of auxiliary muscles in the act of breathing were noted. Taking into account the clinical picture and data from an additional study, the diagnosis was made: RDSN, congenital pneumonia, respiratory failure of the III degree, SZRP of the III degree, prematurity 31 weeks. The child was in the neonatal intensive care unit, from the first day respiratory therapy was carried out by the method of mechanical ventilation. On the second day of life according to the claimed method, the blood coagulation system was evaluated by the TEG method. The LY30 value was 12.6%, at the time of blood sampling fiO ₂ was 100%. Calculation according to the formula:

Y = 8.288-0.081 × 12.6-2.553 × 2-0.056 × 100, where

12.6, 2, 100 - quantitative characteristics of the claimed parameters - LY30, mechanical ventilation, fiO ₂ .

Y = -3.44, which is less than zero. The child is predicted to develop bleeding. The child had hemorrhage in the third and fourth lateral ventricles of the brain, hemorrhage in the alveoli and bronchi of the lungs. The child died on the 8th day of life. The forecast for the claimed method was confirmed.

The advantages of the method.

1. To perform the method requires a small amount of blood (0.5 ml).

2. The inventive method, namely TEG, does not require large time expenditures and is carried out within 30 minutes.

3. Provides a quick and comprehensive assessment of the blood coagulation system, which is not available with the usual basic coagulation tests.

4. It allows you to timely determine the tactics of therapeutic measures in premature babies.

5. The proposed method has a high accuracy of 89%, sensitivity of 75%, specificity of 94%.

The results of the study are presented in table 1.

Bibliography

1. Diagnostic and evolutionary aspects of hemorrhagic syndromes of the newborn in Dakar / B.F. Faye [et al.] // Arch Pediatr. - 2013 .-- Vol. 20, No. 2. - P. 164-170.

2. The frequency of hemorrhagic manifestations in deeply premature infants / LB Aliyev, A.G. Antonov, A.S. Burkova, A.A. Lenyushkina // Obstetrics and gynecology. - 2011. - No. 2. - S. 53-57.

3. Features of the provision of medical care to children born in gestational periods of 22-27 weeks / D.O. Ivanov [et al.]; under the editorship of BEFORE. Ivanova, D.N. Surkova. - SPb., 2013 .-- 131 s.

4. Innovative technology for assessing the hemostatic potential of blood of premature infants / G.N. Kuzmenko [et al.] // Russian Pediatric Journal. - 2015. - T. 18, No. 2. - S. 14-17.

5. Functional features of hemostasis of full-term and premature newborns, according to thromboelastography / G.N. Kuzmenko [et al.] // Clinical laboratory diagnostics. - 2013. - No. 5. - S. 14-17.

Claims (7)

A method for predicting bleeding in premature infants by examining peripheral venous blood, characterized in that for a newborn with very low and extremely low body weight, a thromboelastogram index of 30 minutes lysis of a blood clot (LY30) is determined for 1-2 days of life, the type of respiratory therapy is taken into account and the oxygen concentration in the inhaled air (fiO ₂ ) at the time of blood collection, then the discriminant function (Y) is calculated by the formula: Y = 8.288-0.081 × X1-2.553 × X2-0.056 × X3, where X1 - indicator LY30 in%; X2 - type of respiratory therapy: nasal CPAP - 1 point, mechanical ventilation - 2 points; X3 - concentration of fiO ₂ in% and with a value of Y <0, bleeding is predicted.