RU2061960C1 - Method for diagnosing vascular disorders in pregnant women at early development stage of pathologic gestation course - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: method involves determining blood serum antivascular antibodies contents and making conclusion according to the results obtained. Immunoglobulin E concentration in the blood serum, vascular antigen- sensibilized lymphocyte contents, blood platelets number, adhered platelets number, adhered platelets percentage and adhesion index, platelets aggregation index are additionally determined. Changes in the values of these parameters are used to make conclusions concerning vascular disorders in pregnant women witnessing the presence of vascular syndrome in pregnant women . EFFECT: improved accuracy of diagnosis.

Description

 The invention relates to medicine, namely to obstetrics and gynecology, and relates to a method for the diagnosis of vascular disorders in pregnant women at an early stage of the development of the pathological course of gestation.

 In the development of the pathological course of pregnancy (preeclampsia, fetal developmental disorders, detachment of a normally located placenta, fetoplacental insufficiency, miscarriage, prolongation), changes in vascular adaptation play an important role (Serov V.N. Strizhakov A.N. Markin S.A. 1989 /. Currently, data have been obtained indicating that the vascular endothelium and smooth muscle cells are active interconnected structures in normal and pathological conditions, involved in the synthesis of biologically active substances, in regulation I have blood in numerous reactions of immunological and metabolic homeostasis (Olavi Ilikorkala, 1987). In obstetric clinic also traced the role of biologically active metabolites of vascular origin in the pathogenesis of these complications of gestation.

 A known method for predicting damage to the vascular wall in women with physiological and gestational complications of pregnancy by examining blood serum for the presence of antivascular antibodies (PAT) V.A. Melnikov, I.A. Kupaev, I.S. Lipatov. Antivascular antibodies in women with physiological and gestational complications of gestosis. The journal "Obstetrics and Gynecology", N 3-7, 1992, Moscow "Medicine", p. 19-21.

 In the known method for predicting vascular disorders, a woman is sampled in a period of 7-16 weeks. 18-24 weeks 28-36 weeks pregnancy to determine the PAT and the dynamics of changes in their level judge the presence of vascular lesions in the variable.

 The disadvantage of this method is the low accuracy of the diagnosis of vascular disorders in pregnant women at an early stage of the development of the pathological course of gestation due to lack of information when using only one test.

 The aim of the invention is to improve the accuracy of diagnosis by evaluating previously unknown parameters.

 This goal is achieved by the fact that in the method for the diagnosis of vascular disorders in pregnant women at an early stage of the development of the pathological course of gestation by determining the level of PAT, they additionally determine the concentration of serum immunoglobulin E (IHE), the content of lymphocytes sensitized to the vascular antigen, the number of platelets, the number of platelets adhered, the percentage of adhered platelets and platelet aggregation and adhesion indices, and the change in these parameters compared to normal they diagnose vascular disorders, indicating the presence of vascular syndrome of pregnant women.

 On the filing date of the application, the applicant did not find a diagnostic method with the claimed combination of features, as a result of which we conclude that the claimed technical solution meets the criteria of the invention of “novelty”.

 According to the results of a comparative analysis, the totality of the features of the proposed diagnostic method provides it with new properties in the form of increasing the accuracy of diagnosis, that is, according to the applicant, the proposed method meets the criterion of "inventive step".

 The criterion of the invention "industrial applicability" is confirmed by the fact that the inventive diagnostic method can be successfully carried out in mass preventive studies of pregnant women as screening with the identification of accurate and early signs of changes in the vascular system.

 A method for the diagnosis of vascular disorders in pregnant women at an early stage of development of the pathological course of gestation is as follows.

A pregnant woman is examined in the dynamics of gestation in terms of: 7-16 weeks. 18-24 weeks 28-36 weeks, 38-41 weeks. The survey is carried out by determining:
antivascular antibody levels;
serum immunoglobulin E concentrations;
the content of lymphocytes sensitized to the vascular antigen;
platelet counts;
platelet adhesion counts;
the percentage of adherent platelets;
platelet adhesion and aggregation indices.

 In the dynamics of physiological pregnancy, the above parameters have the following meaning.

 The level of PAT is determined by the reaction of passive agglutination (RPHA) with a vascular antigen obtained from the endothelial and subendothelial layers of the aorta according to the method of A.D. Ado and A.D. Polener (1971) and a standardized protein of 400 mg% concentration of IHE (ng / ml) was determined by enzyme immunoassay using kits from Farmacia Diagnostica, Sweden.

C 7 to 16 weeks pregnancy, the level of PAT 1:40 1:80 (ln4,094 ± 0,347), the average level of IHE 262 (ln 5.51 ± 0.037);
from 18 to 24 weeks the level of PAT 1:10 1:20 (ln 2.708 ± 0.346), the concentration of IHE 251 (ln 5.51 ± 0.028);
from 28 to 36 weeks the level of PAT 1:80 (ln 4.605 ± 0.202), the concentration of IHE 328 (ln 5.78 ± 0.042);
at 38 41 weeks. titer PAT 1:20 1:40 (ln 2,326 ± 0,448), IHE 332 (ln 5,79 ± 0,039).

The content of lymphocytes sensitized to the vascular antigen was determined by the method of specific rosette formation according to H. Fremel (1987)
In the period of 7 to 16 weeks. the number of lymphocytes is 28 ± 4.3%
at 18 24 weeks. 16 ± 2.9%
at 28 36 weeks. 18 ± 5.5%
at 38 41 weeks. 24 ± 76.7%
The platelet count ranges from 200,260 thousand / ml. The adhesive properties of platelets were determined by the LIPC method, platelet adhesion on a fiberglass pigtail, and was characterized by the following indicators:
the number of adherent platelets (TA) is normal 34.4 76.24 thousand.

the percentage of adherent platelets (TA%) is normal 21.14% -30.46%
adhesion index (IA) 1.29-l, 58
Platelet aggregation was determined by the method of Borny.VR (1962) in the modification of Zakharin (1986) using collagen aggregation (0.7-1 mg / ml.) As an inducer. Platelet Aggregation Index (IAT) during physiological pregnancy 8.7% -45.4%
Most women with pregnancy complications such as gestosis, fetal growth retardation syndrome, fetoplacental insufficiency syndrome, miscarriage, pretreatment at the preclinical stage, there are vascular disorders that are not pathognomonic for each specific nosological form, but only indicates a pathological course of gestation.

A change in these indicators in the dynamics of pregnancy indicates the presence of pronounced vascular lesions in pregnant women:
continuous increase in PAT titers (from 1: 160-1: 320)
increase in the concentration of IHE more than 400-450 ng / ml
increase in the content of lymphocytes sensitized to vascular antigen (more than 40 ± 4.3%)
decrease in platelet pregnancy dynamics
an increase in the adhesive and aggregation properties of platelets (TA, TA% IA, IAT) compared with indicators characteristic of physiological pregnancy.

EXAMPLE 1. Pregnant H.26 years old, registered in the antenatal clinic of the Regional Perinatal Center with a diagnosis of pregnancy 1, 10- ll weeks. In the dynamics of pregnancy, along with generally accepted examinations, a study was conducted of the level of PAT, IHE, sensitized to the vascular antigen of lymphocytes, platelet counts, their adhesive and aggregation properties in terms of 15,23,28, 34, 38 weeks. At the first study in 15 weeks. The following data were obtained: PAT level 1:40, IHE concentration 250 ng / ml sensitized lymphocyte content 25% platelet count 220x10 ⁹ / L, platelet adherence 50 thousand percent platelet adherence 22.7% adhesion index 1.3, platelet aggregation index 18.6% According to other research methods (tetrapolar rheovasography, conjunctival biomicroscopy, determining the height of the uterine fundus, the content of blood hormones), deviations from the physiological course of gestation were not detected. In a period of 23 weeks. the level of PAT 1: 80-1: 160, the concentration of IHE was 410 ng / ml, the content of lymphocytes sensitized to vascular antigen 48%, the number of platelets 220x10 ⁹ / l, the number of platelets adhered 82 thousand percent platelets adhered 37.2% adhesion index 1.59, platelet aggregation index 40.1% Prior to other examination methods (ultrasound photometry, cardiotocography, blood hormone immunoassay, conjunctival biomicroscopy, tetrapolar rheography, clinical examination, generally accepted laboratory tests ) Lesions were found. Given the deviations of specific indicators characterizing vascular disorders, an increase in the level of PAT, IHE, sensitized lymphocytes, and a violation of the adhesive properties of platelets, the pregnant woman was prescribed vascular defense therapy on an outpatient basis: calcium antagonists, dipyridomole, antioxidants, glutamic acid, aspirin, electrophoresis with reopoliglyukin to the uterus. At 28 weeks the level of PAT was 1: 320-1: 640, the concentration of IHE was 480 ng / ml, the content of sensitized lymphocytes 56%, the number of platelets 195 × ^{10 9} / l, the number of platelets adhered 90 thousand percent of platelets adhered 46% adhesion index 1.6, platelet aggregation index 53% Clinically, a pregnant woman has an uneven increase in body weight, the difference in blood pressure on the right and left arm is 15 mm Hg. (125/75 and 110/70 mmHg), the difference in blood pressure when changing the position from a sedentary to horizontal 20 mmHg Clinical diagnosis: pregnancy 1.28 honey. Pretoxicosis. Given the increase in vascular disorders, despite the ongoing treatment, the onset of clinical symptoms of pretoxicosis of the pregnant woman continues the therapy started in a day hospital. In addition to treatment, herbal medicine, oxygen therapy, potassium orotate. When examined at 34 weeks. HELL 140/90 and 145/95 mm Hg in the urine protein 0.23 g / l, posture of the legs. PAT level 1: 640, IHE concentration of 502 ng / ml, content of lymphocytes sensitized to vascular antigen 68%, platelet count 190x10 ⁹ / l, platelet adherence 95 thousand percent platelet adherence 50% adhesion index 2, platelet aggregation index 60% Microcirculation protein membrane according to conjunctival biomicroscopy: the vascular background is moderate, the arterioles along the entire length are accompanied by venules, the ratio of their diameters is 1: 6: 8: 12, in some vessels perivascular edema, intravascular aggregation I am in 15-18% of the vessels, no hemorrhages. According to tetrapolar rheography, changes in the hemodynamics of blood vessels of the region of the abdominal region and the region of the lower extremities are noted.

 Diagnosed with pregnancy 1.34 weeks. preeclampsia of the second half of a mild pregnancy, the woman is hospitalized in the regional perinatal center in the department of pathology of pregnant women.

The department provides therapy aimed at correcting preeclampsia (replenishment of bcc, hemodilution, antihypertensive therapy and therapy aimed at improving metabolic processes). Against the background of the treatment, the woman's condition is satisfactory, the dynamics of increasing the severity of gestosis is negative. The results held in 38 weeks. studies: PAT level 1: 640, IHE concentration 510 ng / ml, sensitized lymphocyte content 56% platelet count 195x10 ⁹ / l, platelet adherence 90 thousand percent platelet adherence 46% adhesion index 1.0, platelet aggregation index 70% Delivery were timely at 39-40 weeks, proceeded without complications. A live full-term boy was born, weighing 3300 g, 52 cm long, without asphyxiation (Hangar score of 8 points, after 5 minutes 8 points), without signs of morphofunctional immaturity. In the period of early adaptation and during the entire stay in the neonatal ward, the child was in a satisfactory condition. The postpartum period in the mother proceeded without complications, the puerpera and the newborn were discharged home on the 6th day after delivery in a satisfactory condition.

EXAMPLE 2. Pregnant G. 32 years old, registered with the antenatal clinic of the Regional Perinatal Center with a diagnosis of pregnancy 1.11-12 weeks. Nulliparous older. Burdened obstetric history (2 medical abortions in terms of 8-9, 7-8 weeks. Without complications). In the periods of 15-16,22-23, 28, 36 weeks. a study was conducted of the level of PAT, IHE, sensitized to the vascular antigen of lymphocytes, platelet counts, their adhesive and aggregation properties. When examined in 15-16 weeks. the following indicators were obtained that characterize the degree of vascular disorders: PAT level 1:80, IHE concentration of 232 ng / ml, sensitized lymphocyte content 20%, platelet count 240x10 ⁹ / l, platelet count 60 thousand percent adhesion platelet count 25% adhesion index 1, 31, platelet aggregation index 22% General clinical and instrumental examination of deviations did not reveal. In the period of 22-23 weeks. the examination yielded the following results: the PAT level was 1: 160 1: 320, the concentration of IHE was 469 ng / ml, the content of lymphocytes sensitized to the vascular antigen 54%, the number of platelets 220x10 ⁹ / l, the number of platelets adhered 78 thousand percent of the adherent platelets 35.4 % adhesion index 1.53, platelet aggregation index 59.5% Other methods for examining pathological deviations from the physiological course of pregnancy have not been identified. Given the presence of vascular disorders detected by specific tests, the therapy was carried out for 4 weeks by the method of "vascular protection", including calcium antagonists, aspirin, electrophoresis of reopoliglyukin in the uterus, glutamic acid. Pregnant did not fulfill the appointment. At 28 weeks the level of PAT was 1: 620-1: 1280, the concentration of IHE was 726 ng / ml, the content of sensitized lymphocytes 60%, the number of platelets 185x10 ⁹ / l, the number of platelets adhered 86 thousand percent of platelets 45.4% adhesion index 1.85, index platelet aggregation 76.3% Clinical and laboratory (determination of the height of the uterine fundus, abdominal circumference, content of fetal and placental hormones by the enzyme immunoassay, etc.) and instrumental methods (ultrasound photometry, dopplerometric examination of blood flow in the vessels of the uterine of the lacental-fetal circle of blood circulation, tetrapolar rheovasography with determination of the parameters of peripheral and central hemodynamics) showed that the pregnant woman had data for chronic fetoplacental insufficiency syndrome and intrauterine growth retardation (the average size of the chest and abdomen of the fetus was lagging behind due to gestational age by gestational age 2-3 weeks). With a clinical diagnosis: pregnancy 1.28 weeks. HFPN, SZRP 1-2 degrees, a primipara of an older age, a burdened obstetric history, a woman was hospitalized in the Department of Pregnancy Pathology of the Regional Perinatal Center. In order to treat fetoplacental insufficiency, corrective therapy was carried out aimed at improving the uteroplacental blood flow (chimes, reopoliglyukin, calcium antagonists, aspirin, aminophylline), to improve the nutrition of the fetus, they prescribed a nutrient mixture of veloton, antihypoxants, methionine, unitiol acid, vitamin B12 , vitamin C, glutamic acid, potassium orotate, sigetin, oxygen therapy was carried out. Against the background of therapy, a positive dynamics was noted, confirmed by the data of ultrasound investigation, dopplerometry, cardiophetonomy observation. A follow-up examination was performed at 36 weeks: the PAT level was 1: 80-1: 160, the concentration of IHE was 396 ng / ml, the content of sensitized lymphocytes was 48%, the number of platelets was 200x10 ⁹ / l, the number of platelets was adhered to 72 thousand percent of the adherent platelets were 36% index adhesion of 1.56, platelet aggregation index of 42.4% Delivery occurred at 39-40 weeks, without complications. A live full-term girl was born with a body weight of 3000 g, a length of 50 cm, without asphyxiation (8-point mark on the Hangar scale, 5 points in 5 minutes), without signs of morphofunctional immaturity. In the period of early adaptation and during the observation of the newborn in the department for newborns, the condition was satisfactory. The postpartum period of the mother went smoothly. In satisfactory condition, the postpartum woman with the baby was discharged home on the 6th day after the birth.

 Thus, vascular disorders in women, which are characteristic of the early stage of the pathological course of gestation, are distinguished into vascular syndrome of pregnant women, which transforms in the course of an unfavorable course into clinical variants of the complicated course of pregnancy (gestosis, fetal growth retardation syndrome, fetoplacental insufficiency, etc.).

 A change in the indicators proposed for the characterization of vascular lesions indicates a disruption in the adaptive capabilities of the pregnant body and the need for their urgent correction by the method of "vascular protection".

 The positive effect of the proposed diagnostic method is a fundamentally new opportunity for early diagnosis of vascular disorders in pregnant women at an early stage of the development of the pathological course of gestation due to the assessment of previously unused parameters. The method is non-invasive and safe for the health of the patient.

Claims (1)

 A method for diagnosing vascular disorders in pregnant women at an early stage of the development of a pathological course of gestation, including determining the level of antivascular antibodies of blood serum with subsequent analysis of indicators, characterized in that they further determine the concentration of serum immunoglobulin E, the content of lymphocytes sensitized to vascular antigen, platelet count, platelet count and the percentage of platelets adhered, the platelet adhesion and aggregation index and when these indicators change at pared with the norm diagnose vascular disorders in pregnant women, indicating the presence of a vascular syndrome pregnancy.