CRUCIAL APPROACHES TO DIAGNOSTICS AND ANAEMIA TREATMENT IN PREGNANT WOMEN WITH HEART FAILURE AT THE EXTRAGENITAL PATHOLOGY CLINIC

According to modern concepts, aneamia can be a cause of chronic heart failure (CHF) and its result. According to diff erent sources aneamia of chronic disease is the most frequent among patients with the CHF and it

W ithin the last twenty years a range of problems and their nature, the specialists of the High Risk Pregnancy Department are facing, has signifi cantly increased.
For a number of years the congenital heart diseases and a part of the congenital heart di seases were considered to be a contraindication for getting pregnant and carrying of a pregnancy. Today, a consensus among cardiac surgeons, cardiologists, and obstetrician-gynecologistshas been reached: the most of such patients will have an opportunity to carry the pregnancy and to deliver a baby without health damage subject to adequate assessment of cardiac reserve, peculiarities of haemodynamics, and proper psychological and medical supervision.
In modern perinatology and at thehigh risk pregnancyclinic a great attention is paid to stratifi cation of «cardiac events» risks and perinatal complications. A great contribution to this was made by development and practical use of CarPreg and ZAHARA risk scales; prediction is defi ned by a score method and includesassessment of a heart disease type, availability and a degree of circulatory ineffi ciency, a degree of pulmonary hypertension, and hypoxemia intensity. These are the factors that aggravate the prediction, cause pregnancy complications and problems withphysiological fetal development. The main reason in forming obstetric and perinatal complications is due to prolonged hypoxia and heart failure in women with congenial heart diseases (CHD) [6,7].
Taking into consideration signing of WHO Resolution on Protecting reproductive rights by our country, it is necessary to ensure the rights ofwomen with severe somatic and neurologic pathology such as the right toobtain adequate information concerning their health state and possible eff ect of the present pathology on a gestational process and future baby; to have an access to safe, effi cient, inexpensive, and aff or dable birth control methods up to their choice; to have access to relevant public health services ensuring safe pregnancy and labour to every woman, as well as arrangement of the best opportunities for married couples to have a healthy child.
Taking into account the foregoing, the necessity to hospitalize pregnant women with the most severe diseases to the Department of Ob-stetric Problems in High Risk Pregnancy in the Institute of Pediatrics, Obstetrics, and Gynecology of NAMS of Ukraine, is performed in compliance with the regionalization principles toperinatal care in Ukraine, as well as an extension of modern diagnostics and treatment methods, prevention of perinatal complications. Thus we need to work out an approach to each pregnant woman without modern clinical practice guidelines for a number of nosological forms (including the cases of oncology pathology, severe cardiovascular pathology, etc.). It presupposes search of new approaches to solve both common and individual clinical cases.

CARDIOVASCULAR PATHOLOGY AND ANEAMIA
Aneamia can be a cause of chronic heart failure (CHF) and its result. Today it is considered that pathogenesis of aneamia association with CHF has not been still found out, it can comprise a number of mechanisms: renal dysfunction (reduction of erythrogenesis in cases of aneamia), infl ammation (erythropoietin resistence), age, the female sex, decrease in a body mass index, intestinal absorption disorders, long-term administration of aspirin, proteinuria. A special role in the pathogenesisis assigned to proinfl ammatory cytokines that promote aneamia of chronic disease (ACD) in cases of CHF [1,4,8].
The ACD is the second most frequent type of aneamia after asiderotic anemia (AA). According to diff erent sources this type of anemia is the most frequent among patients with the CHF and it is observed in cases of over than 50% patients [11,12]. Results of the latest researches proved that the basis of the ACD is an immune-mediated mechanism: imbalance of cytokine and reticuloendothelial system cell interaction causes disorders of iron homeostasis, proliferation of erythropoiesis precursors, erythropoietin production, and life time of erythrocytes [2,7,8]. Discovery of hepcidin -an acute-phase iron-regulating protein had a revolutionary signifi cance that proved connection between an immune mechanism of iron metabolism disorders and progress of the ACD [3,7,9].
Under the infl uence of infl ammatory stimuli (mainly IL6) in the liver enhancement of hepcidin synthesis occurs. It causes reduction in intestinal

CRUCIAL APPROACHES TO DIAGNOSTICS AND ANAEMIA TREATMENT IN PREGNANT WOMEN WITH HEART FAILURE AT THE EXTRAGENITAL PATHOLOGY CLINIC
absorption of iron and blocking iron release from macrophages. Disorder of iron metabolism regulation results in further insuffi ciency of available iron for the erythropoiesis precursors, reduction in proliferation of these cells due to an adverse eff ect of heme biosynthesis imbalance on them [2,4,6,8,10]. The necessity to manage iron defi ciency in pregnant women having cardiovascular diseases is absolutely reasonable, as iron participates in a great number of essential biochemical processes: oxygen transportation and storage (haemoglobin, myoglobin); participation in cell proliferation; participation in forming active centers of oxidation-reduction enzymes (oxidase, hydroxylase); electron transportation (cytochromes, ironserum proteides); generation of active forms of oxygen and ATP; iron transportation and storage (transferrin, ferritin, hemosiderin, chelating agents).
In addition, in experimental studies iron deficiency promoted progress of diastolic dysfunction of the left ventricle, its hypertropia, dilation, and fi brosis.
According to the foregoing we proved the following examination algorithm for pregnant women with heart diseases of various ethiology and NYHA II-III heart failure.
1. Clinical blood test (reduction in a haemoglobin level below the standard by trimesterstreatment of aneamia).
If the heamoglobin level remains within normal limits for a certain trimester but there have been observed signs of apparent heart failure, disorders of life qualities (dyspnea, undue fatiguability, cardiac pains), then the algorithm provides the following examination: 2. C-reactive protein (avoidance of the active phase of the infl ammatory process, mg/l).
3. Ferritin (μg/L). 4. Transferrin saturation (TSAT, %). 5. Brain natriuretic peptide (BNP, pg/ml). Let's provide a clinic example. A pregnant woman V., 24 years old, gestation period is 34 weeks, dilated cardiomyopathy, NYHA III. The clinical blood test shows the heamoglobin level of 106 g/l, SRP-5.6mg/l (norm), ferritin -98.6 μg/L, iron -6.38 mcmol/l (reduced level), transferring -4.3 g/l (increased level), TSAT -6%, BNP -108 pc/ml. As per recommendations of the European Society of Cardiology related toprenatal care and labour of women having cardiovascular pathology dated 2011 as a labour methodfor this patient it was chosen the Cesarean section due to low ejection fraction (32%). Taking into account common approaches to prevention and treatment of the asiderotic an-eamia, if in the third trimester the heamoglobin level is over 105 g/l, then treatment by means of ferruginous preparations is not recommended. At the same time the patient experienced reduction of ferritin level (< 100 μg/L) and transferrin saturation (< 20%), and she has a high level of heart failure biomarker (BNP > 100 pg/ml) that requires change in medications and prescription of ferruginous preparations under conditions of the scheduled abdominal labour with expected supra-physiological hemorrhage.
To correct the aneamic state it was chosen an iron polymaltose complex (Maltofer) in a dose of 1 tablet twice per day. A basis for choice of this preparation was its pharmacological advantages over ionic ferruginous preparations: an opportunity to combine administration with other preparations, avoidance of potential oxidative stress aggravation of the woman having heart failure. The therapy was started three weeks before the scheduled delivery and continued during the postoperative period. Within the postoperative period the heamoglobin level made 103 g/l, TSAT -25%, ferritin level -120 μg/L.
Let's provide another clinic example. A pregnant woman L., 20 years old, gestation period is 34 weeks, coarctation of aorta, the heart was operated in 1997, restenosis, NYHA of II degree. Clinical blood test: Hb -108 g/l, SRP -7.3 mg/l (norm), ferritin-99.1 μg/L (reduced level), iron -8.91 mcmole/l (reduced level), transferrin -4.1 g/l (norm), TSAT -8% (reduced level), BNP -118.6 pg/ml (increased level). Taking into consideration indices of the cardiac reserve as a delivery method it is chosen the Cesarean section. Based on data of the laboratory test, echocardiography parameters, aggravation of heart failure it was decided to carry out premature delivery on the term of 36 weeks. During two weeks before the surgical delivery and two weeks during the postoperative supervision the patient is prescribed Maltofer in a dose of 1 tablet twice per day. The postoperative period was smooth, the heamoglobin level was 102 g/l, TSAT -22%.
Let's provide the third clinical case. A pregnant woman А., 29 years old, gestation period is 22-23 weeks, CHD -Fallot's tetrad, the heart was operated in 1996, NYHA II. Clinical blood test: heamoglobin -105 g/l, SRP -4.6 g/l (norm), TSAT -19% (reduced level), BNP -94 pg/ml (norm). Taking into account that there is an indication for reduction of transferrin saturation it is recommended Maltofer therapy in a dose of 1 tablet twice per day with follow-up control of iron metabolism indices. In two weeks after the therapy had been started it was noted reduction of fatiguability, exertional dyspnea, in one month the heamoglobin level was 110 g/l, TSAT 22%. It should be noted that among 48 pregnant women having CHD of «acyanotic type» rate of asiderotic aneamia was 29.6%, their average heamoglobin level was 97.6 + 3.4 g/l. In this group the iron polymaltose complex was prescribed within therapeutic dosage for 2-3 months with further recommendations to take a maintenance dose. Neither of the women had complaints of the gastrointestinal tract, there were no cases of rejection of the therapy. An average improvement of heamoglobin indices was noted in 10.2  3.1 days, eff ect duration made 94.2 4.2 days.

DISCUSSION
It is required to note that aneamia is still the least understandble among a variety of comorbide states and complications of the CHF. However, there can be no doubt that this combination of aneamia and heart failure aggravates the prediction, increases a risk of severe «cardiac events», and perinatal complications. Overlap of aneamia and heart failure can cause a high risk of fetus growth inhibition, prematurity, a low-birthweight infant.
In 2009 it was published ameta-analysis of 20 clinical researches (97,699 patients) which confi rmed an actual level of aneamia availability with a high risk of fatal outcome in cases of HF. Moreover, these patients had worse exercise tolerance (NYHA III-IV) and lower ejection fraction of the left ventricle (LVOT) [3].
It is worth to analyze a review of 34 researches (153,180 patients having CHF). According to it, death rate of patients withaneamiawas 46.8% compared to 29.5% of patients who did not suffer from aneamia (р < 0.001) irrespective of a type of heart failure [9].
But it should be underlined that the research data mainly referred to groups of patients of elder age. Genesis of their heart failure diff ered from the one that had young patients. Researches in this sphere are to be continued. They will provide an opportunity to improve life quality and perinatal outcomes signifi cantly in the group of pregnant women having severe cardiovascular pathology.
Today due to a tendency towards unifi cation of medical care and standard orientation, eff ective recommendations are based on demonstrative researches of a particular time period. They are not able to predict uniqueness of the human organism, individual compensatory and adaptive reactions. Therefore it is required a scientifi c research, analysis of the «best practices», a translation approach to improvement of diagnostics and medical management, especially in groups of pregnant women having a high risk by maternal and perinatal complications...
Overlap of aneamia and heart failure can cause a high risk of fetus growth inhibition, prematurity, a low-birth-weight infant