Thrombotic storm, hemostasis disorders and thromboinflammation in COVID-19

The rate of thrombosis and disseminated intravascular coagulation (DIC) has been increasing in COVID-19 patients. Key features related to such condition include minimal or no risk of bleeding, moderate thrombocytopenia, high plasma fibrinogen as well as complement components level in the areas of thrombotic microangiopathy. The clinical picture is not typical for classic DIC. This review systematizes the pathogenetic mechanisms of hypercoagulation in sepsis and its extreme forms in patients with COVID-19. The latter consist of the thrombosis-related immune mechanisms, the complement activation, the macrophage activation syndrome, the formation of antiphospholipid antibodies, the hyperferritinemia, and the dysregulation of the renin-angiotensin system. Taking into consideration the pathogenetic mechanisms, the biomarkers had been identified related to the prognosis of the disease development. Patients with pre-existing cardiovascular disease and other risk factors, including obesity, diabetes, hypertension, and aging pose the peak risk of dying from COVID-19. We also summarize new data on platelet and endothelial dysfunction, immunothrombosis, and, as a result, thrombotic storm as essential components of COVID-19 severe features

Pathogenetically differentiated management of pregnancy in patients with retrochorial hematoma

Introduction. Intrauterine hematomas commonly found in routine ultrasound examinations represent one of causes resulting in early pregnancy loss. The most common is retrochorial hematoma resulting from fetal egg detachment from the uterine wall. Retrochorial hematoma often leads to pregnancy complications and affects gestational process.Aim: to develop a personalized approach to the diagnosis, prevention and management of pregnancy with retrochorial hematomas in the early stages.Materials and methods. A prospective examination of 70 females, aged 22 to 37 years old, with retrochorial hematoma was performed at gestational age ranging from 5 to 12 weeks. Here, we examined serum level for lupus anticoagulant, antiphospholipid antibodies (AFA), antibodies to cardiolipin, fi2-glycoprotein I, to annexin V and prothrombin, and ADAMTS-13. All women were examined for genetic mutations linked to high thrombogenic risk and low thrombogenic risk polymorphisms. Patients were also examined for urinary tract infections.Results. It was found that 43 (61 %) females had aggravated obstetric anamnesis (non-developing pregnancy, spontaneous miscarriage in early stages, antenatal fetal death), whereas 13 (18.5 %) subjects had burdened familial thrombotic history (heart attack, stroke, and thrombosis occurred before the age of 55 years in first-line relatives). In addition, 22 (31.4 %) females were found to have genetic and acquired forms of thrombophilia; 6 (8.5 %) were detected to have circulatory ADAMTS-13 inhibitor; 5 females were confirmed to have decreased blood coagulation factor activity; and 38 (54.2 %) had vaginal dysbiosis.Conclusion. Our work demonstrates that a personified and pathogenetically differentiated algorithm for diagnostics and management of pregnant women with chorionic detachments in early stages allows to lower frequency of early abortions and increases the therapeutic effectiveness

ASSISTED REPRODUCTIVE TECHNOLOGY AND ANTIPHOSPHOLIPID SYNDROME

The antiphospholipid antibodies (APA) exert multiple effects on the hemostasis system causing damage to all of its protective components including the endothelial barrier, natural anticoagulant function and endogenous fibrinolysis and activating the platelet phase of hemostasis, which is associated with numerous obstetrical complications andinfertility. The question is, what is the frequency of circulating APA in women who underwent IVF failure and whether there is a relationship between the presence of APA and poor reproduction outcome? This study aimed at elucidating the effect of the presence of APA on the outcomes of assisted reproductive technology (ART). A total of 267 women diagnosed with infertility and planning to get pregnant using the assisted reproductive technology (ART) have been examined. The results of examination demonstrated a high prevalence of circulating APA in a group of women who underwent IVF failure. High titers of APA were found in 42.1% of female patients who had undergone IVF failure. The fraction of women in whom fertility treatment using ART succeeded was 19.1%

Management of pregnancy and labor in female with combination of homozygous Leiden and heterozygous prothrombin G20210A mutations

Here we describe a clinical case of successfully managed pregnancy and labor in female with multigenic thrombophilia (combination of homozygous Leiden and heterozygous prothrombin G20210A mutations) associated with high risk of thrombosis by using proper anticoagulant therapy. It was underlined that females with obstetric complications should be examined for inherited and acquired types of thrombophilia

Treatment of postmenopausal vulvovaginal atrophy with estriol: a scientific update for 2014–2018

Due to the increase in life expectancy, today, most women live in a state of estrogen deficiency for more than a third of their life time. According to the recent document on the stages of aging of the female reproductive system (the STRAW+10 working group), there are three main stages that include the reproductive period, the menopausal transition, and postmenopause. One of the most common manifestations of postmenopause is vulvovaginal atrophy or genitourinary syndrome, which leads to a dramatic decrease in the woman’s quality of life. Up to 45 % of postmenopausal women suffer from this disorder, and 80 % of them experience a negative impact on their quality of life. The main symptoms of vulvovaginal atrophy are dryness, itching, burning, and dyspareunia. Caution must be exercised in relation to “silent” atrophy, which is not manifested by subjective complaints of vaginal mucosa atrophy, and can only be visualized by colposcopy. According to the recommendations of the International Menopause Society (IMS), updated in 2016, therapy should be started before the atrophic changes become irreversible; the treatment should continue for a long time to maintain the achieved therapeutic effect. If no symptoms other than vulvovaginal atrophy are noted, local estrogen therapy is indicated. Estriol has advantages over other medications due to its lower affinity for estrogen receptors. In earlier studies as well as those updated here (2014–2018), estriol applied topically as a vaginal cream or vaginal suppositories, has a selective effect on the urogenital tract and practically does not interfere with the proliferation of the uterine endometrium. The confirmed efficacy and safety of estriol allow for its permanent use, beginning with the starting dose and then switching to the maintenance one

Efficacy and safety of glucosaminylmuramyl dipeptide in treatment of human papillomavirus-associated diseases: a systematic review

Introduction. Human papillomavirus infection (HPV-infection) remains one of the most important health problems as it significantly reduces the quality of life and stigmatizes the patients. Also, the prevalence of cervical cancer – the most severe outcome of the HPV-infection is 5 % of the global burden of cancer. Although vaccination against human papillomavirus has been proved efficient, its availability in Russia continues to be limited. Therefore, it is important to review other methods of HPV-infection control. A number of studies have confirmed the efficacy of glucosaminylmuramyl dipeptide (GMDP) in the treatment of diseases associated with HPV-infection, but no systematic evaluation of these studies has been published in the available literature.Aim: to analyze the data on the efficacy and safety of GMDP in the treatment of diseases and conditions associated with HPVinfection.Materials and methods. We used the PRISMA approach. The search for the relevant publications was conducted in international scientific databases: the Scientific Electronic Library, the Google Scholar, the ScienceDirect, the Cochrane Community Library, the Pubmed/MEDLINE, and clinical research registries. For this systematic analysis, only full-text publications were used. We evaluated the reliability of evidence and the methodological quality of the studies.Results. We used the following search queries: "glucosaminyl-muramyl dipeptide", "glucosamine L'muramyl dipeptide", "H-acetylglucosaminyl-H-acetylmuramyl dipeptide", "GMDP", "Licopid" (both in Russian and English transcriptions). Based on the results of the screening, 14 full-text publications were selected. At the final stage, review articles with secondary data were excluded; also excluded were original articles published in doubtful resources and those with an unclear status of peer reviewing. This systematic analysis includes 7 publications of acceptable methodological quality. Here, we summarize the consistent conclusions derived from these reports: the addition of therapy with GMDP to local (surgical) methods increases the efficacy of treatment and the duration of remission; destruction of condylomas is more effective when combined with the course of GMDP as compared to using the local destruction alone; GMDP enhances the production of cytokines that have a direct antiviral and antiproliferative effect in HPV-infection (interleukin-1, tumor necrosis factor alpha, gamma-interferon); GMDP causes normalization of cellular and humoral immunity (T-lymphocytes, T-cytotoxic lymphocytes, B-lymphocytes, CD3+, CD4+, CD8+, CD16+, and CD72+ lymphocytes, as well as the production of serum immunoglobulins IgA, IgG, and IgM). A high safety profile of GMDP is evidenced from the absence of reports on adverse events.Discussion. The recommendation for the inclusion of GMDP into a comprehensive treatment for HPV-infection in addition to local interventions is a strong recommendation. The differences between the Russian and international approaches can be explained by the difference in the available resources and funding. We propose to test whether using GMDP for reducing the risk of recurrent HPV-infection is beneficial in terms of pharmacoeconomics. Conclusion. The high efficacy and safety of GMDP in the combined therapy of HPV-infection has been confirmed. Further carefully designed studies on GMDP are needed

Clinical and hemostatic characteristics of women with menopausal syndrome receiving the «Extra youth» dietary supplement

Aim: to study the clinical and hemostatic changes in women with menopausal syndrome (MS), receiving the dietary supplement Doctor sea «Extra youth» (EY), containing hydrolyzed caviar of sea urchins, calcium alginate and rosehip extract. Materials and methods. The study involved 60 women with MS aged 45–55 years. The patients were divided into 2 groups: the main group consisted of 30 women who received the EY supplement, the comparison group – 30 women who received no EY. During the study, women in the main group received two EY capsules twice a day for 1 month. The severity of the menopausal symptoms and the characteristics of hemostasis before and after taking the EY were evaluated. Results. After 1 month on the EY, the menopausal symptoms (hot flashes, sweating, heart palpitations, nervousness, fatigue) alleviated, general well-being improved, and a better hemostatic performance occurred (chronometric and structural hypercoagulation, a decrease in platelet aggregation and the D-dimer level). Conclusion. The dietary supplement EY can be recommended for use in general clinical practice as a means to improve the well-being of women in pre- and post-menopausal period and also to prevent thrombotic complications

Disseminated intravascular coagulation in perinatal medicine

Introduction. Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by intravascular activation of blood clotting without specific localization and arising from various causes. DIC is the most complex and high-priority problem in contemporary clinical medicine including obstetrics and perinatology. DIC significance is related to its peak perinatal mortality, as well as a large rate of complications during childbirth and postpartum period.Aim: to conduct comprehensive data assessment related to DIC pathogenesis and management in pregnant women and newborns.Materials and methods. A search for DIC-related publications within the past 10 years was conducted in international research databases: Scientific Electronic Library Online eLibrary, Google Scholar, ScienceDirect, Cochrane Library, PubMed/Medline. The data regarding DIC diagnostic criteria and markers, as well as current approach to its treatment are presented.Results. DIC may be considered as one of the causes resulting in massive obstetric bleeding. The majority of pregnancy-related complications is manifested as preeclampsia, premature detachment of normally situated placenta and anaphylactoid syndrome of pregnancy. Any massive bleeding should be perceived as hemorrhage resulting from the DIC progression.Conclusion. Knowledge of the DIC pathogenetic mechanisms is necessary for conducting a differential diagnosis and applying timely treatment

THE PATHOGENETIC BASIS FOR USING NATURAL PROGESTERONE THERAPY IN OBSTETRIC PRACTICE

Progesterone is a natural female hormone. Called “the pregnancy hormone,” it is essential before and during pregnancy. After ovulation occurs, the ovaries start to produce progesterone needed by the uterus. Progesterone causes the uterine lining or endometrium to thicken. This helps prepare a supportive environment in your uterus for a fertilized egg.A supply of progesterone to the endometrium continues to be important during pregnancy. Following a successful implantation, progesterone helps maintain a supportive environment for the developing fetus