Pathological Bleeding Research Articles

Factor XI/XIa Inhibitors: A New Approach to Anticoagulation.

For more than 60 years, anticoagulation drugs have served as a mainstay in preserving and improving the cardiovascular health of patients across the globe. Functioning to reduce a patient's ability to produce blood clots, prescription rates for anticoagulants have been steadily rising year-over-year both in the United States and abroad. Despite decades of clinical usage, modern-day anticoagulants have been shown to predispose an individual to pathological bleeding. Even in seemingly benign instances of bleeding, patients on anticoagulation therapy might require intensive and expensive medical procedures or monitoring. Understanding the clinical implications of pathological bleeding, research and development of future anticoagulants seeking to minimize these effects. One emerging category of anticoagulant drugs are Factor XI/XIa (FXI) inhibitors. Targeting the coagulation cascade, clinical trials of Factor XIa inhibitors have shown promising results in preventing blood clot formation without increasing the instances of spontaneous and/or pathological bleeding events. While still in phase II and III clinical trials, and potentially years away from being implemented as standard of care, these novel drugs might have the potential to improve the safety and quality of life of patients taking anticoagulants. In this review, we discuss a brief history of anticoagulation therapy, followed by an analysis of the potential risks, benefits, and implications of Factor XI/XIa inhibitors across elements of patient care.

Prothrombin consumption as an indicator of hemorrhagic phenotype in mild platelet function disorders.

The bleeding risk of patients with mild platelet function disorders is difficult to assess and their phenotype remains ill-explored. This study was designed to establish a comprehensive biological phenotype of patients with mild platelet function disorders. Twenty patients were included with persistent abnormal light transmission aggregometry (LTA). The ISTH bleeding assessment tool (ISTH-BAT) was assessed to identify laboratory analyses associated with an abnormal hemorrhagic score. The majority of patients had defects that might affect Gαi protein signaling pathways or minor abnormalities. No LTA nor flow cytometry parameters were associated with an above-normal hemorrhagic score. However, prothrombin consumption, which corresponds to the ratio of serum residual factor II to plasma residual factor II, was significantly higher (p = .006) in the abnormal ISTH-BAT group (mean = 14%, SD = 6) compared with the normal ISTH-BAT group (mean = 8%, SD 4). Prothrombin consumption was significantly associated with ISTH-BAT score (r = .5287, IC 95% 0.0986-0.7924, p = .0165). In this group of patients, there was an association between a pathological bleeding score and increased prothrombin consumption. This test could be used as an additional indicator of platelet function abnormality liable to be related to bleeding risk.

VHrare study: Prevalence, clinical features and management of severe rare bleeding disorders in a large cohort.

Rare bleeding disorders (RBD) constitute 5% of total hereditary bleeding disorders, although the number could be higher, due to the presence of undiagnosed asymptomatic patients. The objective of this study was to analyze the prevalence and characteristics of patients with severe RBDs in our area. We analyzed the patients with RBD followed at a tertiary-level hospital between January 2014 and December 2021. A total of 101 patients were analyzed, with a median age at diagnosis of 27.67 years (range 0-89), of which 52.47% were male. The most frequent RBD in our population was FVII deficiency. Regarding the diagnostic reason, the most frequent cause was a preoperative test and only 14.8% reported bleeding symptoms at the time of diagnosis. A genetic study was carried out in 63.36% of patients and the most frequent mutation type found was finding a missense mutation. The distribution of RBDs in our centre is similar to the one reported in the literature. The majority of RBDs were diagnosed from a preoperative test and this allowed preventive treatment prior to invasive procedures to avoid bleeding complications. 83% of patients did not have a pathological bleeding phenotype according to ISTH-BAT.

Bleeding in neonates with severe thrombocytopenia: a retrospective cohort study

BackgroundSevere neonatal thrombocytopenia is a rare disease with multiple etiologies. Severe thrombocytopenia with bleeding is life-threatening and has attracted significant attention from clinicians. However, only a few studies have focused on the association between severe thrombocytopenia and bleeding. Thus, this study aimed to describe the neonates’ postnatal age at which severe thrombocytopenia was first recognized, clinical characteristics, bleeding patterns, and outcomes and to evaluate the association between minimum platelet count and bleeding.MethodsA single-center retrospective cohort study for neonates with severe thrombocytopenia (platelet count ≤ 50 × 109/L) was conducted. Neonates who were admitted to our neonatal intensive care unit between October 2016 and February 2021 and developed severe thrombocytopenia were analyzed. Data were collected retrospectively until the patients were referred to other hospitals, discharged, or deceased.ResultsAmong the 5819 neonatal inpatients, 170 with severe thrombocytopenia were included in this study. More than 30% of the patients had severe thrombocytopenia in the first 3 days of life. Among the 118 neonates with bleeding, 47 had more than one type of pathological bleeding. Neonates with very severe thrombocytopenia (point estimate: 53.7%, 95% confidence interval [CI]: 44.2%–63.1%) had a higher incidence rate of cutaneous bleeding than those with severe thrombocytopenia (point estimate: 23.4%, 95% CI: 12.3%–34.4%). The gestational age (median: 36.2 [interquartile range [IQR]: 31.4–39.0] weeks) and birth weight (median: 2310 [IQR: 1213–3210] g) of the major bleeding group were the lowest among no bleeding, minor bleeding, and major bleeding groups. Regression analysis controlled for confounders and confirmed that a lower platelet count (odds ratio [OR]: 2.504 [95% CI: 1.180–5.314], P = 0.017) was associated with a significant increase in the rate of bleeding. Very severe thrombocytopenia (point estimate: 49.1%, 95% CI: 39.6%–58.6%) had a higher rate of platelet transfusion than severe thrombocytopenia (point estimate: 5.7%, 95% CI: 0.7%–10.7%). The mortality rate was higher in neonates with bleeding than in those without bleeding (point estimates with 95% CI: 33.1% [24.4%–41.7%] vs. 7.7% [0.2%–15.2%]).ConclusionsThese findings describe the incidence of severe thrombocytopenia and demonstrate that a lower platelet count is associated with an increased bleeding rate in patients with severe thrombocytopenia.

Adipose Triglyceride Lipase Deficiency Attenuates In Vitro Thrombus Formation without Affecting Platelet Activation and Bleeding In Vivo.

According to genome-wide RNA sequencing data from human and mouse platelets, adipose triglyceride lipase (ATGL), the main lipase catalyzing triglyceride (TG) hydrolysis in cytosolic lipid droplets (LD) at neutral pH, is expressed in platelets. Currently, it is elusive to whether common lipolytic enzymes are involved in the degradation of TG in platelets. Since the consequences of ATGL deficiency in platelets are unknown, we used whole-body and platelet-specific (plat)Atgl-deficient (−/−) mice to investigate the loss of ATGL on platelet function. Our results showed that platelets accumulate only a few LD due to lack of ATGL. Stimulation with platelet-activating agonists resulted in comparable platelet activation in Atgl−/−, platAtgl−/−, and wild-type mice. Measurement of mitochondrial respiration revealed a decreased oxygen consumption rate in platelets from Atgl−/− but not from platAtgl−/− mice. Of note, global loss of ATGL was associated with an anti-thrombogenic phenotype, which was evident by reduced thrombus formation in collagen-coated channels in vitro despite unchanged bleeding and occlusion times in vivo. We conclude that genetic deletion of ATGL affects collagen-induced thrombosis without pathological bleeding and platelet activation.

ОСОБЛИВОСТІ ПЕРЕБІГУ ВАГІТНОСТІ ТА РОЗРОДЖЕННЯ ЖІНОК З ЕКСТРАКОРПОРАЛЬНИМ ЗАПЛІДНЕННЯМ З ГРУПИ ВИСОКОГО РИЗИКУ ПО ВИНИКНЕННЮ ПЕРЕДЧАСНИХ ПОЛОГІВ

The article is a part of the research project at the Department of Obstetrics and Gynecology No.2 of Higher Education Institution Poltava State Medical University "The role of chronic infection of the uterus and lower genital tract in the formation of obstetric and gynecological pathology" (state registration No. 0117U005276, implementation period 2017-2022). In modern reproductive medicine, infertility in marriage is considered a problem of particular importance. That is why modern assisted reproductive technologies are chosen as a method of treatment for many married couples, and their increased application necessitates intensive monitoring of the course of pregnancy and delivery. Pregnant women after in vitro fertilization programs are at high risk of miscarriage and preterm birth. The aim of the research was to study the features of pregnancy, childbirth and the condition of newborns in women after in vitro fertilization, which are classified as high risk for preterm birth. Women were included in the study at 18-20 weeks 6 days of pregnancy. We examined 85 women who became pregnant after in vitro fertilization (study group A: 37 pregnant women who refused preventive treatment and received medications in accordance with regulations; study group B: 48 pregnant women who have received the proposed treatment since their inclusion in the study. The control group included 20 apparently healthy pregnant women with its natural pregnancy onset. In pregnant women of study group A, pregnancies ended in premature birth by 1.7 times more often, and most of them occurred before 34 weeks; during pregnancy, there was a greater risk of preterm birth, which required enhanced correction in addition to conservative measures: suturing the cervix and the use of obstetric unloading pessary; the frequency of delivery by cesarean section prevailed by 1.3 times. Moreover, only in this group, pathological bleeding was observed, surgery was performed and perinatal mortality was recorded. Pregnant women who agreed to preventive treatment developed fewer preterm births after 34 weeks. Complications of pregnancy and childbirth were much less common in these women. Surgical intervention in childbirth and the frequency of delivery by cesarean section were also much less common.

Viscoelastic tests in liver disease: where do we stand now?

Hemostasis is a complex physiological process based on the balance between pro-coagulant and anticoagulant systems to avoid pathological bleeding or thrombosis. The changes in standard coagulation tests in liver disease were assumed to reflect an acquired bleeding disorder, and cirrhotic patients were considered naturally anticoagulated. In the light of the new evidence, the theory of rebalanced hemostasis replaced the old concept. According to this model, the hemostatic alteration leads to a unique balance between pro-coagulant, anticoagulant, and fibrinolytic systems. But the balance is fragile and may prone to bleeding or thrombosis depending on various risk factors. The standard coagulation tests [INR (international normalized ratio), platelet count and fibrinogen] only explore parts of the hemostasis, not offering an entire image of the process. Rotational thromboelastometry (ROTEM) and thromboelastography (TEG) are both point of care viscoelastic tests (VET) that provide real-time and dynamic information about the entire hemostasis process, including clot initiation (thrombin generation), clot kinetics, clot strength, and clot stability (lysis). Despite prolonged PT/INR (international normalized ratio of prothrombin time) and low platelet counts, VET is within the normal range in many patients with both acute and chronic liver disease. However, bleeding remains the dominant clinical issue in patients with liver diseases, especially when invasive interventions are required. VET has been shown to asses more appropriately the risk of bleeding than conventional laboratory tests, leading to decrial use of blood products transfusion. Inappropriate clotting is common but often subtle and may be challenging to predict even with the help of VET. Although VET has shown its benefit, more studies are needed to establish cut-off values for TEG and ROTEM in these populations and standardization of transfusion guidelines before invasive interventions in cirrhotic patients/orthotopic liver transplantation.

ОЦЕНКА ЧУВСТВИТЕЛЬНОСТИ И СПЕЦИФИЧНОСТИ ДЕТСКОГО ОПРОСНИКА КРОВОТОЧИВОСТИ ПРИ РАЗЛИЧНЫХ ГЕМОРРАГИЧЕСКИХ ЗАБОЛЕВАНИЯХ

Determination of significant bleeding in the anamnesis is quite difficult, since mild mucocutaneous bleeding can occur both in patients with hereditary bleeding disorders and in healthy people. As a result, there is a growing interest among researchers and clinicians in accurate and objective quantification of hemorrhage symptoms. Objective of the study: to evaluate the effectiveness of the Pediatric bleeding questionnaire as a tool for identifying a group of children requiring further laboratory examination. Materials and methods of research: the study was a retrospective, uncontrolled, comparative, nonrandomized, single-center study. Based on the analysis of the database of the Consultive department of the Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology from January 2017 to December 2019, out of the total number of visits to doctors, patients under 18 years old who complained of increased bleeding were selected. The manifestations of hemorrhagic syndrome were evaluated using the pediatric bleeding scale – PBQ (Pediatric Bleeding Questionnaire), followed by a series of laboratory examinations to verify the diagnosis in all children. The sensitivity and specificity of this questionnaire was assessed at various threshold values using the ROC AUC curve, and a comparison of the scores on the scale in patients with different nosologies was made. Results: the study included 346 people, 174 were diagnosed, 172 had no data for coagulopathy/thrombocytopathy found – the patients were considered healthy. The discriminatory ability of the scale under study, studied using the ROC-AUC, was 0,815 (95% CI 0,772–0,858) – satisfactory. With a threshold value of pathological bleeding of 2 points, the sensitivity of the method was 98%, specificity – 12%. The best ratio of sensitivity and specificity (69% and 79%, respectively) was achieved when the threshold value was increased to 4 points. Conclusion: this questionnaire is a convenient addition, with the help of which it is easy to collect a history of bleeding, to assess the severity of bleeding, but it cannot be used as a screening method due to the large number of falsepositive results.

Byzantine Healing Amulets from Southwestern Crimea

Introduction. The article presents two unique items from the Southwestern Crimea – a bronze finger ring with an image of a lion-headed serpent Chnoubis, originating from a female burial of the first quarter of the 7 th century of the Gothic-Alanian burial ground near the village of Luchistoye, and a bronze medallion, which was found in the area of the village of Goncharnoye, with magic signs, formulas and an image of Chnoubis, which is tied to an altar, fighting a snake. Methods. According to some similar findings from the territory of the Eastern Roman Empire, the ring and the medallion are attributed to the group of Byzantine medical amulets. The amulets of the Early Byzantine time demonstrate continuity with pre-Christian magical practices, therefore, late ancient magical gems and texts were involved to decipher the plots and inscriptions engraved on those amulets. Analysis. The finger ring was intended to improve digestion and to treat diseases of a digestive tract. The woman who owned the item was wearing it in a chest necklace, at the level of her stomach – just as it was recommended in medical treatises to wear amulets for abdominal pain. The medallion was a complex amulet intended for women. Chnoubis in the scene of fighting the snake and the spell ÐÉÍÏ are depicted on both sides of the medallion. In one case, Chnoubis is a guardian of a stomach and a fighter against diseases of the digestive tract, whose actions are enhanced by the three times repeated spell ÐÉÍÏ, which contributes to better digestion. In the second case, Chnoubis is a defender of women’s health, and the disappearing word ÐÉÍÏ should help stop pathological uterine bleeding. The action of the amulet is enhanced by a formula against demons that cause disease, and its healing properties are confirmed by the inscription ÕÃÉÁ (health). Such an amulet should be worn suspended from the neck by a long cord, or fastened to the belt. Results. Both items belong to the group of medical magic amulets. They were brought from the Eastern Mediterranean provinces of the Empire, where in the 6th – 7th centuries there were magic amulets similar in form and repertoire of protective means. The appearance of such items among the Gothic-Alanian population of the Southwestern Crimea is not surprising. The influence of the Byzantine civilization on all aspects of the life of the local population in the Early Middle Ages can be traced both from written sources and from numerous archaeological findings.

Bleeding of unknown cause and unclassified bleeding disorders; diagnosis, pathophysiology and management.

Bleeding of unknown cause (BUC), also known as unclassified bleeding disorders (UBD), has been defined as a clear bleeding tendency in the presence of normal haemostatic tests. There are challenges in the diagnosis and management of these patients. BUC/UBD encompasses a heterogenous group of disorders which may include undiagnosed rare monogenic diseases, polygenic reasons for bleeding; and patients without a clear bleeding disorder but with a previous bleeding event. Nevertheless, these patients may have heavy menstrual bleeding or be at risk of bleeding when undergoing surgical procedures, or childbirth; optimizing haemostasis and establishing a mode of inheritance is important to minimize morbidity. The bleeding score has been used to clinically assess and describe these patients, but its value remains uncertain. In addition, accurate distinction between normal and pathological bleeding remains difficult. Several studies have investigated cohorts of these patients using research haemostasis tests, including thrombin generation and fibrinolytic assays, yet no clear characteristics have consistently emerged. Thus far, detailed genetic analysis of these patients has not been fruitful in unravelling the cause of bleeding. There is a need for standardization of diagnosis and management guidelines for these patients. This review gives an overview of this field with some suggestions for future research.

Assessment of the impact of sodium and potassium metabolism in women undergoing hysteroscopy due to pathological uterine bleeding

Assessment of the impact of sodium and potassium metabolism in women undergoing hysteroscopy due to pathological uterine bleeding

P0086FOCAL SEGMENTAL GLOMERULOSCLEROSIS AND TROMBOCYTOPENIA WITHOUT BLEEDING DIATHESIS: WHEN GENETICS MATTER

Abstract Background and Aims A 45-year old patient presented to our renal unit because of increased serum creatinine (2 mg/dL), proteinuria (2g/24h collection) and haematuria; platelets were 12000/mcL. His family history was negative. He had already undergone cataract surgery and was wearing a hearing device. Alport syndrome was suspected and kidney biopsy performed. Light microscopy showed focal segmental glomerulosclerosis (FSGS), while immunofluorescence was negative. Electron microscopy was not available. No specific treatment was undertaken and he progressed to end-stage renal disease (ESRD) in 10 years. The patient chose peritoneal dialysis. He was considered at high risk of bleeding but the Tenchkoff catheter was inserted without problems. After 3 months he received kidney transplant and again no pathological bleeding occurred. Method A genetic test was requested using next generation sequencing (NGS). Results A mutation of myosin heavy chain 9 (MYH9) gene which encodes the non-muscle myosin heavy chain-IIA (NMMH-IIA) was found. This mutation is associated with thrombocytopenia and proteinuria; platelets are giant and display normal aggregation, even in those patients who have a very low count. Proteinuria can be mild or in the nephrotic range, with or without microhaematuria. Kidney involvement is highly heterogeneous and leads to ESRD in half of the cases. Light microscopy shows FSGS as the prevalent pattern whereas electron microscopy is characterized by podocyte foot process effacement. In fact, NMMH-IIA is expressed in podocytes and controls cytoskeleton and cell migration. The differential diagnosis with Alport disease is challenging because additional features of MYH9 mutation are sensorineural deafness and pre-senile cataract. For all these reasons, accurate kidney biopsy study, family history and genetics are decisive. Conclusion Genetic testing has a pivotal role in understanding kidney diseases and should be more and more used.

Assessment of routine diet (garlic consumption) as a pre- and postoperative protocol in oral and maxillofacial surgical interventions: An evidence-based literature review.

It was hypothesized that pathological bleeding (PB) during and/or after oral surgical procedures is higher in systemically healthy patients who have a history of garlic intake compared to controls (patients without a history of garlic consumption). The aim of the present review article was to identify studies in which garlic consumption was included as a patient management protocol before and after oral and maxillofacial surgery (OMFS). A review of pertinent indexed literature was performed. The focused question that was addressed was "Has diet (garlic consumption) been considered as a patient management protocol before and after OMFS?" The inclusion criteria were: (a) studies published in indexed databases, (b) original studies, (c) studies on OMFS, and (d) studies that considered diet (garlic consumption) as a patient management protocol before and after OMFS. Literature review, commentaries, letters to the editor, and studies published in non-indexed resources were excluded. The pattern of the present review was customized to summarize the pertinent information. The initial search using the terms "oral," maxillofacial," "protocol," and "surgery" yielded 1478 studies. The addition of the term "diet" to this search strategy reduced the number of studies to five. Further filtration of these studies using the terms "garlic" and/or "Allium sativum" showed no studies. Garlic intake predisposes patients to PB. However, there are no studies in the indexed literature that have considered the inclusion of garlic consumption in patient management protocols before and after OMFS.

Klinički značaj primene rotacione tromboelastometrije u detekciji poremećaja hemostaze

Hemostasis represents an equilibrium between procoagulant and anticoagulant processes, but once this balance is shifted to one side, it leads to coagulopathy presented by pathological bleeding or thrombosis. Many conditions could cause coagulopathy. The most common are sepsis, severe traumas and malignancies. Widely used conventional coagulation tests (CCTs), focused only on clot initiation, are primary used to detect hypocoagulability. Viscoelastographic tests (VET), like rotational thromboelastometry (ROTEM), can detect problems in different stages of coagulation, from initiation thought clot elongation and propagation, to the clot lysis and might reveal both, hypercoagulability and hypocoagulability. Rotational thromboelastometry have gained popularity in the care of patients with TIC, as a tool to guide transfusion support. Nowadays it is widely used in other medical specialties, as well. Several studies in septic patients pointed out hypocoagulable ROTEM pattern as a predictor of poor prognosis. Additionally, there is great interest of ROTEM usage in malignancies, although limited research is currently available. It suggests ROTEM have the ability to identify a patient in high risk of thrombosis. Further investigation trough randomized studies is needed to confirm ROTEM utility and to help in making a consensus about its use in different medical occasions.

Indications for increase in caesarean delivery

BackgroundThe increasing caesarean delivery rate worldwide is followed by increased maternal morbidity due to pathological placentation, peripartum hysterectomy and obstetric bleeding. The aim of this study was to investigate the indications for caesarean delivery.Study designA retrospective observational study. Data were retrieved from the Swedish Pregnancy Register and obstetric records at a tertiary hospital in Sweden between the early 1990s and 2015.ResultsCaesarean delivery in Sweden increased from 10% in the early 1990s to 17% in 2015 concomitantly with decreased instrumental delivery and increased labour induction. Most planned caesareans at the tertiary hospital were performed on maternal request with a rate increasing from 0.6 to 4.6% of all deliveries (p < 0.001), and 60% of these women reported secondary fear of vaginal delivery. The second most common indication previous uterine scar increased from 1.2 to 2.3% (p < 0.001). Most urgent caesareans in 2015 were carried out because of prolonged labour with the rate increasing from 2.1% to 5.4% of all deliveries (p < 0.001). The second most common indication was imminent fetal asphyxia which increased from 2.4 to 2.6% (p < 0.01).ConclusionsThe Swedish caesarean delivery rate increased concomitantly with a decrease in instrumental delivery and an increase in labour induction. Most of the planned caesareans were performed on maternal request and most of the urgent caesareans were carried out because of prolonged labour. These findings emphasise the importance of standardised definitions of maternal request and follow-up after a negative birth experience, as well as adequate definitions of prolonged labour and foetal asphyxia to decrease unnecessary caesareans.

Mutation Awareness of von Willebrand&amp;#39;s Disease in Medical and Genetic Differences Screening: A Systematic Review

There were hospitalized patients diagnosed with Von Willebrand disorders (vWD) in this population medical base study. PubMed search bibliographies extracted applicable studies. Ten studies of 3296 patients diagnosed with vWD have been included in numerous research orders, ranging from 29.7% to 100%. The overall prevalence turned was 83.7% (95% CI 29.7-100%). The prevalence was 99.7 % (95 percent CI 99.3-100 %) higher in African and French research studies compared to 29.7% in America. This variation was pleasing to be as the results of different in these studies, which included the recruitment approach to population evaluation methods, blood loss, ethnic composition, and vWD mutation screening techniques criteria. The objective of this systematic review research was to evaluate the techniques of vWD mutation&amp;#39;s screening. The mutation screening and its separate subtypes became a recommendation to use next - generation sequencing (NGS) and multiplex ligation - dependent probe amplification (MLPA) across the globe to check for analytical techniques that needed to be considered specifically for those of Caucasian origin and those with no obvious signs of pathological bleeding

Efficacy of iron sulfate with ascorbic acid in pregnant women with iron deficiency of varying degrees of severity

Iron deficiency anemia (IDA) is one of the most common diseases in the world, characterized by hemoglobin synthesis disorder due to iron deficiency and manifested by anemia. According to WHO, the rate of IDA in pregnant women in different countries ranges from 21 to 80%, judging by the level of hemoglobin, and from 49 to 99% - by serum iron. Lack of treatment of iron-deficient pregnant women with varying degrees of iron deficiency leads to an increase in the frequency of complicated pregnancy, such as the threat of termination of pregnancy, placental insufficiency, delay in intrauterine development and hypoxia of the fetus, premature delivery, poor uterine contraction strength, pathological bleeding, infectious complications. Aim of the study: study of the efficacy of the drug containing iron sulfate (Ferrous sulfate) and ascorbic acid in pregnant women with latent and manifest forms of iron deficiency. Patients and methods: 66 pregnant women were examined. Group 1 consisted of 36 pregnant women with latent iron deficiency, Group 2–30 pregnant women with manifest iron deficiency and moderate anemia. Pregnant women in the 1st group were prescribed the drug only for 1 month due to the fact that there were no manifestations of anemia in this category of patients. Blood parameters were monitored dynamically after 1 month of treatment and after 2 months, which means after 1 month of absence of the drug intake. Patients of the 2nd group received treatment during 2 months, dynamic treatment after laboratory parameters was carried out after 1 and 2 months of treatment. Results of the study. Analyzing the data obtained, it was found that all laboratory parameters differ significantly from those before treatment. Pregnant women of the 1st group have no reliable changes between the parameters after 1 and 2 months of observations, as during this period the patients did not receive iron medication. And even a slight decrease in some indicators is noted, but when compared with laboratory data before treatment, the results differ significantly. Conclusion: Ferrous sulfate and ascorbic acid can be recommended to compensate iron deficiency in pregnant women with LID to prevent the development of anemia, in patients with MID to treat anemia and prevent the development of possible complications in pregnant women associated with this condition. Thus, earlier detection and elimination of LID leads to prevention of anemia later on.

Enzymatically oxidized phospholipids restore thrombin generation in coagulation factor deficiencies.

Hemostatic defects are treated using coagulation factors; however, clot formation also requires a procoagulant phospholipid (PL) surface. Here, we show that innate immune cell–derived enzymatically oxidized phospholipids (eoxPL) termed hydroxyeicosatetraenoic acid–phospholipids (HETE-PLs) restore hemostasis in human and murine conditions of pathological bleeding. HETE-PLs abolished blood loss in murine hemophilia A and enhanced coagulation in factor VIII- (FVIII-), FIX-, and FX-deficient human plasma . HETE-PLs were decreased in platelets from patients after cardiopulmonary bypass (CPB). To explore molecular mechanisms, the ability of eoxPL to stimulate individual isolated coagulation factor/cofactor complexes was tested in vitro. Extrinsic tenase (FVIIa/tissue factor [TF]), intrinsic tenase (FVIIIa/FIXa), and prothrombinase (FVa/FXa) all were enhanced by both HETE-PEs and HETE-PCs, suggesting a common mechanism involving the fatty acid moiety. In plasma, 9-, 15-, and 12-HETE-PLs were more effective than 5-, 11-, or 8-HETE-PLs, indicating positional isomer specificity. Coagulation was enhanced at lower lipid/factor ratios, consistent with a more concentrated area for protein binding. Surface plasmon resonance confirmed binding of FII and FX to HETE-PEs. HETE-PEs increased membrane curvature and thickness, but not surface charge or homogeneity, possibly suggesting increased accessibility to cations/factors. In summary, innate immune-derived eoxPL enhance calcium-dependent coagulation factor function, and their potential utility in bleeding disorders is proposed.

Research progress of hemorrhagic shock and encephalopathy syndrome

Hemorrhagic shock and encephalopathy syndrome (HSES)is a devastating disease in infants which was first proposed by Levin in 1983.The main clinical manifestations of HSES are associated with acute onset of high fever, diarrhea, rapidly followed by convulsions, unconsciousness, bleeding tendency, shock and multiorgan dysfunction.The pathological manifestations include punctate bleeding, necrosis or inflammatory changes in multiple organs.The etiology of this syndrome is unknown, and the prognosis is poor.Despite intensive treatment, the fatality rate is still high and the survival is often associated with severe neurological sequelae.At present, there is no effective treatment for this disease, and mainly early symptomatic and supportive treatment can be obtained. Key words: Hemorrhagic shock and encephalopathy syndrome; Research progress; Child

Entrapment of Autologous von Willebrand Factor on Polystyrene/Poly(methyl methacrylate) Demixed Surfaces.

Human platelets play a vital role in haemostasis, pathological bleeding and thrombosis. The haemostatic mechanism is concerned with the control of bleeding from injured blood vessels, whereby platelets interact with the damaged inner vessel wall to form a clot (thrombus) at the site of injury. This adhesion of platelets and their subsequent aggregation is dependent on the presence of the blood protein von Willebrand Factor (vWF). It is proposed here that the entrapment of vWF on a substrate surface offers the opportunity to assess an individual’s platelet function in a clinical diagnostic context. Spin coating from demixed solutions of polystyrene (PS) and poly(methyl methacrylate) (PMMA) onto glass slides has been shown previously to support platelet adhesion but the mechanism by which this interaction occurs, including the role of vWF, is not fully understood. In this work, we report a study of the interaction of platelets in whole blood with surfaces produced by spin coating from a solution of a weight/weight mixture of a 25% PS and 75% PMMA (25PS/75PMMA) in chloroform in the context of the properties required for their use as a Dynamic Platelet Function Assay (DPFA) substrate. Atomic Force Microscopy (AFM) indicates the presence of topographical features on the polymer demixed surfaces in the sub-micron to nanometer range. X-ray Photoelectron Spectroscopy (XPS) analysis confirms that the uppermost surface chemistry of the coatings is solely that of PMMA. The deliberate addition of various amounts of 50 μm diameter PS microspheres to the 25PS/75PMMA system has been shown to maintain the PMMA chemistry, but to significantly change the surface topography and to subsequently effect the scale of the resultant platelet interactions. By blocking specific platelet binding sites, it has been shown that their interaction with these surfaces is a consequence of the entrapment and build-up of vWF from the same whole blood sample.