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Abstract Background Outcome data about the use of tranexamic acid (TXA) in civilian patients in mature trauma systems are scarce. The aim of this study was to determine how severely injured patients are affected by the widespread prehospital use of TXA in Germany. Methods The international TraumaRegister DGU® was retrospectively analyzed for severely injured patients with risk of bleeding (2015 until 2019) treated with at least one dose of TXA in the prehospital phase (TXA group). These were matched with patients who had not received prehospital TXA (control group), applying propensity score-based matching. Adult patients (≥ 16) admitted to a trauma center in Germany with an Injury Severity Score (ISS) ≥ 9 points were included. Results The matching yielded two comparable cohorts (n = 2275 in each group), and the mean ISS was 32.4 ± 14.7 in TXA group vs. 32.0 ± 14.5 in control group (p = 0.378). Around a third in both groups received one dose of TXA after hospital admission. TXA patients were significantly more transfused (p = 0.022), but needed significantly less packed red blood cells (p ≤ 0.001) and fresh frozen plasma (p = 0.023), when transfused. Massive transfusion rate was significantly lower in the TXA group (5.5% versus 7.2%, p = 0.015). Mortality was similar except for early mortality after 6 h (p = 0.004) and 12 h (p = 0.045). Among non-survivors hemorrhage as leading cause of death was less in the TXA group (3.0% vs. 4.3%, p = 0.021). Thromboembolic events were not significantly different between both groups (TXA 6.1%, control 4.9%, p = 0.080). Conclusion This is the largest civilian study in which the effect of prehospital TXA use in a mature trauma system has been examined. TXA use in severely injured patients was associated with a significantly lower risk of massive transfusion and lower mortality in the early in-hospital treatment period. Due to repetitive administration, a dose-dependent effect of TXA must be discussed.

B-cell lymphoproliferative diseases may be associated with acquired hemostasis disorders, such as acquired hemophilia A (AHA) caused by autoantibodies that neutralize factor VIII activity, and δ-storage pool deficiency, an abnormality of platelet function due to defective dense granules and impaired secretion. We describe the case of a 67-year-old man in whom these two acquired bleeding disorders were concomitantly present as the first clinical manifestation of an indolent non-Hodgkin lymphoma. Immunosuppressive therapy with prednisone was initially started to eradicate anti-FVIII antibodies, subsequently boosted with cyclophosphamide and rituximab, these medications being also chosen to treat the associated indolent lymphoma. Bleeding symptoms were first tackled with limited benefit by using rFVIIa and then rescued using recombinant porcine FVIII. After a 6 month’s follow-up lymphoma and AHA were in remission and platelet function was improved. This case underlines the need of multiple and complex diagnostic and therapeutic approaches to rare acquired bleeding disorders associated with lymphoproliferative diseases.

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.

Mortality from diseases of the circulatory system is a challenge for the modern health care. Arterial hypertension (AH) mostly contributes to development of cardiovascular complications. It often proceeds against the background of metabolic disorders. Pathogenesis of hypertension is currently being considered a multifactorial disease. Pathogenesis of hypertension certainly has distinct features in presence of metabolic disorders,. Therefore, it is relevant to summarize current literature on the role of immunological disorders, endothelial dysfunction and hemostatic disorders in AH genesis during metabolic syndrome (MS). Most authors agree with existence of several mechanisms that determine relationships between AH and insulin resistance. Development of hypertension in MS patients with is a consequence of immunometabolic processes. Abdominal obesity is an important component of MS. It is associated with chronic inflammation of visceral adipose tissue, its excessive infiltration by immune cells, and increased production of adipokines and cytokines (TNFα, IL-6) with hypertension. AH is associated with a significant increase in T cells, that mediate endothelial dysfunction (ED) and provide a link between hypertension and subsequent atherosclerosis. T lymphocytes trigger a cascade of reactions. IL-17 is the end product of these events It is involved not only in increasing blood pressure, but also contributes to the development of vascular wall stiffness in АН patients. Thus, the relationship between several types of immune cells leads to inflammatory reactions, including those of vascular wall, initiating endothelial dysfunction. Chronic non-specific inflammation in MS, supported by the cytokine system, is a triggering mechanism for ED progression. Excessive production of endothelin-1 and inhibition of nitric oxide production are the classic markers of ED. Immune damage leads to imbalance in the production of vasoconstrictor and vasodilating substances, proliferative and antiproliferative factors in endothelium. It was shown that ED is an integral aspect of the insulin resistance syndrome in pathogenesis of arterial hypertension associated with metabolic disorders, and contributes to its worsening, increased vascular reactivity and further AH development. According to modern studies, it has been shown that excessive synthesis of pro-inflammatory cytokines introduces disturbances in the system of vascular hemostasis. When studying the effects of metabolic disorders upon hemostatic system, we may conclude that activation of fibrinolytic and plasma chains occurs in the same way for both men and women, with small gender characteristics of individual components. The rheological properties of the blood are also changed with developing MS. Systematization of the available literature data on the issue under study can serve as a basis for determining prognostic criteria of hypertension progression and risk of thrombotic complications.

Abstract The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already taken on pandemic proportions, affecting over 213 countries in a matter of weeks. In this context, several studies correlating hemostatic disorders with the infection dynamics of the new coronavirus have emerged. These studies have shown that a portion of the patients affected by Coronavirus Disease 2019 (COVID-19) have prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), elevated D-dimer levels and other fibrinolytic products, antithrombin (AT) activity reduced and decrease of platelet count. Based on these hallmarks, this review proposes to present possible pathophysiological mechanisms involved in the hemostatic changes observed in the pathological progression of COVID-19. In this analysis, it is pointed the relationship between the downregulation of angiotensin-converting enzyme 2 (ACE2) and storm cytokines action with the onset of hypercoagulability state, other than the clinical events involved in thrombocytopenia and hyperfibrinolysis progression.

Objective. To study the pathogenetic significance of genetic and acquired thrombophilia and improve the principles of prevention of preeclampsia.Materials and Methods. 65 patients were examined, who were divided into 2 groups: I group consisted of 35 women – pregnant women with repeated episodes of preeclampsia in the present pregnancy, in the II group consisted of 30 primigravida women with preeclampsia during the current pregnancy.Results. Pathogenetically substantiated prophylaxis with low molecular weight heparin, vitamins and antioxidants in patients with preeclampsia and multigenic thrombophilia in early pregnancy has improved during gestation and perinatal outcomes in pregnant women. This was significantly better outcomes have occurred in patients who were treated with early pregnancy and childbearing cycle.Conclusion. Early (antenatal) diagnosis, prevention and differentiated pathogenetic therapy can not only prevent the development of obstetric complications, and, consequently, reduce maternal mortality and morbidity, and improve perinatal outcomes in patients with various forms of thrombophilia. Pathogenic prevention of recurrent episodes of preeclampsia should be based on prevention of manifestations of pro-inflammatory status and genetic thrombophilia.

Objective: to develop a procedure to reduce perinatal blood loss, by permitting the lower use of allogeneic blood. Subjects and methods. The investigation enrolled 96 female patients with moderate and severe preeclampsia, whose status was complicated by massive blood loss. The women were divided into 2 groups: a study group (n=55) that was treated by a package of proposed measures and a control group (n=41) that was retrospectively assessed. During the study, the investigators made a dynamic assessment of peripheral blood parameters and hemostatic system markers, monitored blood and central venous pressures, hourly and daily diuresis, acid base and water electrolyte balance parameters, and collected medical history data. Results. The investigation established that a package of proposed measures to reduce massive obstetric blood loss significantly accelerated the restoration of general clinical and biochemical parameters in the early postoperative period. Conclusion. The proposed procedure is easy-to-use and it is of obvious practical use because it can reduce the use of donor blood components by twice and the length of hospital stay by 6. 5 bed-days.

Bothrops snakebites usually present systemic bleeding, and the clinical–epidemiological and laboratorial factors associated with the development of this manifestation are not well established. In this study, we assessed the prevalence of Bothrops snakebites with systemic bleeding reported at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, in Manaus, Amazonas State, Brazil, and the clinical–epidemiological and laboratorial factors associated with systemic bleeding. This is an observational, cross-sectional study carried out between August, 2013 and July, 2016. Patients who developed systemic bleeding on admission or during hospitalization were considered cases, and those with non-systemic bleeding were included in the control group. Systemic bleeding was observed in 63 (15.3%) of the 442 Bothrops snakebites evaluated. Bothrops snakebites mostly occurred in males (78.2%), in rural areas (89.0%) and in the age group of 11 to 30 years old (40.4%). It took most of the patients (59.8%) less than 3 h to receive medical assistance. Unclottable blood (AOR = 3.11 (95% CI = 1.53 to 6.31; p = 0.002)) and thrombocytopenia (AOR = 4.52 (95% CI = 2.03 to 10.09; p < 0.001)) on admission were independently associated with systemic bleeding during hospitalization. These hemostatic disorders on admission increase the chances of systemic bleeding during hospitalization. Prospective studies are needed to clarify the pathophysiology of systemic bleeding in Bothrops snakebites in the Amazon region.

Current experimental and clinical data was analyzed to evaluate the ultrastructural changes of platelets and their interaction with other cells in conditions of impaired hemostasis during the type 2 diabetes development and following complications. Special attention was paid to determine the correlations between the revealed morphological changes of platelets and the functional and clinical data. We show that ultrastructural studies to reveal the morphological signs of platelets abilities to activate, as well as studies of their structural and functional changes in the conditions of hyperglycemia, and the features of their interaction with the blood cells and endothelial cells are among the most important questions in the field. Addressing these issues will contribute to the understanding of the important mechanisms of pathogenesis, as well as to explain the cascade of clinically relevant lesions, which not only complicate the course of the disease, but also determine its outcome.

The aim of this paper is to review the literature and identify orofacial manifestations of hematological diseases, with particular reference to anemias and disorders of hemostasis. A computerized literature search using MEDLINE was conducted for published articles on orofacial manifestations of hematological diseases, with emphasis on anemia. Mesh phrases used in the search were: oral diseases AND anaemia; orofacial diseases AND anaemia; orofacial lesions AND anaemia; orofacial manifestations AND disorders of haemostasis. The Boolean operator "AND" was used to combine and narrow the searches. Anemic disorders associated with orofacial signs and symptoms include iron deficiency anemia, Plummer-Vinson syndrome, megaloblastic anemia, sickle cell anemia, thalassaemia and aplastic anemia. The manifestations include conjunctiva and facial pallor, atrophic glossitis, angular stomatitis, dysphagia, magenta tongue, midfacial overgrowth, osteoclerosis, osteomyelitis and paraesthesia/anesthesia of the mental nerve. Orofacial petechiae, conjunctivae hemorrhage, nose-bleeding, spontaneous and post-traumatic gingival hemorrhage and prolonged post-extraction bleeding are common orofacial manifestations of inherited hemostatic disorders such as von Willebrand′s disease and hemophilia. A wide array of anemic and hemostatic disorders encountered in internal medicine has manifestations in the oral cavity and the facial region. Most of these manifestations are non-specific, but should alert the hematologist and the dental surgeon to the possibilities of a concurrent disease of hemopoiesis or hemostasis or a latent one that may subsequently manifest itself.