Impaired Blood Coagulation Research Articles

The comparative study between treatment with Cryoprecipitate and recombinant Factor VIII in Hemophilia in children

Introduction: Hemophilia A is a genetic disorder caused by a deficiency or absence of coagulation Factor VIII, leading to impaired blood clotting and prolonged bleeding, especially into joints and muscles. Without appropriate treatment, recurrent bleeding can result in chronic joint damage and disability. Traditionally, Cryoprecipitate, a blood product containing concentrated clotting factors, has been used to manage bleeding episodes in patients with Hemophilia A. However, with advancements in biotechnology, recombinant Factor VIII, a synthetic product, has become an alternative. Recombinant Factor VIII eliminates the risks associated with blood-derived products, such as viral transmission, and offers more consistent dosing and availability. Despite these advantages, recombinant therapies are significantly more expensive. This study seeks to compare the clinical efficacy, safety of Cryoprecipitate versus recombinant Factor VIII in pediatric patients with Hemophilia A, providing critical insights for optimal management strategies. Purpose: The purpose of this study is to compare the clinical outcomes, safety of Cryoprecipitate versus recombinant Factor VIII in the management of children diagnosed with Hemophilia A. Materials and methods: This retrospective study included 32 pediatric patients diagnosed with Hemophilia A, treated either with Cryoprecipitate or recombinant Factor VIII. Clinical data were collected on bleeding frequency, Factor VIII recovery. Statistical analyses were conducted to determine significant differences between the two groups. Results: The study demonstrated that treatment with recombinant Factor VIII resulted in significantly improved clinical outcomes compared to Cryoprecipitate. In the group treated with recombinant Factor VIII, patients required scheduled hospitalizations for routine follow-up and management, with no reports of acute bleeding episodes during these admissions. This contrasts sharply with the Cryoprecipitate group, where all hospitalizations were precipitated by acute bleeding events, necessitating urgent intervention. Conclusions: Recombinant Factor VIII demonstrates superior efficacy in managing Hemophilia A in children compared to Cryoprecipitate. Recombinant therapy provides better clinical outcomes, justifying its use in modern treatment protocols.

Antimicrobial and Hemostatic Diatom Biosilica Composite Sponge.

The 3D nanopatterned silica shells of diatoms have gained attention as drug delivery vehicles because of their high porosity, extensive surface area, and compatibility with living organisms. Tooth extraction may result in various complications, including impaired blood clotting, desiccation of the root canal, and infection. Therapeutic sponges that possess multiple properties, such as the ability to stop bleeding and kill bacteria, provide numerous advantages for the healing of the area where a tooth has been removed. This study involved the fabrication of a composite material with antibacterial and hemostatic properties for dental extraction sponges. We achieved this by utilizing the porous nature and hemostatic capabilities of diatom biosilica. The antibiotic used was doxycycline. The gelatin-based diatom biosilica composite with antibiotics had the ability to prevent bleeding and release the antibiotic over a longer time compared to gelatin sponge. These properties indicate its potential as a highly promising medical device for facilitating rapid healing following tooth extraction.

Debates Surrounding the Use of Antithrombotic Therapy in Hemophilic Patients with Cardiovascular Disease: Best Strategies to Minimize Severe Bleeding Risk.

Navigating through antithrombotic therapy in patients with both hemophilia and cardiovascular pathology presents a complex scenario with inherent challenges and opportunities. The presence of hemophilia, characterized by impaired blood clotting, adds a layer of complexity to the management of cardiovascular conditions requiring antiplatelet therapy and anticoagulation. Striking a delicate balance between the necessity for antithrombotic treatment to prevent cardiovascular events and the heightened risk of severe bleeding in individuals with hemophilia demands a nuanced and carefully considered approach. The challenges revolve around identifying an optimal therapeutic strategy that effectively mitigates cardiovascular risks without exacerbating bleeding tendencies. In hemophilic patients with cardiovascular disease, the decision to use antiplatelet therapy requires careful consideration of the individual's bleeding risk profile, considering factors such as the severity of hemophilia, history of bleeding episodes, and concurrent medications. The goal is to provide effective antithrombotic treatment while minimizing the potential for excessive bleeding complications. Conventional anticoagulants like warfarin pose difficulties due to their potential to increase the risk of bleeding. On the other hand, emerging options like novel direct oral anticoagulants (DOACs) present an opportunity, offering predictable pharmacokinetics and user-friendly administration. However, a comprehensive exploration of their safety and efficacy in hemophilic patients is imperative. Achieving the right equilibrium between preventing cardiovascular events and minimizing bleeding risk is pivotal in selecting the most effective therapeutic option for individuals with hemophilia and cardiovascular pathology. A multidisciplinary approach, integrating the expertise of hematologists and cardiologists, becomes essential to customize treatments and address the intricacies of this medical challenge.

Oxidative Stress, Persistent Inflammation and Blood Coagulation Alterations in Serum Proteome of Patients with Neovascular Age-Related Macular Degeneration.

Neovascular age-related macular degeneration (AMD) is a major cause of irreversible blindness in elderly populations in developed countries. AMD's etiopathology is multifactorial, with strong environmental and genetic components, but the exact molecular pathomechanisms underlying the disease are still unknown. In this study, we analyzed blood serum collected from 74 neovascular AMD patients and 58 healthy controls to identify proteins that may serve as potential biomarkers and expand our knowledge about the etiopathogenesis of the disease. The study revealed 17 differentially expressed proteins-11 up-regulated and 6 down-regulated-in neovascular AMD, which are involved in the biological processes previously linked with the disease-oxidative stress and persistent inflammation, impaired cellular transport, lipid metabolism and blood coagulation. In conclusion, the differences in the expressions of the proteins identified in this study may contribute to our understanding of the mechanisms underlying AMD and possibly serve in future as promising biomarkers.

Immunogenic and toxic effects of graphene oxide nanoparticles in mouse skeletal muscles and human red blood cells

To investigate immunogenic and toxic effects of graphene oxide (GO) nanoparticles in mouse skeletal muscles and in human blood in vitro. GO nanoparticles prepared using a probe sonicator were supended in deionized H2O or PBS, and particle size and surface charge of the nanoparticles were measured with dynamic light scattering (DLS). Different concentrations (0.5, 1.0 and 2.0 mg/mL) of GO suspension or PBS were injected at multiple sites in the gastrocnemius muscle (GN) of C57BL/6 mice, and inflammatory response and immune cell infiltrations were detected with HE and immunofluorescence staining. We also examined the effects of GO nanoparticles on human red blood cell (RBC) morphology, hemolysis and blood coagulation using scanning electron microscope (SEM), spectrophotometry, and thromboelastography (TEG). GO nanoparticles suspended in PBS exhibited better colloidal dispersity, stability and surface charge effects than those in deionized H2O. In mouse GNs, injection of GO suspensions dose- and time-dependently resulted in sustained muscular inflammation and myofiber degeneration at the injection sites, which lasted till 8 weeks after the injection; immunofluorescence staining revealed obvious infiltration of monocytes, macrophages, dendritic cells and CD4+ T cells around the injection sites in mouse GNs. In human RBCs, incubation with GO suspensions at 0.2, 2.0 and 20 mg/mL, but not at 0.002 or 0.02 mg/mL, caused significant alterations of cell morphology and hemolysis. TEG analysis showed significant abnormalities of blood coagulation parameters following treatment with high concentrations of GO. GO nanoparticles can induce sustained inflammatory and immunological responses in mouse GNs and cause RBC hemolysis and blood coagulation impairment, suggesting its muscular toxicity and hematotoxicity at high concentrations.

Evaluation of Periodontal Status and Oral Health Habits with Continual Dental Support for Young Patients with Hemophilia

Hemophilia is a congenital disorder associated with impaired blood clotting. Routine dental intervention to prevent oral bleeding in patients with hemophilia is considered important, but its effectiveness remains unknown. In the present study, we evaluated the effect of continual dental support on periodontal status and oral health habits in young patients with hemophilia. Of the 168 young patients with hemophilia who visited our clinic for 5 years, we selected subjects who had visited annually since 2015 and were in the mixed and permanent dentitions. To evaluate the periodontal status of these subjects, Community Periodontal Index (CPI) values in the molars and anterior teeth were measured. In addition, a questionnaire regarding oral health habits, including floss use, frequency of brushing by parents, and attending a family dentist, was administered to the subjects and their parents. In the patients with mixed dentition, the CPI values for the upper right molars and lower left central incisor decreased significantly in later years compared with the first year (p < 0.05). In the patients with permanent dentition, only one year recorded a significant decrease in CPI values compared with the first year (p < 0.05), localized in the upper right molars. The results of the questionnaire revealed that continual dental support improved dental floss use and the frequency of brushing by parents only in the mixed dentition group. Furthermore, these oral health habits significantly affected CPI values only in the mixed dentition group (p < 0.01). These results suggest that continual dental support improves the periodontal condition and oral health habits of hemophilic patients, especially those with mixed dentition.

A modern approach to the study of the problem of pathogenesis and prevention venous thromboembolic complications in patients with trauma (literature review)

Relevance. Patients with trauma are at increased risk of venous thromboembolic complications (VTE), which includes deep vein thrombosis of the lower extremities (DVT) and pulmonary embolism (PE). Within surgical and trauma clinics, thromboembolic complications are the most common preventable cause of in-hospital mortality. Numerous studies have shown that the incidence rate of deep vein thrombosis (DVT) in trauma patients without prevention varies from 5 to 80%.Aim. To analyze the pathogenesis of the development of venous thrombosis and explore existing approaches to prevent VTE in trauma patients.Materials and methods. In the course of the work, topical literary sources of domestic and foreign authors on a given topic were analyzed.Results. The mechanism of thrombus formation in trauma involves slowing blood flow, damage to the vessel wall and impaired blood clotting in the form of hypercoagulation. The state of hypercoagulation combined with prolonged immobility increases the risk of VTE. LMWH is the treatment of choice for the prevention of VTE in trauma. Today, there are ongoing studies related to the correction of preventive doses of LMWH and the search for a single standard, depending on numerous factors.Conclusion. Severity and multiplicity of lesions correlate with severity of systemic inflammation, hypercoagulation, and incidence of venous thrombosis. However, this correlation has not been sufficiently studied in the scientific literature. The search for specific methods for the prevention of deep vein thrombosis leading to PE is an urgent problem of surgery of injuries both peaceful and wartime.

In Utero Cell Treatment of Hemophilia A Mice via Human Amniotic Fluid Mesenchymal Stromal Cell Engraftment.

Hemophilia is a genetic disorder linked to the sex chromosomes, resulting in impaired blood clotting due to insufficient intrinsic coagulation factors. There are approximately one million individuals worldwide with hemophilia, with hemophilia A being the most prevalent form. The current treatment for hemophilia A involves the administration of clotting factor VIII (FVIII) through regular and costly injections, which only provide temporary relief and pose inconveniences to patients. In utero transplantation (IUT) is an innovative method for addressing genetic disorders, taking advantage of the underdeveloped immune system of the fetus. This allows mesenchymal stromal cells to play a role in fetal development and potentially correct genetic abnormalities. The objective of this study was to assess the potential recovery of coagulation disorders in FVIII knockout hemophilia A mice through the administration of human amniotic fluid mesenchymal stromal cells (hAFMSCs) via IUT at the D14.5 fetal stage. The findings revealed that the transplanted human cells exhibited fusion with the recipient liver, with a ratio of approximately one human cell per 10,000 mouse cells and produced human FVIII protein in the livers of IUT-treated mice. Hemophilia A pups born to IUT recipients demonstrated substantial improvement in their coagulation issues from birth throughout the growth period of up to 12 weeks of age. Moreover, FVIII activity reached its peak at 6 weeks of age, while the levels of FVIII inhibitors remained relatively low during the 12-week testing period in mice with hemophilia. In conclusion, the results indicated that prenatal intrahepatic therapy using hAFMSCs has the potential to improve clotting issues in FVIII knockout mice, suggesting it as a potential clinical treatment for individuals with hemophilia A.

Subpopulation composition of peripheral blood lymphocytes in COVID-19

The pathogenesis of severe coronavirus infection COVID-19 is associated with activation of immune system, cytokine storm, impaired blood clotting, microvascular thrombosis, organ ischemia and multiple organ dysfunction syndrome. The role of various lymphocyte subpopulations in COVID-19 is still debated. The aim of our study was to analyze the subpopulational profile of peripheral blood lymphocytes in COVID-19 patients as compared with healthy donors.The study included 20 COVID-19 patients (11 males and 9 females,) and 26 healthy donors. Average age of the patients was 52 and 56 years, respectively. Clinical examinations were performed by standard laboratory methods. Peripheral blood lymphocytes were isolated in the Ficoll gradient. The cells were stained with antibodies to specific antigens of main lymphocyte populations, endothelial cells, and apoptotic cell markers. The analysis was performed by flow cytometry. The results showed that all patients had elevated C-reactive protein (14- to 35-fold), ferritin (1.2- to 13-fold), D-dimers (1.2- to 90-fold). 55% of men had a decrease in the absolute number of lymphocytes, in women this index was at the low normal limit. Cytometric analysis showed that, among peripheral blood lymphocytes, the proportion of functional cells expressing the CD45 marker ranged from 2 to 12% in 70% of patients, as compared with 80-99% among the donors. The proportion of CD45+ lymphocytes significantly correlated with the level of hemoglobin, but not with the levels of inflammatory biochemical markers. Among the functional lymphocytes of patients, there was a decrease in the proportion of CD3+, CD4+, CD8+T cells, increased proportion of natural killer CD56+ and the apoptotic (AnnexinV+) cell contents, but the proportion of CD19 and HLA-DR+B cells was not changed. Analysis of the lymphocyte (LC) subpopulations that did not express CD45 marker showed that this fraction contained different lymphocyte subsets with reduced expression of CD4, CD8, CD19, CD56 etc. in the blood of patients and donors. Higher percentage of endothelial cells expressing CD62P marker made the difference between patients and donors.Laboratory determination of lymphocyte subsets in blood samples of COVID-19 patients does not reflect the real severity pattern of the disease, thus requiring studies of the CD45-expressing functional cell populations.

THE EFFECT OF HEALTH EDUCATION ON THE KNOWLEDGE AND BEHAVIOR OF PREGNANT WOMEN ABOUT COVID-19 IN RAMBAH TENGAH HILIR VILLAGE, RAMBAH DISTRICT, ROKAN HULU REGENCY

Complications that often occur in pregnant women infected with the COVID-19 virus include respiratory failure, heart problems, impaired blood clotting, kidney disorders and secondary infections by other microorganisms. While the effect on the baby is premature delivery and fetal death in the womb. The purpose of this study was to determine the effect of health education on knowledge and behavior of pregnant women about the COVID-19 disease in Rambah Tengah Hilir Village, Rambah District, Rokan Hulu Regency. This type of research is a quantitative study using a pre-experimental one group pre-post test design. The number of samples is 64 people who are determined by the total sampling technique. The statistical test used is the paired t test. The results showed that the average knowledge of respondents before being given health education about COVID-19 was 2.10 and after being given health education it was 1.04. As for the behavior of respondents before being given health education the average was 1.46 and after being given health education it was 1.06. Based on the results of statistical tests, there is an effect of health education on mother's knowledge and behavior about COVID-19 with statistical test results obtained p-values are 0.001 and 0.0004 (p<0.05). It is hoped that pregnant women will continue to apply the 5 M (wearing a mask, maintaining distance, washing hands, avoiding crowds and reducing mobility) so that the chain of spreading COVID-19 is broken.

Increased blood viscosity and red blood cell aggregation in patients with COVID‐19

The aim of this study was to (1) analyze blood viscosity, red blood cell (RBC) deformability, and aggregation in hospitalized patients with Coronavirus disease 19 (COVID-19); (2) test the associations between impaired blood rheology and blood coagulation; and (3) test the associations between impaired blood rheology and several indicators of clinical severity. A total of 172 patients with COVID-19, hospitalized in COVID-unit of the Internal Medicine Department (Lyon, France) participated in this study between January and May 2021. Clinical parameters were collected for each patient. Routine hematological/biochemical parameters, blood viscosity, RBC deformability and aggregation, and RBC senescence markers were measured on the first day of hospitalization. A control group of 38 healthy individuals was constituted to compare the blood rheological and RBC profile. Rotational thromboelastography was performed in 76 patients to study clot formation dynamics. Our study demonstrated that patients with COVID-19 had increased blood viscosity despite lower hematocrit than healthy individuals, as well as increased RBC aggregation. In-vitro experiments demonstrated a strong contribution of plasma fibrinogen in this RBC hyper-aggregation. RBC aggregation correlated positively with clot firmness, negatively with clot formation time, and positively with the length of hospitalization. Patients with oxygen supplementation had higher RBC aggregation and blood viscosity than those without, and patients with pulmonary lesions had higher RBC aggregation and enhanced coagulation than those without. This study is the first to demonstrate blood hyper-viscosity and RBC hyper-aggregation in a large cohort of patients with COVID-19 and describe associations with enhanced coagulation and clinical outcomes.

A Randomised-Controlled Clinical Study Examining the Effect of High-Intensity Laser Therapy (HILT) on the Management of Painful Calcaneal Spur with Plantar Fasciitis.

Calcaneal spur and plantar fasciitis are the most common causes of plantar heel pain. There are many effective physical modalities for treating this musculoskeletal disorder. So far, the are no clear recommendations confirming the clinical utility of high-intensity laser therapy (HILT) in the management of painful calcaneal spur with plantar fasciitis. This study aimed to evaluate the effectiveness of HILT in pain management in patients with calcaneal spur and plantar fasciitis. A group of 65 patients was assessed for eligibility based on the CONSORT guidelines. This study was prospectively registered in the Australian New Zealand Clinical Trial Registry platform (registration number ACTRN12618000744257, 3 May 2018). The main eligibility criteria were: cancer, pregnancy, electronic and metal implants, acute infections, impaired blood coagulation, cardiac arrhythmias, taking analgesic or anti-inflammatory medications, non-experience of heel pain, or presence of other painful foot conditions. Finally, 60 patients were randomly assigned into two groups: study group (n = 30, mean age 59.9 ± 10.1), treated with HILT (7 W, 149.9 J/cm2, 1064 nm, 4496 J, 12 min), and placebo-controlled group (n = 30, mean age 60.4 ± 11.9), treated with sham HILT therapy. Both groups received ultrasound treatments (0.8 W/cm2, 1 MHz frequency, 100% load factor, 5 min). Treatment procedures were performed once a day, five times per week for three weeks (total of 15 treatment sessions). Study outcomes focused on pain intensity and were assessed before (M1) and after (M2) the treatment as well as after 4 (M3) and 12 (M4) weeks using the Visual Analogue Scale (VAS) and the Laitinen Pain Scale (LPS). According to VAS, a statistically significant decrease in the study group was observed between M1 and M2 by 3.5 pts, M1 and M3 by 3.7 pts, and M1 and M4 by 3.2 pts (p < 0.001). On the other hand, the control group showed a statistically significant decrease (p < 0.001) between M1 and M2 by 3.0 pts, M1 and M3 by 3.4 pts, and M1 and M4 by 3.2 pts. According to LPS, a statistically significant decrease in the study group was observed between M1 and M2 by 3.9 pts, M1 and M3 by 4.2 pts, and M1 and M4 by 4.0 pts (p < 0.001). On the other hand, the control group showed a statistically significant decrease between M1 and M2 by 3.2 pts (p = 0.002), M1 and M3 by 4.0 pts (p < 0.001), and M1 and M4 by 3.9 pts (p < 0.001). However, there were no statistically significant differences between the groups in VAS and LPS (p > 0.05). In conclusion, the HILT does not appear to be more effective in pain management of patients with calcaneal spurs and plantar fasciitis than the conservative standard physiotherapeutic procedures.

MO240A FATAL CASE OF VASCULITIS AFTER SARS-COV-2 NEGATIVIZATION

Background and AimsSpectrum of acute severe respiratory syndrome Coronavirus 2 (SARS-CoV-2) ranges from mild to critical and probably mortality rate is largely underestimated.Complications may represent different manifestation of a profound endothelial dysfunction and injury.Biopsies reveal macro and microvascular thrombosis involving larger and smaller vessels. Different Authors described accumulation of inflammatory cells across vascular bed, viral inclusions and apoptotic bodies across vascular bed. Endotheliitis leads to loss of vessel integrity with bleedings and lumen restriction with tissue ischemia and necrosis. SARS-CoV-2 also can cause vasculitis and a systemic inflammatory vascular disease with COVID-19-associated coagulopathy.Several cases of vasculitis have been described during COVID-19 pandemy but in literature, to our knowledge, there are few cases of patients developing vasculitis after SARS-CoV-2 infection.MethodA 59-year-old male patient in chronic haemodialysis with hypertension, chronic thrombocytopenia, uncertain history of type 2 diabetes mellitus and recent COVID-19 pneumonia (1 month before) was admitted to our E.R. with psycho-motor slowdown, dyspnoea, profound hypotension, diffuse and extensive purpura especially on extremities and nose with petechiae and ecchymoses, thrombocytopenia, widespread arthritis and myalgia and atrial fibrillation with high ventricular response.Laboratory tests revealed leucocytosis with elevation of inflammatory markers (GB 15.6 x 103/µL CRP 6.61 mg/dl, procalcitonin 2.64 ng/ml), thrombocytopenia (PLTs 55 x 103/µL), Hb 11.2 g/dl, increased amylase (444 UI/L) and lipase (608 UI/L), hyperkaliaemic metabolic acidosis, mild impaired blood clotting with normal fibrinogen and severe D-Dimer elevation (3453 mcg/ml), normal haptoglobin and bilirubin.SARS-CoV-2 rapid antigen test and three molecular swab tests (at admission and during recovery) were negative.Contrast-enhanced chest-abdomen CT did not demonstrate relevant findings.ResultsWe suspected thrombotic thrombocytopenic purpura, COVID-19 related vasculitis or an autoimmune disease reactivation after SARS-CoV-2 or other concurrent viral infections.A peripheral blood smear excluded presence of schistocytes, HBV, HCV, HIV, c-ANCA, p-ANCA, LAC anti-mitochondrial and ENA antibodies were negative, such as complement factor C4 (C3 at low limits). IgA immunoglobulins resulted increased (952 mg/dl).We administered intravenous (IV) hydration, analgesic therapy, broad spectrum antibiotics and Methylprednisolone 40 mg IV without benefit.Three days after clinical conditions were critical with further neurological deterioration and haemodynamic instability, consequently we started methylprednisolone 1 g/day IV for three days, followed by oral prednisone 25 mg/die with rapid improvement of clinical conditions and laboratory findings.A skin biopsy revealed a variable and discontinuous presence of C4d and IgM along capillary walls and traces of IgG, supporting the hypothesis of an immune-mediated vasculitic process.Patient was discharged in stable condition with Prednisone 25 mg/die per os.Later we learned that patient had been hospitalized again for severe anaemia, thrombocytopenia and septic shock with fatal outcome.ConclusionSARS-CoV-2 clinical spectrum appears to be extremely varied; the direct cytolysis and the immune-mediated damage are among the most accredited hypotheses on disease physiopathology, but molecular mimicry mechanisms may also be involved. Vascular endothelium can be considered among the first targets. Vasculitis are frequently described in literature during COVID, this case, instead, is an anecdotal report of severe angiitis arising after swab negativization, underlying the possibility that hyperinflammation can either cause an autoimmune syndrome de novo or trigger a flare-up of a pre-existing condition.

Coagulation, Vascular Morphology, and Vasculogenesis in Spinal Ligament Ossification Model Mice.

In vivo studies of the vascular system in ossification of the posterior longitudinal ligament (OPLL) model mice. The aim of this study was to investigate blood coagulability, vascular morphology, and vasculogenesis capability, known as venous thromboembolism (VTE) risk factors in the ossification model, tiptoe walking (ttw) mice. Patients with OPLL are more likely to develop VTE after spinal cord injury. Capillary mesh invasion of spinal ligaments precedes spinal ligament ossification in ttw mice. Investigation on vascular systems of ttw mice may contribute to clarifying its pathology. Coagulability of blood samples from ttw and C57BL/6 (WT) mice were evaluated at 8, 16, and 24 weeks of age. Vascular morphology was assessed from a Hematoxylin-Eosin stained section by measuring vessel area. A tube formation assay was performed with endothelial cells isolated from the aorta to assess vasculogenesis. Prothrombin time was significantly shorter in ttw mice than in WT at 8 and 16 weeks. Fibrinogen had a greater increase in ttw mice than in WT at 16 weeks. The vascular area and vascular wall area were significantly smaller in ttw mice than in WT at all timepoints. The ratio of vascular wall area to vascular area was significantly smaller in ttw mice than in WT at 24 weeks. The endothelial cells from ttw mice formed significantly higher numbers of total branching points than WT cells. Ossification model mice had impaired blood coagulation and vascular morphology and high capacity for vasculogenesis. With regard to the pathogenesis of VTE, ttw mice harbor an environment that promotes the development of VTE.Level of Evidence: N/A.

Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis.

Hematopoiesis is a complex and intricate process that aims to replenish blood components in a constant fashion. It is orchestrated mostly by hematopoietic progenitor cells (hematopoietic stem cells (HSCs)) that are capable of self-renewal and differentiation. These cells can originate other cell subtypes that are responsible for maintaining vital functions, mediate innate and adaptive immune responses, provide tissues with oxygen, and control coagulation. Hematopoiesis in adults takes place in the bone marrow, which is endowed with an extensive vasculature conferring an intense flow of cells. A myriad of cell subtypes can be found in the bone marrow at different levels of activation, being also under constant action of an extensive amount of diverse chemical mediators and enzymatic systems. Bone marrow platelets, mature erythrocytes and leukocytes are delivered into the bloodstream readily available to meet body demands. Leukocytes circulate and reach different tissues, returning or not returning to the bloodstream. Senescent leukocytes, specially granulocytes, return to the bone marrow to be phagocytized by macrophages, restarting granulopoiesis. The constant high production and delivery of cells into the bloodstream, alongside the fact that blood cells can also circulate between tissues, makes the hematopoietic system a prime target for toxic agents to act upon, making the understanding of the bone marrow microenvironment vital for both toxicological sciences and risk assessment. Environmental and occupational pollutants, therapeutic molecules, drugs of abuse, and even nutritional status can directly affect progenitor cells at their differentiation and maturation stages, altering behavior and function of blood compounds and resulting in impaired immune responses, anemias, leukemias, and blood coagulation disturbances. This review aims to describe the most recently investigated molecular and cellular toxicity mechanisms of current major environmental pollutants on hematopoiesis in the bone marrow.

Dental Management in a Patient with Glanzmann’s Thrombasthenia : A Case Report

Glanzmann’s thrombasthenia (GT) is a rare, autosomal recessive inherited congenital disorder, characterized by impaired blood coagulation due to platelet dysfunction. It was first reported by the pediatrician Glanzmann in 1918.GT affects both males and females, and it is more common in regions of the Middle East, India, and France, where intermarriage is common. It has an incidence of about 1 in 1,000,000 people. In South Korea, according to the Division of Rare Diseases, Korea Centers for Disease Control and Prevention, around 200 cases have been reported in 2018.Clinical symptoms include petechia, ecchymosis, epistaxis, and gingival bleeding. The spontaneous loss of deciduous teeth can result in excessive bleeding with that blood transfusion should be considered. Preventing hemorrhages and hemostasis are most important factors in dental treatment. Local bleeding can be controlled by compression, but platelet transfusion can be required by prolonged bleeding.Pediatric dentists can minimize the gingival bleeding by control of the oral hygiene to prevent gingivitis and dental caries. The importance of oral hygiene and periodic recall check-up should be emphasized. During dental treatment, the examination and the treatment plan of patient should be modified to prevention of hemorrhages carefully.A 6-year-old girl with GT was referred for the treatment of dental caries, and resin restoration was performed under nitrous oxide inhalation sedation. After treatment, compression was required for the bleeding control.

Understanding and prevention of D-dimer elevation in coronavirus disease 2019 in traditional Chinese medicine

2019 Novel coronavirus (2019-nCoV) infection caused a pandemic in the world. From the reported cases in the literatures, the level of D-dimer in patients with coronavirus disease 2019 (COVID-19) is positively correlated with the severity of illness, which needs the attention of clinical workers. According to Western medicine, the increase of D-dimer is related to the hyperactivity of fibrinolytic system and the shortening of prothrombin time (PT), resulting in excessive production and degradation of plasma fibrin and hypercoagulable state of blood, while traditional Chinese medicine (TCM) believes that the above syndromes belong to the pathogenesis of "blood stasis" according to TCM theories. Over the years, TCM has a significant effect on promoting blood circulation, removing blood stasis and improving microcirculation. This article reviews the mechanism, clinical significance, understanding of TCM and common methods of promoting blood circulation and removing blood stasis caused by 2019-nCoV, in order to provide ideas for the prevention and treatment of impaired blood coagulation in patients with COVID-19.

ОСОБЕННОСТИ ДИАГНОСТИКИ И ЛЕЧЕНИЯ АКУШЕРСКИХ КРОВОТЕЧЕНИЙ, СОПРОВОЖДАЮЩИХСЯ КОАГУЛОПАТИЕЙ

The literature of recent years on modern methods of diagnosing and treating coagulation disorders in obstetric bleeding (OB) were studied and analyzed. The literature is presented on the frequency and structure of OB in the world and countries with different levels of development. It has been shown that massive OB is often accompanied by impaired blood clotting and lead to maternal mortality. In the structure of causes of maternal mortality in the world, OB is in the leading position. A theoretical and critical analysis of the literature on modern methods of diagnosing and treating coagulation disorders in OB has shown that it is necessary to continue further research on optimization of diagnostics and individual approaches in infusion-transfusion therapy of women with massive OB. Optimization of the methods of diagnosis and treatment of OB will improve obstetric outcomes in this complication. Keywords: Obstetric bleeding, maternal mortality, coagulopathy, diagnostics, treatment

Crosstalk between inflammation and coagulation in pancreatitis-induced renal injury in experimental and clinic acute pancreatitis

Background: The pathogenesis of organ failure in AP is complicated. Proteases, inflammatory cells and its mediators which secreted from pancreas into blood circulation and impairment of blood coagulation, microcirculations are explaining as the main contributed factors for organ failure in AP. Acute renal failure is a serious early complication in patients with AP significantly increases mortality rates. Materials and Methods: For the experiment were used 42 Wistar albino rats. We examined 98 patients with moderately severe AP, and 57 patients with severe AP. Disorders of kidney function were in 48 patients. We determined the creatinine level, indicators of hemostasis and inflammation. Results: In the kidneys characteristic of experimental acute necrotizing pancreatitis were: edema, inflammatory infiltration of the parenchyma, parenchymal congestion and dilation of capillaries, tubular necrosis. The concentration of creatinine in serum is increase at 86.86%. It was noticed that the level of creatinine significantly directly correlated with the concentration of MPO and activity of iNOS in the tissue of pancreatic, amylase in serum blood, reverse with the concentration of H2S in serum. Renal failure in rats was accompanied by a hypercoagulation. Analysis of the relationship of inflammation and hemostasis in patients with acute pancreatitis and renal dysfunction is accompanied by decreased of activated partial thrombolastin time, increased of thrombin time, fibrinogen concentration, D-dimers level, and level of soluble fibrin-monomer complexes, lack of activity of antithrombin III, increased synthesis of C-reactive protein, excessive production of proinflammatory cytokines IL-2, IL-6, and TNF-α. Was shown a direct correlation between severity of renal failure (SOFA score) and concentrations of IL-6, CRP, D-dimers, soluble fibrin-monomer complexes, and duration of thrombin time. Conclusion: The mechanism of the acute renal injury following severe necrotizing pancreatitis is complicated. The inflammatory cascades and hypercoagulative state are initiated this pathological process.

Practical Guidance for Non-Specialist Physical Therapists Managing People with Hemophilia and Musculoskeletal Complications

People with hemophilia (PWH) have impaired blood coagulation and hemostasis. Bleeding into joints and muscles is the main manifestation of the disorder, causing severe joint damage and muscle complications. Lifelong, regular physical therapy is therefore important for PWH, in order to support recovery from bleeds and reduce recurrences. Ideally, these individuals should be in the care of a hemophilia treatment center (HTC), where a physical therapist (PT) should be a regular part of the comprehensive team. However, not all PWH have convenient access to an HTC, and they may be referred to local non-specialist PTs, who may have only limited experience with the condition, for day-to-day physical therapy treatment. This article, written by four experienced hemophilia PTs, introduces key aspects of the pathology of the hemophilic joint in adult PWH with musculoskeletal complications or established joint disease (or those with inhibitors) that are relevant to PTs. The characteristic differences between the joints of PWH and those of people with similar pathologies are clarified. Practical advice on how the physical therapy consultation can be adjusted for PWH is given, and the importance of communicating with the HTC emphasized. The aim of this narrative review is to raise awareness of hemophilia and joint disease for non-specialist PTs, and serve as helpful background information for PTs who encounter PWH with musculoskeletal complications or established joint disease in their clinics.