Impaired Coagulation Research Articles

Analysis of clinical characteristics and risk factors for patients with heat stroke in western China in 2022: a multicenter retrospective study

ObjectivesTo analyzed the clinical characteristics and treatment modalities of heat stroke (HS) and to identify risk factors for a poor prognosis of HS and provide reference suggestions for its treatment and prevention.Measurements and main resultsWe enrolled a total of 247 patients, with hypertension, diabetes, and psychosis being the top three comorbidities associated with HS. The incidence of HS was higher among males and older individuals. Compared to the control group, the poor prognosis group experienced higher temperatures, a higher incidence of cerebral edema, and gastrointestinal bleeding (all p < 0.05). The poor prognosis group had significantly higher blood pH, HCO3-, Lac, Scr, AST, ALT, DBIL, CKMB, PT, DD, and PLT (all p < 0.05). Furthermore, logistic regression analysis revealed that Lac, Scr, and APACHE II were risk factors for poor prognosis (p < 0.05). The AUC values for the combined diagnostic model were 0.848 (95% CI: 0.781–0.914). Male morbidity, the number of patients with combined hypertension, the prognosis, and the APACHE II score and ALT level were all greater (p < 0.05) in the CHS group. The Kaplan–Meier analysis revealed that the CHS group had a significantly higher mortality rate than the EHS group.ConclusionA high incidence of hypertension, diabetes, psychosis, men, and older persons may be associated with HS. HS patients with high blood cell counts, impaired coagulation, liver and kidney diseases, and those with a specific type of CHS may face a poor prognosis. In patients with heart failure, APACHE II, Lac, and Scr were independent risk factors for a poor prognosis.

The Influence of Vitamin K Levels on Blood Coagulation Factors After Tooth Extraction in Hemophilia Patients

Hemophilia is a genetic disorder resulting from impaired blood clotting. This disorder can be caused by coagulation factor abnormalities due to a deficiency of clotting factors, including vitamin K. A lack of vitamin K disrupts the coagulation process, increasing the tendency for bleeding. This article aims to determine whether there is an influence of vitamin K levels on the blood clotting factors in hemophilia patients. Searching any information needed by analyzing kinds of papers of recent research from the year of 2014 until 2024. Online databases like PubMed, ScienceDirect, Google Scholar, Scopus, and ResearchGate are utilized by inserting relevant keywords, such as hemophilia, blood clotting factors, vitamin K deficiency and extraction. From 10 articles reviewed, a relationship was identified between vitamin K levels and blood clotting factors in hemophilia patients. Individuals with severe hemophilia experience bleeding episodes characterized by delayed onset, as well as bleeding into muscles, joints, and other internal structures, including the brain. Hemophilia is typically diagnosed through the identification of low or absent levels of FVIII:C or FIX:C. The genes encoding FVIII and FIX are located on the long arm of the X chromosome. Hemophilia A and B are the only hereditary clotting disorders inherited in a sex-linked recessive pattern. Vitamin K levels can influence the blood clotting factors in hemophilia patients, particularly those factors synthesized artificially.

Prematurity and growth retardation: different causes of fetal coagulation disorders

prematurity and fetal growth retardation complicates in general one in five pregnancies. The combination of prematurity with severe growth retardation and hypoxia worsens the prognosis due to increase of periventricular hemorrhage incidence, and later coronary heart disease, hypertension, stroke, miscarriage and fetal growth retardation in own pregnancies in adulthood. The causes of impaired blood coagulation and fibrinolysis in retardated and premature newborns remain poorly understood. The goal of the study - to compare the parameters of blood acid-base and gases balance, coagulation and fibrinolysis in prematurity and growth retardation. Material and methods. Newborns of three clinical groups were examined. 24 full-term newborns with a postnatal diagnosis of I-II growth retardation stage constituted group I. 18 newborns of group II were born prematurely, corresponding to pregnancy term of 28-34 weeks. Control group III consisted of 20 full-term healthy infants. The birth took place without emergency interventions and without perinatal losses. Blood samples of the umbilical cord artery were obtained immediately after it was clamped. The parameters of blood acid-base and gas compositionof mothers and newborns blood and the fetal kinetic characteristics of blood coagulation and fibrinolysis were compared. Results. Newborns of group I had a pH of 7.27±0.012, in group II - 7.33±0.022, in group III - 7.30±0.024, which corresponded to the difference between maternal and fetal values of 0.10; 0.07 and 0.13. The pH difference in growth retarded fetuses is higher than in premature fetuses, closely to that of full-term fetuses, despite the lowest pH. Parameters of pO2 and pCO2 in labor do not have an indicative difference in newborns of all groups. Thromboelastometric parameters of the premature infants blood indicate low density and accelerated clot lysis, but while growth retarded fetuses accelerated formation and incomplete clot lysis. That is because of notable predominance of endothelial origin procoagulant factors in growth retarded fetuses. Indicators of acid-base and gas balance in newborns with growth retardation are shifted towards acidosis, in contrast to anthropometrically similar premature infants, whose indicators are higher than full-term fetuses ones.

EXPLORATION OF PERCEIVED FEARS AMONG HAEMOPHILIA PATIENTS IN PAKISTAN

Background: Haemophilia is a chronic genetic disorder characterized by impaired blood clotting, leading to recurrent bleeding episodes that significantly impact physical and psychological well-being. Patients often face various challenges, including social restrictions, stigma, and identity challenges, which give rise to different fears. These fears can affect their quality of life, mental health, and ability to perform daily activities. Limited research has explored the perceived fears of haemophilia patients, particularly in developing countries like Pakistan, where healthcare resources and awareness are constrained. Objective: This study aimed to explore the perceived fears of haemophilia patients in Pakistan, evaluate their causes and effects on various life domains, and assess the pathways they adopt to cope with internal bleeding episodes using the fear-avoidance model. Methods: A qualitative study design was employed, utilizing semi-structured interviews based on pre-developed interview guidelines. A total of 28 participants, including 20 males and 8 females aged 14 to 35 years, were recruited through snowball and convenience sampling techniques. The participants were from Rawalpindi, Lahore, Raiwind, Bahawalnagar, Gujranwala, and Hafizabad. Data collection continued until saturation was achieved, and thematic analysis was conducted following Byrne's guidelines (2021). Themes and subthemes were developed using QSR Nvivo 10 software. The fear-avoidance model was applied to assess the pathways adapted by patients during internal bleeding episodes. Results: The study identified several fears among haemophilia patients, including fear of bleeding (6/28), rejection (4/28), injury (4/28), pain (3/28), disability (2/28), and death (2/28). Fear of treatment, illness, emotional trauma, losing social roles, and discrimination or stigma were also reported. Patients commonly employed avoidance as a coping mechanism, leading to negative consequences such as psychological distress, isolation, and disability. The findings highlighted the significant physical and mental challenges faced by patients, including social restrictions, dependence, and identity struggles. Conclusion: Haemophilia patients in Pakistan face multifaceted challenges that give rise to various perceived fears, profoundly impacting their physical, psychological, and social well-being. The study emphasized the importance of addressing these fears through improved healthcare strategies, awareness programs, and supportive interventions to enhance the quality of life for haemophilia patients.

A Novel Multi-organ Male Model of Alcohol-induced Acute-on-chronic Liver Failure Reveals NET-mediated Hepatocellular Death, Which is Prevented by RIPK3 Inhibition.

Alcohol abuse is the most frequent precipitating factor of acute-on-chronic liver failure (ACLF). We aimed at developing an alcohol-induced ACLF model and dissecting its underlying molecular mechanisms. ACLF was triggered by a single alcohol binge (5 g/kg) in a bile duct ligation (BDL) liver fibrosis murine model. Liver, kidney, and brain tissues and behavior were assessed in mice. Livers from patients with sclerosing cholangitis with and without ACLF were also evaluated. In advanced fibrosis induced by BDL, an alcohol binge induced features of ACLF, including significant liver damage, systemic inflammation (increased endotoxin and pro-inflammatory cytokines), and hepatocyte dysfunction compared with BDL alone. ACLF was associated with extrahepatic manifestations, including increased blood urea nitrogen and creatinine, impaired coagulation, and features of encephalopathy. We discovered significantly increased neutrophil count and neutrophil extracellular traps (NETs) in the liver, kidney, and brain in murine ACLF. Livers from ACLF mice showed increased pyroptosis (gasdermin D) and necroptosis (receptor-interacting protein kinase 3 [RIPK3]), when compared with BDL. Invitro, cell-free NETs were induced by alcohol and/or bile acids and triggered pyro-/necroptotic death in hepatocytes. NETosis, pyroptosis, and RIPK3 activation were validated in human livers with ACLF. Moreover, pharmacological inhibition of necroptosis with a RIP3 inhibitor-ameliorated inflammation, NETs, and liver fibrosis, improving multi-organ ACLF pathophysiology. Our novel ACLF model triggered by alcohol binge mimics key features of pathophysiology and multi-organ impairment in human ACLF. Our results indicate that neutrophil infiltration and NETs contribute to hepatocyte cell death via pyroptosis and necroptosis in ACLF, identifying RIPK3 as a potential therapeutic target.

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.

Determination of Citrate Content of Commonly Transfused Blood Products

Abstract Background Citrate is a calcium-chelating anion used as an anticoagulant in the collection and manufacturing of blood products for transfusion. Overwhelming of normal hepatic catabolism of infused citrate, such as in liver failure or in massive transfusion, may cause citrate toxicity. Resultant hypocalcemia, impaired coagulation, and metabolic alkalosis results in increased patient mortality and morbidity. The citrate load per blood product unit is rarely known to the transfusionist, precluding precise calcium repletion. Manufacturing data of citrate content is available, but it is unreliable and often contradictory. The aim of this project is to directly measure the citrate concentrations of common blood products including packed red blood cells (pRBCs), plasma, and apheresis platelets. Methods Blood products (or samples thereof) were obtained, centrifuged, and assayed using a benchtop enzymatic citrate assay (Sigma-Aldrich). This technique generates a chromogenic product detectable via spectrophotometry at 570nm via conversion of citrate to a pyruvate intermediate. Blood products were serially diluted to the assay’s concentration measurement range based on estimations from the product manufacturing processes. Validation studies were performed to verify no significant interference from native pyruvate or from hemolysis at the dilutions used. All samples were run with a paired reference standard. Product type, storage duration, volume, and anticoagulant/preservative solution were recorded. Results Preliminary testing was performed on eleven pRBC units, twelve apheresis platelet units, and four whole blood(WB)-derived plasma. Measured citrate content of AS-1 and AS-5 units ranged from 43.56 - 114.5 mg while that of AS-3 units ranged from 327.23 – 816.82 mg, compared to manufacturing estimates of 188 mg and 883 mg, respectively. Measured citrate content of apheresis platelets ranged from 822-1533 mg compared to manufacturing estimates of 805 mg. Measured citrate content of WB-derived plasma also exceeded the manufacturing estimate of 1201 mg. Interference from pyruvate and hemolysis were insignificant at the dilutions used for testing. Validation of pRBC segment sampling is ongoing. Conclusion Varying guidelines exist for the correction of hypocalcemia during ongoing trauma resuscitation; however, guidance is limited regarding repletion by specific blood product. Our investigation affirms significant heterogeneity in pRBC citrate concentrations by collection method and identifies lower citrate concentrations than expected. This may be due to citrate metabolism by RBCs during storage. Platelet and FFP products contain significantly greater citrate masses by comparison, with a high degree of variation observed due to inherent product volume variability. Further sampling and testing are ongoing to establish reliable expected citrate loads for commonly transfused blood products.

A novel miniaturized roller pump circuit for simulation of extracorporeal circulation.

Extracorporeal circulation induces pronounced effects on haemostasis and rheology. To study these, an ex vivo simulation model is an attractive alternative but often requires large amounts of blood. We sought to create a miniaturized roller pump circuit requiring minimal amounts of blood and to test if the circuit could be used to compare coagulation, platelet function and blood rheology between a dextran-based and a crystalloid-based priming solution. A miniaturized roller pump circuit requiring only 27 ml of blood was created. Blood samples from 8 cardiac surgery patients were mixed with either a dextran-based or a crystalloid-based solution and circulated for 60 min. Coagulation was assessed by rotational thromboelastometry, and platelet function by impedance aggregometry and flow cytometry, before and at 5 and 60 min of circulation. A time-dependent impairment of coagulation was observed in both groups. Maximum clot firmness was lower with dextran-based than with crystalloid-based priming at 5 min (HEPTEM 37 ± 4 vs 43 ± 4 mm, P < 0.001; EXTEM 37 ± 4 vs 43 ± 4 mm, P < 0.001; FIBTEM 3 ± 2 vs 9 ± 2 mm, P < 0.001) and at 60 min (HEPTEM 29 ± 9 vs 38 ± 5 mm, P < 0.001; EXTEM 30 ± 7 vs 39 ± 5 mm, P < 0.001; FIBTEM 3 ± 2 vs 8 ± 3 mm, P = 0.002). The EXTEM clotting time was longer with dextran-based solution at 5 (109 ± 19 vs 63 ± 7 sec, P < 0.001) and at 60 min (176 ± 72 vs 73 ± 7 sec, P = 0.004). The novel miniaturized roller pump circuit can be used to mimic extracorporeal circulation for selected research questions. Dextran-based priming caused a significant impairment in haemostasis compared with a standard crystalloid solution.

Clinical, Laboratory Aspects and Management of Factor X Deficiency.

Coagulation factor X (FX), originally named Stuart-Prower factor, plays a pivotal role in the coagulation cascade, activating thrombin to promote platelet plug formation and prevent excess blood loss. Genetic variants in F10 may lead to FX deficiency and to impaired coagulation. FX variants are phenotypically classified as being type I, with the concomitant reduction of FX coagulant activity and FX antigen levels or type II, corresponding to a reduction in activity with normal antigen plasma levels. Patients affected with FX deficiency tend to be one of the most seriously affected among those with rare bleeding disorders. They show a variable bleeding tendency strongly associated with FX coagulant activity levels in plasma and may present, in the severe form of the deficiency, life-threatening symptoms such as gastrointestinal and umbilical stump bleeding and intracranial hemorrhages or central nervous system bleeding. Treatment of FX deficiency was originally based on the replacement of the missing factor using fresh frozen plasma, cryoprecipitate and prothrombin complex concentrates; however, a plasma-derived concentrate, shown to be safe and effective in clinical trials, is now available. In addition, novel nonreplacement therapy such as small interference RNA, gene therapy, drug repurposing, and gene editing may also represent novel therapeutic approaches for FX deficiency, but further, much focused studies are needed before considering this emerging therapy in such patients.

Effects of physical training on coagulation parameters, interleukin-6, and angiotensin-converting enzyme-2 in COVID-19 survivors

COVID-19 is a highly contagious virus that uses Angiotensin-converting enzyme 2 (ACE2) as a receptor to enter human cells. The virus leads to an increase in inflammatory cytokines (i.e. IL-6) and an impaired coagulation system, which can cause serious complications during and after the disease. Physical exercise has been shown to improve COVID-19 complications through various mechanisms, such as modulation of the immune and coagulation systems. Therefore, this study investigated the effects of 8 weeks of training on inflammatory, coagulation, and physical factors in patients with COVID-19 during the recovery phase. Twenty-seven male and female volunteers (age 20–45 years) who recently recovered from COVID-19 were assigned to the control (n = 13) or the training group (n = 14). Blood samples, aerobic capacity and muscle endurance were collected 24 h before the start of the interventions and 24 h after the final training session in week 4 and 48 h after the final training session in week 8. IL-6, ACE2, fibrinogen, and D-dimer were measured using ELISA. The training group showed a significant increase in muscle endurance (p = 0.004) and aerobic capacity (p = 0.009) compared to the control group. Serum levels of IL-6 and fibrinogen decreased in the training group but this decrease was not statistically significant (p > 0.05). Despite a slight increase in the quality of life and sleep in the training group, no statistically significant difference was observed between the training and the control group. It appears that physical training has beneficial effects on the coagulation system, inflammatory factors, and sleep quality and can facilitate the recovery of COVID-19 patients.

Scientific opinion on the tolerable upper intake level for vitamin E.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for vitamin E. As α-tocopherol is recognised as the only essential form of vitamin E, the Panel restricted its evaluation to α-tocopherol. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of vitamin E, namely risk of impaired coagulation and bleeding, cardiovascular disease and prostate cancer. The effect on blood clotting and associated increased risk of bleeding is considered as the critical effect to establish an UL for vitamin E. No new evidence has been published that could improve the characterisation of a dose-response. The ULs for vitamin E from all dietary sources, which were previously established by the Scientific Committee on Food, are retained for all population groups, i.e. 300 mg/day for adults, including pregnant and lactating women, 100 mg/day for children aged 1-3 years, 120 mg/day for 4-6 years, 160 mg/day for 7-10 years, 220 mg/day for 11-14 years and 260 mg/day for 15-17 years. A UL of 50 mg/day is established for infants aged 4-6 months and a UL of 60 mg/day for infants aged 7-11 months. ULs apply to all stereoisomeric forms of α-tocopherol. ULs do not apply to individuals receiving anticoagulant or antiplatelet medications (e.g. aspirin), to patients on secondary prevention for CVD or to patients with vitamin K malabsorption syndromes. It is unlikely that the ULs for vitamin E are exceeded in European populations, except for regular users of food supplements containing high doses of vitamin E.

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.

Acquired hemophilia successfully treated with recombinant factor VIIa: A case report

Acquired Hemophilia A (AHA) is a disorder characterized by the impaired clotting ability of the blood, primarily resulting from a deficiency in factor VIII, a crucial clotting protein. It is an infrequent disorder that affects a minority of individuals. This condition can pose a life-threatening risk, with reported mortality rates reaching as high as 22%. The diagnosis of AHA is challenging owing to its non-specific presentation and low prevalence rate. The primary objectives of treatment for AHA encompass the cessation and prevention of bleeding episodes, eradication of the inhibitor, and management of the underlying disease in secondary cases. This case report summarizes the successful treatment of a patient with AHA and major bleeding with the repeated use of prednisolone, recombinant factor VIIa, and rituximab.

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.

Pro‑coagulant Considerations in Patients with Arterial Hypertension and Multifocal Atherosclerosis

The aim of the work to determine the features of hemostasis and blood rheology in patients with arterial hypertension (HTN) and multifocal atherosclerosis (MFA).Materials and methods. The study enrolled male and female patients aged from 40 to 70 years, including 59 patients with controlled stage I–II hypertension and multifocal vascular lesions (Group 1) and 42 patients with controlled stage III hypertension, who have suffered an ischemic stroke and have multifocal vascular lesions (Group 2). A test using the Thrombodynamics analyser system T-2 (GemaKor, LLC, Moscow, Russia) was performed to detect the impairment of hemostasis.Results. Patients with HTN and MFA have an impaired coagulation hemostasis system (an increase in the initial and stationary clot growth rate and the size of the clot, as well as the presence of spontaneous clots), which leads to a high residual risk of cerebral complications, despite BP lowering to target figures and control of lipid profile.Discussion. Elevated blood pressure in patients with MFA leads to endothelial dysfunction, which is accompanied by activation of coagulation and fibrinolysis pathways. These changes lead to a violation of microcirculatory hemostasis in the brain, the development and progression of cerebral ischemia, and subsequently the occurrence of stroke, both the first and repeated.Conclusion. An important result of this study is the first registered change in the coagulation link of hemostasis in patients with HTN and MFA aged from 40 to 70 years, which can be considered an additional criterion for stroke prediction.

Temperature effect on coagulation function in mild hypothermic patients undergoing thoracic surgeries: thromboelastography (TEG) versus standard tests

PurposeOur previous research has revealed that mild hypothermia leads to excessive bleeding in thoracic surgeries, while the underlying mechanism stayed unrevealed by the standard coagulation tests. The research question in this study was as follows: “How does mild hypothermia impair the hemostatic function in patients receiving thoracic surgeries?”. The purpose was to detect the disturbed coagulation processes by comparing the TEG parameters in patients receiving active vs. passive warming during thoracic surgeries.MethodsStandard coagulation tests and thromboelastography (TEG) were adopted to compare the hemostatic functions in patients receiving active vs. passive warming during thoracic surgeries. Furthermore, blood samples from passive warming group were retested for TEG at actual core body temperatures.ResultsSixty-four eligible patients were included in this study. TEG revealed that mild hypothermia significantly disturbed coagulation by decreasing MA (59.4 ± 4.5 mm vs. 64.2 ± 5.7 mm, p = 0.04) and α angle (70.4 ± 5.2° vs. 74.9 ± 4.4°, p = 0.05) and prolonging ACT (122.2 ± 19.3 s vs. 117.3 ± 15.2 s, p = 0.01) and K time (1.9 ± 1.0 s vs. 1.3 ± 0.4 min, p = 0.02). TEGs conducted under core body temperatures revealed more impaired coagulation than those incubated at 37 °C. Furthermore, postoperative shivering and waking time were significantly increased in mild hypothermic patients.ConclusionMild hypothermia significantly impaired coagulation function in patients receiving thoracic surgeries, which could be detected by TEGs other than the standard coagulation tests. Temperature-adjusted TEGs may provide a preferable method of hemostatic monitoring and transfusion guidance in thoracic surgeries, which warrants further clinical investigations.

Extensive ecchymosis and retroperitoneal hemorrhage due to acquired hemophilia-A following influenza vaccination: A case report.

Acquired hemophilia-A (AHA) is a rare but potentially life-threatening impaired coagulation disorder characterized by the development of autoantibodies against clotting factor VIII. Only a few case reports have been experienced with influenza vaccine-triggered AHA. Here, we report a case of severe hemorrhagic disorder due to AHA following influenza vaccine, which was successfully treated. The patient presented to the emergency department because of several severe, progressively worsening bruises after receiving the influenza vaccination. Consequently, the patient required intubation due to nasal-oral bleeding, which compromised the airway, and retroperitoneal hemorrhage with shock also developed. AHA was confirmed through a coagulation factor assay, including coagulation activity and antibody testing, which is possibly triggered by influenza vaccination. Low-dose cyclophosphamide and hydrocortisone were prescribed until activated partial thromboplastin time showed normal levels. Coagulation factor VIIa was administered, and aggressive blood transfusion was carried out concurrently to address the blood loss. The upper airway bleeding subsided and bleeding tendencies had been corrected to normal. The patient was smoothly weaned from the ventilator and recovered from critical illness. She was then discharged on the 19th day. The activated partial thromboplastin time mixing test can be performed immediately to establish the initial differential diagnosis and treatment plan for severe coagulopathy. AHA may be triggered by vaccination, with the hypothesis of activation of autoantibodies and molecular mimicry; this mechanism should be further studied.

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.

Mechanisms of Pulmonary Vasculopathy in Acute and Long-Term COVID-19: A Review.

Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of its pathogenesis, highlighting the fact that there is a specific pulmonary vascular disorder. Indeed, COVID-19 may predispose patients to thrombotic disease in both venous and arterial circulation, and many cases of severe acute pulmonary embolism have been reported. The demonstrated presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the endothelial cells suggests that direct viral effects, in addition to indirect effects of perivascular inflammation and coagulopathy, may contribute to pulmonary vasculopathy in COVID-19. In this review, we discuss the pathological mechanisms leading to pulmonary vascular damage during acute infection, which appear to be mainly related to thromboembolic events, an impaired coagulation cascade, micro- and macrovascular thrombosis, endotheliitis and hypoxic pulmonary vasoconstriction. As many patients develop post-COVID symptoms, including dyspnea, we also discuss the hypothesis of pulmonary vascular damage and pulmonary hypertension as a sequela of the infection, which may be involved in the pathophysiology of long COVID.

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.