Coagulation Dysfunction Research Articles

The significance of hyperglycaemia and other comorbidities during the COVID‐19 pandemic

The significance of hyperglycaemia and other comorbidities during the <scp>COVID</scp>‐19 pandemic

Extracellular histones and xenotransplantation.

Xenotransplantation may be an alternative source of organs for patients with end-stage organ failure, but problems remain to be overcome. Five factors that are problematic are (a) a sustained systemic inflammatory response in the xenograft recipient, (b) thrombotic microangiopathy and disseminated intravascular coagulation, (c) ischemia-reperfusion injury, (d) complement activation, and (e) vascular endothelial cell injury. In xenotransplantation, histones, which are positively charged proteins, are released into the extracellular space from damaged and activated cells, cause cell and tissue damage, and act as danger/damage-associated molecular patterns (DAMPs) that mediate inflammation, coagulation disorders, an immune response, and cytotoxicity. We have previously demonstrated that serum histones increase after pig-to-baboon organ transplantation and infection. Treatment of the recipient with tocilizumab (interleukin-6 receptor blockade) reduces the level of serum histones and C-reactive protein. In this review, the potential role of extracellular histones in xenotransplantation is discussed, and we briefly summarize the relationship between extracellular histones and the inflammatory response, coagulation dysfunction, ischemia-reperfusion injury, the complement system, and vascular endothelial cell injury.

Mesenchymal stem cell research progress for the treatment of COVID-19.

At the end of 2019, novel coronavirus (COVID-19) infection was detected in Wuhan City, Hubei Province, China. The COVID-19 infection characteristics include a long incubation period, strong infectivity, and high fatality rate, and it negatively affects human health and social development. COVID-19 has become a common problem in the global medical and health system. It is essentially an acute self-limiting disease. Patients with severe COVID-19 infection usually progress to acute respiratory distress syndrome, sepsis, metabolic acidosis that is difficult to correct, coagulation dysfunction, multiple organ failure, and even death within a short period after onset. There remains a lack of effective drugs for such patients clinically. Mesenchymal stem cells (MSCs) are expected to reduce the risk of complications and death in patients because they have strong anti-inflammatory and immunomodulatory capabilities, which can improve the microenvironment, promote neovascularization, and enhance tissue repair capabilities. China is currently conducting several clinical trials on MSCs for the treatment of COVID-19. Here, we review the research progress related to using stem cells to treat patients with COVID-19.

188. The safety and efficacy of hydrogen peroxide in controlling blood loss and surgical site infection after multi-segmental lumbar spine surgery: a retrospective, case-controlled study of 2,626 patients

BACKGROUND CONTEXT Multiple-level lumbar fusion surgery is associated with prolonged duration of surgery and significant blood loss, which are deemed significant risk factors for postoperative SSI. Controlling the blood loss and improving local resistance to pathogens is extremely valuable to reduce perioperative complications, including SSI, and speed up recovery after surgery. Concerns regarding the safety profile of TXA, whether it increases the incidence of thromboembolic events, such as deep vein thrombosis (DVT), pulmonary embolism (PE), and myocardial infarctions (MI), have been raised frequently, especially for the patients who have accompanying cardiovascular and cerebrovascular diseases, which are relatively common in patients with degenerative spinal disease. Additionally, it is strongly debated whether the usage of vancomycin powder can induce culture-negative seroma formation and affect bone healing. Hydrogen peroxide (H2O2) is an inexpensive and readily available option whose hemostatic and antiseptic properties have been separately confirmed in several previous studies. However, whether H2O2 can integrate the advantages of vancomycin and TXA in controlling blood loss and postoperative SSI simultaneously after lumbar spine surgery has not been explored, neither have its complications. PURPOSE This study aimed to explore the safety and efficacy of H2O2 in controlling blood loss and SSI after multi-segmental lumbar spine surgery. STUDY DESIGN/SETTING Retrospective case-control study. PATIENT SAMPLE A total of 2,626 patients who underwent multi-segmental lumbar spinal surgery between January 2015 and January 2018 were included in this study. According to whether H2O2 irrigation was applied, they were divided into control group (1,345 patients) and experimental group (1,281 patients).The inclusion criteria were: (1) patients were diagnosed with thoracic and/or lumbar degenerative diseases, such as spinal canal stenosis, disc herniation, spondylolisthesis, and/or degenerative scoliosis; (2) patients treated with multilevel (operated level > 2) posterior lumbar interbody fusion (PLIF) with or without posterolateral fusion. The exclusion criteria were: patients diagnosed with spinal fracture-dislocation, infection, tuberculosis, tumor, congenital spinal deformity or received revision surgery; patients with a coagulation or hemoglobin dysfunction before surgery; dura tear accompanied by cerebrospinal fluid leakage detected intraoperatively; the perioperative use of hemostatic agents such as TXA or treatment with antifibrinolytic drugs. OUTCOME MEASURES The primary outcome evaluated was the incidence of SSI. The definition of SSI including superficial and deep infection after lumbar spinal surgery was derived from the guidelines published by the U.S. Centers for Disease Control and Prevention. Superficial infection is defined as occurring within 30 days after surgery, involving only the incision skin and subcutaneous tissue. Deep infection is defined as occurring within 1 year after operation, characterized by superficial infection, the involving fascia and myometrium. Besides the demographic parameters, the laboratory examination results and surgery related information such as operative time, numbers of operated levels, intraoperative blood loss, postoperative drainage, postoperative SSI and extubation time were recorded. The perioperative complications including pneumocephalus, symptomatic DVT, PE and MI were included in the evaluation. METHODS A standard posterior midline incision and exposure was applied; and irrigation with 1 L of saline was performed before skin closure in all patients. For the experimental group, the incision was soaked with 50 mL of 3% H2O2 solution for 30 s before the saline irrigation. RESULTS No significant differences were seen regarding demographic parameters, laboratory examination results, comorbidities and surgical related information. The extubation time and postoperative drain collection were lower in the experimental group (3.6±0.5 days vs 4.1±0.6, p=0.402; 251.8±67.5 vs 291.8±71.3, p=0.013). In the control group, the rate of SSI was 2.4% (32/1345), including 17 superficial wound infections and 15 deep wound infections. In the experimental group, the SSI rate was 1.4% (18/1281), including 15 patients with superficial wound infection and three with deep wound infection. Staphylococcus aureus was the most common organism, especially in the experimental group (66.7% vs 50%). There was no significant difference between both groups in the perioperative complications such as hematencephalon, DVT, PE and MI (p>0.05, respectively). Pneumocephalus was not observed in either group. CONCLUSIONS The application of H2O2 in PLIF does not increase the perioperative complications such as hematencephalon, DVT, PE, MI, and especially pneumocephalus; it also reducing the blood loss and SSI after surgery, which is quite promising for patients with a high risk of thromboembolic events and beneficial for controlling the increasing number of vancomycin-resistant bacteria. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Pathophysiology and Pathology of Acute Kidney Injury in Patients With COVID-19.

Acute kidney injury (AKI) is common among hospitalized patients with Coronavirus Infectious Disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. The variability in the occurrence of AKI has been attributed to the difference in geographic locations, race/ethnicity, and severity of illness. AKI among hospitalized patients is associated with increased length of stay and in-hospital deaths. Even patients with AKI who survive to hospital discharge are at risk of developing chronic kidney disease or end-stage kidney disease. An improved knowledge of the pathophysiology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who developed AKI during COVID-19. The goal of this article is to provide our current understanding of the etiology and the pathophysiology of AKI in the setting of COVID-19.

A clinical coagulopathy score concurrent with viscoelastic testing defines opportunities to improve hemostatic resuscitation and enhance blood product utilization during liver transplantation

BackgroundAn NIH clinical coagulopathy score has been devised for trauma patients, but no such clinical score exists in transplantation surgery. We hypothesize that that this coagulopathy score can effectively identify laboratory defined coagulopathy during liver transplantation and correlates to blood product utilization. MethodsTEGs were performed and coagulopathy scores (1, normal bleeding – 5, diffuse coagulopathic bleeding) were assigned by the surgeons at 5 intra-operative time points. Blood products used during the case were recorded between time points. Statistical analyses were performed to identify correlations between coagulopathy scores, TEG-detected abnormalities, and blood product utilization. ResultTransfusions rarely correlated with the appropriate TEG measurements of coagulation dysfunction. Coagulopathy score had significant correlation to various transfusions and TEG-detected coagulopathies at multiple points during the case. High aggregate coagulopathy scores identified patients receiving more transfusions, re-operations, and longer hospital stays ConclusionThe combination of viscoelastic testing and a standardized clinical coagulopathy score has the potential to optimize transfusions if used in tandem as well as standardize communication between surgery and anesthesia teams about clinically evident coagulopathy.

Application of an elevated plasma D-dimer cut-off value improves prognosis prediction of advanced non-small cell lung cancer.

BackgroundTumor-related coagulation dysfunction has been reported to be closely associated with poor prognosis. The present study is aimed to evaluate the prognostic prediction of an elevated plasma D-dimer cut-off value in advanced non-small cell lung cancer (NSCLC).MethodsA total of 233 patients initially diagnosed with advanced NSCLC were retrospectively analyzed, an elevated plasma cut-off value 981 ng/mL of D-dimer, which was instead of the clinical cut-off value 500 mg/mL, was used to determine the high and low. Univariate analysis using the Kaplan-Meier method and log-ranking test, and the multivariate analysis using the Cox proportional hazard regression model were performed.ResultsResults showed when using the D-dimer value of 500 ng/mL as an evaluation standard, there was no significant difference in gender, age, smoking status, histopathology and overall survival rate between normal D-dimer (≤500 ng/mL) and high D-dimer (>500 ng/mL) group. However, when the evaluation standard for plasma D-dimer was set at 981 ng/mL, the age distribution of the high D-dimer (>981 ng/mL) group was significantly different from the normal D-dimer (≤981 ng/mL) group. Moreover, the overall survival rate in the high D-dimer (>981 ng/mL) group was significantly lower than that in the normal D-dimer (≤981 ng/mL) group.ConclusionsThe present study implied that increasing the plasma D-dimer cut-off value to 981 ng/mL is more beneficial to prognosis prediction in advanced NSCLC.

Standards of care for Kasabach-Merritt phenomenon in China.

Kasabach-Merritt phenomenon (KMP) is a rare disease that is characterized by severe thrombocytopenia and consumptive coagulation dysfunction caused by kaposiform hemangioendothelioma or tufted hemangioma. This condition primarily occurs in infants and young children, usually with acute onset and rapid progression. This review article introduced standardized recommendations for the pathogenesis, clinical manifestation, diagnostic methods and treatment process of KMP in China, which can be used as a reference for clinical practice.

Research epidemiology, Clinical Manifestation and Laboratory Findings of Severe Adenovirus Pneumonia in the Intensive Care Unit of Thanh Hoa Pediatric Hospital

Objective: To describe the epidemiology, clinical manifestation and laboratory findings of severe adenovirus pneumonia in the ICU of Thanh Hoa Pediatric Hospital.&#x0D; Subject and Method: This is a descriptive study with the enrollment of 90 patients diagnosed with severe and very-severe adenovirus pneumonia form 11/2016 to 06/2018 in the ICU of Thanh Hoa Pediatric Hospital.&#x0D; Result: the male and female ratio is 5:1, under 12 months of age patients accounted for 84.4%. The infection was mostly happened in the healthcare facility at 56.7%. The majority of the patients had high grade fever (&gt;39oC) and lasted 7 days: 56.7% and 60%. 82.2% patients had symptoms of upper respiratory tract infection, 40% had gastrointestinal symptoms,16.7% and 8.7% had conjunctivitis and rash, respectively. Respiratory failure, crackles, hepatomegaly: 78.9%, 93.4% and 52.2% respectively. SIRS, septic shock, multiorgans failure: 78.9%, 52.2% and 34.4% respectively. Neutrophilia 32.2%, low hemoglobin count 72.2%, coagulation dysfunction 68.6%, elevated CRP (&gt; 10 mg/dL) 80%, elevated procalcitonin (&gt;0.05 ng/L) 96.7%, low total plasma protein (&lt;55 g/L) 50%, low plasma albumin (≤ 35g/L) 74.4%, elevated GOT (≥100U/L) 53%. There was 81.3% of the patients had low oxygenated blood conversion rate. Decreased humoral immunity 29.4%, decreased cell-mediated immunity 84%. In conventional chest Xray, the most common findings were localized or diffused infiltrations: 42.2% and 46.7% respectively. Co-infection 43.3%; Co-CMV infection 74.5%, Co-EBV infection 22.2%. About 18.9% of the case had positive culture.&#x0D; Conclusion: mainly under 12 months of age children got infected with the most common source of infection is from the hospital. Prolonged length of stay.Unspecific signs and symptoms.Hypoxemia, high rate of co-infection. In Xray, main findings were diffuse infiltration or localized. The majoritiy of the patients had decreased cell-mediated immunity.

Intranasal exposure of African green monkeys to SARS-CoV-2 results in acute phase pneumonia with shedding and lung injury still present in the early convalescence phase

We recently reported the development of the first African green monkey (AGM) model for COVID-19 based on a combined liquid intranasal (i.n.) and intratracheal (i.t.) exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we followed up on this work by assessing an i.n. particle only route of exposure using the LMA mucosal atomization device (MAD). Six AGMs were infected with SARS-CoV-2; three animals were euthanized near the peak stage of virus replication (day 5) and three animals were euthanized during the early convalescence period (day 34). All six AGMs supported robust SARS-CoV-2 replication and developed respiratory disease. Evidence of coagulation dysfunction as noted by a transient increases in aPTT and circulating levels of fibrinogen was observed in all AGMs. The level of SARS-CoV-2 replication and lung pathology was not quite as pronounced as previously reported with AGMs exposed by the combined i.n. and i.t. routes; however, SARS-CoV-2 RNA was detected in nasal swabs of some animals as late as day 15 and rectal swabs as late as day 28 after virus challenge. Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals. These findings are consistent with human COVID-19 further demonstrating that the AGM faithfully reproduces the human condition.

Management plan of a paediatric outpatient department during the SARS-CoV-2 epidemic.

With the novel coronavirus (2019-nCoV) infection outbreak and spread, serious cases of infection and neonatal infection have been reported. Moreover, children show milder cases and a better prognosis than adults. The outpatient Department of Paediatrics has played a crucial role in the prevention and control of novel coronavirus (2019-nCoV) infection in children. Based on previous experience and existing diagnosis and treatment guidelines, we present the relevant strategies of this particular paediatric outpatient department when responding to the epidemic. Conclusion: Concurrently, we hope that this article can act as a reference in the fight against SARS-CoV-2 infection. Further modifications will be made in the future with the increase in clinical experience and changes in the disease. This article is protected by copyright. All rights reserved.

Derivation and Validation of Novel Phenotypes of Multiple Organ Dysfunction Syndrome in Critically Ill Children

Multiple organ dysfunction syndrome (MODS) is a dynamic and heterogeneous process associated with high morbidity and mortality in critically ill children. To determine whether data-driven phenotypes of MODS based on the trajectories of 6 organ dysfunctions have prognostic and therapeutic relevance in critically ill children. This cohort study included 20 827 pediatric intensive care encounters among 14 285 children admitted to 2 large academic pediatric intensive care units (PICUs) between January 2010 and August 2016. Patients were excluded if they were older than 21 years or had undergone cardiac surgery. The 6 subscores of the pediatric Sequential Organ Failure Assessment (pSOFA) score were calculated for the first 3 days, including the subscores for respiratory, cardiovascular, coagulation, hepatic, neurologic, and renal dysfunctions. MODS was defined as a pSOFA subscore of at least 2 in at least 2 organs. Encounters were split in a 80:20 ratio for derivation and validation, respectively. The trajectories of the 6 subscores were used to derive a set of data-driven phenotypes of MODS using subgraph-augmented nonnegative matrix factorization in the derivation set. Data analysis was conducted from March to October 2019. The primary exposure was phenotype membership. In the subset of patients with vasoactive-dependent shock, the interaction between hydrocortisone and phenotype membership and its association with outcomes were examined in a matched cohort. The primary outcome was in-hospital mortality. Secondary outcomes included persistent MODS on day 7, and vasoactive-free, ventilator-free, and hospital-free days. Regression analysis was used to adjust for age, severity of illness, immunocompromised status, and study site. There were 14 285 patients with 20 827 encounters (median [interquartile range] age 5.2 years [1.5-12.7] years; 11 409 [54.8%; 95% CI, 54.1%-55.5%] male patients). Of these, 5297 encounters (25.4%; 95% CI, 24.8%-26.0%) were with patients who had MODS, of which 5054 (95.4%) met the subgraph count threshold and were included in the analysis. Subgraph augmented nonnegative matrix factorization uncovered 4 data-driven phenotypes of MODS, characterized by a combination of neurologic, respiratory, coagulation, and cardiovascular dysfunction, as follows: phenotype 1, severe, persistent encephalopathy (1019 patients [19.2%]); phenotype 2, moderate, resolving hypoxemia (1828 patients [34.5%]); phenotype 3, severe, persistent hypoxemia and shock (1012 patients [19.1%]); and phenotype 4, moderate, persistent thrombocytopenia and shock (1195 patients [22.6%]). These phenotypes were reproducible in a validation set of encounters, had distinct clinical characteristics, and were independently associated with outcomes. For example, using phenotype 2 as reference, the adjusted hazard ratios (aHRs) for death by 28 days were as follows: phenotype 1, aHR of 3.0 (IQR, 2.1-4.3); phenotype 3, aHR of 2.8 (IQR, 2.0-4.1); and phenotype 4, aHR of 1.8 (IQR, 1.2-2.6). Interaction analysis in a matched cohort of patients with vasoactive-dependent shock revealed that hydrocortisone had differential treatment association with vasoactive-free days across phenotypes. For example, patients in phenotype 3 who received hydrocortisone had more vasoactive-free days than those who did not (23 days vs 18 days; P for interaction < .001), whereas patients in other phenotypes who received hydrocortisone either had no difference or had less vasoactive-free days. In this study, data-driven phenotyping in critically ill children with MODS uncovered 4 distinct and reproducible phenotypes with prognostic relevance and possible therapeutic relevance. Further validation and characterization of these phenotypes is warranted.

Effect of temperature maintenance by forced-air warming blankets of different temperatures on changes in inflammatory factors in children undergoing congenital hip dislocation surgery.

BackgroundHypothermia is associated with many adverse clinical outcomes in pediatric patients, and thus, it is important to find an effective and safe method for preventing peri-operative hypothermia and its associated adverse outcomes in pediatric patients. This study aimed to investigate the effect of forced-air warming blankets with different temperatures on changes in the transforming growth factor-β (TGF-β), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10 levels in children undergoing surgical treatment for developmental displacement of the hip (DDH).MethodsThe study included 123 children undergoing surgery for DDH under general anesthesia. The patients were randomly assigned to three groups, using a random number table: the 32, 38, and 43°C groups according to the temperature setting of the forced-air warming blankets. For each patient, body temperature was recorded immediately after anesthesia induction and intubation (T0), at initial incision (T1), at 1 h after incision (T2), at 2 h after incision (T3), at the end of surgery (T4), immediately upon return to the ward after surgery (T5), and then at 12 h (T6), 24 h (T7), 36 h (T8), and 48 h (T9) after the surgery. The serum levels of TGF-β, TNF-α, IL-1β, and IL-10 were measured at T0 and T4 for all groups.ResultsThe number of patients with fever in the 38°C group was significantly less than those in the 32 and 43°C groups (χ2 = 6.630, P = 0.036). At T0, the body temperatures in the 38 and 43°C groups were significantly higher than that in the 32°C group (F = 17.992, P < 0.001). At T2, the body temperature was significantly higher in the 43°C group than those in the 32 and 38°C groups (F = 12.776, P < 0.001). Moreover, at T4, the serum levels of TGF-β (F = 3286.548, P < 0.001) and IL-10 (F = 4628.983, P < 0.001) were significantly increased in the 38°C group, and the serum levels of TNF-α (F = 911.415, P < 0.001) and IL-1β (F = 322.191, P < 0.001) were significantly decreased in the 38°C group, compared with the levels in the 32 and 43°C groups.ConclusionForce-air warming blankets set at 38°C maintained stable body temperature with less adverse outcome and effectively inhibited the inflammatory response in pediatric patients undergoing surgery for DDH.Clinical trial registrationChiCTR1800014820; http://www.chictr.org.cn/showproj.aspx?proj=25240.

Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection.

Understanding the pathophysiology of SARS-CoV-2 infection is critical for therapeutic and public health strategies. Viral-host interactions can guide discovery of disease regulators, and protein structure function analysis points to several immune pathways, including complement and coagulation, as targets of coronaviruses. To determine whether conditions associated with dysregulated complement or coagulation systems impact disease, we performed a retrospective observational study and found that history of macular degeneration (a proxy for complement-activation disorders) and history of coagulation disorders (thrombocytopenia, thrombosis and hemorrhage) are risk factors for SARS-CoV-2-associated morbidity and mortality-effects that are independent of age, sex or history of smoking. Transcriptional profiling of nasopharyngeal swabs demonstrated that in addition to type-I interferon and interleukin-6-dependent inflammatory responses, infection results in robust engagement of the complement and coagulation pathways. Finally, in a candidate-driven genetic association study of severe SARS-CoV-2 disease, we identified putative complement and coagulation-associated loci including missense, eQTL and sQTL variants of critical complement and coagulation regulators. In addition to providing evidence that complement function modulates SARS-CoV-2 infection outcome, the data point to putative transcriptional genetic markers of susceptibility. The results highlight the value of using a multimodal analytical approach to reveal determinants and predictors of immunity, susceptibility and clinical outcome associated with infection.

COVID-19 and coagulation dysfunction in adults: A systematic review and meta-analysis.

The outbreak of 2019 novel coronavirus disease (COVID‐19) has posed a grave threat to the global public health. The COVID‐19‐induced infection is closely related to coagulation dysfunction in the affected patients. This paper attempts to conduct a meta‐analysis and systematically review the blood coagulation indicators in patients with severe COVID‐19. A meta‐analysis of eligible studies was performed to compare the blood coagulation indicators in patients with severe and nonsevere COVID‐19. PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies published between 1 December 2019 and 7 May 2020. A total of 13 studies with 1341 adult patients were enrolled in this analysis. Platelet (weighted mean difference [WMD] = −24.83, 95% confidence interval [CI]: −34.12 to −15.54; P < .001), d‐dimer (WMD = 0.19, 95% CI: 0.09‐0.29; P < .001), and fibrinogen (WMD = 1.02, 95% CI: 0.50‐1.54; P < .001) were significantly associated with the severity in patients with COVID‐19. The meta‐analysis revealed that no correlation was evident between an increased severity risk of COVID‐19 and activated partial thromboplastin time (WMD = −1.56, 95% CI: −5.77 to 2.64; P = .468) or prothrombin time (WMD = 0.19, 95% CI: −0.13 to 0.51; P = .243). The single arm meta‐analysis showed that compared with the nonsevere group, the severe group had a lower pooled platelet (165.12 [95% CI: 157.38‐172.85] vs 190.09 [95% CI: 179.45‐200.74]), higher d‐dimer (0.49 [95% CI: 0.33‐0.64] vs 0.27 [95% CI: 0.20‐0.34]), and higher fibrinogen (4.34 [95% CI: 1.98‐6.70] vs 3.19 [95% CI: 1.13‐5.24]). Coagulation dysfunction is closely related to the severity of patients with COVID‐19, in which low platelet, high d‐dimer, and fibrinogen upon admission may serve as risk indicators for increased aggression of the disease. These findings are of great clinical value for timely and effective treatment of the COVID‐19 cases.

Clinical characteristics of COVID-19 in patients with preexisting ILD: A retrospective study in a single center in Wuhan, China.

Since the outbreak of 2019 novel coronavirus (SARS‐CoV‐2) pneumonia, many patients with underlying disease, such as interstitial lung disease (ILD), were admitted to Tongji hospital in Wuhan, China. To date, no data have ever been reported to reflect the clinical features of Corona Virus Disease 2019 (COVID‐19) among these patients with preexisting ILD. We analyzed the incidence and severity of COVID‐19 patients with ILD among 3201 COVID‐19 inpatients, and compared two independent cohorts of COVID‐19 patients with pre‐existing ILD (n = 28) and non‐ILD COVID‐19 patients (n = 130). Among those 3201 COVID‐19 inpatients, 28 of whom were COVID‐19 with ILD (0.88%). Fever was the predominant symptom both in COVID‐19 with ILD (81.54%) and non‐ILD COVID‐19 patients (72.22%). However, COVID‐19 patients with ILD were more likely to have cough, sputum, fatigue, dyspnea, and diarrhea. A very significantly higher number of neutrophils, monocytes, interleukin (IL)‐8, IL‐10, IL‐1β, and D‐Dimer was characterized in COVID‐19 with ILD as compared to those of non‐ILD COVID‐19 patients. Furthermore, logistic regression models showed neutrophils counts, proinflammatory cytokines (tumor necrosis factor‐alpha, IL6, IL1β, IL2R), and coagulation dysfunction biomarkers (D‐Dimer, PT, Fbg) were significantly associated with the poor clinical outcomes of COVID‐19. ILD patients could be less vulnerable to SARS‐CoV‐2. However, ILD patients tend to severity condition after being infected with SARS‐CoV‐2. The prognosis of COVID‐19 patients with per‐existing ILD is significantly worse than that of non‐ILD patients. And more, aggravated inflammatory responses and coagulation dysfunction appear to be the critical mechanisms in the COVID‐19 patients with ILD.

Localized intravascular coagulation in venous malformations: A system review.

Venous malformation is one of the slow-flow vascular malformations. Dysfunction of coagulation often occurs in most venous malformations, especially the diffuse and multifocal lesions, referred to as localized intravascular coagulopathy. It is characterized by the elevation of D-dimers and fibrin degradation products, low levels of fibrinogen, FV, FVIII, FXIII, and antithrombin III, and sometimes minor-to-moderate thrombocytopenia. Here we reviewed the clinical manifestations, pathogenesis, diagnosis, and treatment of localized intravascular coagulopathy in venous malformations.

Covid 19 Enfeksiyonu Olan Hastalarda Koagülasyon Sistem Anormallikleri

COVID-19 infection caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) in China led to a pandemic all over the world. Although mortality rate between 4.3% to 14.6%, studies have shown that coagulation dysfunction is a major cause of death in patients with severe COVID-19 infection. The majority of the severely ill patients have underlying disease (i.e. diabetes, cardiovascular disease, hypertension) and initially present with respiratory insufficiency but some of them progress to systemic disease causing multiple organ dysfunction. This manuscript reviews coagulation system abnormalities in patients with COVID-19 infection.

Characterization of a novel STAT 2 knock-out hamster model of Crimean-Congo hemorrhagic fever virus pathogenesis

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen causing a febrile illness in humans, which can progress to hemorrhagic manifestations, multi-organ failure, and death. Current mouse models of CCHFV infection reliably succumb to virus challenge but vary in their ability to reflect signs of disease similar to humans. In this study, we established a signal transducer and activator of transcription 2 (STAT2) knockout hamster model to expand the repertoire of animal models of CCHFV pathogenesis that can be used for therapeutic development. These hamsters demonstrated a systemic and lethal disease in response to infection. Hallmarks of human disease were observed including petechial rash, blood coagulation dysfunction, and various biochemistry and blood cell count abnormalities. Furthermore, we also demonstrated the utility of this model for anti-CCHFV therapeutic evaluation. The STAT2 knock-out hamster model of CCHFV infection may provide some further insights into clinical disease, viral pathogenesis, and pave the way for testing of potential drug and vaccine candidates.

Prevalence and Impact of Coagulation Dysfunction in COVID-19 in China: A Meta-Analysis.

Background The aim of this meta-analysis is to assess the prevalence of coagulation dysfunction in Chinese COVID-19 patients and to determine the association of coagulopathy with the severity and prognosis of COVID-19. Methods A meta-analysis of the prevalence of different abnormal coagulation indicators in COVID-19 patients in China was performed. The difference of coagulation indicators and the incidence of DIC were compared between severe cases and nonsevere cases as well as nonsurvivors and survivors, respectively. Results A total of 22 Chinese studies involving 4,889 confirmed COVID-19 inpatients were included. The average D-dimer value of COVID-19 patients is 0.67 µg/mL (95% confidence interval [CI]: 0.56–0.78), and 29.3% (95% CI: 20.1–38.5%) of patients showed elevated D-dimer values. Severe patients had significantly higher D-dimer levels and prolonged prothrombin time (PT) compared with nonsevere patients. Nonsurvivors had significantly higher D-dimer levels, prolonged PT, and decreased platelet count compared with survivors. In total, 6.2% (95% CI: 2.6–9.9%) COVID-19 patients were complicated by disseminated intravascular coagulation (DIC), in which the log risk ratio in nonsurvivors was 3.267 (95% CI: 2.191–4.342, Z = 5.95, p < 0.05) compared with that in survivors. Conclusion The prevalence of coagulopathy in Chinese COVID-19 inpatients is high, and both the abnormal coagulation indicators and DIC are closely associated with the severity and poor prognosis of these COVID-19 patients. Therefore, attention should be paid to coagulation dysfunction in COVID-19 patients. Closely monitoring of coagulation indicators and application of appropriate anticoagulation may improve the prognosis of COVID-19 inpatients in China.