Severe Coagulation Disorders Research Articles

Bromadiolone may cause severe acute kidney injury through severe disorder of coagulation: a case report

BackgroundBromadiolone is a wide-use long-acting anticoagulant rodenticide known to cause severe coagulation dysfunction. At present, there have been no detailed reports of acute kidney injury (AKI) resulting from bromadiolone poisoning.Case presentationA 27-year-old woman was admitted to the hospital due to severe coagulopathy and severe AKI. Coagulation test revealed a prothrombin time exceeding 120 s and an international normalized ratio (INR) greater than 10. Further examination for coagulation factors showed significantly reduced level of factors II, VII, IX and X, indicating a vitamin K deficiency. The AKI was non-oliguric and characterized by gross dysmorphic hematuria. Following the onset of the disease, the patient’s serum creatinine rose from 0.86 to 6.96 mg/dL. Suspecting anticoagulant rodenticide poisoning, plasma bromadiolone was identified at a concentration of 117 ng/mL via gas chromatography/mass spectrometry. All other potential causes of AKI were excluded, except for the presence of a horseshoe kidney. The patient’s kidney function fully recovered after the coagulopathy was corrected with high doses of vitamin K and plasma transfusion. At a follow-up 160 days post-discharge, the coagulation function had normalized, and the serum creatinine had returned to 0.51 mg/dL.ConclusionBromadiolone can induce AKI through a severe and prolonged coagulation disorder. Kidney function can be restored within days following treatment with high-dose vitamin K1.

Comparison between COVID-19 and DHF co-disease with COVID-19 alone in two pediatric sibling patients

We report herein the difference between Corona virus disease-19 (COVID-19) and dengue hemorrhagic fever (DHF) co-infection compared with COVID-19 alone in two pediatric sibling patients. This case report highlights a 10-year-old boy with both COVID-19 and DHF who had less severe coagulation disorder than his sister with COVID-19 alone. In a patient with a dual infection, the presence of dengue antibodies may induce immunological protection against COVID-19. We found reports of milder symptoms in patients who had dengue prior to SARS- CoV-2 infection; however, the opposite occured when SARS-CoV-2 infection precedes dengue.

Clinical characteristics of children with severe SARS-CoV-2 infection in Yunnan

Objective: To investigate the clinical characteristics of 130 children with severe SARS-CoV-2 infection in Yunnan province after the relaxation of non-pharmaceutical interventions, and analyze the risk factors for mortality. Methods: This study is a retrospective case summary that analyzed the demographic data, underlying diseases, clinical diagnoses, disease outcomes, and laboratory results of 130 children with severe COVID-19 infections admitted to nine top-tier hospitals in Yunnan Province from December 2022 to March 2023. According to the prognosis, the patients were divided into survival group and death group. The clinical and laboratory data between the two groups were compared, and the risk factors of death were evaluated. The χ2 test and Mann-Whitney U test were employed to compare between groups, while Spearman correlation test and multiple Logistic regression were used to analyze the risk factors for death. The predictive value of independent risk factors was evaluated by receiver operating characteristic curve. Results: The 130 severe patients included 80 males and 50 females with an onset age of 28.0 (4.5, 79.5) months. There were 97 cases in the survival group and 33 cases in the death group with no significant differences in gender and age between the two groups (P>0.05). Twenty-five cases (19.2%) out of the 130 patients had underlying diseases, and the number with underlying diseases was significantly higher in death group than in survival group (36.4% (12/33) vs. 13.4%(13/97), χ2=8.36, P=0.004). The vaccination rate in the survival group was significantly higher than that in the death group (86.1% (31/36) vs. 7/17, χ2=9.38, P=0.002). A total of 42 cases (32.3%) of the 130 patients were detected to be infected with other pathogens, but there was no significant difference in the incidence of co-infection between the death group and the survival group (39.3%(13/33) vs. 29.9% (29/97), χ2=1.02, P>0.05). Among the 130 cases, severe respiratory cases were the most common 66 cases (50.8%), followed by neurological severe illnesses 34 cases (26.2%) and circulatory severe 13 cases (10%). Compared to the survival group, patients in the death group had a significantly higher levels of neutrophil, ferritin, procalcitonin, alanine aminotransferase, lactate dehydrogenase, creatine kinase isoenzyme, B-type natriuretic peptide, interleukin-6 and 10 (6.7 (4.0, 14.0) vs. 3.0 (1.6, 7.0)×109/L, 479 (298, 594) vs. 268 (124, 424) μg/L, 4.8 (1.7, 10.6) vs. 2.0 (1.1, 3.1) μg/L, 66 (20, 258) vs. 23 (15, 49) U/L, 464 (311, 815) vs. 304 (252, 388) g/L, 71(52, 110) vs. 24(15, 48) U/L, 484 (160, 804) vs. 154 (26, 440) ng/L, 43 (23, 102) vs. 19 (13, 27) ng/L, 216 (114, 318) vs. 86 (45, 128) ng/L, Z=-4.21, -3.67, -3.76, -3.31, -3.75, -5.74, -3.55, -4.65, -5.86, all P<0.05). The correlated indexes were performed by multivariate Logistic regression and the results showed that vaccination was a protective factor from death in severe cases (OR=0.01, 95%CI 0-0.97, P=0.049) while pediatric sequential organ failure assessment (PSOFA) (OR=3.31, 95%CI 1.47-7.47, P=0.004), neutrophil-to-lymphocyte ratio (NLR) (OR=1.56, 95%CI 1.05-2.32, P=0.029) and D dimer (OR=1.49, 95%CI 1.00-1.02, P=0.033) were independent risk factors for death (all P<0.05). The area under the curve of the three independent risk factors for predicting death were 0.86 (95%CI 0.79-0.94), 0.89 (95%CI 0.84-0.95) and 0.87 (95%CI 0.80-0.94), all P<0.001, and the cut-off values were 4.50, 3.66 and 4.69 mg/L, respectively. Conclusions: Severe SARS-CoV-2 infection can occur in children of all ages, primarily affecting the respiratory system, but can also infect the nervous system, circulatory system or other systems. Children who died had more severe inflammation, tissue damage and coagulation disorders. The elevations of PSOFA, NLR and D dimer were independent risk factors for death in severe children.

Catastrophic Morbidly Adherent Posterior Placenta: Case Reports, Literature Review Current Through at Long Time Since Cases Registration

There are analyzed the difficulties and accuracy of diagnosis, in conjunction to the moment technical opportunities at long interval after registration (2009, 2012) in two cases of posterior Morbidly Adherent Placenta/Placenta Accreta Spectrum (MAP/PAS), with deep myometrial invasion (grade 3B) and uterine serosa perforation (grade 3E), a contemporary serious disease generating severe maternal coagulation disorders, multiple organ failure and hemorrhagic shock up to death, after total hemostasis hysterectomy. Undiagnosed or suspicious second trimester posterior MAP/PAS, in low-lying placenta, morbid obesity (BMI&gt;40), in an intact uterus, or in a scar uterus post cesarean delivery (CD) were followed by maternal death. In countries with low-to-middle income/ resources, and few centers of excellence, medical staff surgical qualities, and well trained interdisciplinary team must meet patients’ and their families trust and cooperation, and timely available life-saving resources for complex therapies in critical care cases, and hospital infrastructure to benefit from actual expanded knowledge and guidelines.

Neutrophil extracellular traps - a potential trigger for the development of thrombocytopenia during extracorporeal membrane oxygenation.

Neutrophil extracellular traps (NETs) have recently emerged as a potential link between inflammation, immunity, and thrombosis, as well as other coagulation disorders which present a major challenge in the context of extracorporeal membrane oxygenation (ECMO). By examining blood from ECMO patients for NETs and their precursors and correlating them with clinical and laboratory biomarkers of coagulation and inflammation, this study aims to evaluate the association between the presence of NETs in the bloodstream of ECMO patients and the development of potentially severe coagulation disorders during ECMO therapy. Therefore, blood samples were collected from healthy volunteers (n=13) and patients receiving veno-venous (VV) ECMO therapy (n=10). To identify NETs and their precursors, DNA and myeloperoxidase as well as granulocyte marker CD66b were visualized simultaneously by immunofluorescence staining in serial blood smears. Differentiation of DNA-containing objects and identification of NETs and their precursors was performed semiautomatically by a specific algorithm using the shape and size of DNA staining and the intensity of MPO and CD66b signal. Neutrophil extracellular traps and their precursors could be detected in blood smears from patients requiring VV ECMO. Compared to volunteers, ECMO patients presented significantly higher rates of NETs and NET precursors as well as an increased proportion of neutrophil granulocytes in all detected nucleated cells. A high NET rate prior to the initiation of ECMO therapy was associated with both increased IL-6 and TNF-α levels as an expression of a high cytokine burden. These patients with increased NET release also presented an earlier and significantly more pronounced decrease in platelet counts and ATIII activity following initiation of therapy compared with patients with less elevated NETs. These findings provide further indications for the development of immune-mediated acquired thrombocytopenia in ECMO patients.

Earliest Possible Detection and Intervention for Synovitis in Hemophilia- Results from a Single Center Retrospective Cohort Study

Introduction There is scientific evidence to suggest that the most serious health problems for hemophilic patients arise from joint damage, which in turn results from joint bleeding, which is overlooked and therefore not treated. The ankle joint was affected the earliest in most hemophilic patients. Strategies for detecting and treating bleeding in hemophilic patients need to be further developed and made more widely known by clinicians. Aim of our study The aim of our retrospective, single-center cohort study was to compare the effects of reactive versus preventive joint ultrasound as guidance for adjustments of treatment regimens for patients with severe hemophilia at our Hemophilia Comprehensive Care Center (HCCC) in Duisburg, Germany. Methods Before 2020, we used ultrasound according to the German hemophilia-synovitis guidelines in 2018. This meant that we sonographed the ankle joints and knees of most of our patients when they reported discomfort in the joint or when a joint bleeding had occurred. In these cases, prophylactic hemophilia treatment was immediately adjusted to a level at which the bleeding and/or discomfort stopped. If the factor treatment was not sufficient to accomplish this goal, the joints were treated with radiosynoviorthesis (RSO). In 2020, we changed our diagnostic strategy from reactive to preventive measures. Thus, we used ultrasound on every ankle and knee joint of our severely hemophilic patients at least once a year. If we found so called “silent symptoms,” which means touch-sensitive joints, the joints were sonographed once every three months. In cases of signs of joint degradation, we adjusted the prophylactic factor treatment accordingly. Results From 2020 to 2022, we examined a total of 1193 joints of 688 patients with hemophilia A or B, as well as with vWD disease type 2 or 3 and other severe coagulation disorders (factor VII deficiency, factor XIII deficiency, afibrinogenemia, and Glanzman disease). Of these, 103 had severe hemophilia A or B. In this study, we examined 656 joints sonographically. Of these, we examined 281 ankle joints in 80 patients and 175 knees in 64 patients, and adjusted the therapy regimens accordingly in these patients if necessary. Seven RSOs of the ankle joints and three RSOs of the knees were performed in the cohort up to 2020. After 2020, only two RSOs of the ankle joints were performed in the cohort. Conclusions At least for patients at our HCCC in Duisburg, Germany, we were able to show for the period 2020-2022 that closer ultrasound monitoring of ankle joints and knees in patients with severe hemophilia A or B and appropriate adjustment of prophylactic factor therapy was associated with less severe and less frequent joint degradation.

Antithrombin III activity is associated with prognosis, infection, and inflammation in patients with hepatitis B virus-related acute-on-chronic liver failure.

Patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) are characterized by severe liver function impairment, coagulation disorder, and multiple organ function impairment. The aim of this study was to explore the predictive value of antithrombin Ⅲ activity to the prognosis of HBV-ACLF patients. A total of 186 HBV-ACLF patients were included in the analysis, and the baseline clinical data of patients were recorded to analyze the risk factors affecting the 30-day survival outcome of patients. Bacterial infection, sepsis, and hepatic encephalopathy were observed in ACLF patients. Antithrombin Ⅲ activity and serum cytokine levels were determined. The antithrombin Ⅲ activity of ACLF patients in the death group was significantly lower than that in the survival group, and antithrombin Ⅲ activity was independent factors affecting the 30-day outcome. The areas under the receiver operation characteristic (ROC) curve of antithrombin Ⅲ activity to predict the 30-day mortality of ACLF was 0.799. Survival analysis showed that the mortality of patients with antithrombin Ⅲ activity less than 13% was significantly increased. Patients with bacterial infection and sepsis had lower antithrombin Ⅲ activity than those without infection. Antithrombin Ⅲ activity was positively correlated with platelet count, fibrinogen, interferon (IFN)-γ, interleukin (IL)-13, IL-1β, IL-4, IL-6, tumor necrosis factor-α, IL-23, IL-27, and IFN-α, but negatively correlated with C-reactive protein, D dimer, total bilirubin, and creatinine levels. As a natural anticoagulant, antithrombin Ⅲ can be regarded as a marker of inflammation and infection in patients with HBV-ACLF, and as a predictor of survival outcome in patients with ACLF.

Endothelial glycocalyx injury is involved in heatstroke-associated coagulopathy and protected by N-acetylcysteine.

Damage to endothelial glycocalyx (EGCX) can lead to coagulation disorders in sepsis. Heat stroke (HS) resembles sepsis in many aspects; however, it is unclear whether EGCX injury is involved in its pathophysiology. The purpose of this study was to examine the relationship between the damage of EGCX and the development of coagulation disorders during HS. We retrospectively collected 159 HS patients and analyzed coagulation characteristics and prognosis of HS patients with or without disseminated intravascular coagulation (DIC). We also replicated a rat HS model and measured coagulation indexes, pulmonary capillary EGCX injury in HS rats. Finally, we evaluated the effect of the antioxidant N-acetylcysteine (NAC) on HS-initiated EGCX injury and coagulation disorders. Clinical data showed that HS patients complicated with DIC had a higher risk of death than HS patients without DIC. In a rat HS model, we found that rats subjected to heat stress developed hypercoagulability and platelet activation at the core body temperature of 43°C, just before the onset of HS. At 24h of HS, the rats showed a consumptive hypo-coagulation state. The pulmonary capillary EGCX started to shed at 0h of HS and became more severe at 24h of HS. Importantly, pretreatment with NAC substantially alleviated EGCX damage and reversed the hypo-coagulation state in HS rats. Mechanically, HS initiated reactive oxidative species (ROS) generation, while ROS could directly cause EGCX damage. Critically, NAC protected against EGCX injury by attenuating ROS production in heat-stressed or hydrogen peroxide (H2O2)-stimulated endothelial cells. Our results indicate that the poor prognosis of HS patients correlates with severe coagulation disorders, coagulation abnormalities in HS rats are associated with the damage of EGCX, and NAC improves HS-induced coagulopathy, probably through its protection against EGCX injury by preventing ROS generation.

Hemostatic disorders associated with extracorporeal membrane oxygenation.

Hemostatic disorders are common during extracorporeal membrane oxygenation (ECMO)-therapy. This includes both bleeding and thrombotic complications. Particularly bleeding is often associated with fatal outcome. The early identification of hemorrhagic diathesis and the diagnosis of the underlying pathology are essential. A distinction into device-, disease-, and drug-related disorders appears reasonable. However, both correct diagnosis and therapy can be challenging and sometimes counterintuitive. Since bleeding seems to be more frequent and dangerous compared to thrombosis, the understanding of coagulation disorders and minimizing anticoagulation has been focused in recent years. Due to progress in membrane coating and configuration of modern ECMO circuits it is even possible to perform ECMO without any anticoagulation in well selected cases. It became apparent that routine laboratory tests are likely to miss severe coagulation disorders during ECMO-therapy. Better understanding can also help to individualize anticoagulation in patients and hence preventing complications. Acquired von Willebrand syndrome, platelet dysfunction, waste coagulopathy as well as silent hemolysis should be taken into account when bleeding or thromboembolic complications appear. Recognizing impaired intrinsic fibrinolysis may favour intensified anticoagulation even in patients exhibiting signs of bleeding. Drug monitoring with standard coagulation tests, viscoelastic tests and anti-Xa-levels as wells as screening for disorders of primary hemostasis should be implemented in clinical routine to guide physicians through complex anticoagulative therapy. The patient's coagulative status should be interpreted taking the underlying disease and current therapy into account in order to enable a personalized approach to hemostasis in patients treated with ECMO.

Post-viral idiopathic purpura fulminans is associated with inherited thrombophilia and anti-cardiolipin antibodies.

Idiopathic purpura fulminans (IPF) is a rare and severe coagulation disorder, associated with transient anti-protein S (anti-PS) antibodies in the context of post-viral infection such as varicella. Anti-protein S antibodies are frequently found in the context of varicella, in contrast with the rarity of IPF. Other factors such as anti-phospholipid antibodies (APL) and inherited thrombophilia may be associated with severe vascular complication. This is an ancillary study of a French multicenter retrospective series and systematic review of literature. We analyzed patients who were tested for inherited thrombophilia, namely antithrombin, protein C, protein S deficiency; prothrombin gene G20210A polymorphism (FII:G20210A),Factor V R506Q polymorphism (FV:R506Q); and/or for APL (lupus anticoagulant (LA), anti-cardiolipin antibodies (ACL), or anti-beta 2-GPI antibodies (Aβ2GP1). Among the 25 patients tested for inherited thrombophilia, 7 (28%) had positive results. Three had FV R506Q, two FII:G20210A, one compound heterozygote FV:R506Q associated to FII:G20210A, and one protein C deficiency. APL testing was performed in 32 patients. It was positive in 19 patients (59%): 17 ACL (53%), 5 LA (16%), 4 Aβ2GP1 (13%). The risk of severe complications was not associated with presence of inherited thrombophilia or APL presence, with RR: 0.8 [95% CI: 0.37-1.71], p = 1 and RR: 0.7 [95% CI: 0.33-1.51], p = 0.39, respectively. We found a high prevalence of inherited thrombophilia or APL in a population of patients with IPF. However, we do not find an association with the occurrence of severe vascular complications or venous thromboembolism.

Elevated Pancreatic Enzymes Associated with Acute Liver Injury Were Mediated by Tumor Necrosis Factor-Alpha Signaling

Background: Acute liver failure (ALF) is caused by massive hepatocyte death and accompanied by severe coagulation disorder and encephalopathy. It often leads to multiple organ failure and subsequently death. However, the association between ALF and other organ failure remains unclear. Objectives: Here, we evaluated patients with acute liver injury (ALI) and elevated pancreatic enzymes to demonstrate the association between ALI and pancreatic disorder. Methods: We conducted a single-center retrospective study to analyze patients with ALI. Between 2012 and 2017, 163 patients with ALI were treated in our hospital. We stratified patients based on whether serum amylase and lipase were elevated above 1.5 times the upper limit of normal. We compared the baseline characteristics, severity, prognosis, and serum cytokine levels between the two groups. Results: Of the 163 patients, 75 (54.0%) presented elevated pancreatic enzymes above 1.5 times the upper limit of normal. Computed tomography imaging findings associated with pancreatitis were observed in 29 patients (17.8%). The elevation of pancreatic enzymes was associated with ALI severity. High level of serum tumor necrosis factor-alpha (TNF-α) was associated with the elevation of pancreatic enzymes (elevation group Vs. no elevation group: 134.0 ± 177.2 pg/mL Vs. 89.4 ± 159.8 pg/mL). Conclusions: The elevation of pancreatic enzymes was often accompanied by ALI and associated with ALI severity. TNF-α signaling was involved in the elevation of pancreatic enzymes. It is possible that the pancreatic disorder reflected ALI severity, consequently correlated with mortality, and did not directly aggravate ALI pathogenesis. These findings provide novel insights into the pathogenesis of ALF.

Identification of novel biomarkers and therapeutic target candidates for stasis-heat symptom pattern of acute intracerebral hemorrhage by quantitative plasma proteomics.

To explore the novel biomarkers and therapeutic target candidates related to the stasis-heat syndrome of acute intracerebral hemorrhage (AICH). Applying an isobaric tagging for relative and absolute quantitation-(iTRAQ-) based quantitative proteomic approach, plasma samples from AICH patients with stasis-heat, and AICH patients with non-stasis-heat and healthy control subjects were collected and analyzed to distinguish differentially expressed proteins (DEPs) correlated to AICH with stasis-heat in this block design. The standard Western blot was applied to verify DEPs. Additionally, DEPs were analyzed via bioinformatic platforms and further approved via Ingenuity Pathway Analysis (IPA). A total of 26 DEPs were found among AICH with the stasis-heat, AICH with non-stasis-heat, and healthy control group. The seven DEPs compared with the non-stasis-heat group are closely related to the pathogenesis of stasis heat. These proteins showed three different protein expression patterns. The alpha-1-b glycoprotein (A1BG) and copper-protein (CP) were up-regulated in the stasis-heat group, but down-regulated in the non-stasis-heat group. Compared with the non-stasis-heat group, the expression abundance of actinin, alpha 1 (ACTN1), carbonic anhydrase I (CA1), peroxiredoxin 2 (PRDX2), and vinculin (VCL) is higher in the stasis-heat group, while the CD44 is the opposite. These differences reflect that stasis-heat syndrome has more severe inflammatory immune response, coagulation disorders and damage. Bioinformatics analysis revealed that a wide variety of cellular and metabolic processes and some signaling pathways were involved in the pathophysiology of AICH with stasis-heat. AICH with stasis-heat syndrome showed more severe inflammatory reactions, tissue damage, and coagulation disorders than non-stasis heat syndrome. There are differences in the protein expression patterns between the stasis-heat syndrome and non-stasis-heat syndrome. These differences reflect that stasis-heat syndrome has more severe damage. CD44, CP, ACTN1, CA1, VCL, PRDX2, and A1BG could be the potential biomarkers and therapeutic target candidates of the stasis-heat subtype. This study provides a reasonable explaination for Liangxue Tongyu decoction through anti-inflammatory and brain protection treatment.

Neglected vitamin K deficiency causing coagulation dysfunction in an older patient with pneumonia: a case report

BackgroundThe development of coagulation disorders can be dangerous and fatal in the older people, especially those with multiple medical conditions. Vitamin K-dependent coagulation disorders are easily overlooked when anticoagulant drugs are not used and the patient shows no signs of bleeding.Case presentationWe report a case of a 71-year-old male suffering from pulmonary infection with severe coagulation disorder without bleeding symptoms. He also had a history of Parkinson’s disease, Alzheimer’s disease and cardiac insufficiency. Coagulation tests were normal at the time of admission, prothrombin time (PT) is 13.9 (normal, 9.5–13.1) seconds and the activated partial thromboplastin time (APTT) is 30.2 (normal, 25.1–36.5) seconds. But it turned severely abnormal after 20 days (PT: 136.1 s, APTT: 54.8 s). However, no anticoagulants such as warfarin was used and no bleeding symptoms were observed. Subsequent mixing studies with normal plasma showed a decrease in prothrombin times. Vitamin K deficiency was thought to be the cause of coagulation disorders considering long-term antibiotic therapy, especially cephalosporins, inadequate diet and abnormal liver function. After supplementation with 20 mg of vitamin K, coagulation dysfunction was rescued the next day and serious consequences were effectively prevented.ConclusionsOverall, timely vitamin K supplementation with antimicrobials that affect vitamin K metabolism requires clinician attention, especially in older patients who are multimorbid, frail or nutritionally compromised, and are admitted to hospital because of an infection that needs antimicrobial therapy are at risk of clotting disorders due to abnormal vitamin K metabolism secondary to altered gut flora, which can exacerbate existing nutritional deficiencies.

Thromboelastographic method for early decision on anticoagulant therapy in moderate to severe COVID-19 patients

BACKGROUND Coagulopathy is a serious COVID-19 complication that requires rapid diagnosis and anticoagulation. This study aimed to determine the role of coagulation examination using thromboelastography (TEG) on the decision-making time of anticoagulant therapy in COVID-19 patients and its clinical outcomes.&#x0D; METHODS A prospective observational study was conducted in Cipto Mangunkusumo Hospital, Indonesia, from October 2020 to March 2021. We consecutively recruited moderate and severe COVID-19 patients in the high and intensive care units. Turnaround time, time to anticoagulant therapy decision, and clinical outcomes (length of stay and 30-day mortality) were compared between those who had a TEG examination in addition to the standard coagulation profile examination (thrombocyte count, PT, APTT, D-dimer, and fibrinogen) and those who had only a standard coagulation profile laboratory examination.&#x0D; RESULTS Among 100 moderate to severe COVID-19 patients recruited, 50 patients had a TEG examination. The turnaround time of TEG was 45 (15–102) min versus 82 (19–164) min in the standard examination (p&lt;0.001). The time to decision was significantly faster in the TEG group than the standard group (75 [42–133] min versus 184 [92–353] min, p&lt;0.001). The turnaround time was positively correlated with time to decision (r = 0.760, p&lt;0.001). However, TEG did not improve clinical outcomes such as length of stay (10.5 [3–20] versus 9 [2–39] days) and 30-day mortality (66% versus 64%).&#x0D; CONCLUSIONS The TEG method significantly enables quicker decision-making time for moderate to severe coagulation disorder in COVID-19 patients.

Endoscopic balloon cryoablation against single instillation after transurethral resection of bladder cancer: A multicenter, randomized, controlled noninferiority trial.

e16561 Background: Cryotherapy is a prevalent percutaneous ablative therapy for solid tumors. However, studies on the clinical practice of endoscopic cryotherapy for intraluminal malignancies are lacking. We aim to explore the feasibility of endoscopic cryotherapy for bladder cancer. Methods: In this multicenter, randomized, parallel controlled, non-inferiority trial, we compared endoscopic balloon cryoablation (EBCA) with a single instillation (SI) of pirarubicin after transurethral resection (TUR).Men or women aged 18-85 years with a clinical diagnosis of bladder cancer (tumor number no more than 3 and maximal tumor size no more than 3 cm) were included. The exclusion criteria were as follows: locally advanced urinary bladder cancer (clinical stage T3 or T4), lymph node involvement (N1) or distant metastasis (M1), severe organ dysfunction, severe coagulation disorder, sepsis, concomitant neoplastic malignancy and other conditions unsuitable for surgery or intravesical chemotherapy. Women in pregnancy or lactation were also excluded. Eligible participants were randomly assigned (1:1) to the TUR-EBCA or TUR-SI group. The primary endpoint was the residual-free rate at repeated TUR. A non-inferiority test was used to compare the primary endpoint with a chosen margin of 10%. The secondary endpoints included the recurrence-free survival (RFS), progression-free survival (PFS) and adverse events. Results: We recruited 227 participants between November, 2017, and September, 2020. In total, 205 patients received EBCA or SI after TUR, of whom 163 completed all the required interventions and follow-up. In the per-protocol analyses, 75 (91.5%) of 82 patients had no residual tumor in the TUR-EBCA group compared with 61 (76.5%) of 81 in the TUR-SI group (risk difference 14.9%; 95% confidence interval [CI] 0.03 to 0.27, P &lt; 0.001), meeting the criteria for non-inferiority. Similar results were found in the after intention-to-treat analysis. After a median follow-up of 21 months, the TUR-EBCA group had better RFS(HR = 0.49; 95% confidence interval [CI] 0.24 to 0.99; Log-rank P = 0.046) and PFS (HR = 0.25; 95% confidence interval [CI] 0.08 to 0.77; Log-rank P = 0.0092). There were no significant differences in the SAEs rate (3.0% vs. 3.9%, p = 0.52). Conclusions: EBCA is a safe and effective adjuvant alternative to TUR for bladder cancer with the potential advantage of “energetically resecting” the tumor base. Clinical trial information: NCT02760953.

A Case of Redo Ascending Aortic Replacement for Anastomotic Pseudoaneurysm through Right Thoracotomy in a Patient with Severe Coagulation Disorder

A Case of Redo Ascending Aortic Replacement for Anastomotic Pseudoaneurysm through Right Thoracotomy in a Patient with Severe Coagulation Disorder

A Novel Coagulation Classification and Postoperative Bleeding in Severe Spontaneous Intracerebral Hemorrhage Patients on Antiplatelet Therapy.

Background and PurposeFor patients with severe spontaneous intracerebral hemorrhage on antiplatelet therapy (patients with APT-SICH), postoperative rebleeding (PR) is an important cause of poor outcomes after surgery. As impacted by coagulation disorder caused by APT, patients with APT-SICH are likely to suffer from PR. This study aimed to assess the risk of PR in patients with APT-SICH receiving emergency surgery using a novel coagulation classification.MethodsThis prospective, multicenter cohort study consecutively selected patients with APT-SICH between September 2019 and March 2021. The preoperative coagulation factor function was recorded, and the platelet function was assessed using thrombelastography. Based on platelet and coagulation factor function, a novel four-type coagulation classification, i.e., Type I (severe coagulation disorder), Type IIa (low platelet reserve capacity), Type IIb (normal coagulation), and Type III (hypercoagulation), was presented. The primary outcome was PR, defined as the rebleeding in the operative region or new intracerebral hemorrhage correlated with the operation.ResultsOf the included 197 patients with APT-SICH, PR occurred in 40 patients (20.3%). The novel coagulation classification categorized 28, 32, 122, and 15 patients into Type I, Type IIa, Type IIb, and Type III, respectively. The Type I patients had the highest incident rate of PR (39.3 per 100 persons), followed by the Type IIa patients (31.3 per 100 persons). In the PR-related analysis, the large hematoma volume (hazard ratio (HR): 1.02; 95% CI: 1.02–1.03; p < 0.001), Type I (HR: 9.72; 95% CI: 1.19–79.67; p = 0.034), and Type IIa (HR: 8.70; 95% CI: 1.09–69.61; p = 0.041) were correlated with the highest risk of PR. The coagulation classification could discriminate the PR patients from no PR (NPR) patients (p < 0.001), and it outperformed the conventional coagulation assessment (only considering platelet count and coagulation factor function) (c-statistic, 0.72 vs. 0.55).ConclusionThe novel coagulation classification could discriminate the patients with APT-SICH with the highest risk of PR preoperatively. For the Type I and Type IIa patients, emergency surgery should be performed carefully.

A novel compound heterozygous variant linked to hematuria in a family with hereditary factor VII deficiency.

Hereditary factor VII deficiency (FVIID) is a rare congenital autosomal recessive bleeding disorder. In clinical manifestations, its onset is caused by variant of the F7 gene (NM_019616) with strong heterogeneity. We identified a family with hematuria caused by a novel F7 compound heterozygous variant and investigated the FVIID-dependent mechanism impacted by these variants. Coagulation factors in the proband were functionally verified. We located pathogenic variants in relevant genes using next-generation sequencing after target enrichment and verified them by Sanger sequencing. We examined the coagulation activity and secretion pattern of recombinant FVII variants expressed in cells and observed their location and stability by immunofluorescence. We found a missense variant c.1207G>A (p.Gly403Ser) and a frameshift variant c.154_155del (p.Arg53fs) in the F7 gene of the proband. FVII activity tests showed that the variants significantly decreased its presence in the cell culture supernatant. Moreover, the R53fs mutant lacked the FVII functional domain and had no detectable activity. Immunofluorescence indicated that the p.Gly403Ser variant was distributed to the cell membrane and cytoplasm, whereas the FVII R53fs variant was not detected. Deficient FVII protein function and severe coagulation disorder are the likely causes of hematuria and other bleeding symptoms in the proband. The newly discovered F7 gene variants enrich the spectrum of hereditary FVII deficiency and provide a new foundation for the diagnosis and treatment of this type of coagulation disorder.

Successful treatment of acute empyema caused by Aeromonas sobria in an advanced liver cirrhosis patient: A case report

Bacterial empyema is a rare complication of liver cirrhosis (LC) patients. The treatment of patients was challenge and associated with poor outcome. Case report: In this article, we reported for the first time a 55-year-old patient with decompensated LC due to alcohol abuse who was diagnosed with acute empyema. Bacterial culture of pleural fluid indicated Aeromonas sobria (A. sobria) as a causative pathogen. The patient also performed severe coagulation disorder with INR 2.56; platelet counts 24G/L. The patient was successfully managed by board-spectrum antibiotics and drainage of the pleural with pigtail catheter. He was followed for a year without relapsing. Conclusion: We reported the first case of severely acute empyema caused by A. sobria in a patient with decompensated LC and successful treatment with appropriate antibiotics in combination with pigtail drainage in our clinical setting.

Idiopathic purpura fulminans associated with anti-protein S antibodies in children: a multicenter case series and systematic review

AbstractIdiopathic purpura fulminans (IPF) is a rare but severe prothrombotic coagulation disorder that can occur after chickenpox or human herpesvirus 6 (HHV-6) infection. IPF leads to an autoantibody-mediated decrease in the plasma concentration of protein S. We conducted a retrospective multicenter study involving patients with IPF from 13 French pediatric centers and a systematic review of cases in published literature. Eighteen patients were included in our case series, and 34 patients were included as literature review cases. The median age was 4.9 years, and the diagnostic delay after the first signs of viral infection was 7 days. The lower limbs were involved in 49 patients (94%) with typical lesions. In all, 41 patients (78%) had a recent history of varicella-zoster virus infection, and 7 patients (14%) had been infected by HHV-6. Most of the patients received heparin (n = 51; 98%) and fresh frozen plasma transfusions (n = 41; 79%); other treatment options were immunoglobulin infusion, platelet transfusion, corticosteroid therapy, plasmapheresis, and coagulation regulator concentrate infusion. The antithrombin level and platelet count at diagnosis seemed to be associated with severe complications. Given the rarity of this disease, the creation of a prospective international registry is required to consolidate these findings.