Prognostic factors in patients with secondary hemophagocytic lymphohistioc ytosis in a Chinese cohort.

Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome with high mortality mediated by an unbridled and persistent activation of cytotoxic T lymphocytes and natural killer cells. However, the influence factors of early death in adult sHLH patients are still not fully elucidated, which need further investigating. We have conducted an observational study of adult HLH patients between January 2016 and December 2022. All patients are enrolled according to HLH-2004 criteria. Clinical manifestations, laboratory data, treatments, and outcomes have been recorded. Influence factors associated with prognosis are calculated by using logistic regression models. Overall, 220 patients enrolled in this study. The etiologies of HLH were divided into five groups including autoimmune-associated hemophagocytic syndrome (AAHS) (n = 90, 40.9%), malignancies (n = 73, 33.2%), EBV-HLH (n = 18, 8.2%), infection excluded EBV (n = 24, 10.9%), and other triggers (n = 15, 6.8%). Among them, EBV-HLH had the highest mortality (77.8%), and AAHS had the lowest mortality (14.4%). Multivariate analysis indicated that age (≥ 38 years old), cytopenia ≥ 2 lines, platelets (≤ 50 × 109/L), aspartate aminotransferase (≥ 135U/L), prothrombin time (≥ 14.9 s) and activated partial thromboplastin time (≥ 38.5s), EBV, and fungal infection are independent risk factors for poor prognosis of HLH. Adult HLH patients with elder age, cytopenia ≥ 2 lines, levels of decreased platelets, increased AST, prolonged PT and APTT, EBV, and fungal infection tend to have a poor prognosis.

Coagulation dysfunction events associated with echinocandins: a real-world study from FDA adverse event reporting system (FAERS) database.

BACKGROUND: Echinocandins belong to the fourth generation of antifungals, and there are no systematic studies on their risk in coagulation dysfunction; this study will predict the risk of coagulation dysfunction of echinocandins using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHOD: Data from January 2004 to March 2024 were obtained from FAERS. We examined the clinical characteristics of the coagulation dysfunction events and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare echinocandins with the full database. RESULTS: There were 313 reports of coagulation dysfunction related to echinocandins as the primary suspect (PS) drug. The median time to incident for coagulation dysfunction was 3 (interquartile range [IQR] 1-9) days. Compared to triazoles and polyenes, echinocandins have a stronger signal (ROR 3.18, 95%CI 2.81-3.51, p < 0.01) of coagulation dysfunction. Compared to caspofungin and micafungin, anidulafungin has a stronger signal (ROR 6.84, 95%CI 4.83-9.70, p < 0.01). The strongest signal corresponding to disseminated intravascular coagulation (DIC), platelet count decreased, thrombocytopenia, gastrointestinal haemorrhage, cerebral haemorrhage, pulmonary haemorrhage and thrombotic thrombocytopenic purpura (TTP) is micafungin (ROR 27.19, 95%CI 18.49-39.98), micafungin (ROR 3.50, 95%CI 2.36-5.19), anidulafungin (ROR 9.75, 95%CI 5.22-18.19), micafungin (ROR 3.17, 95%CI 2.02-4.97), micafungin (ROR 4.95, 95%CI 2.81-8.72), caspofungin (ROR 20.76, 95%CI 11.77-36.59), micafungin (ROR 20.43, 95%CI 8.49-49.14), respectively. CONCLUSIONS: For coagulation dysfunction, we found stronger signals for echinocandins than triazoles and polyenes, and stronger signals for anidulafungin than micafungin and caspofungin. Coagulation parameters should be closely monitored while using the respective drugs.

Coagulation dysfunction events associated with tigecycline: a real-world study from FDA adverse event reporting system (FAERS) database.

BACKGROUND: Tigecycline has broad-spectrum anti-bacterial activity and often used for critically ill patients with complicated infections. Only a few clinical studies have reported the coagulation disorder induced by tigecycline. The aim of this study was to investigate the association between tigecycline and coagulation dysfunction using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHOD: Data from January 2005 to December 2020 in FAERS were retrieved. We investigated the clinical characteristics of the coagulation dysfunction events and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare tigecycline with the full database and other antibiotics. RESULTS: The total number of reports of coagulation dysfunction related to tigecycline as the primary suspect drug was 223. The median time to event of the coagulation dysfunction events was 10 (interquartile range [IQR] 6.75-13) days. 80.72% coagulation-related adverse events appeared within the first 14 days since the initiation of tigecycline administration. The overall ROR (95% CI) for coagulation-related adverse events was 3.55 (3.08, 4.09). The RORs (95% CI) for thrombocytopenia, hypofibrinogenaemia, coagulopathy, activated partial thromboplastin time prolonged, international normalized ratio increased, prothrombin time prolonged were 8.21 (6.34, 10.62), 705.41 (526.81, 944.54), 30.67 (21.92, 42.92), 42.98 (24.85, 74.31), 4.67 (2.51, 8.71), and 27.99 (15.01, 52.19), respectively. In analyses stratified on comparing tigecycline to vancomycin and daptomycin, significant coagulation dysfunction signals were found with the RORs (95% CI) 2.74 (2.34, 3.22) and 3.08 (2.57, 3.70). CONCLUSIONS: We found a strong signal of high frequency of reporting coagulation dysfunction in tigecycline. Health professionals should be aware of the potential coagulation disorders risk and monitor coagulation parameters during anti-bacterial therapy with tigecycline, particularly the need to monitor fibrinogen levels.

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

BACKGROUND: The 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 PRESENTATION: We 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. CONCLUSIONS: Overall, 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.

Preoperative clinical application of human fibrinogen in patients with acute Stanford type A aortic dissection: A single-center retrospective study.

OBJECTIVE: To evaluate the perioperative clinical efficacy of preoperative human fibrinogen treatment in patients with acute Stanford type A aortic dissection (ATAAD). METHODS: Data of 159 patients with ATAAD who underwent emergency surgical treatment in our hospital from January 2019 to December 2020 were retrospectively analyzed. Patients were divided into two groups according to whether human fibrinogen was administered before surgery: patients in group A received fibrinogen before surgery, while those in group B did not. The preoperative clinical data, surgical data, postoperative data, complications related to the coagulation function, and mortality of the two groups were compared and analyzed. RESULTS: The in-hospital mortality was similar in the two groups (2.9% vs. 9.3%, p = .122). However, group A had a significantly shorter operation time (279.24 ± 39.03 vs. 298.24 ± 45.90, p = .008), lower intraoperative blood loss (240.48 ± 96.75 vs. 353.70 ± 189.80, p < .001), and reduced intraoperative transfusion requirement of red blood cells (2.61 ± 1.18 vs. 6.05 ± 1.86, p < .001). The postoperative suction drainage within 24 h in group A was significantly decreased (243.24 ± 201.52 vs. 504.22 ± 341.08, p = .002). The incidence of postoperative acute kidney injury (AKI) in group A was lower than that in group B (3.8% vs. 14.8%, p = .023). Similarly, the incidence of postoperative hepatic insufficiency in group A was lower than that in group B (1.9% vs. 9.3%, p = .045). In group A, the mechanical ventilation time was shorter (47.68 ± 28.61 vs. 118.21 ± 173.16, p = .004) along with reduced intensive care unit stay time (4.06 ± 1.18 vs. 8.09 ± 9.42, p = .003), and postoperative hospitalization days (19.20 ± 14.60 vs. 23.50 ± 7.56, p = .004). CONCLUSION: Preoperative administration of human fibrinogen in patients undergoing ATAAD surgery can effectively reduce the intraoperative blood loss, amount of blood transfused, operation time, and postoperative complications, and improve the early prognosis of patients. In addition, this procedure is highly safe.

Coagulation dysfunction is associated with severity of COVID-19: A meta-analysis.

To systematically analyze the blood coagulation features of coronavirus disease 2019 (COVID-19) patients to provide a reference for clinical practice. An electronic search in PubMed, EMbase, Web of Science, Scopus, CNKI, WanFang Data, and VIP databases to identify studies describing the blood coagulation features of COVID-19 patients from 1 January 2020 to 21 April 2020. Three reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies, then, the meta-analysis was performed by using Stata 12.0 software. Thirty-four studies involving 6492 COVID-19 patients were included. Meta-analysis showed that patients with severe disease showed significantly lower platelet count (weighted mean differences [WMD]: -16.29 × 109 /L; 95% confidence interval [CI]: -25.34 to -7.23) and shorter activated partial thromboplastin time (WMD: -0.81 seconds; 95% CI: -1.94 to 0.33) but higher D-dimer levels (WMD: 0.44 µg/mL; 95% CI: 0.29-0.58), higher fibrinogen levels (WMD: 0.51 g/L; 95% CI: 0.33-0.69) and longer prothrombin time (PT; WMD: 0.65 seconds; 95% CI: 0.44-0.86). Patients who died showed significantly higher D-dimer levels (WMD: 6.58 µg/mL; 95% CI: 3.59-9.57), longer PT (WMD: 1.27 seconds; 95% CI: 0.49-2.06) and lower platelet count (WMD: -39.73 × 109 /L; 95% CI: -61.99 to -17.45) than patients who survived. Coagulation dysfunction is common in severe COVID-19 patients and it is associated with severity of COVID-19.

Progress in multiple genetically modified minipigs for xenotransplantation in China.

Pig-to-human organ transplantation provides an alternative for critical shortage of human organs worldwide. Genetically modified pigs are promising donors for xenotransplantation as they show many anatomical and physiological similarities to humans. However, immunological rejection including hyperacute rejection (HAR), acute humoral xenograft rejection (AHXR), immune cell-mediated rejection, and other barriers associated with xenotransplantation must be overcome with various strategies for the genetic modification of pigs. In this review, we summarize the outcomes of genetically modified and cloned pigs achieved by Chinese scientists to resolve the above-mentioned problems in xenotransplantation. It is now possible to knockout several porcine genes associated with the expression of sugar residues, antigens for (naturally) existing antibodies in humans, including GGTA1, CMAH, and ß4GalNT2, and thereby preventing the antigen-antibody response. Moreover, insertion of human complement- and coagulation-regulatory transgenes, such as CD46, CD55, CD59, and hTBM, can further overcome effects of the humoral immune response and coagulation dysfunction, while expression of regulatory factors of immune responses can inhibit the adaptive immune rejection. Furthermore, transgenic strategies have been developed by Chinese scientists to reduce the potential risk of infections by endogenous porcine retroviruses (PERVs). Breeding of multi-gene low-immunogenicity pigs in China is also presented in this review. Lastly, we will briefly mention the preclinical studies on pig-to-non-human primate xenotransplantation conducted in several centers in China.

Risk Factors of Sepsis-Associated Thrombocytopenia among Patients with Sepsis Induced Coagulopathy.

The study aims to evaluate the prognosis and risk factors of sepsis-associated thrombocytopenia (SAT) among patients with coagulopathy, and to provide evidence of the relationship between adverse outcomes and potential risks. Patients with sepsis-associated coagulopathy were included in the study from January 2014 to December 2022. The primary outcome was sepsis-associated thrombocytopenia (platelet count less than 100 *109/L), which was evaluated by logistic regression models adjusted for demographic characteristics and comorbidities. Among patients in the SAT group, 54% developed severe SAT, while 16% of these patients recovered from thrombocytopenia. The in-hospital mortality rate was significantly higher in the SAT group compared to the non-SAT group (31% in SAT group vs 23.9% in non-SAT group, p = 0.029). Even after adjusting for age, gender, Charlson comorbidity, white blood cell, and Sequential Organ Failure Assessment score, the differences in mortality rate persisted (Odds Ratio 0.72, [95% Confidence Interval 0.52-0.92]). Correlation analyses revealed that prothrombin time (r = 0.08, p = 0.50), international normalized ratio (r = 0.08, p = 0.42), prothrombin activity (r = -0.06, p > 0.999), D-dimer (r = -0.02, p > 0.999), and inflammatory parameters such as C-reactive protein (r = -0.11, p = 0.37) were not significantly correlated with platelet counts. According to subgroup analyses, patients with lung infection complicated by SAT had slightly higher mortality (OR 0.66, [95% CI, 0.46 to 0.94]). Sepsis-associated coagulopathy indicates a subset of critical ill patients, with those experiencing thrombocytopenia at greater risk for in-hospital death compared to those without it.

Coagulation dysfunction of severe burn patients: A potential cause of death.

BACKGROUND: Research on coagulation dysfunction following burns is controversial. This study aimed to describe the coagulation changes in severe burn patients by examining coagulation parameters. METHODS: Patients with third-degree total body surface area (TBSA) burns of ≥30% were enrolled between 2017 and 2020. Platelet (PLT) count and coagulation indexes (including APTT, INR, FIB, DD, and AT Ⅲ) were measured at admission and once weekly for 8 weeks, and statistical analysis was performed. The patient medical profiles were reviewed to extract demographic and clinical data, including TBSA, third-degree TBSA, and inhalation injury. The total intravenous fluids and transfusions of crystalloids, fresh frozen plasma (FFP), and red blood cells (RBC) were calculated during the forty-eight-hour period. The number of sepsis cases was recorded. RESULTS: We enrolled 104 patients , and while the overall coagulation trend fluctuated, inflection points appeared around one week and demonstrated hypercoagulability. INR was significantly higher in the non-survival group than in the survivors' group from admission to three weeks after burn (all p<0.01). From post-injury week 1 to post-injury week 3, the APTT in the non-survival group was greater than in the survival group, but the non-survival group's PLT count was lower than that in the survival group (all p<0.05). At two and three weeks after burns, the FIB levels in the non-survival group were significantly lower than those of the survival group (both p<0.01). The prevalence of inhalation injury and the proportion of sepsis cases were significantly higher in the non-survival group than in the survival group ( p ＜ 0.05, p ＜ 0.001, respectively). At the time of death, APTT, INR, and FDP levels were significantly higher in the non-survival group in the survivor group, and FIB, ATIII, and PLT were significantly lower than in the survivor group (all p<0.01). On the day of death, nine of the 12 dead patients had disseminated intravascular coagulation (DIC). CONCLUSIONS: Coagulation dysfunction was most prominent in severe burn patients 1 week after injury and presented as hypercoagulability. Large-area burn injury, large amounts of fluid resuscitation, inhalation injury, and sepsis may all contribute to coagulation dysfunction, which can further develop into DIC and even death in severe burns patients.

Nanoplastic-induced vascular endothelial injury and coagulation dysfunction in mice.

Nanoplastics are the persistent pollutants in a variety of environments, representing a potential threat to human health. Notably, plastic particles have been detected in sample of human bloodstream. It is thus significant to investigate the effects of nanoplastics on the cardiovascular system owing to its ease transfer through the bloodstream to other organs. However, few studies have been performed to evaluate the cardiovascular toxicity of nanoplastics. Herein, we pursued to investigate the adverse cardiovascular impacts of polystyrene (PS), PS-NH2 and PS-COOH nanoplastics on mice. Experimental results demonstrated that the exposure to these nanoplastics could result in structural damage of vascular endothelial cells and inflammatory response. Moreover, it was found out that the dysfunctions of coagulation and prethrombotic state were caused by nanoplastics, which could be ascribed to the activation of JAK1/STAT3/TF signaling pathway. In summary, results clearly indicated that nanoplastic exposure lead to vascular toxicity to mice, which serves as a basis for future studies about the potential physiological threat of nanoplastics to humans.

Interaction between Acute Hepatic Injury and Early Coagulation Dysfunction on Mortality in Patients with Acute Myocardial Infarction.

BACKGROUND: In acute myocardial infarction (AMI), acute hepatic injury is an independent risk factor for prognosis and is associated with complex coagulation dynamics. This study aims to determine the interaction between acute hepatic injury and coagulation dysfunction on outcomes in AMI patients. METHODS: The Medical Information Mart for Intensive Care (MIMIC-III) database was used to identify AMI patients who underwent liver function testing within 24 h of admission. After ruling out previous hepatic injury, patients were divided into the hepatic injury group and the nonhepatic injury group based on whether the alanine transaminase (ALT) level at admission was >3 times the upper limit of normal (ULN). The primary outcome was intensive care unit (ICU) mortality. RESULTS: Among 703 AMI patients (67.994% male, median age 65.139 years (55.757-76.859)), acute hepatic injury occurred in 15.220% (n = 107). Compared with the nonhepatic injury group, patients with hepatic injury had a higher Elixhauser comorbidity index (ECI) score (12 (6-18) vs. 7 (1-12), p < 0.001) and more severe coagulation dysfunction (85.047% vs. 68.960%, p < 0.001). In addition, acute hepatic injury was associated with increased in-hospital mortality (odds ratio (OR) = 3.906; 95% CI: 2.053-7.433; p < 0.001), ICU mortality (OR = 4.866; 95% CI: 2.489-9.514; p < 0.001), 28-day mortality (OR = 4.129; 95% CI: 2.215-7.695; p < 0.001) and 90-day mortality (OR = 3.407; 95% CI: 1.883-6.165; p < 0.001) only in patients with coagulation disorder but not with normal coagulation. Unlike patients with coagulation disorder and normal liver, patients with both coagulation disorder and acute hepatic injury had greater odds of ICU mortality (OR = 8.565; 95% CI: 3.467-21.160; p < 0.001) than those with normal coagulation. CONCLUSIONS: The effects of acute hepatic injury on prognosis are likely to be modulated by early coagulation disorder in AMI patients.

Spontaneous Prostatic Hemorrhage in a COVID-19 Patient: A Case Report.

Hematuria occurring in patients with acute kidney injury caused by Corona Virus Disease 2019 (COVID-19) infection has been reported. However, cases of macroscopic hematuria in COVID-19 patients leading to a severe decrease in hemoglobin have not been reported heretofore. Herein, we describe the case of a 56-year-old male patient who suffered from spontaneous prostatic hemorrhage caused by thrombocytopenia and coagulation dysfunction associated with COVID-19 infection, which manifested as macroscopic hematuria, bladder blood clot tamponade and severe hemoglobin decline. Prostatic hemorrhage was diagnosed by endoscopy. There was no recurrence of macroscopic hematuria after undergoing transurethral prostate electrocoagulation for hemostasis, infusing plasma to supplement coagulation factors and taking finasteride. One month after the bleeding event, the patient's blood routine reexamination revealed that the platelet count returned to the normal value and coagulation was normal.

Severe coagulopathy caused by cefminox sodium in a liver cirrhosis patient: a case report.

Cefminox sodium is an antimicrobial agent with broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria. Cefminox sodium has high security in clinical practice for its few adverse effects such as coagulation dysfunction, which is rare in clinical treatment. Even in patients suffering from chronic liver disease with coagulation dysfunction, it rarely leads to further deterioration of coagulation function. Therefore, patients with chronic liver disease develop severe coagulation dysfunction during the application of cefminox sodium, which is often mistaken for worsening of liver disease other than considered to be the side effect of the drug. Therefore, we report a 55-year-old female patient with liver cirrhosis and hepatocellular carcinoma treated with cefminox sodium intravenously twice for peritonitis. During the treatments, severe coagulopathy occurred, and the coagulation function quickly recovered after drug withdrawal. The diagnosis and treatment of this patient provides us with ideas for dealing with similar problems in clinical practice in the future.

Clinical significance of R-TEG in severe burn patients with coagulation dysfunction.

INTRODUCTION: The aim of this study was to retrospectively analyze Thrombelastography (TEG) data of severe burn patients to provide a clinical basis for timely diagnosis and treatment of coagulation dysfunction. METHODS: The present study comprised burn patients with full thickness TBSA ≥ 60%. The patients included in the study were admitted to the Third Affiliated Hospital of Inner Mongolia Medical University between March 2019 and March 2022 and died within 10 days. Patient demographic and clinical data, including abbreviated burn severity index (ABSI) score, full thickness and overall total surface burn area (TBSA), injury cause, International Society on Thrombosis and Hemostasis (ISTH) score, were retrieved from the electronic medical record system. TEG data (including ACT, K, α, MA and LY30), platelet count (PLT), mean platelet volume (MPV) and platelet distribution width (PDW) data were obtained from the records of included patients for analysis. RESULTS: A total of 9 patients were enrolled. The average burn area was 90.0% TBSA and the full-thickness TBSA was 72.0%. The results showed that α, MA and PLT count values were significantly lower relative to those at obtained throughout admission period (all p < 0.05). PDW and MPV were significantly higher compared with the values at admission (all p < 0.05). ACT time was significantly longer from day 2 after severe burn compared with the ACT time at admission (all p < 0.05). LY30 value from day 3 after severe burn was significantly higher compared with the value at admission (p < 0.05). One patient was diagnosed with diffuse intravascular coagulation (DIC) on admission, whereas eight patients were diagnosed with DIC on the day of death. CONCLUSION: Coagulation dysfunction after severe burn is mainly characterized by procoagulant disorders and hyperfibrinolysis, which can be timely detected by TEG. Coagulation after severe burn exhibits a gradual aggravation, and can lead to death of patients.

Clinical characteristics and risk factors of COVID-19 patients with chronic hepatitis B: a multi-center retrospective cohort study.

The Coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (⩾ 245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528-29.523; P < 0.001) and coagulation-related biomarker D-dimer (⩾ 0.5 µg/mL, HR = 4.321, 95% CI = 1.443-12.939; P = 0.009) and decreased albumin (< 35 g/L, HR = 0.131, 95% CI = 0.048-0.361; P < 0.001) and albumin/globulin ratio (< 1.5, HR = 0.123, 95% CI = 0.017-0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.

Acquired coagulation dysfunction resulting from vitamin K-dependent coagulation factor deficiency associated with rheumatoid arthritis: A case report.

BACKGROUND: Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease with the main clinical feature of progressive joint synovial inflammation, which can lead to joint deformities as well as disability. RA often causes damage to multiple organs and systems within the body, including the blood hemostasis system. Few reports have focused on acquired coagulation dysfunction resulting from vitamin K-dependent coagulation factor deficiency associated with RA. CASE SUMMARY: A 64-year-old woman with a history of RA presented to our hospital, complaining of painless gross hematuria for 2 wk. Blood coagulation function tests showed increased prothrombin time, international normalized ratio, and activated partial thromboplastin time. Abnormal blood coagulation factor (F) activity was detected (FII, 7.0%; FV, 122.0%; and FX, 6.0%), indicating vitamin K-dependent coagulation factor deficiency. Thromboelastography and an activated partial thromboplastin time mixed correction experiment also suggested decreased coagulation factor activity. Clinically, the patient was initially diagnosed with hematuria, RA, and vitamin K-dependent coagulation factor deficiency. The patient received daily intravenous administration of vitamin K1 20 mg, etamsylate 3 g, and vitamin C 3000 mg for 10 d. Concurrently, oral leflunomide tablets and prednisone were administered for treatment of RA. After the treatment, the patient's symptoms improved markedly and she was discharged on day 12. There were no hemorrhagic events during 18 mo of follow- up. CONCLUSION: RA can result in vitamin K-dependent coagulation factor deficiency, which leads to acquired coagulation dysfunction. Vitamin K1 supplementation has an obvious effect on coagulation dysfunction under these circumstances.

Expression and diagnostic value of plasma protein Z and protein Z-dependent protease inhibitor in fetal growth restriction.

OBJECTIVES: Investigating the expression levels of plasma protein Z (PZ) and protein Z-dependent protease inhibitor (ZPI) in fetal growth restriction (FGR) and to explore their diagnostic value in FGR. MATERIAL AND METHODS: In this study, the number of pregnant women with FGR, healthy pregnant women (Healthy Control, HC), and childbearing-age women without pregnancy (Blank Control, BC) is 79, 79, and 60, respectively; their plasma PZ and ZPI levels in each group are determined by ELISAs. Then, the correlations between these indices and FGR were assessed using Spearman analysis. Moreover, these indices' diagnostic values for FGR are evaluated using the receiver operating characteristics (ROC) curves. RESULTS: The plasma levels of PZ and ZPI are significantly decreased in the HC and FGR groups compared against the BC group (P < 0.001), whilst the levels of PZ and ZPI in the FGR groups are lower than those in the HC group (P < 0.01) notably. PZ plasma concentration has positive relationship with ZPI concentrations in the HC and FGR groups. The combination of PZ and ZPI, with the Area under the Curve (AUC) 0.92 (95% CI = 0.88-0.96), the sensitivity 0.82, and the specificity 0.88, outperforms everyone. CONCLUSIONS: Plasma PZ and ZPI are significantly decreased in pregnant women with FGR, which can be used for pregnant women's FGR screening.

Elevated plasma D-dimer levels are associated with the poor prognosis of critically ill children.

Background: D-dimer has been shown as a valuable predictor for the prognosis of sepsis. But the prognostic association of an elevated D-dimer with adverse outcomes of all critical illnesses in pediatric intensive care unit (PICU) has received far less emphasis. Methods: This was a single-center retrospective study, including 7,648 critical patients aged between 28 days and 18 years from the pediatric intensive care (PIC) database from 2010 to 2018. The primary outcome was the in-hospital mortality rate. Results: Higher levels of D-dimer, INR, PT, APTT, and lower Fib were observed in the non-survivor group (all P < 0.001). D-dimer, INR, PT and APTT were independent risk factors for prognosis in critically ill children. There was the highest AUROC in D-dimer for predicting in-hospital mortality of critically ill patients compared with INR, PT, APTT, and Fib (D-dimer: 0.77 vs. INR: 0.73 vs. PT: 0.73 vs. APTT: 0.64 vs. Fib: 0.60). The cut-off value, sensitivity, and specificity of D-dimer were 1.53, 0.65, and 0.77, respectively. Subgroup analysis showed a stable evaluation effectiveness of D-dimer for predicting in-hospital mortality of critically ill patients in the age and gender groups. Conclusions: We found poorer coagulation function in the non-survivors compared with the survivors. Among the coagulation indicators, D-dimer was most strongly associated with in-hospital mortality of unselected critically ill children.

Genetic engineering of pigs for xenotransplantation to overcome immune rejection and physiological incompatibilities: The first clinical steps.

Xenotransplantation has the potential to solve the shortfall of human organ donors. Genetically modified pigs have been considered as potential animal donors for human xenotransplantation and have been widely used in preclinical research. The genetic modifications aim to prevent the major species-specific barriers, which include humoral and cellular immune responses, and physiological incompatibilities such as complement and coagulation dysfunctions. Genetically modified pigs can be created by deleting several pig genes related to the synthesis of various pig specific antigens or by inserting human complement- and coagulation-regulatory transgenes. Finally, in order to reduce the risk of infection, genes related to porcine endogenous retroviruses can be knocked down. In this review, we focus on genetically modified pigs and comprehensively summarize the immunological mechanism of xenograft rejection and recent progress in preclinical and clinical studies. Overall, both genetically engineered pig-based xenografts and technological breakthroughs in the biomedical field provide a promising foundation for pig-to-human xenotransplantation in the future.

Chinese expert consensus on diagnosis and treatment of trauma-induced hypercoagulopathy.

Trauma-induced coagulopathy (TIC) is caused by post-traumatic tissue injury and manifests as hypercoagulability that leads to thromboembolism or hypocoagulability that leads to uncontrollable massive hemorrhage. Previous studies on TIC have mainly focused on hemorrhagic coagulopathy caused by the hypocoagulable phenotype of TIC, while recent studies have found that trauma-induced hypercoagulopathy can occur in as many as 22.2-85.1% of trauma patients, in whom it can increase the risk of thrombotic events and mortality by 2- to 4-fold. Therefore, the Chinese People's Liberation Army Professional Committee of Critical Care Medicine and the Chinese Society of Thrombosis, Hemostasis and Critical Care, Chinese Medicine Education Association jointly formulated this Chinese Expert Consensus comprising 15 recommendations for the definition, pathophysiological mechanism, assessment, prevention, and treatment of trauma-induced hypercoagulopathy.