Predictive value of thrombin-antithrombin III complex and tissue plasminogen activator-inhibitor complex biomarkers in assessing the severity of early-stage acute pancreatitis.

BACKGROUND AND AIM: The development of acute pancreatitis (AP) is strongly linked to blood clotting and fibrinolysis issues. Modern clinical practices now utilize advanced blood markers like thrombin-antithrombin III complex (TAT), plasmin-α2-plasmin inhibitor complex, thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) to assess thrombosis risk. Our study used a highly sensitive chemiluminescence technique to measure these markers in AP patients, aiming to determine their early predictive value for AP severity. METHODS: There were 173 patients with AP, all of whom developed symptoms within 72 h; 102 individuals had onset symptoms within 48 h. The biomarkers were measured upon admission before determining the severity of AP. RESULTS: The levels of TAT, plasmin-α2-plasmin inhibitor complex, TM, and t-PAIC were significantly higher in the severe acute pancreatitis (SAP) group compared with the mild acute pancreatitis and moderate severe acute pancreatitis groups. For the patients within 72 h of onset, TAT, TM, and t-PAIC predicted the occurrence of SAP. For the patients within 48 h of onset, TAT and t-PAIC predicted the occurrence of SAP. The area under the curve (AUC) of prediction models is similar to Bedside Index for Severity in Acute Pancreatitis (BISAP) but significantly higher than C-reactive protein (P < 0.05). Notably, t-PAIC had a larger AUC than TAT, BISAP, and C-reactive protein. CONCLUSION: In the initial 48 h, plasma TAT and t-PAIC levels may predict the development of SAP. Within 72 h, plasma levels of TAT, TM, and t-PAIC may predict the development of SAP, and the TAT + TM + t-PAIC prediction model achieved a maximum AUC of 0.915, comparable to BISAP.

The clinical significance of TAT, PIC, TM, and t-PAIC in vascular events of BCR/ABL-negative myeloproliferative neoplasms.

Predicting the likelihood vascular events in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN) is essential for the treatment of the disease. However, effective assessment methods are lacking. Thrombin-antithrombin complex (TAT), plasmin-α2- plasmininhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) are the new direct indicators for coagulation and fibrinolysis. The aim of this study was to investigate the changes of these four new indicators in thrombotic and hemorrhagic events in BCR/ABL1-negative MPN. The study cohort of 74 patients with BCR/ABL negative myeloproliferative disorders included essential thrombocythemia, polycythemia vera, and primary myelofibrosis (PMF). A panel of 4 biomarkers, including TAT, PIC, TM, and t-PAIC were determined using Sysmex HISCL5000 automated analyzers, whereas fibrin/fibrinogen degradation products (FDP), D-dimer and Antithrombin III (ATIII) were analyzed using Sysmex CS5100 coagulation analyzer. A total of 24 (32.4%) patients experienced thrombotic events and hemorrhagic events occurred in 8 patients (10.8%). Compared to patients without hemorrhagic-thrombotic events, patients with thrombotic events had higher fibrinogen (FIB) level, FDP level and lower ATIII activity, while patients with hemorrhagic events had lower white blood cell count and hemoglobin level, higher FDP level (P < 0.05). Patients with a JAK2V617F mutation were more likely to experience thrombotic events (P < 0.05). In addtion, patients with thrombotic events had higher TAT, PIC, TM, and t-PAIC levels than patients without hemorrhagic-thrombotic events (P < 0.05), whereas patients with hemorrhagic events had a lower median value in TAT and TM (no statistical difference, P > 0.05). Patients with higher TAT, TM and t-PAIC were more likely to experience thrombotic events (P < 0.05), and only TAT was positively correlated with thrombotic events (Spearman r =0.287, P = 0.019). TAT, PIC, TM, and t-PAIC combined with ATIII and FDP have a certain value for predicting thrombosis in patients with BCR/ABL1-negative MPN. These 6 parameters are worth further exploration as predictive factors and prognostic markers for early thrombotic events.

Red blood cell transfusion is associated with an increased risk of splanchnic vein thrombosis in patients with cirrhosis.

BACKGROUND: Haemorrhage and coagulation disorders are common complications in cirrhotic patients, which cause blood products transfusion, and mounting evidence suggested that red blood cells (RBCs) were associated with pathologic thrombosis and RBC transfusion increased the risk of venous thromboembolism (VTE). AIMS: The aim of the study was to investigate the association of RBC transfusion with splanchnic vein thrombosis (SVT) in cirrhotic patients. MATERIALS & METHODS: We retrospectively reviewed patients with cirrhosis admitted in the Hunan Provincial People's Hospital between January 2010 and September 2020. Demographic data, the development of SVT, blood transfusion product type and RBC transfusion dose were collected. Multivariate logistic regression analyses and propensity matching analysis (PSM) were performed to identify the association between RBC transfusion and development of SVT. RESULTS: A total of 4479 patients with cirrhosis were enrolled in the study. SVT occurred in 48 (12.4%) cirrhotic patients in RBC transfusion group, and 233 (5.7%) cirrhotic patients in non-RBC transfusion group. RBC transfusion was significantly associated with an increased risk of SVT (unadjusted odds ratio [OR] 2.345, 95% confidence interval [CI] 1.686-3.262, p < 0.001). Notably, this association remained robust after PSM, and the volume of RBC transfusion was associated with SVT in a dose-dependent manner. CONCLUSION: This study suggested that RBC transfusion was associated with an increased risk of SVT in cirrhotic patients. High quality clinical study will be needed to further validate the association between RBC transfusion and SVT.

[Recurrent epistaxis with coagulation disorders in a boy aged 2 years]. / 2岁男孩反复鼻衄伴凝血功能异常.

A boy, aged 2 years and 5 months, had recurrent epistaxis, and the coagulation function examination showed that activated partial thromboplastin time (APTT) was significantly prolonged. Further laboratory examinations showed that the prolonged APTT was not immediately corrected in the APTT correction test, with positive lupus anticoagulant and low prothrombin activity. The boy was diagnosed with hypoprothrombinemia-lupus anticoagulant syndrome. The condition was improved after treatment with glucocorticoid, immunoglobulin, and vitamin K1. The boy has been followed up for 6 months, and no epistaxis was observed. Prothrombin activity returned to normal, and lupus anticoagulant remained positive. This is a relatively rare disease, and for patients with bleeding symptoms and coagulation disorders, it is recommended to perform the tests such as APTT correction test, lupus anticoagulant testing, and coagulation factor dilution test, which can improve the detection rate of this disease, so as to achieve early diagnosis, provide rational treatment in the early stage, and improve the prognosis.

Establishment and verification a nomogram for predicting portal vein thrombosis presence among admitted cirrhotic patients.

Background: Portal vein thrombosis (PVT) is an increasingly recognized complication of cirrhosis and possibly associated with mortality. This study aims to evaluate provoking factors for PVT, then establish a concise and efficient nomogram for predicting PVT presence among admitted cirrhotic patients. Materials and methods: All cirrhotic patients admitted in Hunan Provincial People's Hospital between January 2010 and September 2020 were retrospectively reviewed, the clinical and laboratory data were collected. Multivariate logistic regression analysis and the least absolute shrinkage and selection operator regression method were used for screening the independent predictors and constructing the nomogram. The calibration curve was plotted to evaluate the consistent degree between observed outcomes and predicted probabilities. The area under the receiver operating characteristics curve was used to assess the discriminant performance. The decision curve analysis (DCA) was carried out to evaluate the benefits of nomogram. Results: A total of 4,479 patients with cirrhosis were enrolled and 281 patients were identified with PVT. Smoking history, splenomegaly, esophagogastric varices, surgical history, red blood cell transfusion, and D-dimer were independent risk factors for PVT in cirrhosis. A nomogram was established with a good discrimination capacity and predictive efficiency with an the area under the curve (AUC) of 0.704 (95% CI: 0.664-0.745) in the training set and 0.685 (95% CI: 0.615-0.754) in the validation set. DCA suggested the net benefit of nomogram had a superior risk threshold probability. Conclusion: A concise and efficient nomogram was established with good performance, which may aid clinical decision making and guide best treatment measures.

In vitro and in vivo growth inhibition of human leukemia cells by Nodakenetin are mediated via mitochondrial apoptosis, cell cycle arrest and inhibition of cell migration and invasion.

PURPOSE: To study the anticancer potential of a plant-derived coumarin, Nodakenetin, against acute lymphocytic leukemia HL-60 cells. METHODS: The proliferation rate of the leukemia cells was checked by CCK-8 assay. Apoptotic cell death was studied by acridine orange (AO)/ethidium bromide (EB) staining. Cell cycle analysis was performed by flow cytometery. Cell migration and invasion were checked by transwell assay. Protein expression were determined by immuno blotting. Xenografted mice models were used for in vivo evaluation of Nodakenetin. RESULTS: Nodakenetin could significantly inhibit the proliferation of the all the leukemia cells. The anticancer activity of Nodakenetin against the HL-60 cells was found to be due to G2/M cell cycle arrest and induction of apoptosis. Nodakenetin prompted mitochondrial apoptosis which was also associated with alteration in the apoptosis-related protein expression (Bax and Bcl-2). It was also observed that Nodakenetin could inhibit the migration and invasion of the leukemia cells in a concentration-dependent manner. The effects of the Nodakenetin were also investigated in vivo in xenografted mice models and it was found that this molecule could inhibit the growth of xenografted tumors. CONCLUSIONS: These results indicate Nodakenetin significantly inhibits the growth of leukemia cells in vitro and in vivo and may be a valuable molecule in the management of leukemia, and as such needs further in depth investigations.

A low serum Tat-interacting protein 30 level is a diagnostic and prognostic biomarker for hepatocellular carcinoma.

The present study aimed to evaluate the diagnostic and prognostic value of Tat-interacting protein 30 (HTATIP2/TIP30) levels alone and in combination with α-fetoprotein (AFP) for the evaluation of hepatocellular carcinoma (HCC) patients. ELISA and immunohistochemical measurements on the serum and tissue of HTATIP2/TIP30 protein from HCC patients and normal controls were made. Receiver operating characteristic (ROC) curve analyses of AFP and HTATIP2/TIP30 were performed, as well as logistic regression analysis of APF combined with HTATIP2/TIP30. Log-rank analysis was used to correlate the prognosis with various levels of HTATIP2/TIP30. HTATIP2/TIP30 levels were significantly lower in the HCC group compared with the control group (4.50±2.63 vs. 9.50±2.04 ng/ml, P<0.001). ROC analysis revealed an optimal cut-off point at 7.27 ng/ml HTATIP2/TIP30 for separating the HCC from the control groups. The sensitivity and specificity were 84.6 and 93.7% (P<0.001), respectively. ROC areas of HTATIP2/TIP30 (0.928, P<0.001) were significantly higher than those for AFP (P<0.001). The area under the curve of the HTATIP2/TIP30 and AFP combination was 0.950 (P<0.001). Log-rank tests revealed that the recurrence-free survival time of the group with HTATIP2/TIP30>5.71 ng/ml was significantly higher than that of the control group (P<0.001). This is the first study to demonstrate that HTATIP2/TIP30 levels in serum may be an effective biomarker for the diagnosis and prognosis of HCC.