Thrombosis remains a major public health problem. Although traditional anticoagulants, vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) have been used with success over the last decades for prevention of venous thromboembolism (VTE) and stroke in non-valvular atrial fibrillation (AF), their use exposes the patient to an increased risk of bleeding. To overcome these limitations, new approaches are exploring contact phase inhibitors, specifically targeting factors XI, XIa, XII, and XIIa. Contact phase inhibitors including antisense oligonucleotides, monoclonal antibodies, small peptidomimetic molecules, aptamers and natural inhibitors seem promising in term of efficacy and safety. A common assay can be used to measure the anticoagulant activity of different drugs within a same pharmacological class (INR for VKAs) or even across different pharmacological classes (anti-Xa for all heparins and for direct factor Xa inhibitors). Because of the diversity of contact phase inhibitors, no specific common assay has been proposed so far. Activated partial thromboplastin time (aPTT) could play a role in the assessment of these new anticoagulants, but its relevance need to be confirmed. We aim at providing an overview of the pharmacological properties of contact phase inhibitors, the safety and efficacy outcomes from clinicals trials, as well as the possible coagulation assays relevant for patient follow-up.
Original Articles
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Objectives Intraoperative PTH (IOPTH) can be challenging to offer through central laboratories despite its clinical benefit. We describe the implementation of a central laboratory-based IOPTH assay and workflow in a tertiary care centre. Methods The Elecsys ® PTH STAT assay was assessed in EDTA plasma on the Cobas ® e411 analyzer. Assay validation included precision, linearity, coefficient of variation (CV), accuracy, stability, and dilution. Samples were transported to the central laboratory and resulted via telephone to the operating room. We describe a case series of patients with primary hyperparathyroidism (PHPT) who underwent parathyroid surgery using our described IOPTH workflow. Results Within- and between-day CV was ≤3.0 % for quality control material that ranged from 2.2–44.6 pmol/L. Passing–Bablok regression yielded a slight proportional negative bias between the two Cobas e411 instruments [Elecsys ® PTH our centre=0.95 (95 % CI: 0.90–1.00) × Elecsys ® PTH Toronto − 0.05 (95 % CI: −0.20 to 0.09) (n=22)], but high correlation (r=0.99) as compared to PTH measured on the Vitros ® XT 7600 analyzer [Elecsys ® PTH=0.91 (95 % CI: 0.73–1.1) × Vitros ® PTH + 0.1 (95 % CI: −0.34 to 0.76), r=0.96 (n=40)]. The mean operating time across ten patients surgically cured for PHPT was 47.1 min (±9.1) and no patients required intraoperative frozen tissue analysis. Conclusions The Elecsys ® PTH STAT assay demonstrated acceptable analytical performance, and the described IOPTH workflow was implemented successfully via a collaborative hospital-wide initiative. We discuss our model to help guide other institutions in implementing and improving IOPTH workflows.
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Objectives To investigate the diagnostic value of serum soluble endorphin (sENG) combined with BISAP score for severe acute pancreatitis (SAP) complicated with septic shock. Methods A total of 150 cases of SAP complicated with sepsis were selected and categorized into the group with shock (n=88) and the group without shock (n=42). The general clinical data and laboratory indexes of the two groups were compared. The factors affecting the occurrence of septic shock were explored, and the correlation between serum sENG, BISAP, APACHEII, and SOFA scores was analyzed. The value of sENG and BISAP scores for diagnosis of SAP complicated with sepsis was assessed. Results APACHEII score, SOFA score, BISAP score, and serum sENG levels were higher in the group that developed septic shock. Increased BISAP score and elevated serum sENG level were independent risk factors for septic shock in patients with SAP. sENG level was positively correlated with BISAP score, APACHEII, and SOFA score in patients with SAP-complicated sepsis, and BISAP score was also positively correlated with APACHEII and SOFA score. sENG level and BISAP score had a predictive value for patients with SAP complicated with septic shock (AUC=0.723, 0.703), and the combination of the two had the highest value for the diagnosis of SAP complicated with septic shock (AUC=0.838). In addition, the AUC values of the two in predicting poor prognostic outcomes in patients with SAP complicated with sepsis were 0.757 and 0.706, respectively, and the AUC of the combination was 0.796. Conclusions Serum sENG and BISAP scores are predictors of septic shock in patients with SAP, and the combination of the two has a more powerful predictive effect and better evaluation significance.
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Objectives To contrast the level of lactate dehydrogenase (LDH) and its isoenzymes between general mycoplasma pneumoniae pneumonia (GMPP) and refractory mycoplasma pneumoniae pneumonia (RMPP) groups and to investigate their predictive value for RMPP in children. Methods A total of 160 children with GMPP and 100 children with RMPP were enrolled from August 2022 to April 2023 in our hospital. Serum LDH and its isoenzymes levels were assessed between the two groups. LDH and its isoenzymes were entered into multivariate logistic regression analysis to identify risk factors for RMPP, and variables with significance were used to analyze their diagnostic values for RMPP. ROC curves were drawn, and the AUC was calculated, with sensitivity and specificity obtained. Results Children with RMPP displayed more blatant inflammatory responses as well as more alarming imaging findings compared to those with GMPP. The levels of serum LDH and its isoenzymes in children with RMPP were significantly higher than those in children with GMPP. In the multivariate logistic regression analysis, LDH (OR=1.02, p<0.001), LDH2 (OR=1.05, p=0.010) and LDH5 (OR=1.04, p˂0.001) showed statistically significant differences. When the cut-off values were 372.5, 97.46, and 49.29 U/L respectively, the AUCs of LDH (sensitivity=0.80, specificity=0.89), LDH2 (sensitivity=0.83, specificity=0.71), and LDH5 (sensitivity=0.82, specificity=0.72) predicting RMPP were 0.91, 0.81, and 0.82, respectively. The AUC of [LDH + LDH5] (0.92) was the highest. Conclusions Serum LDH, LDH2, and LDH5 have good diagnostic values for RMPP and possess the potential to be biological markers in children with RMPP. And the predictive value is higher when used in combination.
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Objectives Circular RNAs (circRNAs) are known to be associated with cardiovascular diseases. At present, an ideal biomarker for the early diagnosis of coronary heart disease (CHD) is still lacking. Methods We screened differentially expressed circRNAs (DEcircRNAs) in the peripheral blood monocytes (PBMCs) of patients with CHD, using the microarray technology in comparing the transcriptome. We identified upregulated and downregulated circRNAs. At the same time, we collected the patient clinical medical records and the PBMCs, the above results were analyzed and validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), using 374 patients. Results We identified 183 upregulated and 41 downregulated circRNAs. Among these DEcircRNAs, hsa_circ_0000745/hsa_circRNA_101996 was significantly upregulated in a cohort of 297 patients with CHD and 77 non-CHD controls. Among patients with CHD, hsa_circ_0000745/hsa_circRNA_101996 was significantly upregulated in the unstable angina pectoris (UAP) and acute myocardial infarction (AMI) subgroups compared to the stable angina pectoris (SAP) subgroup. By dividing hsa_circ_0000745/hsa_circRNA_101996 expression into quartiles, we observed that the highest hsa_circ_0000745/hsa_circRNA_101996 expression quartile was a risk factor for CHD compared to the lowest quartile (odds ratio [OR]: 2.709; 95 % confidence interval [CI]: 1.126–6.519, p=0.026), after adjusting for the traditional risk factors (age, sex, body mass index [BMI], smoking, alcohol, C-reactive protein [CRP], small and dense low-density lipoprotein [sdLDL] and lipoprotein-associated phospholipase A2 [LP-PLA2]). Conclusions These data suggest that upregulated hsa_circ_0000745/hsa_circRNA_101996 in PBMCs is a risk factor for CHD and could be used as a biomarker of CHD.
Congress Report
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