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Background The role of factor XIII in acute bleeding situations is gaining more and more importance. It has previously been shown that prepartum factor XIII activity has a significant impact on postpartum blood loss. Whether factor XIII antigen behaves in a similar manner is unknown. As postpartum hemorrhage is one of the leading causes of maternal morbidity and mortality worldwide and factor XIII antigen determination might be available more readily in some centers as compared to factor XIII activity, this is an important question to answer, especially in the emergency situation of a postpartum hemorrhage. Objective To assess the correlation of prepartum factor XIII antigen with prepartum factor XIII activity and to evaluate the correlation between prepartum factor XIII antigen on measured postpartum blood loss. Methods This is a secondary analysis of a prospective cohort study which analyzed the impact of prepartum blood coagulation factor XIII activity on postpartum blood loss in 1300 women at the University Hospital Zurich, Switzerland between October 2015 and November 2016 (“ PPH-1300 study ”). Blood loss was quantified using a previously validated technique. The association of factor XIII activity and factor XIII antigen was assessed by means of a Spearman rank correlation and differences were displayed using Bland–Altman plot and Passing–Bablok regression. The effect of the prepartum factor XIII antigen on blood loss was estimated by continuous outcome logistic regression. Results Prepartum factor XIII activity significantly correlated with prepartum factor XIII antigen (Spearman rank correlation coefficient for prepartum values 0.89, p  < 0.001 and postpartum values 0.902, p  < 0.001). Elevated values of prepartum factor XIII antigen showed a trend toward lower measured postpartum blood loss. Conclusion The correlation of factor XIII activity with factor XIII antigen (subunit A) in a large real-world sample as well as an association of prepartum factor XIII antigen and postpartum blood loss is observed. Factor XIII antigen determination, a highly automatable test, could be useful in emergency situations such as a PPH (as well as other bleeding situations) if the determination of factor XIII activity is not possible. To evaluate whether FXIII replenishment reduces blood loss is the focus of ongoing studies.

Diseases such as myocardial infarction, ischaemic stroke, peripheral vascular disease and venous thromboembolism are major contributors to morbidity and mortality. Procoagulant, anticoagulant and fibrinolytic pathways are finely regulated in healthy individuals and dysregulated procoagulant, anticoagulant and fibrinolytic pathways lead to arterial and venous thrombosis. In this review article, we discuss the (patho)physiological role and laboratory assessment of fibrin, factor XIII and endogenous fibrinolysis, which are key players in the terminal phase of the coagulation cascade and fibrinolysis. Finally, we present the most up-to-date evidence for their involvement in various disease states and assessment of cardiovascular risk.

Objective To establish the reference intervals of plasma Plasminogen, Factor XII activity, and Factor XIII Antigen in healthy adults in Guangzhou. Methods A total of 168 young people (75 males and 93 females, aged 18–65 years) who underwent physical examination in Zhujiang Hospital of Southern Medical University from 2020 to 2022 were recruited. Sysmex CS5100 automatic coagulation analyzer and matching reagents were used to detect Plasminogen. Factor XII activity and Factor XIII Antigen were detected using the ACL TOP 700 (Instrumentation Laboratory, Bedford, MA, USA) automatic coagulation analyzer and matching reagents; reference intervals were established. Results Plasma Plasminogen and Factor XIII Antigen were normally distributed, and plasma Factor XII activity showed a skewed distribution with no statistical significance in gender. The established reference intervals were as follows: Plasminogen: 71.6-123.0%; Factor XIII Antigen: 55.1-113.1%; Factor XII: 42.3-144.1%. Conclusion The reference intervals for special coagulation items of the laboratory population in a particular area should be established to provide results that align with the population characteristics for assessing the coagulation status of clinical patients.

Hereditary factor XIII (FXIII) deficiency is a rare autosomal bleeding disorder which can cause life-threatening bleeding. Acquired deficiency can be immune-mediated or due to increased consumption or reduced synthesis. The most commonly used screening test is insensitive, and widely used quantitative assays have analytical limitations. The present study sought to validate Technofluor FXIII Activity, the first isopeptidase-based assay available on a routine coagulation analyser, the Ceveron s100. Linearity was evidenced throughout the measuring range, with correlation coefficients of >0.99, and coefficients of variation for repeatability and reproducibility were <5% and <10%, respectively. A normally distributed reference range of 47.0–135.5 IU/dL was derived from 154 normal donors. Clinical samples with Technofluor FXIII Activity results between 0 and 167.0 IU/dL were assayed with Berichrom® FXIII Activity, a functional ammonia release assay, and the HemosIL™ FXIII antigen assay, generating correlations of 0.950 and 0.980, respectively. Experiments with a transglutaminase inhibitor showed that Technofluor FXIII Activity can detect inhibition of enzymatic activity. No interference was exhibited by high levels of haemolysis and lipaemia, and interference by bilirubin was evident at 18 mg/dL, a level commensurate with severe liver disease. Technofluor FXIII Activity is a rapid, accurate and precise assay suitable for routine diagnostic use with fewer interferents than ammonia release FXIII activity assays.

Introduction This study investigated the roles of d-dimers, fibrinogen, activated partial thromboplastin time (aPTT), and Factor XIII (FXIII) in critically ill COVID-19 patients. Methods 68 patients were included into the study based on the inclusion criteria. Severe illness was defined as COVID-19 pneumonia leading to acute respiratory failure requiring mechanical ventilation and ICU (Intensive Care Unit) care. Patients who received Extracorporeal Membrane Oxygenation therapy were excluded due to its effects on the coagulation system. Blood samples were collected on day one and days five to seven, to measure coagulation parameters (aPTT, d-dimer, fibrinogen, and FXIII). Results In total, 59% of the patients died during their hospital stay. Coagulation parameters showed elevated d-dimer levels in 95.6% of patients, while FXIII activity significantly decreased during the first week in ICU. A drop in FXIII activity over the first week (FXIII Δ) emerged as a significant predictor of in-hospital mortality (HR = 2.174, P = .031), while d-dimers did not. No significant changes in aPTT, fibrinogen, or d-dimer levels were observed between days one and five to seven. Conclusion The change in Factor XIII activity during the first week in ICU (FXIII Δ) emerged as an independent predictor of in-hospital mortality. D-dimer levels were elevated in nearly all patients, but did not serve as an independent predictor of in-hospital mortality, possibly due to the homogeneity of the cohort. Overall, the results emphasize the importance of monitoring d-dimers and Factor XIII in predicting disease severity and outcomes in COVID-19 patients.

Acute leukemia (AL) is a malignancy from hematologic stem cells (HSC). Consolidation with intensive chemotherapy is required after induced remission and repeatedly causes treatment-related bleeding that is usually attributed to chemotherapy-induced thrombocytopenia (CIT). However, our previous study demonstrated that severe deficiency of plasma coagulation factor XIII (pFXIII) also participated in the bleeding of CIT in AL. However, the relationship between pFXIII deficiency and consolidation chemotherapy was unknown. Here, we observed the concentration of pFXIII in patients with AL before and after consolidation chemotherapy and reevaluated the correlation to bleeding in myelosuppression. Thus, we found that the concentration of pFXIII before chemotherapy in all patients was markedly lower than in the control data and was further decreased by chemotherapy, related to bleeding in myelosuppression. These findings indicated that chemotherapy-induced pFXIII deficiency should be of concern and explored in depth.

Surgical re-exploration due to postoperative bleeding is associated with increased morbidity and mortality. The aim of our study was to assess a potential association between the level of postoperative FXIII activity and need for re-exploration due to bleeding in patients undergoing cardiothoracic surgery. In our prospective single center observational cohort study, we enrolled patients who underwent elective cardiothoracic surgery. Patients who required re-exploration (RE group) were matched to patients from the study population (non-RE group). The study included 64 patients, out of a cohort of 678 patients, of whom 32 required surgical re-exploration due to bleeding within the first 24 h. Between patients of the RE and non-RE group, a significantly reduced FXIII activity was observed postoperatively (59.0 vs 71.1; p = .014). Multivariable analysis revealed reduced FXIII activity (p = .048) as a parameter independently associated with surgical re-exploration. Further, reduced FXIII activity (p = .037) and surgical re-exploration (p = .01) were significantly associated with increased 30 day mortality. In multivariable analysis re-exploration was independently associated with increased risk of 30 day mortality (p = .004, HR 9.68). Reduced postoperative FXIII activity may be associated with the need for surgical re-exploration. Postoperative assessment of FXIII activity should therefore be considered in patients undergoing elective cardiothoracic surgery. •After cardiac surgery, a significantly reduced FXIII activity may be observed.•Such reduction may be associated with surgical re-exploration for bleeding.•Postoperatively reduced FXIII activity is related to increased 30 day mortality.

Renal transplantation is the preferred treatment of end stage renal disease, but allograft survival is limited by the development of interstitial fibrosis and tubular atrophy in response to various stimuli. Much effort has been put into identifying new protein markers of fibrosis to support the diagnosis. In the present work, we performed an in-depth quantitative proteomics analysis of allograft biopsies from 31 prevalent renal transplant patients and correlated the quantified proteins with the volume fraction of fibrosis as determined by a morphometric method. Linear regression analysis identified four proteins that were highly associated with the degree of interstitial fibrosis, namely Coagulation Factor XIII A chain (estimate 18.7, adjusted p < 0.03), Uridine Phosphorylase 1 (estimate 19.4, adjusted p < 0.001), Actin-related protein 2/3 subunit 2 (estimate 34.2, adjusted p < 0.05) and Cytochrome C Oxidase Assembly Factor 6 homolog (estimate −44.9, adjusted p < 0.002), even after multiple testing. Proteins that were negatively associated with fibrosis (p < 0.005) were primarily related to normal metabolic processes and respiration, whereas proteins that were positively associated with fibrosis (p < 0.005) were involved in catabolic processes, cytoskeleton organization and the immune response. The identified proteins may be candidates for further validation with regards to renal fibrosis. The results support the notion that cytoskeleton organization and immune responses are prevalent processes in renal allograft fibrosis.

The aim of the case-control study was to explore the effect of coagulation factor XIII (FXIII) B subunit (FXIII-B) polymorphisms on the risk of coronary artery disease, and on FXIII levels. In the study, 687 patients admitted for coronary angiography to investigate suspected coronary artery disease and 994 individuals representing the Hungarian population were enrolled. The patients were classified according to the presence of significant coronary atherosclerosis (CAS) and history of myocardial infarction (MI). The F13B gene was genotyped for p.His95Arg and for intron K nt29756 C>G polymorphisms; the latter results in the replacement of 10 C-terminal amino acids by 25 novel amino acids. The p.His95Arg polymorphism did not influence the risk of CAS or MI. The FXIII-B intron K nt29756 G allele provided significant protection against CAS and MI in patients with a fibrinogen level in the upper tertile. However, this effect prevailed only in the presence of the FXIII-A Leu34 allele, and a synergism between the two polymorphisms was revealed. Carriers of the intron K nt29756 G allele had significantly lower FXIII levels, and FXIII levels in the lower tertile provided significant protection against MI. It is suggested that the protective effect of the combined polymorphisms is related to decreased FXIII levels.

Coronary microvascular disease (MVD) remains a major clinical problem due to limited mechanistic understanding and a challenging diagnosis. In the present study we evaluated the utility of targeted imaging of active factor XIII (FXIII) for detection of coronary MVD associated with thrombus. We hypothesized that a high specificity and sensitivity FXIII targeted radiolabeled probe can serve as a biomarker for cross-linked thrombi in the microvasculature, and thus an indicator for underlying coronary MVD. To evaluate this approach, a coronary MVD model was established for local induction of singlet oxygen and reactive oxygen species (ROS) via a photochemical reaction (PCR). PCR was used to induce endothelial injury and microthrombi via focal over-production of ROS only in the coronary microvasculature. Oxidative stress was initially evaluated in primary coronary endothelial cells to optimize parameters of PCR, which were then translated to experiments. To develop the coronary MVD model, 64 mice were assigned to one of four groups after thoracotomy: 1) sham control; 2) rose bengal; 3) green light; or 4) their combination. Following interventions, the mice underwent transmission electron microscopy, fluorescent myocardial perfusion, coronary angiography, and immunohistochemical staining. Echocardiography (n = 12) and gene expression (n = 10) studies were also performed after MVD induction to monitor serial changes in cardiac function and explore possible mechanisms. To diagnose early onset MVD, FXIII radioactivity was assessed in 104 mice using gamma well counting (GWC) and in 14 mice using serial single photon emission computed tomography / computed tomography (SPECT/CT) imaging of a FXIII targeted technetium-labeled probe ( Tc-NC100668). experiments demonstrated that photosensitizer concentration and light illumination time were critical parameters for PCR. experiments demonstrated manifestations of clinical MVD, including endothelial damage, a \"no flow zone,\" arteriole rarefaction with patent epicardial coronary arteries, infiltration of inflammatory cells in the PCR-treated region, and preserved cardiac function. Gene expression also demonstrated a pro-thrombotic and impaired fibrinolytic status. In the early stages of MVD, enhanced FXIII activity was confirmed within the MVD region using GWC and SPECT/CT imaging. Our results demonstrate that molecular imaging of FXIII activity may allow for early detection of coronary MVD associated with thrombus, in a novel pre-clinical model.