Fibrinogen Measurements Research Articles

Markers of coagulation and early coronary stent thrombosis

Abstract Background Acute stent thrombosis is a rare but deleterious event after percutaneous coronary intervention (PCI). Hemostatic factors such as D-Dimer, fibrinogen, and platelet count have emerged as potential indicators of increased thrombotic risk. However, data regarding the association with early stent thrombosis (ST) is sparse. Purpose The aim of this study was to investigate whether markers of coagulation are associated with increased risk of early (< 30 days after PCI) ST. Methods Within a prospective single-center registry, we retrospectively analyzed the association between pre-procedural platelet count, plasma levels of fibrinogen and D-Dimer with the occurrence of early ST within 30 days after PCI. Results We included 10,714 consecutive patients who underwent percutaneous coronary intervention (PCI) with implantation of drug-eluting stents (DES). Pre-procedural measurements of platelet count, fibrinogen and D-Dimer was available in 6,337, 6,155 and 956 patients, respectively. The number of definite early ST within 30 days was 58 (0.92 %). Pre-procedural platelet count (p<0.05) and plasma levels of fibrinogen (p<0.05) were significantly higher in patients with early ST as compared to patients without ST. Whereas D-Dimer was not associated with early ST, patients in the fifth quintile of platelet count had a significant increased risk for early ST (HR 2.43; 95% CI 1.43 - 4.14; p=0.001) as compared to patients in the lower four quintiles and patients in the fifth quintile of fibrinogen had a significant increased risk for early ST (HR 1.86; 95% CI 1.07 – 3.26; p<0.05) as compared to patients in the lower four quintiles. These associations were independent of clinical risk factors, the presence of acute coronary syndromes and the number of stents. Conclusions Pre-procedural platelet count and plasma levels of fibrinogen are associated with the risk of early ST in patients after implantation of DES. Device-level risk factors like stent-type or size and procedure-level risk factors like peri-interventional medication and complications during stent apposition are associated with ST. Platelet count and plasma levels of fibrinogen may be additional patient-level risk factors that have to be taken in account in the development of future personalized strategies to prevent these rare but deleterious complications.

Dual guided heparin monitoring with anti-Xa and APTT during micro-axial flow pump support for cardiogenic shock

Abstract Background Precise management of unfractionated heparin (UFH) is key to avoid coagulopathic complications in patients on percutaneous mechanical circulatory support (pMCS) for cardiogenic shock (CS). While the activated partial thromboplastin time (APTT) is commonly used for this purpose, it can be affected by various laboratory factors during critical illness. Alternatively, the anti-Xa test directly measures UFH activity. We proposed a parallel anti-Xa/APTT-based protocol for UFH titration during pMCS. (1) Purpose We aimed to investigate the correlation between parallel anti-Xa/APTT measurements in a CS population on pMCS. We also evaluated mortality correlation in samples exhibiting prolonged APTT and in-range anti-Xa levels, based on fibrinogen levels and INR. Methods We assessed all CS patients with isolated left-sided ImpellaTM-support (>24h) and UFH anticoagulation monitoring per protocol at two pMCS-institutions from April-2017 to June-2022. Overall correlation between parallel anti-Xa/APTT samples was assessed by Pearson correlation coefficient (with ≤0.7 considered to confer a weak correlation). Anti-Xa levels were defined as 0.20-0.30IU/mL or 0.31-0.50IU/mL, with corresponding APTT values of 40-55s and 55-80s, respectively. Samples with prolonged APTT as compared to the in-range anti-Xa were stratified based on fibrinogen (<1.5g/dL or ≥ 1.5g/dL) and INR (<1.5 or ≥1.5) on the same day as the index sample. Mortality of patients with normal fibrinogen ànd INR was then compared to those with abnormal fibrinogen and/or INR via a Chi² test. Results Ninety-three ImpellaTM-runs (77 men, 83%) with a median age of 56 years (IQR 46-66) were analyzed. Median support was 6 days (IQR 4-12). In 2447 parallel anti-Xa/APTT samples, the Pearson correlation coefficient was 0.50 (p<0.001). Among the 1914 in-range anti-Xa samples, APPT was shortened in 460 (24%), in-range in 986 (52%) and prolonged in 468 (24%) samples. In the 59 patients with samples with prolonged APTT, two patients (with 80 samples) were excluded due to absence of fibrinogen and/or INR measurements on the same day. The mortality in patients with prolonged APTT but normal fibrinogen levels and normal INR (N=29; APTT prolongation due to FXI/FXII-consumption) was significantly lower compared to the remaining 28 patients who showed samples with reduced fibrinogen levels and/or prolonged INR (suffering from concomitant conditions) (10% vs. 32%; p=0.043). Conclusion We highlight a weak correlation between anti-Xa and APTT in an anti-Xa guided UFH anticoagulated CS population during left-sided ImpellaTM support. Patients with APTT-prolongation due to concomitant conditions with INR prolongation and/or fibrinogen shortage are at highest mortality risk. The APTT/Anti-Xa coefficient can serve as an independent risk factor whilst managing critically CS patients.

Prognostic impact of fibrinogen in patients with resistant hypertension.

In this study, we investigated the long-term prognostic effects of fibrinogen levels in patients with resistant hypertension. A total of 266 patients with resistant hypertension who had serum fibrinogen measurements and 5 years of follow-up information were retrospectively included in the study. The patients were stratified according to their fibrinogen levels, which were then divided into tertiles. Clinical outcomes for major adverse cardiovascular events (MACE) were assessed at 5 years. MACE was defined as all-cause mortality, cardiovascular mortality, non-fatal myocardial infarction (MI), non-fatal stroke, a new diagnosis of heart failure, or hospitalization for heart failure and peripheral arterial disease. The incidence of MACE at 5 years in patients with resistant hypertension was higher in the highest tertile of fibrinogen. Multivariate analysis identified fibrinogen as an independent predictor of MACE in patients with resistant hypertension (odds ratio = 1.002; 95% CI: 1.001-1.004; p = 0.009). Compared to the lowest tertile, MACE was approximately 2.5 times higher in tertile 2 and approximately 6.9 times higher in the highest tertile. Fibrinogen was able to predict MACE in patients with resistant hypertension (AUC for MACE 0.662 (95% CI 0.596-0.727; p < 0.001) based on receiver operating characteristic curve analysis. In the Kaplan-Meier curve showing follow-up without MACE (MACE-free) according to the fibrinogen cut-off value, the 5-year incidence of MACE was significantly higher in the high fibrinogen group (p < 0.001). Fibrinogen is a risk marker for MACE in patients with resistant hypertension. Antihypertensive therapy aimed at lowering fibrinogen levels may improve prognosis.

The Kinetics of Inflammation-Related Proteins and Cytokines in Children Undergoing CAR-T Cell Therapy-Are They Biomarkers of Therapy-Related Toxicities?

CD19-targeted CAR-T cell therapy has revolutionized the treatment of relapsed/refractory (r/r) pre-B acute lymphoblastic leukemia (ALL). However, it can be associated with acute toxicities related to immune activation, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokines released from activated immune cells play a key role in their pathophysiology. This study was a prospective analysis of proinflammatory proteins and cytokines in children treated with tisagenlecleucel. Serial measurements of C-reactive protein, fibrinogen, ferritin, IL-6, IL-8, IL-10, IFNγ, and TNFα were taken before treatment and on consecutive days after infusion. The incidence of CRS was 77.8%, and the incidence of ICANS was 11.1%. No CRS of grade ≥ 3 was observed. All complications occurred within 14 days following infusion. Higher biomarker concentrations were found in children with CRS grade ≥ 2. Their levels were correlated with disease burden and CAR-T cell dose. While cytokine release syndrome was common, most cases were mild, primarily due to low disease burden before lymphodepleting chemotherapy (LDC). ICANS occurred less frequently but exhibited various clinical courses. None of the toxicities were fatal. All of the analyzed biomarkers rose within 14 days after CAR-T infusion, with most reaching their maximum around the third day following the procedure.

Microbial reduction of prebagged human plasma using 405 nm light and its effects on coagulation factors

Bacterial contamination is the most prevalent infectious complication of blood transfusion in the developed world. To mitigate this, several ultraviolet light-based pathogen reduction technologies (PRTs), some of which require photo-chemicals, have been developed to minimize infection transmission. Relative to UV light, visible 405-nm light is safer and has shown potential to be developed as a PRT for the in situ treatment of ex vivo human plasma and platelet concentrates, without the need for photo-chemicals. This study investigates the effect of 405-nm light on human plasma, with focus on the compatibility of antimicrobial light doses with essential plasma clotting factors. To determine an effective antimicrobial dose that is compatible with plasma, prebagged human plasma (up to 300 mL) was seeded with common microbial contaminants and treated with increasing doses of 405-nm light (16 mW cm−2; ≤ 403 J cm−2). Post-exposure plasma protein integrity was investigated using an AOPP assay, in vitro coagulation tests, and ELISA-based measurement of fibrinogen and Protein S. Microbial contamination in 300 mL prebagged human plasma was significantly reduced (P ≤ 0.05) after exposure to ≤ 288 J cm−2, with microbial loads reduced by > 96.2%. This dose did not significantly affect the plasma protein quality parameters tested (P > 0.05). Increased doses (≥ 345 J cm−2) resulted in a 4.3% increase in clot times with no statistically significant change in protein activity or levels. Overall, this study has demonstrated that the effective microbicidal 405 light dose shows little to no negative effect on plasma quality.

Anti-Xa/APTT discrepancy in heparinized ImpellaTM-supported cardiogenic shock patients can predict mortality

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Fonds Wetenschappelijk Onderzoek Flanders. Background Meticulous management of unfractionated heparin (UFH) is important to avoid complications in patients receiving percutaneous mechanical circulatory support (pMCS) for cardiogenic shock (CS). Whereas the anti-Xa assay directly measures UFH activity, the activated partial thromboplastin time (APTT) remains the most frequently used test. The APTT covers the intrinsic and common coagulation pathway and can be influenced by various confounding (laboratory) factors during critical illness, unrelated to the patient’s (anti)coagulation state. Purpose We investigated a CS population supported with isolated left-sided Impella™ and UFH-anticoagulation. UFH-levels were guided by anti-Xa with APTT in parallel. Here, we focus on those samples with anti-Xa in-range and discrepantly prolonged parallel APTT-measurements. We differentiated the APTT-prolongation according to reduced fibrinogen levels and/or prolonged INR (factor XI/XII consumption vs. concomitant conditions) and correlated this with mortality during Impella™-support. Methods Between April-2017 and June-2022, all CS patients with isolated left-sided ImpellaTM-support (&amp;gt;24h) and UFH anticoagulation monitored by anti-Xa with APTT in parallel were assessed at two high-volume tertiary institutions. In-range anti-Xa samples (between 0.20-0.30IU/mL or 0.31-0.50IU/mL based on the patient’s profile) were selected. In-range APTT values were considered between 40-55s and 55-80s respectively. Samples with prolonged APTT as compared to the in-range anti-Xa were allocated in 4 groups based on fibrinogen (&amp;lt;1.5g/dL or ≥ 1.5g/dL) and INR (&amp;lt;1.5 or ≥1.5) on the same day as the sample with prolonged APTT. Mortality of patients with normal fibrinogen ànd INR was then compared to those with abnormal fibrinogen and/or INR via a Chi² test. Results Ninety-three ImpellaTM-runs (77 men, 83%) with a median age of 56 years (IQR 46-66) were analyzed. Median support was 6 days (IQR 4-12). Among the 1914 in-range anti-Xa samples, parallel APTT was prolonged in 468 samples (24%) across 59 patients. 80 Samples from 2 patients were excluded due to absence of fibrinogen and/or INR measurements on the same day. The mortality in patients with prolonged APTT but normal fibrinogen levels and normal INR (N=29; due to FXI/FXII-consumption) was significantly lower compared to the remaining 28 patients who showed samples with reduced fibrinogen levels and/or prolonged INR (10% vs. 32%; p=0.043). Conclusions Fibrinogen-levels and INR uncover the underlying etiology in discrepant APTT-prolongation as compared to an in-range anti-Xa value in a CS population during left-sided ImpellaTM support. In patients with prolonged APTT and reduced fibrinogen (&amp;lt;1.5 g/dL) and/or prolonged INR (≥1.5), the risk of mortality is significantly elevated. This is due to concomitant conditions with high mortality (liver failure, sepsis, DIC,…). We advocate to monitor such patients carefully and treat them in a patient/disease tailored approach.

Validation and comparative analysis of sodium sulphite precipitation (SSP) method for fibrinogen measurement: A practical approach for dysfibrinogenemia diagnosis

Validation and comparative analysis of sodium sulphite precipitation (SSP) method for fibrinogen measurement: A practical approach for dysfibrinogenemia diagnosis

Current Clinical Practice of Laboratory Testing of the Hemostasis and Coagulation System in Patients with Sepsis: A Nationwide Observational Study in Japan.

The clinical benefit of hemostasis molecular indicators such as thrombin-antithrombin complex (TAT), soluble fibrin (SF), and prothrombin fragment 1 + 2 (F1+2) for the diagnosis of disseminated intravascular coagulation (DIC) is reported. Recently, novel DIC diagnostic criteria that adopt them were proposed in Japan. Despite the theoretical understanding of their function, the practical use of these markers remains unclear. The present study aimed to provide a descriptive overview of current clinical practice regarding the measurement of hemostasis markers in sepsis management in Japan. This retrospective observational analysis used the Japanese Diagnosis Procedure Combination inpatient database containing data from more than 1500 acute-care hospitals in Japan. We identified adult patients hospitalized for sepsis between April 2018 and March 2021. Descriptive statistics for measuring several hemostasis laboratory markers were summarized using patient disease characteristics, hospital characteristic, and geographical location. This study included 153,474 adult sepsis patients. Crude in-hospital mortality was 30.0%. Frequency of measurement of fibrinogen, fibrin degradation products (FDP), and D-dimer in sepsis patients on admission was 43.2%, 36.1%, and 46.4%, respectively. Novel and specific hemostasis molecular markers such as TAT, SF, and F1+2 were seldom measured (1.9%, 1.7%, and 0.02%, respectively). Hemostasis molecular markers were more frequently measured with progression of thrombocytopenia. Measurement of these clinically favorite hemostasis markers was influenced not only by disease characteristics but also hospital characteristic or geographical location. Hemostasis molecular markers such as TAT, SF, and F1+2 were rarely measured in clinical settings. Although adopted by several DIC scoring systems, neither fibrinogen, FDP, nor D-dimer was routinely measured.

Plasma fibrinogen and risk of vascular recurrence after ischaemic stroke: An individual participant and summary-level data meta-analysis of 11 prospective studies.

Inflammation is an emerging target for secondary prevention after stroke and randomised trials of anti-inflammatory therapies are ongoing. Fibrinogen, a putative pro-inflammatory marker, is associated with first stroke, but its association with major adverse cardiovascular events (MACE) after stroke is unclear. We did a systematic review investigating the association between fibrinogen and post-stroke vascular recurrence. Authors were invited to provide individual-participant data (IPD) and where available we did within-study multivariable analyses with adjustment for cardiovascular risk factors and medications. Adjusted summary-level data was extracted from published reports from studies that did not provide IPD. We pooled risk ratios (RR) by random-effects meta-analysis by comparing supra-median with sub-median fibrinogen levels and performed pre-specified subgroup analysis according to timing of phlebotomy after the index event. Eleven studies were included (14,002 patients, 42,800 follow-up years), of which seven provided IPD. Fibrinogen was associated with recurrent MACE on unadjusted (RR 1.35, 95% CI 1.17-1.57, supra-median vs sub-median) and adjusted models (RR 1.21, 95% CI 1.06-1.38). Fibrinogen was associated with recurrent stroke on univariate analysis (RR 1.19, 95% CI 1.03-1.39), but not after adjustment (RR 1.11, 95% CI 0.94-1.31). The association with recurrent MACE was consistently observed in patients with post-acute (⩾14 days) fibrinogen measures (RR 1.29, 95% CI 1.16-1.45), but not in those with early phlebotomy (<14 days) (RR 0.98, 95% CI 0.82-1.18) (Pinteraction = 0.01). Similar associations were observed for recurrent stroke. Fibrinogen was independently associated with recurrence after stroke, but the association was modified by timing of phlebotomy. Fibrinogen measurements might be useful to identify patients who are more likely to derive benefit from anti-inflammatory therapies after stroke.

A single-center, retrospective analysis to compare measurement of fibrinogen using the TEG6 analyzer to the Clauss measurement in children undergoing heart surgery.

Newer generation viscoelastic tests, TEG6s, offer point-of-care hemostatic therapy in adult patients. However, their efficacy in estimating fibrinogen levels in pediatric patients undergoing cardiac surgery is not well established. This study evaluates TEG6s for estimating fibrinogen levels in pediatric cardiac surgery patients and its predictive capability for post-bypass hypofibrinogenemia. A single-center, retrospective study on pediatric patients (under 18 years) who underwent cardiac surgery with cardiopulmonary bypass from August 2020 and November 2022. Blood samples for estimated whole blood functional fibrinogen level via TEG6s (Haemonetics Inc.) and concurrent laboratory-measured plasma fibrinogen via von Clauss assay were collected at pre- and post-cardiopulmonary bypass. Paired data for TEG6s estimated functional fibrinogen levels and plasma fibrinogen were analyzed for 432 pediatric patients pre-bypass. It was observed that functional fibrinogen consistently overestimated plasma fibrinogen across all age groups with a mean difference of 138 mg/dL (95% confidence interval [CI]: 128-149 mg/dL). This positive bias in the pre-bypass data was confirmed by Bland-Altman analysis. Post-bypass, functional fibrinogen estimates were comparable to plasma fibrinogen in all patient groups with a mean difference of -6 mg/dL (95% CI: -20-8 mg/dL) except for neonates, where functional fibrinogen levels underestimated plasma fibrinogen with a mean difference of -38 mg/dL (95% CI: -64 to -12 mg/dL). The predictive accuracy of functional fibrinogen for detecting post-bypass hypofibrinogenemia (plasma fibrinogen ≤250 mg/dL) demonstrated overall fair accuracy in all patients, indicated by an area under the curve of 0.73 (95% CI: 0.65-0.80) and good accuracy among infants, with an area under the curve of 0.80 (95% CI: 0.70-0.90). Similar performance was observed in predicting critical post-bypass hypofibrinogenemia (plasma fibrinogen ≤200 mg/dL). Based on these analyses, optimal cutoffs for predicting post-bypass hypofibrinogenemia were established as a functional fibrinogen level ≤270 mg/dL and MAFF ≤15 mm. This study demonstrates that whole blood functional fibrinogen, as estimated by TEG6s, tends to overestimate baseline plasma fibrinogen levels in pediatric age groups but aligns more accurately post-cardiopulmonary bypass, particularly in neonates and infants, suggesting its potential as a point-of-care tool in pediatric cardiac surgery. However, the variability in TEG6s performance before and after bypass highlights the need for careful interpretation of its results in clinical decision-making. Despite its contributions to understanding TEG6s in pediatric cardiac surgery, the study's design and inherent biases warrant cautious application of these findings in clinical settings.

Distinctions between survivors and non-survivors with SARS-CoV-2 vaccine-induced thrombotic thrombocytopenia: A systematic review and meta-analysis

Vaccine-inducing immune thrombocytopenia, thrombosis, and bleeding emerge as infrequent and potential complications with mortality risk in healthy subjects. However, differences between survivors and non-survivors with SARS-CoV-2 vaccine-induced thrombotic thrombocytopenia (VITT) are unclear. MethodsAccording to the PRISMA statement, we conducted a systematic review and meta-analysis, and the protocol was registered in PROSPERO. The main objective is to identify differences among survivors and non-survivors of SARS-CoV-2 VITT patients. We systematically searched through PubMed, Scopus, and Web of Science. We included cohorts, case series, and case reports. We classified bleeding complications according to the ISTH definition. Statistics: unpaired Student’s t-test or one-way ANOVA, Wilcoxon, and Kruskal-Wallis. ResultsWe systematically searched from January 2021 to June 2021 and identified 51 studies that included 191 patients. Non-survivors had the most severe thrombocytopenia (p 0.02) and lower fibrinogen measurements (p 0.01). Subjects vaccinated with mRNA vaccines (BNT162b2 and mRNA-1273) had an earlier onset of adverse events following immunization (p 0.001). We identified a higher trend of overall thrombotic events (p 0.001) in recipients of viral mechanism-dependent vaccines (Table 2). Non-survivors with cerebral venous sinus thrombosis (CVST) had more severe thrombocytopenia (p 0.01) than survivors with CVST. Finally, 61 % of survivors and 50 % with thrombosis received heparin. ConclusionWe identified more severe thrombocytopenia, lower fibrinogen measurements, and a higher trend of overall thrombotic events, including CVST and thrombotic storm, particularly with viral mechanisms-dependent vaccines in non-survivors VITT patients.

Comprehensive Characterization of Coagulation Parameters in Venous Malformations

Introduction: Localized intravascular coagulopathy (LIC) is a well-recognized, though poorly characterized complication of venous malformations (VM) that can lead to bleeding, thrombosis, and phlebolith formation. While LIC has classically been characterized by elevations in D-dimer and reductions in fibrinogen, no comprehensive studies of coagulation parameters in VM have been performed to date. Since 2021, all patients with VM undergoing evaluation for LIC in the Yale Vascular Malformations Program (VaMP) and the Yale Classical Hematology clinic have been subjected to an extensive set of coagulation tests to fully analyze LIC. Our aim was to use these laboratory test results to comprehensively characterize LIC in this population. Methods: We conducted a retrospective chart review of all VM patients presenting to the Yale VaMP and the Yale Classical Hematology clinic for assessment of LIC from 2021 to 2023. All included patients were evaluated for LIC using the following coagulation parameters: von Willebrand Factor (VWF) antigen, VWF activity, factor VIII (FVIII), alpha-2 antiplasmin (A2AP), plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex (TAT), D-dimer (DD), fibrinogen, prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (PTT). Measurements of VWF antigen, VWF activity, FVIII and A2AP were performed using an ACL TOP system (Instrumentation Laboratory; Bedford, MA, USA), while D-dimer and fibrinogen were measured using a BCS XP System (Siemens; Malvern, PA, USA) at our institution's clinical laboratory. PAI-1 and TAT were processed at national Clinical Laboratory Improvement Amendment-certified reference laboratories using ELISA-based assays. Baseline patient characteristics and coagulation test results were extracted via manual chart review. Data analysis was done using IBM SPSS statistics software and GraphPad Prism 9 software. Categorical variables were described using frequency and percentages, while quantitative variables were described using central tendency and dispersion measures. We performed univariate analysis using the Chi-square test. We also analyzed the coagulation tests using a correlation matrix. Statistical significance was set at p&amp;lt;0.05. This project was approved by our Institutional Review Board. Results: A total of 23 patients with VM were included in the analysis (Table 1). The mean age was 38 ± 16 years; the majority (82.6%) were female. The most common anatomic location was the head and neck (52.2%), while the most frequent extent of tissue involvement was muscle (54.5%), with most patients having a single lesion (59.1%) rather than multiple ones. No patients had venous thromboembolism. Normal DD and high TAT levels were observed in most patients (68.2% and 69.6%, respectively). VWF activity, VWF antigen, FVIII, PAI-1, and fibrinogen all were positively correlated (Figure 1). TAT was positively correlated with PAI-1 and inverselycorrelated withPT and INR. DD was positively correlated only with vWF activity. TAT and DD had a poor correlation; among patients with a normal TAT (n=7), 85.7% had a normal DD, while among patients with a normal DD (n=15), only 40% had a normal TAT. Three out of 4 (75%) patients with skin involvement had a high TAT with normal DD, while 2 out of 3 (66.7%) patients with visceral involvement had both high TAT and DD, although these patternswere not statistically significant (P=0.42 and 0.31, respectively). Among patients with muscle involvement (n=11), 45.5% had a high TAT and normal DD while 36.3% had both high TAT and DD. Conclusions: In this first comprehensive hematologic study of VM, we demonstrate that VM-related LIC is characterized by derangements of multiple coagulation parameters. Due to this, measurements of DD and fibrinogen alone may be inadequate for assessing LIC, and the addition of TAT and multiple other coagulation tests may yield a more complete picture of hemostatic derangements in LIC. A lack of correlation between DD and TAT is unexpected and merits further study. Differences in the depth of the VM tissue involvement and TAT/DD correlation may indicate a progression of coagulopathy related to the extent of VM but require further investigation in a larger study.

High blood levels of brain-derived neurotrophic factor (BDNF) mRNA in early psychosis are associated with inflammatory markers

The brain-derived neurotrophic factor (BDNF) single nucleotide polymorphism (SNP) rs6265C > T, Val66Met, affects BDNF secretion and has been related to inflammatory processes. Both the rs6265 and BDNF protein levels have been widely investigated in neuropsychiatric disorders with conflicting results. In the present study we examined BDNF mRNA expression in blood considering the SNP rs6265 and its relationship with inflammatory markers in the early stages of psychosis. The rs6265 genotype and blood BDNF mRNA levels were measured in 34 at-risk mental states (ARMS) individuals, 37 patients with first-episode psychosis (FEP) and 42 healthy controls (HCs) by quantitative PCR and reverse transcription (RT)-qPCR using validated TaqMan assays. We also obtained measures of interleukin-6 (IL6) mRNA levels, fibrinogen, neutrophil-to-lymphocyte ratio (NLR) and high-sensitivity C-reactive protein. We identified that BDNF mRNA levels were associated with the rs6265 genotype in an allele-dose-dependent manner, with low expression levels associated with the T allele (Met substitution). Thus, we controlled for the rs6265 genotype in all analyses. Blood BDNF mRNA levels differed between diagnostic groups: patients with FEP exhibited higher blood BDNF mRNA levels than ARMS individuals, and the lowest levels were observed in HC. In addition, we observed significant correlations between BDNF mRNA levels and inflammatory markers (IL6 mRNA levels and NLR), controlled by the rs6265 genotype, in ARMS and FEP groups. This exploratory study suggests that the rs6265 genotype is associated with differential blood mRNA expression of BDNF that increases with illness progression and correlated with inflammation in the early stages of psychosis.

Improving blood product management in placenta accreta patients with severe bleeding: institutional experience

BackgroundPlacenta accrete spectrum (PAS) is a significant risk factor for postpartum hemorrhage and effective blood product management is critical in ensuring patient safety. In PAS patients undergoing cesarean section (CS) blood transfusion management guided by the combined clinical experience of the anesthesiologist and surgeon with point-of-care coagulation testing appears safe and effective. We describe and evaluate our experience and identify potential areas for improvement with blood product management in this patient population. MethodsA retrospective chart review of peri-operative demographic, anesthetic, and obstetric data was conducted for all patients with PAS undergoing CS between 2012 and 2018 at our center. To facilitate a practical evaluation of blood product management, we divided patients into two groups based on the severity of bleeding. ResultsA total of 221 parturients with PAS underwent CS, with 133 in group 1 requiring excessive amounts of transfusion and 88 in group 2 requiring management similar to other uncomplicated CS cases. There were no deaths or instances of disseminated intravascular coagulation, and intensive care unit admission occurred in five cases (2.2%). Patients in group 1 had higher mean nadir values of intra-operative hemoglobin and platelet count. We observed a high rate of missing data for peri-operative measurement of lactate and fibrinogen, PAS grade documentation, and temperature monitoring. ConclusionGiven no significant morbidity or mortality, clinical judgment in experienced centers appears safe for the management of PAS patients undergoing CS. The adoption of an institutional protocol and point-of-care coagulation testing could decrease over-transfusion and associated complications.

Acute Phase Protein Response in Native and Imported Horses After Routine Combination Vaccination Protocol

Fibrinogen and serum amyloid A (SAA) are commonly measured equine acute phase proteins. Limited data exist on SAA and fibrinogen responses to combination vaccination protocols in horses. A prospective cohort study evaluating SAA, fibrinogen, and rectal temperature following a standard combination vaccination. Blood for measurement of SAA and serum fibrinogen and rectal temperatures were obtained before (0 hour) and after vaccination (24, 48, 72, 96, 168 hours). After vaccination, SAA and fibrinogen increased in all horses. Imports had elevated SAA from 24–168 hours, whereas native horses returned to baseline by 168 hours. Compared to native horses, SAA was significantly higher in imports (coefficient 24–168 hours 358, 95%CI: 46–671 mg/L; P = .03). Fibrinogen increased significantly from 24 to 168 hours postvaccination, but groups did not differ (coefficient −16; 95%CI: −69 to 37 mg/dL; P = .5). Absolute rectal temperatures were significantly higher in imports throughout, including 0 hour (median 37.8; IQR 37.7–38.0 vs. 37.3; 37.1–37.3; P = .002). At 24 hours postvaccination when temperatures significantly increased above baseline in both groups, there was a small but significant difference in the percent change relative to baseline (coefficient 1.9; 95%CI 0.8%–2.9%; P = .002). A standard combination vaccination protocol elicited an acute phase response in all horses. Compared to native previously vaccinated horses, imports had a stronger SAA response. The observed response is worthy of consideration when examining recently vaccinated imported horses.

Change of routine coagulation parameters in plasma samples with different hematocrit values

Abstract Aim There are many preanalytical variables affecting routine coagulation tests. Increased hematocrit (Htc) levels are one of these variables. However, no study has been conducted to determine the effect of low Htc values on coagulation tests. Therefore, in this study, we aimed to evaluate whether low Htc values affect coagulation tests besides high Htc values. Methods Standard human plasma was injected into coagulation tubes containing 3.2% sodium citrate to reflect hematocrit rates of 5% to 75% and prothrombin time (PT), active partial thromboplastin time (aPTT), thrombin time (TT) and fibrinogen measurements were performed. Results Three groups were formed according to Htc levels: A (5-25%), B (30-50%) and C (55-75%). PT (s) were found 13.7±0.30 in group A, 14.88±0.57 s in group B, 20.16 ±4.66 s in group C respectively. aPTT (s) results were 35.79±1.39 s in group A, 42.48 ± 3.51 s in group B and 76.47 ± 31.55 in group C. TT (s) results were found to be 26.42 ± 0.77 s (group A), 28.24±1.17 s (group B) and 32.02±2.60 (group C). Fibrinogen levels (g/L) were measured as 2.30 ± 0,05, 2.21 ± 0,07 and 1.90 ± 0.20 in groups A, B, C, respectively. For all measured parameters, group A reflecting low Htc was significantly (P &lt; 0 ,0001) different from the other groups. Conclusion Previous studies have reported that high Htc (&gt; 55%) levels affected routine coagulation tests. In our study, low Htc (5-25%) values were also shown to cause errors in the test results.

MONITORING THE INFLAMMATORY PROCESS OF FELINE LOWER URINARY TRACT DISEASE

This study aimed to compare the hemato-biochemical parameters in cats suffered from FLUTD with those of healthy cats, and to evaluate the inflammatory process by measuring serum amyloid A, alpha-1-Acid glycoprotein, and plasma fibrinogen concentrations. Cats frequently suffer from feline lower urinary tract disease (FLUTD), which causes acute renal failure, electrolyte buildup, and acid-base imbalance. Acute-phase proteins can be used to monitor the inflammatory processes of feline lower urinary tract disease.The present study included thirty cats of both sexes, nine cats defined as clinically healthy cats and 21 cats with signs of idiopathic cystitis and/ or urethral obstruction for up to 24 hours were defined as cat with FLUTD group. Blood samples were collected from cephalic vein for hematological, biochemical assays and the measurement of acute-phase protein concentrations, including SAA, AGP, and fibrinogen. Serum SAA and AGP were measured using commercial ELISA kits.In cats with FLUTD, the total white blood cell count, neutrophils, and platelets count increased significantly, as did the mean values of hematological and biochemical indices. However, there was a significant decrease in the mean value of red blood cells, hemoglobin, and PCV. Blood urea nitrogen, creatinine, total proteins, albumin, potassium, and phosphorus levels all increased significantly, while sodium and chloride levels decreased significantly. When compared to clinically healthy cats, plasma fibrinogen, serum alpha-1- acid glycoprotein, and serum amyloid A levels were significantly higher in cats with FLUTD. There was a significant positive correlation between the concentrations of acute phase proteins biomarkers (SAA, AGP, and fibrinogen) and blood urea nitrogen and creatinine. It is concluded that, in cats with FLUTD, serum amyloid A, AGP, and fibrinogen could be employed as an indicator of inflammatory processes.

Diagnostic Tests for Hypofibrinogenemia Resulting from Green Pit Viper (Trimeresurus albolabris) Envenomation: A Simulated In Vitro Study.

The green pit viper (GPV) Trimeresurus albolabris is found in Southeast Asia. Its venom has a thrombin-like activity that can cause hypofibrinogenemia. Fibrinogen measurement is not always available. We aimed to establish a more available diagnostic tool indicating hypofibrinogenemia caused by GPV envenomation. This was an in vitro study, in which healthy subjects aged 20 to 45 y were enrolled. There were 2 experiments. In Experiment 1, blood samples from 1 subject had varying amounts of T albolabris venom added to determine its effect on the fibrinogen level (FL). In Experiment 2, 3 sets of blood samples were obtained from another 25 subjects. The 2 venom doses established in Experiment 1 were used on 2 sets of the samples to simulate severe (FL <1.0 g·L-1) and mild hypofibrinogenemia (FL 1.0-1.7 g·L-1). The third set of samples was venom-free. All samples were used for platelet counts, prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT), and 2 bedside clotting tests. Diagnostic parameters were calculated against the target FL of <1.0 g·L-1 and <1.7 g·L-1. Twenty-five subjects were enrolled in Experiment 2. On referencing normal cutoff values (platelet count >150,000 cells/mm3, venous clotting time <15 min, normal 20-min whole blood clotting time, INR <1.2, aPTT <30), we found abnormalities of 5, 0, 0, 3, and 22%, respectively. The highest correlation with hypofibrinogenemia was provided by PT/INR. For an FL of <1.0 g·L-1, PT and INR revealed the highest areas under the receiver operating characteristic curve, 0.76 (95% CI, 0.55-0.97) and 0.76 (95% CI, 0.57-0.97), respectively. The highest accuracy and the highest sensitivity were provided by PT/INR. PT/INR could be used as a diagnostic test for severe hypofibrinogenemia in GPV envenomation because of its high accuracy and area under the receiver operating characteristic curve.

Measurement of Plasma Fibrinogen and D-dimer Levels in Sudanese Hypertensive Patients at Khartoum state

Background: Hypertension is a chronic elevation of blood pressure that, in the long-term, causes end organ damage and results in increased morbidity and mortality. Thrombosis often appears to complicate the course of patients with hypertension; thrombosis in some patients with hypertension could be developed to organ damage. The aim of this study was to measure fibrinogen and D-dimer level among sudanese patients with hypertension.&#x0D; Materials and method: This was a case control study conducted at Khartoum state, Sudan during the period from May 2022 to August 2022 to measure fibrinogen and D-dimer levels in sudanese patients with hypertension. Blood samples were collected, 50 from the patients as case group, and 50 from normal healthy subjects as control group. A total of three ml of whole blood were collected from each participant in sodium citrated tube. The fibrinogen and D-dimer level measurement was done by using coagulometer (M1 coatron) and ichroma II device respectively.&#x0D; Results: The results of this study revealed that when compared Fibrinogen level and D-dimer between cases and control group; the results revealed that fibrinogen level was significant increase in hypertensive patients with P-value of 0.000. Also, D-dimer was significant increase in hypertensive patients when compared with the results of control group, and showed significant association with P-value of 0.000. There was a negative correlation between hypertension and the gender, but the age showed positive correlation with hypertension and with D-dimer, where both fibrinogen and D-dimer showed positive correlation with the duration of hypertension.&#x0D; Conclusion: This study concluded; when compared the fibrinogen level and D- dimer between cases and control group, there was significant increase in fibrinogen and D- dimer.&#x0D; Keywords: Hypertension, fibrinogen level, D-dimer, coronary artery disease, ischemic heart disease, Cardiovascular disease, DIC, fibrin degradation products

Major Bleeding During Thrombolytic Therapy for Acute Lower Limb Ischaemia: Value of Laboratory Tests for Clinical Decision Making, 17 Years of Experience

Regular measurement of fibrinogen as dose guidance in catheter directed thrombolysis (CDT) for acute limb ischaemia (ALI) has recently been dropped from European guidelines based on inconsistent literature. This study aimed to determine whether low fibrinogen levels and high activated partial thromboplastin time (APTT) are associated with an increased major bleeding risk during CDT. All consecutive patients treated with CDT for ALI in two Dutch hospitals between January 2004 and April 2021 were analysed retrospectively. Patients were treated with two dosing regimens (low dose: 50 000 IU/hour; high dose: 100 000 IU/hour) of urokinase and, after 2018, with a single low dose regimen of alteplase (rtPA) due to urokinase manufacturing problems. The incidence of major bleeding and associated APTT and fibrinogen levels were reviewed from patient charts. Of the 443 included cases, 277 underwent CDT with urokinase and 166 with rtPA. The incidence of major bleeding in the whole cohort was 7%. Patients with a fibrinogen levels < 1.0 g/L developed more major bleeding than those in whom the fibrinogen level did not drop below 1.0 g/L (15% vs. 6%; p= .041). Systemic heparinisation during CDT or high (> 80 seconds) APTT were not significantly associated with major bleeding. Angiographic success (47% vs. 72%; p= .003) and 30 day amputation free survival (53% vs. 82%; p < .001) were lower for cases with major bleeding. Older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02 - 1.11), cardiac history (OR 3.35, 95% CI 1.39 - 8.06), high dose regimens (≥ 75 000 IU/hour urokinase; OR 2.67, 95% CI 1.18 - 6.04), and fibrinogen values < 1.0 g/L (OR 5.59, 95% CI 1.98 - 15.77) were independent predictors for major bleeding during CDT. High dose thrombolytic regimens and fibrinogen levels of ≤ 1.0 g/L are associated with more major bleeding during thrombolytic therapy. Major bleeding significantly worsened the clinical outcome. A prospective comparative study is needed to assess the benefit of monitoring fibrinogen levels.