The association of fibrinogen-albumin ratio and neutrophil-lymphocyte ratio with the severity of respiratory syncytial virus infection in children.

Respiratory syncytial virus (RSV) is a common cause of respiratory infections. It is responsible for more than half of lower respiratory tract infections in infants requiring hospitalization. This study aimed to investigate the correlation between the fibrinogen-albumin ratio (FAR) and the severity of RSV infection and to compare its effectiveness with the neutrophil-lymphocyte ratio (NLR). This was a retrospective cohort study with patients aged from 29 days to two years who had been admitted to the pediatric clinic of our hospital. Patients were divided into four groups: group 1 (mild disease), group 2 (moderate disease), group 3 (severe disease), and group 4 (control). FAR and NLR were measured in all groups. FAR was significantly higher in group 3 than in the other groups, in group 2 than in groups 1 and 4, and in group 1 than in group 4 (p<0.001 for all). NLR was significantly higher in group 4 than in the other groups and in group 3 than in groups 1 and 2 (p<0.001 for all). FAR totaled 0.078 ± 0.013 in patients with bronchiolitis; 0.099 ± 0.028, in patients with bronchopneumonia; and 0.126 ± 0.036, in patients with lobar pneumonia, all with statistically significant differences (p<0.001). NLR showed no significant statistical differences. This study found a statistically significant increase in FAR in the group receiving invasive support when compared to that receiving non-invasive support (0.189 ± 0.046 vs. 0.112 ± 0.030; p=0.003). Mechanical ventilation groups showed no differences for NLR. FAR was used to identify severe RSV-positive patients, with a sensitivity of 84.4%, a specificity of 82.2%, and a cutoff value of >0.068. This study determined a cutoff value of ≤1.49 for NLR, with a sensitivity of 62.2% and a specificity of 62.2% to find severe RSV-positive patients. Also, statistically significant associations were found between FAR and hospitalization and treatment length and time up to clinical improvement (p<0.001 for all). NLR and hospitalization and treatment length showed a weak association (p<0.001). In children with RSV infection, FAR could serve to determine disease severity and prognosis and average lengths of hospitalization, treatment, and clinical improvement. Additionally, FAR predicted disease severity more efficiently than NLR.

[Effects of Different Nutritional Scoring Systems on Prognosis of Elderly Patients with Multiple Myeloma].

OBJECTIVE: To analyze the prognostic nutritional index (PNI), controlling nutritional status (CONUT) and fibrinogen/albumin ratio (FAR) levels in elderly patients with multiple myeloma (MM) and their prognostic impact. METHODS: The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed. The optimal cut-off values for PNI, CONUT score and FAR were obtained by receiver operating characteristic (ROC) curve, which were used for grouping patients. The correlation of above three indexes with clinical parameters such as sex, serum calcium (Ca), ß2-microglobulin (ß2-MG), serum creatinine (Cr) in elderly MM patients were analyzed. The survival rates of patients with different levels of each index were compared. Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed. RESULTS: The optimal cut-off values for PNI, CONUT score and FAR were 39.775, 3.5 and 0.175, respectively, according to which the patients were divided into high and low group. Statistical analysis showed that there were significant differences in albumin level among different groups (all P < 0.05). In addition, there was a significant difference in hemoglobin between high-PNI group and low-PNI group (P < 0.05), while in sex distribution between high-FAR and low-FAR group (P < 0.05). The survival rate of elderly MM patients with increased PNI, decreased CONUT score and FAR was higher (all P < 0.05). Univariate and multivariate analysis showed that ß2-MG, Cr, PNI, CONUT score and FAR were independent prognostic factors for elderly MM patients. CONCLUSION: PNI, CONUT score and FAR are related to some clinical indicators of elderly MM patients, and have an impact on the prognosis.

H-type Hypertension Status and Influencing Factors of the Elderly People Over 80 Years Old Based on Random Forest Model.

Hypertension is a common chronic disease in elderly people over 80 years old. Clinically, H-type hypertension occurs when hypertension coexists with hyperhomocysteinemia level of ≥ 10 umol/L. Effective identification of risk factors for H-type hypertension in the elderly can greatly improve patient prognosis.Consecutively, 494 patients with hypertension admitted to the Fourth Affiliated Hospital of Harbin Medical University from January 2019 to December 2021 were selected as the study population. They were divided into H-type hypertension (n = 197) and non-H-type hypertension groups (n = 297). Patient data were collected, including basic information, history, and clinical data. The random forest model and LASSO analysis were used to screen the influencing factors for H-type hypertension. Multiple stepwise regression analysis was used to analyze the selected variables.A total of 197 elderly people over 80 years old suffered from H-type hypertension, with an incidence rate of 39.88%. The random forest model and LASSO analysis results showed that the top 8 independent variables in importance ranking were ejection fraction (EF), fibrinogen, glycated hemoglobin (HbA1c), B-type natriuretic peptide, creatinine, fasting blood glucose, uric acid, and serum triiodothyronine levels. The results of multivariate analysis showed that EF was the protective factor, while fibrinogen, HbA1c, and creatinine were the risk factors for H-type hypertension in elderly people over 80 years old (P < 0.05).Healthcare professionals can indirectly assess the prevalence of H-type hypertension by focusing on EF, fibrinogen, creatinine, and HbA1c in elderly hypertensive patients. This provided proactive intervention and medical services to improve prognosis outcomes.

Effects of gender affirming hormone therapy with testosterone on coagulation and hematological parameters in transgender people assigned female at birth: A systematic review and meta-analysis.

BACKGROUND: Hormone replacement therapy is associated with an increased thromboembolic risk. The effects of testosterone (T) on coagulation markers in people assigned female at birth (AFAB) under gender affirming hormone therapy (GAHT) are not well described. METHODS: Systematic review and meta-analysis on English-language articles retrieved from PubMed, Scopus and Cochrane Library up to April 2023 investigating T therapy in AFAB people. Coagulation parameters included international normalized ratio (INR), fibrinogen, activated partial thromboplastin clotting time (aPTT), plasminogen activator inhibitor-1 (PAI-1); hematological variables included hemoglobin (Hb) and hematocrit (HCT). We also reported the rate of thromboembolic events. Data were combined as mean differences (MD) with a 95 % confidence interval (CI) of pre- vs post-follow-up values, using random-effects models. RESULTS: We included 7 studies (6 prospective and 1 retrospective) providing information on 312 subjects (mean age: 23 to 30 years) who underwent GAHT with variable T preparation. T therapy was associated with a significant increase in INR values [MD: 0.02, 95 % confidence interval (CI): 0.01-0.03; p = 0.0001], with negligible heterogeneity (I2 = 4 %). T therapy was associated with increased Hb (MD: 1.48 g/dL, 95%CI: 1.17 to 1.78; I2 = 9 %) and HCT (4.39 %, 95%CI: 3.52 to 5.26; I2 = 23 %) values. No effect on fibrinogen, aPTT and PAI-1 was found. None of the study reported thromboembolic events during the follow-up. CONCLUSION: Therapy with T increased blood viscosity in AFAB men. A slight increase in INR values was also found, but the clinical relevance and mechanism(s) of this finding needs to be clarified.

Tigecycline-associated hypofibrinogenemia: A single center, retrospective, controlled study.

BACKGROUND: Tigecycline-associated hypofibrinogenemia has been reported as an important adverse effect in recent years, but controlled studies minimizing confounding factors are needed. The objective of our study was to assess changes in fibrinogen levels in patients for hospitalization, comparing two antibiotic episodes (tigecycline and other) within the same patients. METHODS: The retrospective, self-controlled case series study was conducted at our University Hospitals. The study compared the change in fibrinogen levels during the patient's hospitalization for tigecycline (TigePer) and another antibiotic period (OtherPer). In addition, bleeding events, bleeding risk (determined by the IMPROVE bleeding risk score), as well as 15- and 30-day mortality rates between TigePer and OtherPer were compared. RESULTS: The study enrolled 50 patients with 100 episodes of antibiotic treatment. The median age (interquartile range) of the patients was 68.5 (21.5) years, and 38 % were female. As compared to OtherPer, TigePer had a statistically significant reduction in fibrinogen levels (p < 0.001), with a hypofibrinogenemia rate of 40 % in TigePer as compared to 2 % in OtherPer (p < 0.001). TigePer demonstrated a significantly higher 15-day mortality rate (p = 0.006). No significant differences were observed between the two periods in terms of bleeding risk, rate of bleeding events, and 30-day mortality rate (p > 0.05). CONCLUSION: Hypofibrinogenemia and other coagulopathies, without associated bleeding events, are more frequently observed in patients receiving tigecycline. Therefore, it is crucial for clinicians to monitor fibrinogen levels during tigecycline use.

Body composition markers are associated with changes in inflammatory markers but not vice versa: A bi-directional longitudinal analysis in a population-based sample.

BACKGROUND AND AIM: Growing body of evidence consistently link obesity and inflammation, Although the direction of the association is still unclear. We aimed to investigate longitudinal associations of body anthropometric, composition and fat distribution parameters with inflammatory markers and vice versa. METHOD AND RESULTS: We used data from 2464 individuals of the SHIP-TREND cohort with a median follow-up of 7 years. Linear regression models adjusted for confounders were used to analyze associations of standardized body composition markers derived from classic anthropometry, bioelectrical impedance analysis (BIA) and magnetic resonance imaging (MRI) at baseline with changes in inflammatory markers (C-reactive protein (CRP), white blood cell (WBC), fibrinogen) and vice versa. Higher level of anthropometric markers at baseline were associated with an increase in the change of inflammatory markers. A 13.5 cm higher waist circumference (WC), 16.0 kg body weight and 7.76 % relative fat mass (FM) at baseline was associated with a change in CRP of 0.52 mg/L (95 % confidence interval [CI]: 0.29 to 0.74), 0.51 mg/L (95 % CI: 0.29; 0.74) and 0.58 mg/L (95 % CI: 0.34; 0.82) respectively. Absolute FM showed the strongest association with changes in serum fibrinogen levels (ß for 8.69 kg higher FM: 0.07 g/L; 95 % CI: 0.05; 0.09). Baseline inflammatory markers were only associated with changes in hip circumference. CONCLUSION: Our study indicates the importance of anthropometric, body composition and fat distribution markers as a risk factor for the development of inflammation. To prevent inflammatory-related complications, important is to take measures against the development of obesity.

Prognostic Assessment of Colorectal Cancer Patients after Laparoscopic Surgery: A Comprehensive Evaluation of the Glasgow Prognostic Score and Fibrinogen-to-Prealbumin Ratio.

BACKGROUND Previous studies have shown that systemic inflammation and suboptimal nutritional status are associated with poor cancer prognosis. This study aims to investigate the prognostic value of preoperative Glasgow prognostic score (GPS) and fibrinogen-to-prealbumin ratio (FPR) in patients with CRC (colorectal cancer) after laparoscopic surgery. MATERIAL AND METHODS In this study, the clinical data of 112 patients with CRC who underwent laparoscopic surgery were retrospectively analyzed, and the 3-year and 5-year survival rates of these patients were evaluated. In addition, the prognostic role of preoperative FPR and GPS in CRC patients was assessed using X-tile software, Kaplan-Meier analysis, and Cox regression analysis. Receiver operating characteristic (ROC) curves were generated to assess the predictive value of FPR, GPS, and FPR-GPS for the survival of these patients. RESULTS The results revealed a significant negative correlation between high FPR, elevated GPS, and overall survival (OS) in patients with CRC. Univariate and multivariate Cox regression analyses identified GPS (HR=3.207, 95% CI: 1.746~6.126), FPR (HR=2.669, 95% CI: 1.052~6.772), and lymph node metastasis (HR=2.222, 95% CI: 1.199~4.115) as independent prognostic indicators for overall survival. The ROC analysis demonstrated that the prediction based on FPR and GPS outperformed a single indicator in accurately predicting the prognosis of CRC patients. CONCLUSIONS Combining the preoperative FPR with the GPS contributes to accurate prognosis assessment for CRC patients after laparoscopic surgery. Patients exhibiting high FPR and GPS values are associated with a worse prognosis.

Levels of procoagulant factors and peak thrombin generation in relation to dementia risk in older adults: The Cardiovascular Health Study.

INTRODUCTION: Markers of hemostasis such as procoagulant factors and peak thrombin generation are associated with cardiovascular outcomes, but their associations with dementia risk are unclear. We aimed to evaluate prospective associations of selected procoagulant factors and peak thrombin generation with dementia risk. METHODS: We measured levels of 7 hemostatic factors (fibrinogen, factor VII coagulant activity [FVIIc], activated factor VII [FVIIa], factor VIIa-antithrombin [FVIIa-AT], factor XI antigen [FXI], peak thrombin generation, and platelet count) among participants in the Cardiovascular Health Study, a cohort of older adults free of dementia in 1992/1993 (n = 3185). Dementia was adjudicated and classified by DSM-IV criteria through 1998/1999. Cox proportional hazards models estimated hazard ratios (HRs) for any dementia associated with 1-standard deviation (SD) differences, adjusting for sociodemographic and clinical factors and APOE genotype. Secondary analyses separately evaluated the risk of vascular dementia, Alzheimer's disease, and mixed dementia. RESULTS: At baseline, participants had a median age of 73 years. Over 5.4 years of follow-up, we identified 448 dementia cases. There was no evidence of linear associations between levels of these hemostatic factors with any dementia risk (HRs per 1-SD difference ranged from 1.0 to 1.1; 95 % confidence intervals included 1.0). Results of secondary analyses by dementia subtype were similar. CONCLUSIONS: In this prospective study, there was no strong evidence of linear associations between levels of fibrinogen, FVIIc, FVIIa, FVIIa-AT, FXI, peak thrombin generation, or platelet count with dementia risk. Despite their associations with cardiovascular disease, higher levels of these biomarkers measured among older adults may not reflect dementia risk.

Early prediction for massive fresh frozen plasma transfusion based on fibrinogen/fibrin degradation products and D-dimer in patients with blunt trauma: a single-center, retrospective cohort study.

PURPOSE: This study aimed to examine the association of fibrinogen/fibrin degradation product (FDP) values in comparison with D-dimer and fibrinogen (Fib) values and the need for massive fresh frozen plasma (FFP) transfusion in patients with blunt trauma. METHODS: This retrospective study included patients with blunt trauma aged ≥ 18 years who were transported directly to the tertiary care hospital between April, 2012, and March, 2021. Massive FFP transfusion was defined as a composite outcome of at least 10 units of FFP or death for any cause except for cerebral herniation, within 24 h after hospital arrival. We evaluated the diagnostic accuracy of predicting the need for massive FFP transfusions using FDP, D-dimer, and Fib levels at the time of hospital arrival. RESULTS: A total of 2160 patients were eligible for the analysis, of which 167 fulfilled the criteria for the composite outcome. The area under the curve and 95% confidence interval for FDP, D-dimer, and Fib levels were 0.886 (0.865-0.906), 0.885 (0.865-0.906), and 0.771 (0.731-0.810), respectively. When the cutoff values of FDP and D-dimer were set at 90 µg/mL and 45 µg/mL, the sensitivity values were 77% and 78%, the positive predictive values were 28% and 27%, and the negative predictive values were both 98%, respectively. In contrast, the sensitivity of Fib was low regardless of the cutoff value. CONCLUSION: FDP and D-dimer levels at the time of hospital arrival showed a higher predictive accuracy for the need for massive FFP transfusion than Fib.

Ascorbic acid prevents stress-induced hypercoagulability in overweight and obese individuals.

Ascorbic acid (AA) may contribute to restoring hemostatic balance after mental stress (MS) in overweight/obese adults. We aimed to determine the effects of AA administration on hemostatic responses to MS in overweight/obese men. Fourteen overweight/obesity men (27 ± 7 years; BMI: 29.7 ± 2.6 kg m-2) performed the Stroop color-word stress task for 5 min after non-simultaneous infusion of placebo (PL, 0.9% NaCl) and AA (3 g). Blood was collected at baseline, during MS, and 60 min after MS to measure: activated partial thromboplastin time, prothrombin time, and fibrinogen concentration, by coagulometer; platelet-derived microvesicles (PMV, mv/µL), by flow cytometry; nitrite (µM), by chemiluminescence. In PL session, MS led to decreases in PTs (stress, p = 0.03; 60 min, p < 0.001), PT-INR (stress, p < 0.001; 60 min, p < 0.01), aPTTs (60 min, p = 0.03), aPTT ratio (60 min, p = 0.04) and fibrinogen (60 min, p = 0.04), while increased PT activity (60 min, p = 0.01) when compared to baseline. Furthermore, AA increased PTs (60 min, p < 0.001), PT-INR (60 min, p = 0.03) and decreased PT activity (60 min, p < 0.001) and fibrinogen (stress, p = 0.04) when compared to PL. Nitrite was increased in response to stress during AA session (p < 0.001 vs PL). There was no difference in PMV. Ascorbic acid prevented the impaired hemostatic profile and improved nitrite response to stress in the overweight and obese adults.

Point-of-care and traditional erythrocyte sedimentation rate, point-of-care rheometry, and cell-free DNA concentration in dogs with or without systemic inflammation.

RBC aggregation and deformability characteristics are altered by inflammatory, microcirculatory, and hemorheologic disease. These changes can be indirectly evaluated using the erythrocyte sedimentation rate (ESR). Newer point-of-care devices employ syllectometry to evaluate RBC rheology, which can give information beyond the ESR. We evaluated 2 point-of-care rheometers (iSED and MIZAR; Alcor Scientific) in 52 dogs presented to a university teaching hospital. Whole blood samples were analyzed for correlation between the ESR using the Westergren (ESRw) method (measured at 1 h and 24 h) and the predicted ESR using iSED. Plasma fibrinogen and cell-free DNA concentrations were also measured as probable markers of inflammation. The iSED-predicted ESR was positively correlated to the ESRw method at 1 h (r = 0.74; p < 0.001) and 24 h (r = 0.62; p < 0.001). Comparing dogs with or without inflammation (defined as plasma fibrinogen concentration >3.5 g/L [350 mg/dL]), significant differences were seen in the MIZAR parameters of base point, amplitude, integral, and half-time. Median cell-free DNA concentrations were higher in the group of dogs with inflammation (117 [range: 51-266] ng/mL vs. 82.7 [range: 19-206] ng/mL; p = 0.024). The iSED-predicted ESR is a good predictor of the ESRw and was obtained more rapidly. Rheometric parameters measured by MIZAR may be useful in detecting inflammation and monitoring secondary morphologic and functional changes in canine RBCs.

Prognostic value of preoperative white blood cell to hemoglobin ratio and fibrinogen to albumin ratio in patients with colorectal cancer.

The prognostic value of preoperative white blood cell to hemoglobin ratio (WHR) and fibrinogen to albumin ratio (FAR) in colorectal cancer (CRC) is unknown. The purpose of this study was to analyze the correlation between preoperative WHR and FAR and the prognosis of CRC patients. The retrospective study analyzed the medical records of 207 patients with colorectal cancer who were admitted to Linyi People's Hospital between June 1, 2017 and June 1, 2021. The receiver operator curve was used to determine the cutoff value of 4.604 for WHR and 0.086 for FAR, and the patients were divided into high and low groups for comparative analysis of clinical data. Cox proportional hazards regression models were used to assess independent risk factors for disease-free survival (DFS) and overall survival (OS) in univariate and multifactorial analyses. Kaplan-Meier methods were used for survival analysis and logrank tests were used to assess survival differences. Multifactorial Cox analysis showed that tumor pathological stage (HR = 6.224, 95% CI:3.063-12.647, P < .001), and WHR (HR = 3.681, 95% CI:1.768-7.401, P < .001) were the independent risk factors for DFS in CRC patients. Tumor pathological stage (HR = 4.080, 95% CI:1.992-8.360, P < .001), and WHR (HR = 3.397, 95% CI:1.662-6.940, P = .001) were independent risk factors for OS. High levels of WHR and high levels of FAR were associated with lower DFS (P < .001) and OS (P < .001).CRC patients with both higher WHR and FAR had significantly lower DFS (P < .001) and OS (P < .001). DFS and OS may be shorter in CRC patients with high WHR and high FAR, perhaps associated with poor prognosis in CRC patients, and WHR and FAR may be potential CRC prognostic markers.

Primary apical periodontitis correlates to elevated levels of interleukin-8 in a Swedish population: A report from the PAROKRANK study.

AIM: To explore associations between root filled teeth, primary and secondary apical periodontitis, and levels of inflammatory markers in blood from patients with a first myocardial infarction and matched controls. METHODOLOGY: Between May 2010 and February 2014, 805 patients with a first myocardial infarction and 805 controls, matched for sex, age, and postal code area, were recruited to the multicentre case-control study PAROKRANK (periodontitis and its relation to coronary artery disease). All participants underwent a physical and oral examination, as well as blood sampling. Using panoramic radiography, root filled teeth, primary apical periodontitis, and secondary apical periodontitis were assessed by three independent observers. Blood samples were analysed with enzyme-linked immunosorbent assay method for the following inflammatory markers: interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-12p70, tumour necrosis factor-α, and high-sensitivity C-reactive protein (hsCRP). Additionally, white blood cell count and plasma-fibrinogen were analysed. Associations between endodontic variables and the levels of inflammatory markers were statistically analysed with Mann-Whitney U-test and Spearman correlation, adjusted for confounding effects of baseline factors (sex, age, myocardial infarction, current smoking, diabetes, family history of cardiovascular disease, education, marital status, and periodontal disease). RESULTS: Mean age of the cohort was 62 years, and 81% were males. Root fillings were present in 8.4% of the 39 978 examined teeth and were associated with higher levels of hsCRP, fibrinogen, and leukocyte count, but lower levels of IL-2 and IL-12p70. After adjusting for confounders, root filled teeth remained associated with higher levels of fibrinogen, but lower levels of IL-1ß, IL-2, IL-6, and IL-12p70. Primary apical periodontitis was found in 1.2% of non-root filled teeth and associated with higher levels of IL-8 (correlation 0.06, p = .025). Secondary apical periodontitis was found in 29.6% of root filled teeth but did not relate to the levels of any of the inflammatory markers. CONCLUSIONS: This study supports the notion that inflammation at the periapex is more than a local process and that systemic influences cannot be disregarded. Whether the observed alterations in plasma levels of inflammatory markers have any dismal effects on systemic health is presently unknown but, considering the present results, in demand of further investigation.

Elevated fibrinogen to pre-albumin ratio predicts mortality in peritoneal dialysis patients.

BACKGROUND: Fibrinogen to pre-albumin ratio (FPR) is a promising predictor of mortality in various cancers. The aim of this study was to explore the prognostic value of FPR to predict mortality in peritoneal dialysis (PD) patients. METHODS: We retrospectively analyzed 324 incident PD patients form January 2011 to December 2020. Patients were stratified based on the optimal thresholds for FPR at baseline to predict overall and cardiovascular mortality during follow-up. The association of FPR and all-cause and cardiovascular mortality was evaluated by Kaplan-Meier curve and Cox regression analysis. RESULTS: All patients were divided into three groups based on the optimal cutoff value of FPR. Higher FPR levels were strongly correlated with worse overall and cardiovascular mortality in PD patients. Compared with patients in the lowest FPR tertile (<14.3), those in the highest terile (≥18.8) had multivariable-adjusted hazard ratios (95% CI confidence interval) of 3.37 (1.76-6.49) and 2.86 (1.31-6.23) for all-cause and cardiovascular mortality, respectively. Significant differences in overall survival were observed across nearly all subgroups after stratification. CONCLUSIONS: Patients with a high FPR had increased all-cause and cardiovascular mortality. FPR is a potential prognostic indicator in PD patients.

Exploration of rotational thromboelastometry (ROTEM) to characterize the coagulation profiles of newly diagnosed pediatric leukemia patients.

BACKGROUND: Viscoelastic testing has been used in adult hematologic malignancies in conjunction with conventional coagulation tests (CCTs) to predict coagulopathies and tailor blood product replacement. However, there is a paucity of similar pediatric studies. OBJECTIVES: Analyze and correlate leukemia-associated coagulopathy in newly diagnosed pediatric leukemia patients using CCT's and Rotational Thromboelastometry (ROTEM). METHODS: Pediatric patients with newly diagnosed acute leukemia underwent testing with ROTEM and CCTs on days 0, 15 and 29 of induction chemotherapy. RESULTS: Sixty-two patients were enrolled. At presentation, 54.8 % of patients had platelets <50 K/µL, 73 % had prolonged PT, 1.6 % had fibrinogen <150 mg/dL. Fifteen patients (24.2 %) had WHO grade 1 bleeding and two patients (3 %) had WHO grade 4 bleeding. EXTEM/INTEM values at presentation (day 0) reflected hypocoagulability, however FIBTEM revealed hypercoagulability. Patients showed a progressive hypocoagulability in all ROTEM assays by day 15 (day 0 vs day 15, p < 0.001), with improvement by day 29 (day 15 vs day 29, p < 0.001). Day 0 ROTEM parameters were comparable to day 29. Fibrinogen strongly correlated with ROTEM at all three time points (p < 0.0001), along with platelet count with moderate correlations (p < 0.001). CONCLUSION: Fibrinogen and platelets appear to be the drivers of leukemia associated coagulopathy in the pediatric population, suggesting the utility of using CCTs and ROTEM in this population to better evaluate hemostatic function and guide blood product replacement.

Whole blood PT/aPTT assay based on non-contact drop-of-sample acoustic tweezing spectroscopy.

Most coagulation tests are photo-optical turbidimetric assays that require the removal of cellular components from whole blood for optical clearing. If the resulting blood plasma samples are hemolyzed, they may become unsuitable for turbidimetric analysis. To resolve this issue, whole-blood analogs to plasma turbidimetric assays need to be developed. Using samples collected from non-smokers (normal group), smokers (thrombotic group), and hemophilia A (bleeding group) patients, we demonstrate that the reaction time assessed from whole blood viscosity data of the drop-of-blood acoustic tweezing spectroscopy (ATS) technique strongly correlates (Rp ≥ 0.95) with PT/aPTT values obtained from plasma turbidimetric data. Linear correlation (Rp ≥ 0.88) was also obtained between the viscous and elastic outputs of the ATS technique and the fibrinogen concentration. The integration of ATS data enabled the assessment of the functional level of fibrin cross-linkers such as factor XIII. Overall, ATS allows comprehensive sample-sparing analysis of whole blood coagulation for reliable and safe diagnosis of bleeding/thrombosis risks.

International council for standardisation in haematology recommendations on fibrinogen assays, thrombin clotting time and related tests in the investigation of bleeding disorders.

This guidance was prepared on behalf of the International Council for Standardisation in Haematology (ICSH) by an international working group of clinicians and scientists. The document focuses on tests and assays used for the assessment of fibrinogen function, particularly in the scenario of bleeding disorders. Thrombin clotting time (TT) is used as a screening test in some laboratories and also has some utility when direct anticoagulants are in use. The Clauss fibrinogen assay remains the method of choice for the assessment of fibrinogen function, but there are some situations where the results may be misleading. Prothrombin time derived fibrinogen assays are frequently used, but should be interpreted with caution; the results are not interchangeable between different methods and fibrinogen can be overestimated in certain clinical scenarios. Viscoelastic point of care methods may be helpful in emergency situations, while Reptilase time (and similar tests) are useful combined with TT in distinguishing heparin contamination of samples (i.e., if an incorrect blood draw is suspected) and the presence of direct thrombin inhibitors. Fibrinogen antigen assays should be used in the investigation of functional fibrinogen abnormalities; fibrinogen antigen and genetic testing are recommended in the confirmation of congenital fibrinogen disorders. The following recommendations for fibrinogen function assessment are based on published literature and expert opinion and should supplement local regulations and standards.

A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment.

BACKGROUND: Thrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient's prognosis. OBJECTIVES: To investigate the association between genetically determined natural hemostatic factors' levels and increased risk of HT after r-tPA treatment. METHODS: Using data from genome-wide association studies on the risk of HT after r-tPA treatment and data on 7 hemostatic factors (factor [F]VII, FVIII, von Willebrand factor [VWF], FXI, fibrinogen, plasminogen activator inhibitor-1, and tissue plasminogen activator), we performed local and global genetic correlation estimation multitrait analyses and colocalization and 2-sample Mendelian randomization analyses between hemostatic factors and HT. RESULTS: Local correlations identified a genomic region on chromosome 16 with shared covariance: fibrinogen-HT, P = 2.45 × 10-11. Multitrait analysis between fibrinogen-HT revealed 3 loci that simultaneously regulate circulating levels of fibrinogen and risk of HT: rs56026866 (PLXND1), P = 8.80 × 10-10; rs1421067 (CHD9), P = 1.81 × 10-14; and rs34780449, near ROBO1 gene, P = 1.64 × 10-8. Multitrait analysis between VWF-HT showed a novel common association regulating VWF and risk of HT after r-tPA at rs10942300 (ZNF366), P = 1.81 × 10-14. Mendelian randomization analysis did not find significant causal associations, although a nominal association was observed for FXI-HT (inverse-variance weighted estimate [SE], 0.07 [-0.29 to 0.00]; odds ratio, 0.87; 95% CI, 0.75-1.00; raw P = .05). CONCLUSION: We identified 4 shared loci between hemostatic factors and HT after r-tPA treatment, suggesting common regulatory mechanisms between fibrinogen and VWF levels and HT. Further research to determine a possible mediating effect of fibrinogen on HT risk is needed.

A retrospective study on the direct immunofluorescence findings in pigmented purpuric dermatosis.

BACKGROUND: Pigmented purpuric dermatosis (PPD) is characterized by grouped petechiae, purpuric macules, and pigmentation in the bilateral lower extremities. It runs a chronic and relapsing course. Pathophysiology is poorly understood, but it has been proposed to be an immune-complex disease or capillaritis. This study aimed to determine the incidence and patterns of positive direct immunofluorescence (DIF) findings in patients with clinically and histopathologically confirmed PPD. The association between DIF deposition type and clinical profile was also analyzed. METHODS: Patients with a clinical and histopathologic PPD diagnosis who had undergone DIF studies at a tertiary medical center with attached dermatopathology and immunofluorescence diagnostic centers between January 2002 and December 2021 were included in this study. Data on age, sex, disease duration, comorbidities, and drug intake were collected from medical records. RESULTS: There were 65 patients who satisfied the inclusion criteria. Among them, 58 (89%) had at least one positive finding and 53 (82%) were vascular deposition of immunoglobulin (Ig), complement, or fibrinogen. The most common vascular deposition was fibrinogen (71%) followed by C3 (62%), IgM (18%), IgA (6%), and IgG (3%). Fibrinogen deposition was associated with hypertension (p < 0.03). There was no association between vascular DIF deposition of IgG, IgA, and C3, with age, sex, comorbidities, disease duration, and drug history. CONCLUSION: The most common DIF findings in PPD were vascular deposition of fibrinogen and C3, with or without Ig presence. DIF findings supported a vascular origin in PPD but not an immune complex-mediated disease. Hypertension was associated with fibrinogen deposition and may play a role in its pathophysiology.