Fibrinogen Levels Research Articles

Factors Affecting Intraoperative Blood Transfusion Requirements during Living Donor Liver Transplantation.

Background: Intraoperative blood transfusion (IOBT) during liver transplantation (LT) has negative outcomes, and it has been shown that an increasing number of these procedures may no longer require IOBT. Regarding living donor liver transplantation (LDLT), the literature on the pre-transplant predictors of IOBT is quite heterogeneous and deficient. In this study, we reviewed our experience of IOBT among a homogenous cohort of adult right-lobe LDLTs. Methods: We conducted a retrospective analysis of prospectively collected data on adult LDLT recipients between January 2018 and October 2023. Two groups were constructed (No-IOBT vs. IOBT) for the exploration of pre- and intraoperative predictors of IOBT using univariate and multivariate analyses. An ROC curve analysis was applied to identify possible cut-offs. The one-year post-LDLT overall survival was compared using the Kaplan-Meier method. A p-value < 0.05 was considered statistically significant. Results: A total of 219 adult LDLT recipients were enrolled. The No-IOBT (n = 56) patients were mostly males (p = 0.016), with higher preoperative levels of HGB (p < 0.001), fibrinogen (p = 0.005), and albumin (p = 0.007) and a lower incidence of pre-transplant upper abdominal surgery (p = 0.017), portal vein thrombosis (p = 0.04), hepatorenal syndrome (p = 0.015), and ascites (p = 0.02) than the IOBT group (n = 163). The No-IOBT group had a shorter anhepatic phase (p = 0.002) and received fewer intravenous crystalloids (p = 0.001). In the multivariate analysis, the pre-transplant HGB (p < 0.001), fibrinogen (p < 0.001), and albumin (p = 0.04) levels were independent predictors of IOBT, showing the following cut-offs in the ROC curve analysis: HGB ≤ 11.5 (AUC: 0.800, p < 0.001), fibrinogen ≤ 125 (AUC: 0.638, p = 0.0024), and albumin ≤ 3.6 (AUC: 0.663, p = 0.0002). These were significantly associated with the No-IOBT group. The one-year overall survival of the No-IOBT and IOBT groups was 100% and 83%, respectively (p = 0.007). Conclusions: IOBT during LDLT is associated with inferior outcomes. The increased need of IOBT during LT can be predicted by evaluating serum levels of hemoglobin, albumin and fibrinogen before liver transplantation.

Trial Of Pathogen-reduced Cryoprecipitate vs. Cryoprecipitated AHF to Lower Operative Transfusions (TOP-CLOT): study protocol for a single center, prospective, cluster randomized trial

BackgroundIntraoperative hemorrhage in cardiac surgery increases risk of morbidity and mortality. Low pre-operative and perioperative levels of fibrinogen, a key clotting factor, are associated with severity of hemorrhage and increased transfusion of blood components. The ability to supplement fibrinogen during hemorrhagic resuscitation is delayed 45–60 min because cryoprecipitated antihemophilic factor (cryo AHF) is stored frozen, due to a short post-thaw shelf life. Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex, IFC) can be kept thawed, at room temperature, for up to 5 days, making it possible to be immediately available for hemorrhaging patients. This trial will investigate if earlier correction of acquired hypofibrinogenemia with IFC in hemorrhaging cardiac surgery patients reduces the total number of perioperatively transfused allogeneic blood products (red blood cells, plasma, and platelets) as compared to cryo AHF.MethodsThis is a single center, prospective, cluster randomized trial with an adaptive design. Acquired hypofibrinogenemia will be assessed by rotational thromboelastometry (ROTEM) and the threshold for cryo AHF/IFC transfusion defined as FIBTEM A10 ≤ 10 mm in bleeding patients. IFC/cryo AHF will be randomized by 1-month blocks. Cardiac surgery patients will be enrolled in the study if they have an eligible procedure and at least one dose of a cryo AHF/IFC product (approximately 2 g fibrinogen) is transfused. Data from the electronic health record, including the blood bank and lab information systems, will be prospectively collected from the health system’s data warehouse.DiscussionThis trial aims to provide evidence of the clinical efficacy of utilizing readily available thawed IFC during acute bleeding in the cardiac surgery setting compared to traditional cryo AHF.Trial registrationClinicalTrials.gov NCT05711524. Feb 3, 2023.

Preoperative fibrinogen level predicts the risk and prognosis of patients with native valve infective endocarditis undergoing valve surgery.

The aim of this study was to assess the clinical significance and prognostic value of the preoperative fibrinogen (FBG) level in patients with native valve infective endocarditis (NVIE) who underwent valve surgery. This retrospective study included a total of 163 consecutive patients who were diagnosed with NVIE and underwent valve surgery from January 2019 to January 2022 in our hospital. The primary endpoint was all-cause mortality. All-cause mortality was observed in 9.2% of the patients (n = 15). Body mass index (BMI) was lower in the survival group (p = 0.025), whereas FBG (p = 0.008) and platelet count (p = 0.044) were significantly greater in the survival group than in the death group. Multivariate Cox proportional hazards analysis revealed that FBG (HR, 0.55; 95% CI, [0.32-0.94]; p = 0.029) was an independent prognostic factor for all-cause mortality. Furthermore, Kaplan‒Meier survival curve analysis revealed that patients with low FBG levels (<3.28 g/L) had a significantly greater mortality rate (p = 0.034) than did those with high FBG levels (>3.99 g/L). In the trend analysis, the FBG tertiles were significantly related to all-cause mortality in all three adjusted models, and the p values for trend were 0.017, 0.016, and 0.028, respectively. Preoperative FBG may serve as a prognostic factor for all-cause mortality, and an FBG concentration less than 3.28 g/L was associated with a greater risk of all-cause mortality in NVIE patients undergoing valve surgery.

Usability study of the qLabs® FIB: A new point-of-care system for functional fibrinogen testing

BackgroundIdentification of hypofibrinogenemia is particularly important in obstetrics since this predicts progression to severe Post-Partum Haemorrhage (PPH). ObjectivesTo evaluate the usability of qLabs® FIB at the bedside of patients with PPH. MethodsThe qLabs® FIB test was performed using a drop of whole blood from a citrated laboratory tube sampled from each parturient with PPH >1 L by a trained user. A usability survey was completed by each clinician performing the test. ResultsDuring the evaluation, 101 qLabs® FIB tests were performed. One hundred completed surveys and 58 free comments were collected. Satisfaction was achieved in 84 % of tests. Usability in emergency setting, timeliness of results, and the results display were considered positive. The qLabs® FIB results were obtained in <3 min for concentrations below 3 g/L whilst the median time to paired laboratory results was 60 (20–120) minutes. The lower a patient's fibrinogen level, the faster the qLabs® FIB result. ConclusionThe usability study was the first step in the validation process of the qLabs® FIB point of care device in obstetric settings.

The Association between Disseminated Intravascular Coagulation Profiles and Neurologic Outcome in Patients with In-Hospital Cardiac Arrest.

The relationship between disseminated intravascular coagulation (DIC) profiles and survival or neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients is well known. In contrast, the relationship between DIC profiles and neurological outcomes in patients with in-hospital cardiac arrest (IHCA) remains unclear. This study sought to examine the correlation between DIC profiles and neurological outcomes in IHCA patients. A retrospective observational study was conducted on comatose adult IHCA patients treated with targeted temperature management between January 2017 and December 2022. DIC profiles were used to calculate the DIC score, and were measured immediately after the return of spontaneous circulation (ROSC). The primary endpoint was a poor neurological outcome at six months, defined by cerebral performance in categories 3, 4, or 5. Multivariate analysis was used to evaluate the association between DIC profiles and poor neurological outcomes. The study included 136 patients, of which 107 (78.7%) patients demonstrated poor neurological outcomes. These patients had higher fibrinogen (3.2 g/L vs. 2.3 g/L) and fibrin degradation product levels (50.7 mg/L vs. 30.1 mg/L) and lower anti-thrombin III (ATIII) levels (65.7% vs. 82.3%). The DIC score did not differ between the good and poor outcome groups. In multivariable analysis, fibrinogen (odds ratio [OR], 1.009; 95% confidence intervals [CI], 1.003-1.016) and ATIII levels (OR, 0.965; 95% CI, 0.942-0.989) were independently associated with poor neurological outcomes. Decreased fibrinogen and ATIII levels after ROSC were an independent risk factor for unfavorable neurological outcomes in IHCA. The DIC score is unlikely to play a significant role in IHCA prognosis in contrast to OHCA.

Clinical and Biochemical Differences in Patients Having Non-Variceal Upper Gastrointestinal Bleeding on NSAIDs, Oral Anticoagulants, and Antiplatelet Therapy.

Introduction: Upper gastrointestinal bleeding (UGIB) is among the most common causes of morbidity and mortality worldwide, accounting for major resource allocation and increasing incidence. This study aimed to evaluate the severity of non-variceal bleeding in patients at risk of bleeding through the use of NSAIDs, oral anticoagulants, and antiplatelet therapy. Material and Method: The study included 296 patients admitted in the Gastroenterology Department of the Municipal County Emergency University Hospital, Timisoara, between 01.01.2018 and 01.04.2020, and diagnosed via gastroscopy with non-variceal gastrointestinal bleeding. The patients were divided among four groups based on their use of different drugs known to induce UGIB, i.e., aspirin and clopidogrel, NOACs, NSAIDs, and anti-vitamin K drugs, respectively. Statistical analyses were performed based on ANOVA one-way tests for continuous variables and Chi-square tests for categorical variables with pairwise comparisons based on Bonferroni adjusted significance tests. Results: The results showed several parameters having statistical significance among the different groups of patients. Patients on NOACs had statistically significant lower hemoglobin levels, lower hematocrit values, lower erythrocytes, lower RDW and higher fibrinogen levels compared to patients on VKA. Discussion: Surprisingly, the results from our study suggest that the use of NOACs was associated with a higher risk of bleeding when compared to VKA, which differs from the existing literature. Conclusions: One of the important factors causing upper non-variceal bleeding can be iatrogenic, either due to antiplatelet drugs or anticoagulants, to which NSAID treatment is additionally associated for various reasons. In our study, the use of NOACs seemed to have a more severe bleeding spectrum with higher morbidity compared to VKA.

Clinical case of successful thrombolysis in a newborn with thrombosis of the left renal vein

Thrombosis occurring in the neonatal period is a nosology with a large number of complications, often leading to disability and death. This article highlights the successful treatment of a newborn child with renal vein thrombosis using systemic thrombolysis. A clinical case of successful systemic thrombolysis in a full-term boy in the early neonatal period with thrombosis of the left renal vein and transition of the floating part of the thrombus to the inferior vena cava is presented. A child aged 3 days was admitted to the neonatal intensive care unit from a maternity hospital, where thrombosis was suspected. Gross hematuria was observed. Laboratory data revealed thrombocytopenia and increased levels of fibrinogen and D-dimer. Ultrasound showed a sharp increase in the volume of the left kidney, a diffuse change in its parenchyma, a sharp depletion of blood flow, and accumulation of fluid in the perinephric tissue on the left, and a thrombus was observed in the lumen of the left renal vein with the presence of a floating part extending into the inferior vena cava. Thrombolytic therapy with the drug alteplase was started in combination with an infusion of unfractionated heparin. Doses were selected based on coagulogram parameters. On day 2 of therapy, hematuria resolved. On day 4 of therapy, the alteplase infusion was completed, and heparin therapy was continued. On day 13, the child was switched to a low-molecular-weight-heparin therapy. Dynamic ultrasound revealed size reduction, recanalization and further thrombus lysis, and normalization of intrarenal blood flow and kidney size. No renal dysfunction was recorded during observation. The child was transferred to the further care unit at aged 14 days and was discharged home at the age of 25 days in satisfactory condition on ongoing anticoagulant therapy under outpatient supervision of a hematologist. During follow-up observation at aged 1.5 months of life, no clinical, laboratory, and ultrasound indicators of renal function disorders were noted. Currently, there are no approved recommendations and protocols for individual thrombosis in newborns, although this particular age group is due to the vulnerability of hemostasis to the development of a thrombotic process.

Quantitative and functional changes in platelets and fibrinogen following cardiopulmonary by-pass in children

IntroductionCardiopulmonary bypass (CPB) causes coagulopathy, increasing the risk of postoperative bleeding and mortality. The underlying causes of post-CPB coagulopathy and the factors associated with its occurrence are not yet fully understood. This study assesses platelet and fibrinogen concentration and function following CPB in children with congenital heart diseases (CHD).MethodsWe analyzed prospective data from 104 patients aged 0–16 years who underwent CPB surgery for CHD. Blood samples were collected before surgery and within 30 min of CPB completion. In addition to usual coagulation tests, functional analyses were performed using point of care systems with thromboelastometry and impedance aggregometry.ResultsPlatelet count, fibrinogen concentration, and platelet and fibrinogen activities significantly decreased after CPB. The duration of CPB was directly associated with a reduction in platelet count and fibrinogen level (r = −0.38, p &amp;lt; 0.001; r = −0.21, p = 0.03, respectively), but not with their measured activity. Postoperative percentages of baseline values for platelet count (58.36% [43.34–74.44] vs. 37.44% [29.81–54.17], p &amp;lt; 0.001) and fibrinogen concentration (73.68% [66.67–82.35] vs. 65.22% [57.89–70.83], p &amp;lt; 0.001) were significantly higher in patients who did not experience hypothermia during surgery. Age was inversely associated with the decrease in platelet count (r = 0.63, p &amp;lt; 0.001), TRAPTEM AUC (r = 0.43, p &amp;lt; 0.001), fibrinogen concentration (r = 0.44, p &amp;lt; 0.001) and FIBTEM MCF (r = 0.57, p &amp;lt; 0.001).ConclusionPost-CPB coagulopathy is multifactorial and not solely attributed to hemodilution. It also involves functional changes in coagulation cascade components, which can be demonstrated by thromboelastometry and impedance aggregometry. Young children, patients requiring prolonged CPB surgery, or those experiencing hypothermia are particularly affected.

Clinical efficacy and immune response of BCL-2 inhibitors combined with hypomethylating agents in the treatment of acute myeloid leukemia

ObjectiveAcute myeloid leukemia (AML) is a malignant clonal proliferative disease with a high mortality rate. The combination therapy of BCL-2 inhibitor Venetoclax (VEN) and hypomethylating agents (HMAs) has significant anti-leukemia activity.MethodsWe analyzed the efficacy, safety and immune response characteristics of AML patients who were unfit for high-dose chemotherapy and accepted the medication of VEN + HMAs.ResultsAfter VEN + HMAs treatment, 31 newly diagnosed AML patients had the morphologic leukemia-free state rate (MLFS%) of 80.6% (25/31), complete response rate (CR%) of 54.8% (17/31), the minimal residual disease negative rate (MRD-%) of 51.6% (16/31), and the median progression-free survival (PFS) of 14 months. After treatment, the proportion of bone marrow primitive cells, the MRD level, white blood cell (WBC) count, fibrinogen (FIB) level and the proportion of B cells were significantly decreased. The red blood cell (RBC) count, hemoglobin (HGB) level, platelet count (PLT) count, activated partial thromboplastin time (APTT), the proportion of total T cells, CD8 + T cells and the IFN-γ level were significantly increased. After VEN + HMAs treatment, 12 relapsed AML patients had a MLFS% of 50% (6/12), CR% of 33.3% (4/12), MRD-% of 25% (3/12), and a median PFS of 7 months. After treatment, the proportion of bone marrow primitive cells and MRD level were slightly decreased, the proportions of CD8 + T cells and NK cells were significantly increased, the proportion of B cells and IL-10 level were significantly decreased. 12 AML patients who receive microtransplantation (MST) treatment using VEN + HMAs as a pretreatment regimen had a PFS of 20.5 months, which was much greater than VEN + HMAs group alone. Hematological recovery was better in the MST group with significantly increased RBC count, HGB level and PLT count. The most common adverse events were myelosuppression, agranulocytosis, infection and cardiovascular toxicity. No fatal adverse events were reported.ConclusionThe combination of BCL-2 inhibitors and HMAs had good efficacy and safety in AML patients who were unfit for high-dose chemotherapy, which may improve the immune microenvironment and enhance anti-leukemia immune response.

Leucocytosis during induction therapy with all-trans-retinoic acid and arsenic trioxide in acute promyelocytic leukaemia predicts differentiation syndrome and treatment-related complications.

All-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) represent the standard of care for low-intermediate risk acute promyelocytic leukaemia (APL). Leucocytosis during induction with ATRA-ATO represents a common complication with an incidence of up to 60%. To identify predictive factors for this complication, we studied a cohort of 65 low-intermediate risk APL patients treated with ATRA-ATO in three highly specialized Italian centres. Overall, 39/65 (60%) patients developed leucocytosis, with a peak in leucocyte count being most frequent in the second week from diagnosis. All cases were successfully managed with hydroxyurea. Predictive factors for leucocytosis in univariate analysis were lower platelet counts (odds ratio [OR] 0.98, 0.97-1.00, p = 0.018), lower fibrinogen levels (OR 0.36, 0.17-0.66, p = 0.003), higher bone marrow blast infiltration (OR 1.03, 1.01-1.07, p = 0.021) and CD117 expression by flow (OR 1.04, 1.01-1.08, p = 0.012). Multivariate analysis confirmed lower levels of fibrinogen at diagnosis as the strongest predictive factor for the development of leucocytosis (OR 0.36, 0.15-0.72, p = 0.009). Differentiation syndrome (DS) occurred only in patients developing leucocytosis showing a strict correlation with rising leucocytes counts (16/39 vs. 0/26, p < 0.001). In addition, other treatment-related complications including QTc prolongation, cardiac events, liver, and haematological toxicities were significantly more frequent in patients experiencing leucocytosis (22/39 vs. 3/26, p < 0.001). In conclusion, APL patients undergoing ATRA-ATO therapy with lower fibrinogen levels and platelet counts at diagnosis and with a massive bone marrow blast infiltrate should be carefully monitored for the development of leucocytosis during induction. DS and other treatment-related complications seem to occur almost exclusively in patients developing leucocytosis, who should necessarily receive DS prophylaxis and more intensive monitoring and supportive therapy to prevent treatment complications.

Impact of extracorporeal hemadsorption on mortality in critically ill COVID-19 patients in the intensive care unit.

The consequences of COVID-19, such as respiratory failure and mortality, require the search for fast and effective solutions. The aim of this retrospective study is to determine the effect of extracorporeal hemadsorption on mortality in severe COVID-19 cases hospitalized in the intensive care unit (ICU). Our study is retrospective, single-center, and observational. The study included ICU patients diagnosed with COVID-19 who received extracorporeal hemadsorption treatment between March 2020 and December 2020. Effects on mortality were examined by comparing pre- and post-hemadsorption values. Seventeen patients were included in the study. The mortality rate in the study was 64.7%. After hemadsorption, an increase was observed in the lymphocyte numbers, APACHE-II, and SOFA values of the patients (p = 0.026, 0.043, and 0.033; respectively). A significant decrease was observed in CRP and fibrinogen levels (p = 0.003 and 0.005; respectively). In the non-surviving patient group, APACHE-II, SOFA, and procalcitonin values were found to be high before and after the procedure (p = 0.002, 0.048, and 0.06; respectively). In COVID-19 patients, APACHE-II and SOFA scores may be useful in predicting the effectiveness of extracorporeal hemadsorption. Our study found that patients with higher APACHE-II and SOFA scores at baseline had a higher mortality rate after hemadsorption. These findings show that the use of intensive care scoring systems may be useful in determining which patients should receive extracorporeal hemadsorption and that hemadsorption should be performed in the early stages of the disease.

Evaluation of tocilizumab-induced hypofibrinogenemia in rheumatology practice: a retrospective, real-life, single-center experience.

Tocilizumab (TCZ) which is a humanized interleukin (IL)-6 receptor antibody has been increasingly widespread used in rheumatology practice. TCZ-related hypofibrinogenemia is a not well-described side effect, but awareness seems to be incresing as publications on this topic are also becoming more frequent. Our aim in this study was to determine the frequency, timing, and approach to TCZ-related hypofibrinogenemia in rheumatic diseases. We retrospectively screened our patients who received TCZ for inflammatory rheumatic diseases and studied serum fibrinogen at least once before and/or after drug administration. We recorded and analyzed demographic features (age, gender, diagnosis), comorbidities, laboratory parameters, management, and outcome data. 30 patients who received TCZ due to rheumatological diseases and had at least one fibrinogen level were included in this study. 73.3% were female and median age was found to be 65 (42-82) years, with median disease duration of 148 (36-500) months. 90% of the patients received TCZ for RA and 10% for GCA. We examined the fibrogen levels at an average of 24 months (min 1 max 108) following the start of TCZ treatment. The study group was divided into those with normal fibrinogen levels (normal fibrinogen group) and those with low fibrinogen levels (lowfibrinogen group). In total, hypofibrinogenemia was found in 14 (46.6%) patients. Median serum fibrinogen level in the low fibrinogen group after TCZ was calculated to be 151.5mg/dl (min 92 max 171). Most patients were asymptomatic (71.4%). Ecchymoses were in seen 4 (28,6%) patients. No major bleeding were seen. TCZ was discontinued in 5 out of 14 patients (35.7%), while 9 out of 14 patients (64.3%) were closely followed. Outcomes regarding fibrinogen levels (11 out of 14) were as follows: increase in 4 and not checked in one after cessation of the drug, 3 spontaneous increases under the drug, and 3 persistently low levels on TCZ treatment. We found no difference in terms of gender (p = 0.417), platelets (p = 0.343), ESR (p = 0.448), and CRP (p = 0.660) at the time of TCZ initiation between groups. TCZ-related hypofibrinogenemia is more frequent than expected with occurence in both the early and late stages of treatment. Further research is required to determine whether to regularly measure fibrinogen levels in patients using TCZ and how to treat patients with hypofibrinogenemia.

Peculiarities of granulocyte-macrophage and macrophage colony-stimulating factors receptors expression in subpopulations of peripheral blood monocytes of patients with chronic obstructive pulmonary disease

Introduction. To analyze of the severity of respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD), depending on the presence of an exacerbation or novel coronavirus infection (NCVI), taking into account the activity of acute phase blood parameters.Materials and methods. The medical documentation of 162 patients with COPD was studied, which were divided into 3 groups: group 1 (n=61) ‒ COPD and NCVI, group 2 (n=53) – stable COPD, group 3 (n=48) ‒ COPD exacerbation. The severity of respiratory symptoms was assessed using points. To assess the activity of inflammation the following biochemical indicators were used ‒ C-reactive protein (CRP) and fibrinogen (g/L).Results. According to the severity of cough and the intensity of dyspnea on the mMRC scale, the first, second and third groups did not differ statistically (p=0.07). Patients of the first group (82.5%) characterized by the absence of classical criteria for exacerbation of COPD. In terms of the severity of sputum production, the first, second and third groups are statistically different (p=0.0001). The first, second and third groups differ significantly in the level of serum CRP (p=0.0001) and fibrinogen (p=0.009). According to the results of the correlation analysis, some relationships found between respiratory symptoms and the level of CRP and fibrinogen.Conclusion. The clinical feature of the associated course of stable COPD and NCVI is the presence of severe dyspnea and the absence of classic criteria for exacerbation of COPD. Systemic inflammation in NCVI and stable COPD are more pronounced than in isolated stable COPD or exacerbation and correlates with cough and dyspnea. Practitioners for the differential diagnosis of NCVI in stable COPD can use the data obtained.

Do interleukin-17 and interleukin-23 inhibitors alter the coagulation parameters in psoriasis patients?: A retrospective study.

Psoriasis is a chronic inflammatory skin condition associated with systemic inflammation and a higher risk of cardiovascular comorbidities. This study retrospectively evaluates coagulation parameters in psoriasis vulgaris patients treated with IL-17 inhibitors (secukinumab, ixekizumab) and IL-23 inhibitors (risankizumab, guselkumab), compared to those untreated systemically. The study reviewed records from 177 patients treated between January 2019 and March 2023. Patients were grouped into control (n = 77), secukinumab (n = 36), ixekizumab (n = 19), guselkumab (n = 24), and risankizumab (n = 21). Coagulation parameters, including PT, aPTT, PLT, MPV, INR, fibrinogen, D-dimer, and B12 levels, were analyzed. The primary endpoint was the comparison of coagulation parameters between groups. Significant differences were found in PT, with secukinumab-treated patients showing a significantly shorter PT compared to controls (p = 0.002). No significant differences were observed in other coagulation parameters across the groups. The study highlights a potential effect of secukinumab on coagulation pathways, possibly related to IL-17's role in inflammation and endothelial function. Despite current literature suggest a risk of cerebrovascular events with risankizumab, this study did not show any significant changes in coagulation parameters with risankizumab, indicating no hypercoagulability risk associated with this IL-23 inhibitor. Our findings suggest IL-17 and IL-23 inhibitors are generally safe concerning coagulation parameters, but regular monitoring may be warranted for patients on secukinumab due to its effect on PT. Further long-term studies are needed to fully understand the cardiovascular risks associated with these therapies.

Association between fibrinogen and white matter lesions and cerebral atrophy in patients with acute ischemic stroke

BackgroundInflammation is a potential mechanism underlying the development of white matter lesions (WMLs) and cerebral atrophy. We aimed to investigate the relationship of fibrinogen levels with WMLs and cerebral atrophy in patients with acute ischemic stroke (AIS). MethodsA total of 701 AIS patients were enrolled. Participants were divided into four groups according to the quartiles of fibrinogen levels: Q1 < 2.58 g/L, Q2: 2.58-3.12 g/L, Q3: 3.12-3.67 g/L, Q4: ≥ 3.67 g/L. White matter hyperintensity (WMH), periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) were defined according to the Fazekas scale. Cerebral atrophy was defined according to global cortical atrophy scores. Univariate and multivariate logistic regression were used to explore the relationship of fibrinogen levels and WMHs, PVH, DWMH and cerebral atrophy. ResultsAmong 701 AIS patients, 498 (71.0 %), 425 (60.6 %), 442 (63.1 %), and 560 (79.9 %) had WMHs, PVH, DWMH and cerebral atrophy, respectively. After adjustment for potential covariates, the highest fibrinogen quartiles were significantly associated with increased risk of WMHs (odds ratio [OR] 1.97, 95 % confidence intervals [CI] 1.10-3.50), PVH (OR 1.85, 95 % CI 1.08-3.16) and cerebral atrophy (OR 2.53, 95 % CI 1.19-5.40) but not DWMH (OR 1.37 95 % CI 0.81-2.31) compared with the lowest fibrinogen quartile. Moreover, the association between elevated fibrinogen levels and the risk of WMLs and cerebral atrophy remained significant as continuous variables. ConclusionsIncreased baseline fibrinogen levels were independently associated with WMHs, PVH and cerebral atrophy in patients with ischemic stroke. Fibrinogen could be the potential blood biomarker of WMLs and cerebral atrophy.

Platelet Aggregation Alterations in Patients with Severe Viral Infection Treated at the Intensive Care Unit: Implications for Mortality Risk.

Severe viral infections often result in abnormal platelet function, affecting various stages of hemostasis. Activated platelets are often considered prothrombotic and more susceptible to further stimulation. However, emerging evidence suggests that initial hyperactivation is followed by platelet exhaustion and hypo-responsiveness, affecting platelet degranulation, activation, and aggregation. We examined early alterations in platelet aggregation among patients (N = 28) with acute respiratory distress syndrome and SARS-CoV-2 infection who were receiving mechanical ventilation and venovenous extracorporeal membrane oxygenation support. Blood samples were stimulated with four different activators: arachidonic acid, adenosine diphosphate, thrombin receptor-activating protein 6, and ristocetin. Our observations revealed that platelet aggregation was reduced in most patients upon admission (ranging from 61 to 89%, depending on the agonist used), and this trend intensified during the 5-day observation period. Concurrently, other coagulation parameters remained within normal ranges, except for elevated d-dimer and fibrinogen levels. Importantly, we found a significant association between platelet aggregation and patient mortality. Impaired platelet aggregation was more severe in patients who ultimately died, and reduced aggregation was associated with a significantly lower probability of survival, as confirmed by Kaplan-Meier analysis (p = 0.028). These findings underscore the potential of aggregometry as an early detection tool for identifying patients at higher risk of mortality within this specific cohort.

Acute exercise-induced inflammatory and thrombotic response in hypertensive patients.

Vigorous physical activity may acutely trigger the onset of an acute coronary syndrome especially in sedentary persons with established cardiovascular risk factors such as arterial hypertension. The rupture of an inflamed coronary plaque and the activation of the coagulation cascade are the main underlying mechanisms. The present study aimed to determine the effect of acute exercise on the inflammatory and thrombotic response in patients with arterial hypertension as compared to normotensive peers. After excluding patients with any inflammatory or/and coronary artery disease, a total of 60 non-treated hypertensive patients and 65 normotensive individuals underwent a maximal treadmill exercise testing. Βlood samples were drawn at rest and immediately after peak exercise. High-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), white blood cell (WBC), interleukin-6 (IL-6), and total fibrinogen (TF) levels, as well as plasminogen activator inhibitor-1 (PAI-1) activity, were measured. All biomarkers increased with exercise, except PAI-1, which decreased (P < 0.05 for the change between resting and peak exercise for all biomarkers). Αfter adjusting for relevant confounders (duration of exercise, metabolic equivalents, systolic BP, and rate-pressure product achieved at peak exercise), the normotensive group had less marked (P < 0.05) exercise-induced changes than the hypertensive group in hsCRP (7.7 vs. 8.6%), SAA (5.6 vs. 11.9%), WBC (45.0 vs. 51.7%), and PAI-1 (-17.3 vs. -20.1%) and a similar (P = NS) change in IL-6 (23.8 vs. 23.0%) and TF (8.5 vs. 8.5%). In conclusion, the acute exercise-induced inflammatory and thrombotic response seems to be more pronounced in non-treated hypertensive patients than in normotensive controls. Possible clinical implications of this finding merit further examination.

Neutrophil extracellular traps and citrullinated fibrinogen contribute to injury in a porcine model of limb ischemia and reperfusion.

Ischemia/reperfusion injury (IRI) is a complex pathological process, triggered by the restoration of blood flow following an interrupted blood supply. While restoring the blood flow is the only option to salvage the ischemic tissue, reperfusion after a prolonged period of ischemia initiates IRI, triggering a cascade of inflammatory responses ultimately leading to neutrophil recruitment to the inflamed tissue, where they release neutrophil extracellular traps (NETs). NETs are web-like structures of decondensed chromatin and neutrophilic proteins, including peptidyl-arginine deiminase 2 and 4 (PAD2, PAD4), that, once outside, can citrullinate plasma proteins, irreversibly changing their conformation and potentially their function. While the involvement of NETs in IRI is known mainly from rodent models, we aimed to determine the effect of NET formation and especially PADs-mediated extracellular protein citrullination in a porcine model of limb IRI. We conducted our study on amputated pig forelimbs exposed to 1h or 9h of ischemia and then reperfused in vivo for 12h. Limb weight, edema formation, compartmental pressure were measured, and skeletal muscle was analyzed by immunofluorescence (TUNEL assay and dystrophin staining) to evaluate tissue damage. Fibrin tissue deposition, complement deposition and NETs were investigated by immunofluorescence. Citrullinated plasma proteins were immunoprecipitated and citrullinated fibrinogen was identified in the plasma by Western blot and in the tissue by immunofluorescence and Western blot. Our data consolidate the involvement of NETs in a porcine model of limb IRI, correlating their contribution to damage extension with the duration of the ischemic time. We found a massive infiltration of NETs in the group subjected to 9h ischemia compared to the 1h and citrullinated fibrinogen levels, in plasma and tissue, were higher in 9h ischemia group. We propose fibrinogen citrullination as one of the mechanisms contributing to the worsening of IRI. NETs and protein citrullination represent a potential therapeutic target, but approaches are still a matter of debate. Here we introduce the idea of therapeutic approaches against citrullination to specifically inhibit PADs extracellularly, avoiding the downstream effects of hypercitrullination and keeping PADs' and NETs' intracellular regulatory functions.

Whole-genome analysis of plasma fibrinogen reveals population-differentiated genetic regulators with putative liver roles

AbstractGenetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole-genome sequencing (WGS) data provide better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the National Heart, Lung, and Blood Institute’s Trans-Omics for Precision Medicine (TOPMed) program (n = 32 572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (n = 131 340) imputed to the TOPMed or Haplotype Reference Consortium panel. We identified 18 loci that have not been identified in prior genetic studies of fibrinogen. Of these, 4 are driven by common variants of small effect with reported minor allele frequency (MAF) at least 10 percentage points higher in African populations. Three signals (SERPINA1, ZFP36L2, and TLR10) contain predicted deleterious missense variants. Two loci, SOCS3 and HPN, each harbor 2 conditionally distinct, noncoding variants. The gene region encoding the fibrinogen protein chain subunits (FGG;FGB;FGA) contains 7 distinct signals, including 1 novel signal driven by rs28577061, a variant common in African ancestry populations but extremely rare in Europeans (MAFAFR = 0.180; MAFEUR = 0.008). Through phenome-wide association studies in the VA Million Veteran Program, we found associations between fibrinogen polygenic risk scores and thrombotic and inflammatory disease phenotypes, including an association with gout. Our findings demonstrate the utility of WGS to augment genetic discovery in diverse populations and offer new insights for putative mechanisms of fibrinogen regulation.

Menorrhagia in inherited bleeding disorders in Iraqi women

Abstract: BACKGROUND: Menorrhagia, or excessive menstrual bleeding, is a common symptom in women with inherited bleeding disorders; they are conditions where the blood ability to clot is impaired. Some of the common bleeding disorders include von Willebrand disease (VWD), clotting factor deficiencies, and platelet function disorders. OBJECTIVE: To assess different types of inherited bleeding disorders in women with menorrhagia referred to the National Center of Hematology/Mustansiriyah University in Baghdad/Iraq. PATIENTS AND METHODS: A prospective study was carried out on 193 women who had experienced menorrhagia for a duration of 3 years, from 2020 to 2023. These women sought consultation at the National Centre of Hematology/Mustansiriyah University. All participants were diagnosed through various laboratory tests, including complete blood count, blood film, blood group and Rh, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen level, factor assay, von Willebrand factor antigen using ELISA technique, ristocetin cofactor, and platelet function test. RESULTS: Out of the 193 women with menorrhagia who participated in this study, the majority of whom had an unidentified cause (36.3%), followed by VWD (30.1%) and platelet function disorders (21.2%). Other bleeding disorders (thrombocytopenia and factors deficiencies) were 5.7% and 6.7%, respectively. Furthermore, the results showed that there was a significant difference in family history and consanguinity between patients with a hereditary bleeding disorder and nonhereditary bleeding disorder (P &lt; 0.001). CONCLUSIONS: Fifty eight percent of females with Menorrhagia in this study have inherited bleeding disorders(IBDs), VWD, and thrombasthenia account for 51.3% are the most common causes of inherit bleeding disorder (IBD). Consanguineous marriage should be discouraged in Iraqi society to reduce such inherited diseases.