Higher Fibrinogen Research Articles

Major bleeding complications in critically ill patients with COVID-19 pneumonia.

As patients with COVID-19 pneumonia admitted to intensive care unit (ICU) have high rates of thrombosis, high doses of thromboprophylaxis have been proposed. The associated bleeding risk remains unknown. We investigated major bleeding complications in ICU COVID-19 patients and we examined their relationship with inflammation and thromboprophylaxis. Retrospective monocentric study of consecutive adult patients admitted in ICU for COVID-19 pneumonia requiring mechanical ventilation. Data collected included demographics, anticoagulation status, coagulation tests and outcomes including major bleeding and thrombotic events. Among 56 ICU COVID-19 patients, 10 (18%) patients had major bleeding and 16 (29%) thrombotic events. Major bleeding occurred later than thrombosis after ICU admission [17(14–23) days versus 9(3–11) days respectively (p = 0.005)]. Fibrinogen concentration always decreased several days [4(3–5) days] before bleeding; D-dimers followed the same trend. All bleeding patients were treated with anticoagulants and anticoagulation was overdosed for 6 (60%) patients on the day of bleeding or the day before. In the whole cohort, overdose was measured in 22 and 78% of patients receiving therapeutic anticoagulation during fibrinogen increase and decrease respectively (p < 0.05). Coagulation disorders had biphasic evolution during COVID-19: first thrombotic events during initial hyperinflammation, then bleeding events once inflammation reduced, as confirmed by fibrinogen and d-dimers decrease. Most bleeding events complicated heparin overdose, promoted by inflammation decrease, suggesting to carefully monitor heparin during COVID-19. Thromboprophylaxis may be adapted to this biphasic evolution, with initial high doses reduced to standard doses once the high thrombotic risk period ends and fibrinogen decreases, to prevent bleeding events.

The effect of preprocedural serum albumin to fibrinogen ratio on arteriovenous fistula maturation

Background/Aim: Inflammation and inflammatory parameters are known to have unfavorable effects both on the surgical success and survival. The reference point of the present study are the results of an investigation of the effects of blood proteins such as albumin and fibrinogen, which affect blood viscosity, and other hematological parameters, on the success of arteriovenous fistula operations. Methods: This retrospective cohort study includes the data of 135 patients who underwent arteriovenous fistula surgery by the same surgeon in the same center. The patients were divided into two groups, as those with an active fistula 8–12 weeks after surgery and those with a dysfunctional fistula. After applying the exclusion criteria, the remaining data were compared using appropriate statistical methods to evaluate the influence on fistula maturation rates. Results: A statistical analysis performed after the evaluation of the fitness of the data to a normal distribution revealed fistula maturation to be associated with fibrinogen (P<0.001), albumin (P<0.001), fibrinogen-to-albumin ratio (FAR) (P<0.001) and neutrophil-to-lymphocyte ratio (NLR) (P=0.002). It was further noted that C-reactive protein (CRP) (P<0.001), CRP-to-albumin ratio (CAR) (P<0.001), neutrophil count (P=0.003) and lymphocyte count (P=0.03) all played a role in this process. A receiver operating characteristic (ROC) curve analysis revealed the cut-off values for fibrinogen (P<0.001, AUC: 0.930), CRP (P<0.001, AUC: 0.892), FAR (P<0.001, AUC: 0.988), CAR (P<0.001, AUC: 0.916), neutrophil count (P=0.011, AUC: 0.661) and albumin (P<0.001, AUC: 0.946) in terms of fistula maturation. Conclusion: The present study reveals that low albumin and high fibrinogen levels negatively affect AVF maturation. As reported previously in literature, and supported by the present study, high CRP levels may be associated with early AVF dysfunction.

Suggestions for global coagulation assays for the assessment of COVID-19 associated hypercoagulability

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is associated with a clear prothrombotic phenotype. Although the exact pathophysiological mechanisms are not yet fully understood, thrombosis is clearly a highly important in the prognosis and outcome of COVID-19. As such, there is a need for diagnostic analysis and quantification of the coagulation potential in these patients, both at diagnosis and follow-up. Global coagulation assays like thrombin generation (TG) and rotational thromboelastometry (ROTEM) might be suitable in estimating COVID-19 associated coagulopathy and thrombosis risk. Therefore, we aimed at validating both assays for samples with high levels of fibrinogen and in the presence of anticoagulant heparins, such as commonly observed for COVID-19 ICU patients. Materials and methodsCalibrated Automated Thrombography (CAT) was optimized to assess plasma thrombin generation in the presence of heparins. The final conditions with either 10 μg/mL Ellagic acid (EA) or PPP Reagent HIGH (high tissue factor; HPPH) were validated according to the EP5 protocol for within-run and between-run variability. Overall variability was well below 10%. To estimate the influences of heparins and high fibrinogen levels, CAT was performed on spiked plasma aliquots from 13 healthy volunteers. Comparable to the CAT method, tPA-ROTEM was used to validate the effect of high fibrinogen and heparins on clotting time, clot firmness and clot lysis parameters. ResultsOur adjusted COVID-19 assay showed a heparin dose dependent decrease in peak height and endogenous thrombin potential (ETP) for both EA and HPPH triggered variants. High fibrinogen did not alter the inhibitory effect of either LMWH or UFH, nor did it influence the peak height or ETP in any of the conditions. The tPA-ROTEM showed a significant prolongation in clotting time with the additions of heparin, which normalized with the addition of high fibrinogen. MCF was markedly increased in all hyperfibrinogenemic conditions. A trend towards increased lysis time and, thus, decreased fibrinolysis was observed. ConclusionThrombin generation and tPA-ROTEM protocols for measurements in the COVID-19 populations were adjusted and validated. The adjusted thrombin generation assay shows good sensitivity for measurements in heparin spiked plasma. High levels of fibrinogen did not alter the assay or the effectiveness of heparins as measured in this assay. t-PA ROTEM was effective in measurement of both high fibrinogen and heparins spiked samples and was sensitive to the expected relevant coagulant changes by these conditions. No clear fibrinolytic effect was observed in different conditions.

Fibrinogen heterogeneity in horses.

BackgroundFibrinogen heterogeneity has been observed in humans and can influence fibrinogen measurements when using the modified Clauss assay. We hypothesized that fibrinogen heterogeneity also exists in horses.ObjectivesTo determine whether fibrinogen heterogeneity exists in horses.AnimalsFive clinically healthy horses from the university equine teaching herd.MethodsPresumed fibrinogen was purified from pooled citrated plasma and electrophoresis performed. The purified protein was subjected to Western blotting using sheep antiserum against human fibrinogen, and liquid chromatography‐tandem mass spectrometry (LC‐MS/MS).ResultsGel electrophoresis of nonreduced equine purified protein yielded 2 protein bands (approximately 377 and 318 kDa) that corresponded with the molecular weights of human high molecular weight fibrinogen and low molecular weight fibrinogen fractions, respectively. Electrophoretograms of reduced purified protein, Western blots, and LC‐MS/MS supported that the purified nonreduced protein bands were fibrinogen.ConclusionFibrinogen heterogeneity exists in horses.

Analysis of the levels of inflammatory parameters in persons over the age of 90.

Chronic inflammatory conditions resulting from elevated levels of circulating proinflammatory mediators are common in the elderly. The aim of the paper was to analyze the balance between proinflammatory and anti-inflammatory markers in longevous individuals. The study was conducted in persons aged >90years old, residents of Poland living either at home or staying at residential care facilities. The study included 90 persons (69 women and 21 men) aged between 90 and 103years. Persons with abnormal CRP presented with a statistical tendency toward higher fibrinogen and lower IL10 and IL-1α levels compared to patients in whom CRP level was within the normal range. IL-6 concentration predicted abnormality within CRP. Inflammation in persons above the age of 90years old might be linked to abnormal fibrinogen and IL-6 levels.

Higher Fibrinogen Levels among Patient with End-Stage Kidney Disease Post Initiation of Peritoneal Dialysis: Cardiovascular Risk Attenuation

Defects in both coagulation initiation and fibrinolysis have been identified in Chronic Kidney Disease (CKD) patients and patients on dialysis may have higher rates of Cardiovascular Disease (CVD) events.

Risk Factors and Relation with Mortality of a New Acquisition and Persistence of Pseudomonas aeruginosa in COPD Patients

The isolation of Pseudomonas aeruginosa (PA) in patients with chronic obstructive pulmonary disease (COPD) is associated with increased mortality. Yet, factors associated with first PA sputum isolation, and PA persistence have not been investigated before. The objective of the present study was to investigate risk factors for new acquisition and persistence of PA infection and their relationship with all-cause mortality in patients with COPD. Post-hoc analysis of prospectively collected cohort of 170 COPD patients (GOLD II-IV) who were free of previous PA isolation and followed up every 3-6 months for 85 [50.25-110.25] months. PA was isolated for the first time in 41 patients (24.1%) after 36 [12-60] months of follow-up. Risk factor for first PA isolation were high cumulative smoking exposure, severe airflow limitation, previous severe exacerbations, high fibrinogen levels and previous isolation of Haemophilus Influenzae. PA was isolated again one or more times during follow-up in 58.5% of these patients. This was significantly associated with the presence of CT bronchiectasis and persistence of severe exacerbations, whereas the use of inhaled antibiotic treatment after the first PA isolation (at the discretion of the attending physician) reduced PA persistence. During follow-up, 79 patients (46.4%) died. A single PA isolation did not increase mortality, but PA persistence did (HR 3.06 [1.8-5.2], p = 0.001). We conclude that PA occurs frequently in clinically stable COPD patients, risk factors for a first PA isolation and PA persistence are different, and the latter (but not the former) is associated with increased all-cause mortality.

Outcome of Major Hemorrhage at a Major Cardiothoracic Center in Patients with Activated Major Hemorrhage Protocol versus Nonactivated Protocol.

This study aimed to determine the impact of major hemorrhage (MH) protocol (MHP) activation on blood administration and patient outcome at a UK major cardiothoracic center. MH was defined in patients (> 16 years) as those who received > 5 units of red blood cells (RBCs) in < 4 hours, or > 10 units in 24 hours. Data were collected retrospectively from patient electronic records and hospital transfusion databases recording issue of blood products from January 2016 to December 2018. Of 134 patients with MH, 24 had activated MHP and 110 did not have activated MHP. Groups were similar for age, sex, baseline hemoglobin, platelet count, coagulation screen, and renal function with no difference in the baseline clinical characteristics. The total number of red cell units (median and [IQR]) transfused was no different in the patients with activated (7.5 [5-11.75]) versus nonactivated (9 [6-12]) MHP (p = 0.35). Patients in the nonactivated MHP group received significantly higher number of platelet units (median: 3 vs. 2, p = 0.014), plasma (median: 4.5 vs. 1.5, p = 0.0007), and cryoprecipitate (median: 2 vs. 1, p = 0.008). However, activation of MHP was associated with higher mortality at 24 hours compared with patients with nonactivation of MHP (33.3 vs. 10.9%, p = 0.005) and 30 days (58.3 vs. 30.9%, p = 0.01). The total RBC and platelet (but not fresh frozen plasma [FFP]) units received were higher in deceased patients than in survivors. Increased mortality was associated with a higher RBC:FFP ratio. Only 26% of patients received tranexamic acid and these patients had higher mortality at 30 days but not at 24 hours. Deceased patients at 30 days had higher levels of fibrinogen than those who survived (median: 2.4 vs. 1.8, p = 0.01). Patients with activated MHP had significantly higher mortality at both 24 hours and 30 days despite lack of difference in the baseline characteristics of the patients with activated MHP versus nonactivated MHP groups. The increased mortality associated with a higher RBC:FFP ratio suggests dilutional coagulopathy may contribute to mortality, but higher fibrinogen at baseline was not protective.

Preoperative Predictors of Early Mortality Risk in Isocitrate Dehydrogenase-Wild-Type Glioblastoma Patients Treated with Standard Therapy.

PurposeEarly identification of early mortality for glioblastoma (GBM) patients based on laboratory findings at the time of diagnosis could improve the overall survival. The study aimed to explore preoperative factors associated with higher risk of early death (within 1 year after surgery) for isocitrate dehydrogenase (IDH) -wild-type (wt) GBM patients.Patients and MethodsWe conducted a retrospective analysis of 194 IDH-wt GBM patients who underwent standard treatment. The probability of dying within 1 year after gross total resection (GTR) was defined as the end point “early mortality”. Retrospective collection of predictive factors including clinical characteristics and laboratory data at diagnosis.ResultsMedian follow-up time after GTR was 16 months (3–41 months). Forty-two patients died within 1 year after surgery (1‐year mortality rate: 21.6%). All potential predictive factors were assessed on univariate analyses, which revealed the following factors as associated with higher risk of early death: older age (P = 0.013), occurrence of non-seizures symptoms (P = 0.042), special tumor positions (P = 0.046), higher neutrophil-to-lymphocyte ratio (NLR) (P = 0.015), higher red blood cell distribution width (RDW) (P = 0.019), higher lactate dehydrogenase (LDH) (P = 0.005), and higher fibrinogen (FIB) (P = 0.044). In a multivariate analysis, tumor location (P = 0.012), NLR (P = 0.032) and LDH (P = 0.002) were independent predictors of early mortality. The C-index of the nomogram was 0.795. The calibration curve showed good agreement between prediction by nomogram and actual observation.ConclusionTumor location, preoperative elevated NLR and serum LDH level were independent predictors for 1‐year mortality after GTR. We indicate that increased preoperative NLR or LDH may guide patients to review head magnetic resonance imaging (MRI) more frequently and regularly to monitor tumor progression.

Hemostasis functions are associated with hemorrhagic transformation in non-atrial fibrillation patients: a case-control study

BackgroundHemorrhagic transformation (HT) is a serious neurological complication of acute ischemic stroke (AIS) after revascularization. The majority of AIS patients do not have atrial fibrillation (AF) which could also develop into HT. In this study, we aimed to explore whether hemostasis parameters are risk factors of HT in non-AF patients.MethodsWe consecutively enrolled 285 AIS patients with HT. Meanwhile, age- and sex-matched 285 AIS patients without HT were included. The diagnosis of HT was determined by brain CT or MRI during hospitalization. All patients were divided into two subgroups based on the presence of AF and explore the differences between the two subgroups. Blood samples were obtained within 24 h of admission, and all patients were evenly classified into three tertiles according to platelet counts (PLT) levels.ResultsIn this study, we found the first PLT tertile (OR = 3.509, 95%CI = 1.268–9.711, P = 0.016) was independently associated with HT in non-AF patients, taking the third tertile as a reference. Meanwhile, we also found mean platelet volume (MPV) (OR = 0.605, 95%CI = 0.455–0.805, P = 0.001) and fibrinogen (FIB) (OR = 1.928, 95%CI = 1.346–2.760, P < 0.001) were significantly associated with HT in non-AF patients. But in AF patients, hemostasis parameters showed no significant difference. Meanwhile, we found the MPV (OR = 1.314, 95%CI = 1.032–1.675, P = 0.027) and FIB (OR = 1.298, 95%CI = 1.047–1.610, P = 0.018) were significantly associated with long-term outcomes in non-AF HT patients.ConclusionsLow PLT, low MPV, and high FIB levels were independently associated with HT in non-AF patients. Additionally, MPV and FIB levels were significantly associated with unfavorable long-term outcomes in non-AF HT patients. Our study showed that hemostasis functions at admission may be beneficial for clinicians to recognize patients with a high risk of HT at an early stage and improve unfavorable long-term outcomes in non-AF patients.

Pulmonary thromboembolism in coronavirus disease 2019 patients undergoing thromboprophylaxis.

We aimed to investigate the prevalence of pulmonary thromboembolism (PTE) and its association with clinical variables in a cohort of hospitalized coronavirus disease 2019 (COVID-19) patients receiving low-molecular-weight heparin (LMWH) at prophylactic dosage.In this retrospective observational study we included COVID-19 patients receiving prophylactic LMWH from admission but still referred for lower-limbs venous Doppler ultrasound (LL-US) and computed tomography pulmonary angiography (CTPA) for clinical PTE suspicion. A dedicated radiologist reviewed CTPA images to assess PTE presence/extension.From March 1 to April 30, 2020, 45 patients were included (34 men, median age 67 years, interquartile range [IQR] 60–76). Twenty-seven (60%) had PTE signs at CTPA, 17/27 (63%) with bilateral involvement, none with main branch PTE. In 33/45 patients (73%) patients LL-US was performed before CTPA, with 3 patients having superficial vein thrombosis (9%, none with CTPA-confirmed PTE) and 1 patient having deep vein thrombosis (3%, with CTPA-confirmed PTE). Thirty-three patients (73%) had at least one comorbidity, mainly hypertension (23/45, 51%) and cardiovascular disease (15/45, 33%). Before CTPA, 5 patients had high D-dimer (11.21 μg/mL, IQR 9.10–13.02), 19 high fibrinogen (550 mg/dL, IQR 476–590), 26 high interleukin-6 (79 pg/mL, IQR 31–282), and 11 high C-reactive protein (9.60 mg/dL, IQR 6.75–10.65), C-reactive protein being the only laboratory parameter significantly differing between patients with and without PTE (P = .002)High PTE incidence (60%) in COVID-19 hospitalized patients under prophylactic LMWH could substantiate further tailoring of anticoagulation therapy.

Clinical Value of Low Molecular Weight Heparin in Treatment of Pulmonary Heart Disease Complicated With Respiratory Failure

It is aimed to investigate the clinical value of low-molecular-weight heparin in treatment of pulmonary heart disease complicated with respiratory failure. Between January 2018 and April 2019, we included 120 pulmonary heart disease patients complicated with respiratory failure in this study and divided them into two groups using the double-blind, random method, i.e. the control group and the observation group, with 60 patients in each group. After admission, patients in two groups undertook the regular treatment, while those in the observation group additionally took low molecular weight heparin at 5000 U via subcutaneous injection, twice per d. Before and after treatment, arterial blood-gas indicators [partial pressure of carbon dioxide, partial pressure of oxygen and pH value] and the indicators of hemorheology (high blood viscosity, hematocrit and fibrinogen) and clinical efficacy were evaluated for patients in two groups. Prior to the treatment, comparison of the levels of partial pressure of carbon dioxide, partial pressure of oxygen, pH value, high blood viscosity, hematocrit and fibrinogen between two groups showed no significant differences, while after treatment, significant improvement was demonstrated in these indicators in the observation group as compared to those in the control group (p 0.05). In the observation group, patients had an effectiveness rate of 88.33 % (53/60), significantly higher than 63.33 % (38/60) in the control group (p 0.05), while patients in the observation group had shorter hospitalization time [(14.7±0.4) d] than that [(16.9±0.3) d] in the control group (p<0.05). For pulmonary heart disease patients complicated with respiratory failure, medication of low-molecular-weight heparin gained promising efficacy, with significant improvement in the blood performance, ventilation, and heart and lung functions of patients, thereby increasing the survival rate and shortening the hospitalization time of patients. Thus, it is worthy of being promoted in clinical practice.

Effects of Isovolumic Hemodilution and Platelet-Rich Plasma Separation on Platelet Activation State and Function, Complications, and Inflammation in Patients Undergoing Cardiac Surgery.

To explore the effects of isovolumic hemodilution and platelet-rich plasma separation on platelet activation state and function, complications, and inflammation in patients undergoing cardiac surgery. A total of 80 patients who needed cardiac surgery under extracorporeal circulation from February 2018 to December 2019 in our hospital were selected as research subjects and divided into observation group (n = 40) and control group (n = 40) according to the random number table method. The patients in the observation group underwent platelet-rich plasma separation, while those in control group received acute isovolumic hemodilution. Then the platelet activation state and functional indexes, hemorheological indexes, and the coagulation functional indexes were compared between the two groups of patients before operation. Next, the changes in the levels of hemoglobin and high-sensitivity C-reactive protein (hs-CRP), an inflammatory factor, during blood protection (before and at 6 hours and 12 hours after intervention) were analyzed. Moreover, the dosage of blood products during operation was compared between the two groups, and postoperative complications and recovery in the two groups were statistically assessed. Before operation, the platelet adherence rate and aggregation rate in the observation group were significantly higher than those in control group (p < 0.05), while R and K values in thromboelastograms in the former were notably smaller than those in the latter (p < 0.05). Meanwhile, the whole blood low-shear viscosity, whole blood high-shear viscosity, and plasma viscosity in observation group were remarkably lower than those in control group (p < 0.05). In addition, the observation group exhibited shorter prothrombin time (PT), thrombin time (TT), and activated partial thromboplastin time (APTT) (p < 0.05) and a higher fibrinogen (Fib) level (p < 0.05) than the control group. At 6 hours and 12 hours after intervention and before operation, the hemoglobin level in observation group was markedly higher than that in control group (p < 0.05). In addition, the dosages of red blood cells, fresh frozen plasma, and platelets among blood products during operation in the observation group were evidently lower than those in the control group (p < 0.05), and the number of cases of hemorrhage, pulmonary infection, coagulation dysfunction, and paraplegia after operation in the former was distinctly smaller than that in the latter (p < 0.05). Furthermore, the observation group had an obviously smaller postoperative 24 hours drainage volume (p < 0.05) as well as shorter postoperative mechanical ventilation time and ICU treatment time than control group (p < 0.05). For patients undergoing cardiac surgery under extracorporeal circulation, platelet-rich plasma separation and reinfusion technology can effectively ensure platelet activation state and function, reduce blood viscosity, ensure stable coagulation function, elevate hemoglobin level and decrease inflammatory reaction, and perioperative allogeneic blood infusion, with fewer adverse reactions in treatment, thus efficaciously facilitating the post-operative recovery of patients.

Hypochlorite-induced aggregation of fibrinogen underlies a novel antioxidant role in blood plasma

Fibrinogen, a major constituent of blood plasma, is highly susceptible to reaction with biological oxidants. It has been proposed that fibrinogen plays a role in antioxidant defence, but oxidation of fibrinogen is also known to disrupt normal blood clotting and is implicated in the pathology of atherosclerosis. In the present study, we show that the biological oxidant hypochlorite promotes the formation of soluble high molecular weight fibrinogen assemblies ≥40 × 106 Da, that do not accumulate when fibrinogen is induced to aggregate by other stresses such as heating or hydroxyl-mediated damage in vitro. Hypochlorite-modified fibrinogen is stable at 37 °C as assessed by precipitation assays, and has reduced susceptibility to iron-induced (hydroxyl-mediated) precipitation compared to native fibrinogen. In contrast to hypochlorite-modified albumin, which is known to be immunostimulatory, hypochlorite-modified fibrinogen does not induce RAW 264.7 (macrophage-like) cells or EOC 13.31 (microglia-like) cells to produce reactive oxygen species or induce cell death. Furthermore, depletion of fibrinogen from human blood plasma increases the immunostimulatory property of blood plasma after it is supplemented with hypochlorite in situ. We propose that reaction of hypochlorite with fibrinogen in blood plasma potentially reduces the accumulation of other hypochlorite-modified species such as immunostimulatory hypochlorite-modified albumin. The latter represent a novel role for fibrinogen in blood plasma antioxidant defence.

Complex and prolonged hypercoagulability in coronavirus disease 2019 intensive care unit patients: A thromboelastographic study

BackgroundA high number of thrombotic complications have been reported in critically ill patients with coronavirus disease 2019 (COVID-19) and appear to be related to a hypercoagulable state. Evidence regarding detection, management, and monitoring of COVID-19–associated coagulopathy is still missing. We propose to describe the thrombus viscoelastic properties to investigate the mechanisms of hypercoagulability in patients with COVID-19. MethodsThromboelastography (TEG) was performed in 24 consecutive patients admitted to a single intensive care unit for COVID-19 pneumonia, and 10 had a second TEG before being discharged alive from the intensive care unit. ResultsCompared with a group of 20 healthy participants, patients with COVID-19 had significantly decreased values of reaction time, coagulation time, and lysis index and increased values of α angle, maximum amplitude, clot strength, and coagulation index. Velocity curves were consistent with increased generation of thrombin. These values persisted in surviving patients despite their good clinical course. DiscussionIn patients with COVID-19, TEG demonstrates a complex and prolonged hypercoagulable state including fast initiation of coagulation and clot reinforcement, low fibrinolysis, high potential of thrombin generation, and high fibrinogen and platelet contribution. The antithrombotic strategy in patients with COVID-19 during intensive care hospitalisation and after discharge should be investigated in further studies.

Investigation of Hemostasis Using Plantain Sheath/Stem, Cassava Leaf and Snail Juices in Human Blood in-vitro

Inhabitants of most rural communities of West Africa have limited health care facilities and walk long distances to seek medical attention when injured. This sometimes lead to loss of blood and death. To minimize loss of blood from injured individuals by clot formation, juices from plantain sheath/stem, cassava leaf and snail are applied on injured areas. The present work therefore investigated Musa paradisiaca sheath/stem, Manihot essculanta leaf and Achatina marginata juices for hemostatic property using human blood in-vitro. Screening indicated these juices contain tannins, flavonoids and other secondary metabolites. Morphological studies showed formation of a protein network on adding each of the three juices to fresh whole blood, plasma and serum respectively. The protein network formed was as a result of interactions between tannins found in the juices and proteins in the blood components. Microscopic analysis revealed aggregation of red blood cells as each of the juices was added to whole blood. High molecular weight fibrinogen found in whole blood, could have been caused by tannins and flavonoids found present in the juices. Insoluble proteins increased blood viscosity and inhibited movement of the red blood cells. Coagulatory potencies expressed in Prothrombin Times (PTs), revealed the snail juice of 0.80 mL volume had the least time for clot formation (PT=10.02 seconds), and indicated its hemostatic property. This PT was lesser compared to that of the standard, liquid plastin (PT= 11.0-12.5 seconds). As volumes of the three juices were increased from 0.8 to 1.0 mL, their PTs correspondingly decreased (p< 0.05). The snail juice of 0.9 mL volume had the least PT of 8.52 seconds. The plantain stem juice of 0.9 mL volume was next to the snail juice in order of ranking with a PT of 10.79 seconds, and lastly the cassava leaf juice of 1.0 mL volume with a PT of 14.42 seconds. Comparatively, the PTs for the plantain stem and snail juices were the same as the PT for the liquid plastin (PT=11.0 to 12.5 seconds, p<0.050), and all the three juices had PTs within the range considered for substances to be hemostatic (≤ 20.0 seconds). This demonstrated an increased in hemostasis as volumes of the juices were increased, and therefore the plantain stem, cassava leaf and snail juices possess hemostatic property. A blend of the plantain stem and snail juices (1:1) revealed a lesser PT of 18.20 seconds compared to the PT of ≤ 20.0 seconds considered for hemostatic substances. Thus the plantain stem, cassava leaf and snail juices, and the blend of the plantain stem and snail juices (1:1) investigated in the present research work demonstrated hemostasis, and possess hemostatic property. This scientific evidence supports the use of plantain stem, cassava leaf and snail juices as hemostatic substances.

Fibrinogen Levels and Cognitive Profile Differences in Patients with Mild Cognitive Impairment

Background: Fibrinogen is considered a marker of vascular pathology, indicating a weakened blood-brain barrier, and has a causative role in neuroinflammation and neurodegeneration. Little is known about the relationship between fibrinogen levels and cognitive function in patients with mild cognitive impairment (MCI). We aimed to investigate differences in cognitive profiles according to plasma fibrinogen levels in patients with MCI and the influence of plasma fibrinogen levels on cognitive decline. Methods: This retrospective cohort study included 643 patients with MCI: 323 patients in the high fibrinogen (high fib) group and 320 patients in the low fibrinogen (low fib) group. A multiple linear regression model was performed to compare cognitive test performance between groups. The Cox proportional hazard model was used to analyze the hazard ratio of fibrinogen level for disease progression. Results: The high fib group demonstrated poorer performance in attention, executive function, and confrontation naming than the low fib group. After adjustment for APOE genotype, the high fib group was associated with poor attention and executive function. After adjustment for vascular risk factors including body mass index, hypertension, diabetes mellitus, dyslipidemia, and smoking history, the high fib group showed declined attention and confrontation naming ability. High fibrinogen levels did not predict disease progression to CDR 1. Conclusion: High plasma fibrinogen levels were associated with poor performance in attention in patients with MCI, regardless of APOE genotype or vascular risk factors.

Assessment of endogenous fibrinolysis using a point-of-care assay to identify increased cardiovascular risk in patients with diabetes and ACS

Abstract Introduction Patients with diabetes mellitus (DM) are increased risk of myocardial infarction (MI) and following a MI, patients with DM have an increased risk of recurrent MI and cardiovascular (CV) death. Plasma turbidimetry studies show that hypofibrinolysis is a key abnormality in DM that may drive increased ischaemic risk. Such assays are cumbersome, require specialist expertise and do not provide information in a clinically-relevant timeframe. Assessment of fibrinolysis in whole blood, using a point-of-care assay, has revealed that in ACS patients, impaired fibrinolysis is predictive of adverse CV events. Whether this technique can identify residual risk in patients with DM, is unclear. Purpose It was our aim to compare thrombotic and endogenous fibrinolytic status between patients with and without DM, presenting with ACS. Methods We conducted a prospective, observational study of consecutive patients admitted with ACS. Venous blood was taken to assess thrombotic and thrombolytic status using the point-of-care Global Thrombosis Test, assessing time to occlusive thrombus formation under high shear (occlusion time, OT) and time taken for spontaneous lysis of the thrombus (lysis yime, LT). Blood was taken after dual antiplatelet therapy (DAPT) loading, but before administration of fondaparinux or low molecular weight heparin. Patients with renal or hepatic impairment, known bleeding diathesis, thrombocytopenia and those taking anticoagulation were excluded. Results A total of 775 patients were included, of whom 158 (20%) had DM. Patients with DM, compared to those without DM, more frequently had hypertension (70% vs. 39%, p&amp;lt;0.001), hyperlipidaemia (65% vs. 29%, p&amp;lt;0.001), higher BMI (28.6 [25.3–32.0] vs. 26.6 [23.7–29.8] kg/m2, p&amp;lt;0.001) and prior MI (28% vs 9%, p&amp;lt;0.001), but were less often smokers (23% vs. 34% p=0.007). In all other clinical characteristics DM and non-DM patients were matched. Time to occlusive thrombus formation was similar in patients with and without DM (OT 401 (284–519) s vs. 391 (289–514) s, p=0.603). There was a trend for longer LT in patients with DM compared to those without DM (LT 1634 (130–2321) s vs. 1562 (1247–2147) s, p=0.080). After propensity score matching to adjust for baseline differences in clinical characteristics, we observed a highly significant difference in LT between DM and non-DM patients (LT 1634 [1306–2321] s vs. 1387 [1109–1740] s, p&amp;lt;0.001). Patients with DM also had higher fibrinogen level (4.4 [3.5–5.4] vs. 4.1 [3.5–4.8] g/l, p=0.012) and higher C-reactive protein (5 [2–12] vs. 3 [1–8] mg/l, p=0.002). CRP correlated with LT (r=0.2, p=0.016), but no correlation was observed between fibrinogen and LT (r=0.069, p=0.424). Conclusions Amongst patients with ACS, those with DM exhibit markedly impaired endogenous fibrinolysis compared to those without DM, and this can be detected with a bedside assay using whole blood. This may explain the increased risk of secondary events in patients with ACS and DM. Funding Acknowledgement Type of funding source: None

Comparism Of Cryoprecipitate Production Methods Using Fibrinogen And Factor VIII Assay

Abstract Introduction/Objective cryopecipiitate is of huge importance in the management of some Bleeding disorders especially in a low resource settings like ours where it is still the mainstay of management of disseminated Intravsacular coagulopathy, Haemophilia and Von willebrand Disease. In this study we aimed to compared the quality of cryoprecipitate produced using the Thaw-siphon method (no centrifugation) and the ones produced using the Slow- thawing (with centrifugation) methods Methods Ten units of newly prepared Fresh Frozen plasmas were randomly selected, five of were used to prepare cryoprecipitate using the Thaw-siphon method while cryoprecipitate were prepared using the slow-thawing plus centrifugation method. The Fibrinogen concentration in all the ten units were determined using the modified Claus tehcnique while the Factor Viii assay of each unit was done using the one-stage APTT based Assay method Results using the Thaw-siphon method, the mean fibrinogen concentration (152mg/bag) was found to be lower than that of units prepared with slow-thawing plus centrifugation methods (256mg/bag). In a similar manner Factor Viii concentrations were higher in the Slow-thawing with centrifugation methods, Mean Factor Viii concentration was 172Iu/bag when compared with 82 IU/bag in Thaw-siphon methods Conclusion We concluded that Cryoprecipiate produced usng the Thaw- centrifugation methods have higher Fibrinogen and factor Viii units and as such, smaller quantity will be required for correction of coagulopathy when compared with the Thaw-siphon methods. Despite this glaring and expected findings, it is worthy of note that the cryoprecipitate units produced by Thaw-siphon methods meets the required criteria for quality cryoprecipitate and will be very useful in a low resource settings.

Predictive Factors for Pre-operative Recurrence of Cerebrovascular Symptoms in Symptomatic Carotid Stenosis

Across stroke subtypes, carotid artery stroke carries the highest risk of recurrence. Despite initiation of best medical therapy (BMT), some patients suffer recurrent neurological events before undergoing carotid endarterectomy (CEA). The aim was to identify clinical predictors of early recurrent events in patients with symptomatic carotid stenosis (sCS) awaiting CEA on modern BMT. The Helsinki Carotid Endarterectomy Study 2 (HeCES2) is a cross sectional, longitudinal, prospective, and consecutive cohort study, which enrolled 500 symptomatic or asymptomatic patients with carotid stenosis scheduled for CEA in a tertiary stroke centre. Symptomatic patients were included for this analysis (n=324). Of all 324 patients with sCS, 39 (12%) had a recurrent cerebrovascular event at a median of six days after the index symptom: four had an ischaemic stroke (1.2%), 16 a hemispheric transient ischaemic attack (TIA; 4.9%), and 19 amaurosis fugax (AFX; 5.9%). The recurrence rate was 4.0 % (n=13) within 48h and 9.9% (n=32) within two weeks. None of the patients (n=108) presenting with ocular symptoms (AFX or retinal artery occlusion) suffered recurrent hemispheric TIA or stroke. In Cox regression analysis, comorbid hypertension (hazard ratio [HR] 6.58, 95% confidence interval [CI] 1.33-32.47), hemispheric TIA as the index symptom (HR 3.42, 95% CI 1.70-6.90), the number of prior attacks (HR 1.12, 95% CI 1.08-1.15), and high low density lipoprotein/high density lipoprotein ratio (HR 1.51, 95% CI 1.09-2.11) were independently associated with an increased risk of recurrent event, while a history of major cardiovascular event (HR 0.33, 95% CI 0.11-0.96) and high serum fibrinogen level (HR 0.59, 95% CI 0.41-0.86) were associated with a decreased risk. More than every tenth patient with sCS experienced an early recurrent cerebrovascular event prior to scheduled CEA, despite optimal medication. However, stroke recurrence was lower than in earlier observational studies, which could be explained by improved care pathways, more aggressive medication, and expedited CEA. All recurrent strokes occurred in patients initially presenting with minor stroke.