Higher Fibrinogen Levels Research Articles

Immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy for lymphoma: predictive biomarkers and clinical outcomes.

CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR-T) has emerged as effective for relapsed/refractory large B-cell lymphoma (R/R LBCL). The neurologic toxicity seen with CAR-T, referred to as immune effector cell-associated neurotoxicity syndrome (ICANS), is poorly understood. To better elucidate the clinical characteristics, treatment outcomes, and correlative biomarkers of ICANS, we review here a single-center analysis of ICANS after CAR T-cell therapy in R/R LBCL. Patients (n = 45) with R/R LBCL treated with axicabtagene ciloleucel (axi-cel) were identified. Data regarding treatment course, clinical outcomes, and correlative studies were collected. Patients were monitored and graded for ICANS via CARTOX-10 scoring and Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria, respectively. Twenty-five (56%) patients developed ICANS, 18 (72%) of whom had severe (CTCAE grades 3-4) ICANS. Median time to development of ICANS was 5 days (range, 3-11). Elevated pre-infusion (day 0 [D0]) fibrinogen (517 vs 403 mg/dL, upper limit of normal [ULN] 438 mg/dL, P = 0.01) and D0 lactate dehydrogenase (618 vs 506 units/L, ULN 618 units/L, P = 0.04) were associated with ICANS. A larger drop in fibrinogen was associated with ICANS (393 vs 200, P < 0.01). Development of ICANS of any grade had no effect on complete remission (CR), progression-free survival (PFS), or overall survival (OS). Duration and total dose of steroid treatment administered for ICANS did not influence CR, PFS, or OS. ICANS after CAR-T with axi-cel for R/R LBCL was seen in about half of patients, the majority of which were high grade. Contrary to previous reports, neither development of ICANS nor its treatment were associated with inferior CR, PFS, or OS. The novel finding of high D0 fibrinogen level can identify patients at higher risk for ICANS.

Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.

High levels of plasma fibrinogen and prothrombin time are related to post-stroke emotional impairment

IntroductionStudies have shown that high levels of the fibrinogen (FIB) are related to anxiety and depression. However, the relationship between FIB and post-stroke emotional impairment (PSEI) remains unclear, which includes post-stroke anxiety (PSA) and post-stroke depression (PSD). MethodsA total of 555 patients with acute ischemic stroke (AIS) were enrolled in this study. Ultimately, 443 patients completed 1‐month follow‐up. Blood samples were collected at hospital admission. Clinical depression and anxiety were evaluated 1 month after stroke. ResultsHigh levels of FIB were observed in patients with PSEI compared with the non‐EI group (p = 0.003). Levels of FIB were divided into three tertiles, and the prevalence of PSEI was significantly higher in the third FIB tertile (p = 0.016). After adjusting potential confounders, the third FIB tertile was independently associated with the prevalence of PSEI (OR = 1.785, 95%CI = 1.049–3.039, p = 0.033), taking the first tertile as a reference. In this model, prothrombin time (PT) was also independently associated with the prevalence of PSEI (OR = 1.602, 95%CI = 1.181–2.173, p = 0.002). ConclusionHigh levels of plasma FIB and PT are associated with the prevalence of PSEI.

Serum fibrinogen as a diagnostic and prognostic biomarker for pancreatic ductal adenocarcinoma

Background/ObjectivesEarly diagnosis of pancreatic ductal adenocarcinoma (PDAC) is important as PDAC can lead to mortality; however, no specific biomarker has been identified for its early diagnosis. We previously identified fibrinogen α chain as a promising biomarker for differentiating between patients with and without PDAC using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Here, we aimed to validate the clinical usefulness of serum fibrinogen as a biomarker for PDAC. MethodsFrom 2009 to 2011, blood samples of 67 PDAC patients and 43 healthy adults (controls) were prospectively collected. Serum fibrinogen levels and their clinical significances were evaluated. ResultsMean fibrinogen levels were significantly higher in the PDAC group than in the control group (3.08 ± 0.565 vs. 2.54 ± 0.249 log10 ng/mL, P < 0.001). In the receiver operating characteristic analysis, overall sensitivity, and specificity of serum fibrinogen levels for differentiating PDAC patients from control patients were 67.4% and 83.6%, respectively, with a 427-ng/mL cutoff value. Serum fibrinogen levels were significantly higher in PDAC patients with distant metastasis than in those without distant metastasis (3.38 ± 0.581 vs. 2.93 ± 0.499 log10 ng/mL, P = 0.002). Median overall survival was significantly longer in PDAC patients with low fibrinogen levels (<1000 ng/mL) than in those with high fibrinogen levels (≥1000 ng/mL) [489 days (95% confidence interval, 248.1–729.9) vs. 172 days (58.4–285.6) (P = 0.008)]. Although serum fibrinogen levels were poorly correlated with carbohydrate antigen 19-9 levels, these two biomarkers together predicted survival better. ConclusionsSerum fibrinogen levels may be a useful biomarker for diagnosing and predicting PDAC prognosis.

U-shaped relationship between pre-operative plasma fibrinogen levels and severe peri-operative bleeding in cardiac surgery.

An inverse linear relationship has been reported between pre-operative fibrinogen levels and postoperative blood loss in cardiac surgery. However, recently high pre-operative fibrinogen levels have also been reported to be associated with increased blood transfusion and re-operation. We tested the hypothesis that the relationship between pre-operative fibrinogen levels and severe peri-operative bleeding is not linear. A large-scale (n = 3883) single-centre retrospective study. A tertiary care teaching hospital. We analysed data from our institutional database which includes all patients above 18 years who underwent on-pump cardiac surgery through a sternotomy between September 2010 and May 2014. Peri-operative severe bleeding adapted from the Universal Definition of Peri-operative Bleeding, class 3 or 4. The relationship between pre-operative fibrinogen levels and peri-operative severe bleeding was analysed by binary logistic regression. A cubic B-spline transformation was used to estimate the relationship between pre-operative fibrinogen level associated with excessive peri-operative bleeding. Severe peri-operative bleeding was observed in 957 (24.6%) patients. An L-shaped relationship was observed between pre-operative fibrinogen levels and 24-h postoperative blood loss. The relationship between pre-operative fibrinogen levels and severe peri-operative bleeding (i.e. Universal Definition of Peri-operative Bleeding class 3 or 4) was U-shaped: the risk of severe peri-operative bleeding bottomed at 3.3 g l when the upward sloping curve started at 5.8 g l with a steeper increase above 8.2 g l. We reported a U-shaped relationship between severe peri-operative bleeding and pre-operative fibrinogen levels. While a low-level of fibrinogen appears to be associated with a high risk of bleeding, a high level does not necessarily protect the patient against such a risk and could even be a risk factor for peri-operative bleeding.

The prognostic value of plasma fibrinogen level in patients with acute myeloid leukemia: a systematic review and meta-analysis

Increasing evidence has revealed that plasma fibrinogen levels may serve as prognostic indicators in patients with acute myeloid leukemia (AML), yet the exact association is still elusive. We conducted a systematic review and meta-analysis of all available studies concerning the relationship between plasma fibrinogen level and survival in AML patients. The pooled hazard ratio (HR) and 95% confidence intervals (CIs) for overall survival (OS) were calculated to evaluate the effect. A random-effect model was applied and the robustness of the pooled results was confirmed by subgroup and sensitivity analysis. A total of 9 studies were eligible to assess the association between plasma fibrinogen level and prognosis in AML. Among these investigations above, 5 studies adopted OS as their outcome indicator and were selected for the final meta-analysis. The pooled result suggested that plasma fibrinogen level was significantly relevant to increased mortality risk in AML patients (HR = 1.21, 95% CI: 1.01–1.44, p = .000, I2=85.4%). In conclusion, high plasma fibrinogen level may independently predict worse OS in patients with AML.

Inverse association between bone mineral density and fibrinogen in menopausal women

Objective Inflammatory diseases are risk factors for osteoporosis. We aimed to explore whether fibrinogen, which is linked to chronic inflammation, is associated with bone mineral density (BMD) in menopausal women. Methods In this cross-sectional study, we analyzed 339 menopausal women from Zhejiang Province between January 2016 and October 2019. Linear regression analysis was performed to assess the relationship between fibrinogen and BMD. Results Significant inverse association was observed between the serum fibrinogen level and BMD in menopausal women. The mean BMD in each quartile of fibrinogen level was 0.901, 0.897, 0.892, and 0.855 g/cm2, respectively (p = 0.027). After adjusting for age, body mass index, metabolic profiles, blood inflammatory factors, and serum levels of estradiol, calcium, phosphorus, and alkaline phosphatase, fibrinogen levels remained significantly associated with BMD (regression coefficients for quartiles 1–3 vs. quartile 4 were 0.046, 0.027, and 0.036, respectively; p for trend <0.05). Conclusions Higher fibrinogen levels were associated with lower BMD in menopausal women, which was independent of age, body mass index, estradiol, and other factors. Therefore, serum fibrinogen can be used as a new predictor of reduced BMD in menopausal women.

Clinical and laboratory findings in tick-borne encephalitis virus infection

PurposeTick-Borne Encephalitis (TBE), a disease caused by Tick-Borne Encephalitis Virus (TBEV), is emerging in Italy. This study aimed to characterize the epidemiological, clinical, laboratory, imaging and electroencephalogram characteristics in Belluno, North-East Italy. Results76% were males, mean age 53 years; 50% did not report tick bite. 72% had a biphasic course, 42% a monophasic one, 8 cases of abortive TBE. Mostly no specific symptoms were observed, together with neurological signs and symptoms. None died, but 35% had sequelae at the one-month follow-up. Men had a higher risk of having neurological/neurocognitive sequelae; paresthesia or tremors were associated independently with sequelae. In terms of laboratory data, thrombocytopenia, neutropenia and lymphocytosis were associated with the first phase (p < .01), while monocytosis, lymphocytopenia, high levels of ESR and CRP with the second (p < .05). Other abnormal laboratory data were observed: high levels of transaminases, bilirubin, GGT, fibrinogen, amylase, LDH, CPK and electrolyte disorders. Most of the liquor showed pleocytosis and increased protein levels. No specific findings characterized imaging; electroencephalogram mainly reported general and focal anomalies in the temporal lobe. ConclusionsAlthough patients have not reported a tick bite, TBEV infection should be considered for diagnosis. Usually no specific symptoms are reported along with neurological signs and symptoms. The biphasic course is more often described than the monophasic course; abortive TBE is sometimes present. Paresthesia and tremors are independently associated with neurological/neurocognitive sequelae; men have a higher risk of having sequelae. The first phase is probably associated with thrombocytopenia, neutropenia and lymphocytosis; the second with monocytosis, lymphocytopenia, high levels of CRP and ESR. Electrolyte disorders, high levels of transaminases, GGT, bilirubin, CPK, LDH, fibrinogen and amylase may characterize TBEV infection.

505-P: Relationship between Plasma CRP and Fibrinogen Measured Using Dried Blood Samples and Vascular Complications in Type 2 Diabetes

Background: Measurement of biomarkers associated with cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM) should improve our understanding of the pathogenesis of CVD and enhance disease prediction. Innovative approaches like the use of dried blood samples in assessing these biomarkers could simplify population-based studies. Method: In this ongoing cross-sectional study, we enrolled 44 patients with T2DM (41% male, mean age 63.7 years). Following a fingerstick, five drops of blood were collected using a device containing absorbent paper and a desiccant (HemaSpot-HF®). Levels of C-reactive protein (CRP) and fibrinogen were measured using a Luminex assay. The presence of vascular complications (retinopathy, nephropathy, neuropathy, heart disease or stroke) was determined through an interview of each participant and a detailed chart review. Nonparametric M-W tests with exact p-values were used to compare groups using SPSS and R software. Results: Patients with nephropathy had significantly higher levels of fibrinogen recovered from the devices (147.55 ± 163.27 mg/dl) compared to those without nephropathy (22.64 ± 10.27 mg/dl), (p=0.043). There was no significant relationship between fibrinogen and other vascular complications or CRP with any of the vascular complications associated with T2DM (p&amp;gt;0.05 for all). Conclusion: Higher plasma fibrinogen was found among patients with T2DM and nephropathy compared to those without nephropathy. This may reflect a higher state of systemic inflammation related to tissue damage. The use of a dried blood sample method for biomarker assays can be applied to larger population studies and towards simplifying translational biologic research. Disclosure K. Izuora: None. A. Basu: None. A. Alver: None. A. Salazar: None. A. Capurro: None. C.L. Gewelber: None. C.L. Cross: None. S.J. Williams: None. J.L. Ebersole: None.

Clinicopathological Profile of Disseminated Intravascular Coagulopathy (DIC) in Natural Course of Moderate COVID-19 Patients

Background: Timely and accurately identification of thrombotic complications seems to become an important issue in patients suffering from coronavirus disease 2019 (COVID-19). Preliminary reports on critical ill COVID-19 patients include thrombocytopenia, abnormal coagulation tests, and disseminated intravascular coagulation. While the COVID-19 pandemic is spreading worldwide, the progression of DIC in the natural course of COVID-19 remains unpredictable and enigmatic. Methods: Out of a total of 694 COVID-19 inpatients, we selected 332 adults (≥18 - <65 years old) without any comorbidities from twelve hospitals (Wenzhou, China). The patients were divided into mild, moderate and severe groups, depending on the degree of disease severity. According to patient’s onset time of the first symptoms before admission, the natural course of COVID-19 was categorized at 3-day intervals for analysis, as follows: 1-3 days (D1-3), D4-6, D7-9 and D10-14. Demographic, clinical, treatment, and laboratory data were extracted from electronic medical records and compared between groups at different stages of COVID-19 course. Findings: The nature course of COVID-19 can be classified into two or four stages depending on patients with or without pneumonia. Mild patients without pneumonia showed two stages: virus infection stage (day 1-3) and recovery stage (day 4-6). In contrast, moderate and severe patients with pneumonia had four stages: virus infection stage (day 1-3); inflammation stage (day 4-6) characterized by c-reactive protein (CRP) >10 mg/L and fibrinogen >4 g/L; early stage of DIC (day 7-9) characterized by high fibrinogen levels and d-dimer >500 µg/L; and the stage of overt DIC (day 10-14) characterized by platelet >300×109, high fibrinogen and high d-dimer levels. These data showed that natural course of COVID-19 closely linked with the occurrence and progression of DIC might be one of the major causes for the progression of the disease and the occurrence of events. Interpretation: To elucidate the natural course of COVID-19 accompanying the DIC progression can help clinicians quickly and accurately identify the stage of the disease, make the correct diagnosis and treatment, promote patient recovery and survival. Funding Statement: This work was supported by the National Natural Science Foundation of China (grant 81670336) , the Wenzhou Grant for Scientific Talents, Wenzhou Science and Technology Bureau (RX2016003); the Key Research and Development Program of Zhejiang Province (2019C03011); and Special Project for Significant New Drug Research and Development in the Major National Science and Technology Projects of China (2020ZX09201002);Wenzhou Science and Technology Key problem program (ZY2020001); The Key Research and Development Program of Zhejiang Province (2019C03011). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The Ethics Committee of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University waived the need for a written informed consent.

Anticoagulation Options for Coronavirus Disease 2019 (COVID-19)-Induced Coagulopathy.

As the coronavirus disease 2019 (COVID-19) pandemic is evolving, coagulopathy induced by the disease and its severe complications are raising concerns in the medical community. Because coagulopathy caused by COVID-19 has been difficult to control, it is important to have a better understanding of what therapies have been studied thus far and what therapies have demonstrated better outcomes for hospitalized patients. This review is focused on literature, research, and expert clinical judgments published in 2020 with a few references to articles published earlier. The review introduces the interim guidelines of the International Society of Thrombosis and Haemostasis (ISTH) for management of COVID-19-induced coagulopathy, discusses the efficacy of these guidelines in clinical settings, and summarizes the response of the scientific community to these guidelines and their clinical implications. Due to the failure of patients to respond to the prophylactic doses of heparin recommended by ISTH, higher doses of heparin may be necessary to achieve adequate anticoagulation. Patients’ resistance to prophylactic doses of heparin could be due to low levels of anti-thrombin and high levels of fibrinogen, which would reinforce the use of therapeutic doses of heparin in the early stages of hospitalization. The review also compares low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) as anticoagulant choices for COVID-19 patients. Given the complications specific to COVID-19, UFH may be a better choice of anticoagulant. Outpatient anticoagulation options are also reviewed. Changing qualified patients from vitamin K antagonists (VKA) to direct-acting oral anticoagulant (DOAC) for the convenience of less frequent monitoring may be appropriate. New anticoagulant, nafamostat, used in Japan is also discussed as a possible potentiate for heparin therapy.

Prognostic value of plasma fibrinogen and D-dimer levels in patients with surgically resected non-small cell lung cancer.

A high plasma level of either fibrinogen or D-dimer has been shown to correlate with a poor prognosis in patients with surgically resected non-small-cell lung cancer (NSCLC). The present study aimed to identify whether or not both markers combined had a superior prognostic value to either alone. Of the 1344 patients who underwent surgical resection for NSCLC at our institution between January 2007 and December 2016, 1065 had preoperative plasma fibrinogen and D-dimer data available and were included in the analysis. The recurrence-free survival (RFS) and overall survival (OS) rates were similar for patients with high plasma levels of either or both fibrinogen (> 4.0g/L) or D-dimer (> 1.0μg/mL); therefore, these three groups were combined for a further analysis into a single group with high plasma levels of either or both proteins. The high-level group had significantly lower 5-year RFS (53% vs. 68%, p < 0.001) and 5-year OS (65% vs. 80%, p < 0.001) rates than patients with normal plasma levels of fibrinogen and D-dimer (control group). Our results suggest that preoperative tests for both plasma fibrinogen and D-dimer are necessary to identify patients with surgically resected NSCLC likely to have a poor RFS and OS.

Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy.

A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia.A prospective series of 100 consecutive patients admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response.The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24–72 h and 10 days after tocilizumab administration.Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 [IQR 0–2]), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died.All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10.In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.

Procoagulation, hypercoagulation and fibrinolytic “shut down” detected with ClotPro® viscoelastic tests in COVID-19 patients.

International data indicate that arterial, venous and microvascular thrombosis or disseminated intravascular coagulation occur in more than 30% of hospitalized patients with COVID-19. This condition is characterized by high levels of D-dimer and fibrinogen, prolonged prothrombin time and activated partial thromboplastin time. Blood samples from three COVID-19 patients treated in a Hungarian intensive care unit were collected and analyzed with ClotPro® tests. EX-tests, IN-test, FIB-tests, RVV-tests, and TPA-tests were performed. The results were interpreted with respect to the clinical condition of the patients. Procoagulation, hypercoagulation and either fibrinolysis or a "shut down" phenomenon of the fibrinolytic process were found with ClotPro®. The ClotPro® parameters were consistent with the conventional coagulation tests and corresponded with the criteria of non-overt disseminated intravascular coagulation. These findings encourage further investigations to elucidate the underlying pathophysiology of thromboembolic events in COVID-19 patients and may support the introduction of full dose anticoagulation with or without antiplatelet therapy. Interventional clinical trials may be helpful in defining the appropriate drug(s), for this purpose, the algorithms of administration, and the optimal duration of therapy. At present, the authorization of a clinical trial that attempts to answer these questions is in progress. Orv Hetil. 2020; 161(22): 899-907.

Assessment of the reliability and validity of a novel point-of-care fibrinogen (F-Point) device against an industry standard at fibrinogen levels >2 g/L in non-haemorrhage scenarios

IntroductionA diagnostic accuracy study assessing the reliability and validity of a novel plasma fibrinogen point-of-care (F-Point) device compared with the von Clauss method of assay. MethodsForty-one women presenting for elective caesarean delivery and 43 non-pregnant female patients presenting for elective gynaecological surgery were recruited to assess agreement at normal fibrinogen levels (elective gynaecological cohort) and high fibrinogen levels (elective caesarean section cohort). Validity was assessed by comparing the F-Point results with the gold standard of von Clauss fibrinogen assay performed on the ACL Top 500. Reliability (test–retest) and validity were assessed using the intraclass correlation to control for operator variance (two-way random absolute agreement method), presented as intra class correlation coefficients (ICCs) and 95% confidence interval, and Bland-Altman analysis, presented as mean bias and 95% limits of agreement and coefficient of variation (COV). ResultsThe results demonstrated a high test–retest reliability demonstrated in the paired F-Point measurements with an intraclass correlation coefficient (ICC) of 0.95, a bias of 0 (-00.69 to 0.69) and a COV of 9%. Similarly, there was acceptable agreement demonstrated between F-Point and von Clauss assay with an ICC of 0.91, a bias of −0.1 (−0.96 to 0.75) and a COV of 11%. ConclusionsOur novel plasma fibrinogen point-of-care device has been shown to be reliable and valid when testing fibrinogen levels as low as 2 g/L. Future studies investigating the correlation at lower fibrinogen levels, for example during haemorrhage and in patients with coagulopathies, are required.

In vitro clot model to evaluate fibrin-thrombin effects on fractal dimension of incipient blood clot.

This aim of this study is to investigate the individual effects of varying concentrations of thrombin and fibrinogen on clot microstructure (characterised through the fractal dimension of the incipient clot network, df) and clot formation time (TGP) using a fibrin-thrombin clot model. df and TGP markers are measured using a haemorheological method that has already been investigated for whole blood. This is an in vitro study using three thrombin concentrations (0.1, 0.05 and 0.02 NIH/ml) and two fibrinogen concentrations (8 mg/ml and 12 mg/ml) to investigate a fibrin-thrombin clot model. The haemorheological changes were measured at the gel point using df and TGP. Fractal dimension (df) increased with increasing concentrations of thrombin both at 8 mg/ml (1.60±0.024, 1.67±0.022, 1.74±0.079) and 12 mg/ml fibrinogen concentrations (1.63±0.02, 1.87±0.019, 1.95±0.014). On the other hand, TGP decreased for both 8 mg/ml (1089±265, 637±80, 223±22 seconds) and 12 mg/ml fibrinogen concentrations (2008±247, 776±20, 410±20 seconds). In contrast to previous studies investigating whole blood, TGP increased with higher fibrinogen levels. The findings from this fibrin-thrombin clot model confirmed that df and TGP can detect changes in the incipient clot following manipulation of fibrinogen and thrombin concentration. df increases (indicating stronger clot) with higher concentrations of thrombin and fibrinogen. On the other hand, TGP decreased as expected with higher thrombin level but not with higher fibrinogen concentrations.

High levels of plasma fibrinogen could predict frequent asthma exacerbations

High levels of plasma fibrinogen could predict frequent asthma exacerbations

The Incidence of Venous Thromboembolism and Impact on Survival in Hodgkin Lymphoma

BackgroundThrombosis increase the acute and long-term morbidity and mortality in malignancy patients. We analyzed venous thromboembolism (VTE) in patients with Hodgkin lymphoma, the impact of VTE on survival, predisposing factors for VTE, and predicting value of Khorana and ThroLy score models. Patients and MethodsWe included 150 adult patients with Hodgkin lymphoma between January 2010 and 2018 at our university hospital. ResultsVTE was observed in 31 patients (20.7%). The types of VTE were 18 upper and 3 lower extremity deep vein thrombosis and 10 pulmonary embolism (1 with lower extremity deep vein thrombosis). Twenty-nine patients developed VTE during the treatment with a median time of episode as 5 months. In logistic regression analysis, a body mass index of >32 kg/m2, high fibrinogen levels, initial thrombocytosis and leukocytosis, splenic and extranodal involvement, presence of a central venous line, advanced stage, line of treatment status of thromboprophylaxis, VTE timing, and better Eastern Cooperative Oncology Group performance scores were observed to be related with VTE. Kaplan Meier survival analysis showed a negative impact of VTE on survival. Khorana and ThroLy risk assessment models were found predictive for VTE (P = .000 and P = .003, respectively), although only ThroLy score was associated with the survival. ConclusionThromboprophylaxis and precautions for VTE in patients with Hodgkin lymphoma according to validated risk assessment models can improve prognosis and quality of life owing to the impact of VTE on survival in the study.

Abstract TP128: Determinants of Hemorrhagic Transformation After Emergent Extracranial Internal Carotid Artery Stenting for Tandem Occlusions

Background and Purpose: Extracranial internal carotid artery (ICA) lesion in the setting of tandem occlusions is a therapeutic challenge, and hemorrhagic transformation (HT) is one of the leading causes of poor clinical outcome. We aimed to determine determinants of HT for tandem occlusions undergoing emergent extracranial ICA stenting during endovascular treatment (EVT). Methods: We performed a prospective, observational cohort study of consecutive patients with non-cardioembolic ischemic stroke due to tandem occlusion who underwent EVT with extracranial ICA stent placement during the procedure from April 2013 to June 2019 in a single stroke center. We compared clinical (vascular risk factors, previous antiplatelet treatment, and IV rtPA), radiological (ASPECTS at admission and in-stent thrombosis at 24 hours) and serological (platelet count, fibrinogen, total cholesterol, HDL-cholesterol, and LDL-cholesterol) parameters according to the presence of HT in 24 hours CT-scan. Results: One-hundred and eight patients were included: 78.7% were men, mean age 68.5±14.3 years, median time from symptoms onset to treatment was 220 (150-337.5) minutes, median ASPECTS at admission was 9 (8-10). Eighty-six (79.6%) patients presented an extracranial ICA occlusion, and 22 (20.4%) a high-grade (&gt;50%) stenosis. In 88 (81.5%) patients the etiology of extracranial ICA lesion was ateroma, and in 20 (18.5%) was a dissection. Intravenous rtPA was administered in 47 (43.5%) patients. Successful recanalization (mTICI ≥2b) was achieved in 83 (76.9%) patients, and extracranial ICA recanalization in 108 (100%) patients. Type 2 diabetes (OR 1.5, 95% CI 1.1-3.5), higher fibrinogen levels (OR 4.6, 95% CI 1.6-12.9), and ASPECTS &lt;7 at admission (OR 2.1, 95% IC 1.1-5.1) were found as independent predictors of HT in multiple logistic regression analysis. Conclusions: Patients with a non-cardioembolic ischemic stroke due to tandem occlusion who present type 2 diabetes, higher fibrinogen levels, or ASPECTS &lt;7 at admission are at high risk of HT. In these particular cases, it might be useful to stent with a stent that does not need double antiplatelet treatment immediately after the procedure.

High Preoperative Plasma Fibrinogen Independently Predicts a Poor Prognosis in Patients with Nonmetastatic RCC.

Background: This study aims to determine the relationship between preoperative plasma fibrinogen levels and the prognosis of patients with nonmetastatic renal cell carcinoma (RCC), including overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS).Methods: We retrospectively analysed the clinical data and prognostic information of 1194 nonmetastatic RCC patients who received radical nephrectomy or nephron-sparing surgery between 2005 and 2015 at our institution. Serum was collected for fibrinogen detection in the week prior to curative operation, and prognostic information was regularly collected by specially trained personnel. The cut-off value of the preoperative plasma fibrinogen level was defined by receiver operating characteristic (ROC) analysis. The chi-square test was used to analyse the association between preoperative fibrinogen level and clinical characteristics. Kaplan-Meier analysis was used to calculate survival curves, and significant differences were determined by the log-rank test. Other significant prognostic factors were evaluated by the Cox multivariate proportional hazard model.Results: The median follow-up period after radical or partial nephrectomy was 42.4 months (ranging from 0.433 to 146.37 months). The optimal preoperative plasma fibrinogen concentration was 3.975 g/L. The preoperative fibrinogen level was significantly associated with age, pathological T stage, sarcomatoid differentiation, necrosis and vein tumour thrombus (all p<0.05). High plasma fibrinogen levels were related to poor prognosis in terms of OS (p<0.001), CSS (p<0.001) and PFS (p<0.001). Multivariate analysis showed that the preoperative fibrinogen level remained an independent prognostic factor for OS (HR: 3.22, 95%CI: 1.87-5.55, p<0.001), CSS (HR: 4.12, 95%: 2.15-7.89, p<0.001) and PFS (HR: 3.137, 95%CI: 2.17-4.53, p<0.001).Conclusions: High preoperative plasma fibrinogen level is an independent negative prognostic factor for OS, CSS and PFS in patients with non-metastatic RCC. Preoperative plasma fibrinogen could be an ideal indicator for evaluating the outcomes of postoperative patients with nonmetastatic RCC.