Higher Fibrinogen Research Articles

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.

Intracranial haemorrhage associated with systemic anticoagulation in ventilated COVID-19 Intensive care patients

IntroductionCOVID-19 induces a pro-inflammatory, hypercoagulable state with marked elevations of ferritin, C-reactive protein, interleukin, and D-dimers. Observed consequences include pro-thrombotic disseminated intravascular coagulation (DIC) with a high rate of venous thromboembolism (VTE) and elevated D-dimers with high fibrinogen and low anti-thrombin levels. Pulmonary congestion appears to be due to micro-vascular thrombosis and occlusion on pathological examination.1 The acquired pro-thrombotic state and associated poorer outcomes seen in critically ill COVID-19 patients 2,3 have led to such patients being treated empirically with systemic anticoagulants. Unfractionated heparin (UFH) or low molecular weight heparin (LMWH) have both been used.2,3MethodsReview of COVID-19 positive adult patients admitted to the critical care unit between 10th March and 13th May 2020 with severe respiratory failure requiring invasive ventilation.ResultsIn that period we admitted 59 patients. 6 (10%) females, 56 (90%) males. 45 (76%) patients required therapeutic anticoagulation (27 UFH, 14 LMWH, 4 argatroban). 4 (8.9%) of the 45 anticoagulated patients suffered catastrophic intracranial haemorrhage and subsequently died.DiscussionThe risk for any significant haemorrhage in patients systemically anticoagulated for VTE with unfractionated heparin (UFH) is 2-3%, 4 and that of anticoagulant-related intracranial haemorrhage (AICH) in patients systemically anticoagulated with UFH is 1-2.7% (in patients treated for ischaemic stroke) and 4% with argatroban.5 We report a much higher incidence of nearly 9%. The cases we present fulfilled the advised criteria for systemic anticoagulation. Despite four-hourly monitoring of APPT and anti-Xa activity on the intensive care unit there were significant fluxes in these laboratory markers of anticoagulation. These may be associated with the uncharted nature of this disease process.It is impossible to disassociate the necessary therapeutic-intensity anticoagulation with the observed heightened frequency of life-ending intracranial haemorrhage in these patients.

Prognostic Nomogram That Predicts Overall Survival of Patients with Distal Cholangiocarcinoma After Pancreatoduodenectomy.

PurposeWe aimed to develop a nomogram for predicting the prognosis of patients with distal cholangiocarcinoma (DCC) and to compare its performance with that of the American Joint Committee on Cancer (AJCC) TNM system.Patients and MethodsTo develop a nomogram, we collected the clinical data of 147 patients diagnosed with DCC who underwent pancreatoduodenectomy. Predictive accuracy and discriminative ability were determined using a concordance index and a calibration curve. Predictive performance was compared with that of a current staging systems for DCC.ResultsMultivariate analysis revealed that jaundice, alcohol consumption, high fibrinogen, poorly differentiated tumor cells, positive lymph nodes, and positive margins were significantly associated with overall survival. These variables were incorporated into the nomogram. The concordance index of the nomogram for predicting overall survival was 0.737 (P<0.001), which is significantly higher than the concordance index values (concordance index = 0.586) acquired using the AJCC TNM system (eighth edition). The calibration curve agreed well with predicted prediction and observed overall survival.ConclusionWe developed a nomogram for predicting the prognoses of patients with distal cholangiocarcinoma, which had superior practical clinical value compared with that of the AJCC TNM system.

FATAL INTRACEREBRAL HEMORRHAGE IN A PATIENT WITH SEVERE COVID-19 INFECTION

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Stroke like lesions has been documented in COVID-19 patients. Although the exact stroke-incidence is unknown, it was reported to be around 5 % in a hospitalized cohort in Wuhan and 1.1 % in a study in New York City. CASE PRESENTATION: A 73-year-old male with a past medical history of hypertension and hyperlipidemia presents to ER with fever, cough, myalgia, increasing shortness of breath, and confusion for one day. His daughter is known COVID-19 positive. The patient was noted to be febrile, tachypneic, and hypoxic to 90% at room air. Chest X-ray showed bilateral infiltrates and the COVID-19 test was positive. The patient was immediately intubated due to his significant acute respiratory distress. Inflammatory markers were significantly elevated: Troponin T: 5.86, Lactate dehydrogenase: 542, CRP: 350 mg/l, Ferritin: 1878, D-dimer: >20, fibrinogen: 1094, Total Creatinine kinase: 2260 and creatinine: 5.7. His course was complicated by septic shock requiring three vasopressors; acute kidney injury requiring hemodialysis; Enterococcus Faecalis bacteremia treated with Ampicillin, and Klebsiella pneumonia sensitive to ceftriaxone. EKGs showed new onset of atrial fibrillation without ST changes. Echocardiogram showed normal ejection fraction without wall motion abnormalities. His significant troponin elevation was likely due to myonecrosis related to COVID-19 infection and he was started on heparin drip. The patient respiratory status continued to improve however he remained obtunded. Head CT showed acute right frontal hemorrhage and focal hyperdense foci in the left frontal lobe and basal ganglia. Brain MRI showed a 2.8 x 2.4 cm lesion situated in the right sub-frontal region with appearances of abscess versus necrotic tissue and extensive bilateral scattered deep white matter infarcts. Neurosurgery didn’t recommend any intervention due to poor prognosis. After 27 days of intubation, the family requested comfort measures, and the patient was terminally extubated. DISCUSSION: ‘Sepsis-induced coagulopathy’ is one of the hallmarks of severe COVID-19, usually manifests as a high D-dimer and elevated fibrinogen. It induces a systemic inflammatory response with endothelial dysfunction and microthrombosis predisposing to acute strokes. The risk of developing a cerebrovascular disease is multifactorial and includes cardiovascular risk factors, old age, and severe COVID-19 disease manifestations with sings of hypercoagulability. In this case, the stroke like-lesions could be related to septic emboli with the conversation to hemorrhage due to heparin use in the setting of severe COVID-19 infection. CONCLUSIONS: Ischemic and hemorrhagic stroke has been reported as a complication of severe COVID-19 infection. The definite mechanism is unknown, but these findings can indicate poor prognosis with potential neurological sequelae and increased mortality. Reference #1: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202903/ Reference #2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236667/ Reference #3: https://jamanetwork.com/journals/jamaneurology/fullarticle/2766766 DISCLOSURES: No relevant relationships by Karim Anis, source=Web Response No relevant relationships by Anastasia Maltseva, source=Web Response No relevant relationships by Lady Sanchez Fernandez, source=Web Response

CHANGE OF LUNG MECHANICS AND DEAD SPACE FRACTION IN PATIENTS WITH DIFFUSE ALVEOLAR HEMORRHAGE REQUIRING PRONE POSITIONING: A CASE SERIES

SESSION TITLE: Fellows Diffuse Lung Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Diffuse alveolar hemorrhage (DAH) is a catastrophic syndrome causing respiratory failure (1). Prone positioning improves oxygenation and decreases mortality in patients with acute respiratory distress syndrome (2). In patients with refractory hypoxemia from DAH, prone positioning may be used as rescue therapy. However, we know little about the impact of prone positioning in lung mechanics and gas exchange of patients with DAH. CASE PRESENTATION: Four patients were admitted to the intensive care unit for refractory hypoxemia requiring prone positioning, and ultimately diagnosed with DAH — three through bronchoscopy and one through autopsy. Table 1 shows the demographics, laboratory data, and interventions. Two patients were male and two patients were female. Ages ranged from 19 to 71 years. The etiologies of DAH included: acute lymphoblastic leukemia, pulmonary angiosarcoma, and giant cell vasculitis; one patient had no identified etiology. One patient had pancytopenia from leukemia and the remaining three had leukocytosis and anemia with hemoglobin count from 8.5 to 10.4 g/dL on admission. No significant coagulopathy was noted but a high fibrinogen level was observed in all cases. Three patients had positive bacterial growth in sputum cultures. All patients required vasopressors and neuromuscular blockade prior to prone positioning. Three received pulse-dose steroids (at least 1g of methylprednisone daily for three days) after the diagnosis was made. Table 2 shows the ventilatory settings, gas exchange, and lung mechanics at baseline. Prior to prone positioning, PaO2/FiO2 ratios were less than 150 and dead space fraction ranged from 27% to 60%. Figure 1 shows gas exchange and lung mechanics at different time points. Following prone positioning, all patients had decreased dead space fraction after 8 hours of prone positioning. No specific pattern was identified in the change of lung mechanics and gas exchange while minimal change was observed in mechanical power. DISCUSSION: The histopathologic changes in DAH reveal a distinctive mechanism of lung injury affecting lung mechanics and gas exchange. In an autopsy study comparing ARDS patients with and without DAH, those with DAH had significantly lower static compliance and PaO2/FiO2 (3). Prone positioning could theoretically ameliorate V/Q mismatch and reduce inflammation in DAH. The finding of dead space fraction improvement following prone positioning suggests a possible benefit of applying prone positioning to DAH patients with refractory hypoxemia. Future studies are needed to examine the role of prone positioning in this population. CONCLUSIONS: We present the first case series of change in lung mechanics and dead space fraction in patients with DAH who received prone positioning. While there exists a paucity of evidence to support this modality, prone positioning can potentially be used as a rescue therapy for refractory hypoxemia in DAH. Reference #1: Lara AR, Schwarz MI. Diffuse alveolar hemorrhage. Chest. 2010;137(5):1164-71 Reference #2: Guérin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159-68 Reference #3: Thille AW, Peñuelas O, Lorente JA, Fernández-Segoviano P, Rodriguez JM, Aramburu JA, et al. Predictors of diffuse alveolar damage in patients with acute respiratory distress syndrome: a retrospective analysis of clinical autopsies. Crit Care. 2017;21(1):254 DISCLOSURES: No relevant relationships by James Kornfield, source=Web Response No relevant relationships by Chi Chan Lee, source=Web Response No relevant relationships by Stephanie Nonas, source=Web Response

Does D-Dimer really help in the diagnosis of chronic periprosthetic joint infections (PJI)? A case-control study

IntroductionThe differential diagnosis between aseptic and septic total joint arthroplasty (TJA) revision is fundamental in order to be successful in the surgical treatment. Several serum biomarkers have been proposed as gold standards in the diagnosis of Periprosthetic Joint Infections (PJI). The aim of the current study was (1) to evaluate serum levels of D-dimer in a retrospective series of PJIs diagnosed by traditional methods and (2) to compare the D-dimer performance as a diagnostic test with other well established PJI biomarkers in a case-control study. Materials and methodsA total of 159 TJA revisions were included in the study database: 55 implants in 55 patients met the inclusion criteria. The final study group included 33 aseptic and 22 septic (with micro-organism isolation) TJA revisions; these two groups were not statistically different in terms of demographics. All patients were preoperatively tested with the following serologic tests: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, D-dimer and white blood cell (WBC) count. A standard univariate logistic analysis was performed in order to investigate the association between chronic PJI and the serologic tests. ResultsA gram-positive microorganism was isolated in 15 patients whereas a gram-negative microorganism was isolated in 7 patients. Univariate analysis showed that high D-dimer, ESR or fibrinogen were not associated with a PJI occurrence, whereas high CRP and WBC count >10.000 cells/mm3 were significantly elevated in chronic PJI patients. A multivariate analysis confirmed that leukocytosis was a significant predictor of PJI. ConclusionsThis study showed that D-dimer had a low sensitivity and specificity in diagnosing chronic PJI, especially when evaluated as a single diagnostic biomarker.

Combination of preoperative fibrinogen concentration and neutrophil-to-lymphocyte ratio for prediction of the prognosis of patients with resectable breast cancer.

Previous studies have demonstrated that the combination of high preoperative fibrinogen levels and high neutrophil-to-lymphocyte ratio (NLR) is associated with poor outcomes in various types of cancer. The present study assessed the prognostic value of a scoring system based on the combination of fibrinogen concentration and neutrophil-to-lymphocyte ratio (F-NLR) in untreated patients with resectable breast cancer (BC). The present study retrospectively analyzed 906 patients who received surgery for resectable BC. Univariate and multivariate analyses were performed to explore the association between the F-NLR score and survival status. The cut-off values for fibrinogen and NLR determined via receiver operating characteristic curve analysis were 3.21 g/l and 2.20, respectively. On the basis of these cut-off values, the whole cohort was divided into three groups according to their F-NLR score: Score 2, fibrinogen ≥3.21 g/l and NLR ≥2.20; score 1, fibrinogen ≥3.21 g/l or NLR ≥2.20; and score 0, fibrinogen <3.21 g/l and NLR <2.20. The F-NLR score was significantly associated with age (≤50 years vs. >50 years; P<0.001), tumor size (≤2 cm vs. >2 cm; P=0.001), lymph node status (P=0.029), TNM stage (I vs. II vs. III; P=0.002) and lymphovascular invasion (P<0.001). The 5-year disease-free survival (DFS) rates in the patients with F-NLR scores of 0, 1 and 2 were 95.7, 87.5 and 74.0%, respectively (P<0.001), and the 5-year overall survival (OS) rates were 97.8, 90.9 and 79.9%, respectively (P<0.001). Furthermore, multivariate analysis demonstrated that the F-NLR score independently predicted DFS [hazard ratio (HR), 2.279; 95% CI, 1.758–2.954; P<0.001] and OS (HR, 2.414; 95% CI, 1.738–3.353; P<0.001). In conclusion, the preoperative F-NLR score was an independent prognostic indicator for untreated patients with resectable BC.

Prognostic Value of Fibrinogen and Lymphocyte Count in Intermediate and High Risk Gastrointestinal Stromal Tumors.

PurposeData about the prognostic value of fibrinogen concentration and absolute lymphocyte count for the prognosis of gastrointestinal stromal tumors (GISTs) were limited. Thus, the aim of the present study was to investigate the predictive value of preoperative fibrinogen concentration and absolute lymphocyte count in GISTs.Patients and MethodsFrom March 2002 to December 2017, 143 intermediate and high risk GIST patients treated with R0 resection were enrolled in the present study. Clinicopathological characteristics were recorded. The optimal cut-off values of patients were calculated by X-tile software. Categorical variables were analyzed using Chi-square test or Fisher’s exact test. Disease-free survival was analyzed by the Kaplan–Meier method and compared by a Log rank test.ResultsThere were 71 males (49.65%) and 72 females. The median age was 56 years (range 19–86). The optimal cut-off value was 4.5 g/L for fibrinogen concentration (P=0.000) and 1.0×109/L for lymphocyte count (P=0.002). No significant association was found between lymphocyte level and clinicopathological features. However, elevated fibrinogen level was correlated with tumor location, tumor size and NIH risk category. Tumor size, fibrinogen concentration and lymphocyte count were independent risk factors for the prognosis of patients according to the multivariate analysis. The prognosis of patients with high fibrinogen concentration or low lymphocyte count was significantly worse than that with low fibrinogen concentration or high lymphocyte count. Further, combination of fibrinogen concentration and lymphocyte count could increase the prognostic value for GIST patients.ConclusionFibrinogen concentration and absolute lymphocyte count were independent prognostic factors for intermediate and high risk GIST patients. The combination of fibrinogen concentration and absolute lymphocyte count could further increase the predictive value for the prognosis of GIST patients.

Cryoprecipitate transfusion in bleeding patients.

The management of acquired coagulopathy in multiple clinical settings frequently involves fibrinogen supplementation. Cryoprecipitate, a multidonor product, is widely used for the treatment of acquired hypofibrinogenemia following massive bleeding, but it has been associated with adverse events. We aimed to review the latest evidence on cryoprecipitate for treatment of bleeding. We conducted a narrative review of current literature on cryoprecipitate therapy, describing its history, formulations and preparation, and recommended dosing. We also reviewed guideline recommendations on the use of cryoprecipitate in bleeding situations and recent studies on its efficacy and safety. Cryoprecipitate has a relatively high fibrinogen content; however, as it is produced by pooling fresh frozen donor plasma, the fibrinogen content per unit can vary considerably. Current guidelines suggest that cryoprecipitate use should be limited to treating hypofibrinogenemia in patients with clinical bleeding. Until recently, cryoprecipitate was deemed unsuitable for pathogen reduction, and potential safety concerns and lack of standardized fibrinogen content have led to some professional bodies recommending that cryoprecipitate is only indicated for the treatment of bleeding and hypofibrinogenemia in perioperative settings where fibrinogen concentrate is not available. While cryoprecipitate is effective in increasing plasma fibrinogen levels, data on its clinical efficacy are limited. There is a lack of robust evidence to support the use of cryoprecipitate in bleeding patients, with few prospective, randomized clinical trials performed to date. Clinical trials in bleeding settings are needed to investigate the safety and efficacy of cryoprecipitate and to determine its optimal use and administration.

The effect of fibrin formulation on cell migration in an in vitro tendon repair model

BackgroundThe purpose of this study was to determine the effect of fibrinogen concentration on cell viability and migration in a tissue culture tendon healing model. MethodsForty-eight canine flexor digitorum profundus tendons were randomly divided into three groups. In each group the tendons were lacerated and repaired augmented with a canine bone marrow stromal cell seeded fibrin interposition patch using either 5 mg/ml fibrinogen and 25 U/ml thrombin (physiological as a control), 40 mg/ml fibrinogen and 250 U/ml thrombin (low adhesive), or 80 mg/ml fibrinogen and 250 U/ml thrombin (high adhesive). The sutured tendons were cultured for two or four weeks. ResultsFailure load was not significantly different among the groups. Cell-labeling staining showed that the stromal cells migrated across the gap in the control and low adhesive groups, but there was no cell migration in the high adhesive group at two weeks. Conclusion: A high fibrinogen concentration in a fibrin patch or glue may impede early cell migration. Level of evidenceNot applicable because this study was a laboratory study.

Adherence to dietary approaches to stop hypertension (DASH) and Mediterranean dietary patterns in relation to cardiovascular risk factors in older adults.

The aging process is associated with several chronic diet-related complications, including cardiovascular diseases. Therefore, the objective was to examine the association between DASH and Mediterranean dietary pattern (MDP) on cardiovascular risk factors and inflammatory markers in older adult men. A cross-sectional study was performed on 357 older adult men who were randomly selected from health centers across Tehran, Iran. Dietary intakes, anthropometric measures, biochemical markers, and general characteristics were also collected. Multivariate logistic regression was used to estimate odds ratios of outcomes across medians of dietary patterns, respectively. After adjusting for possible confounders, greater adherence to the MDP was associated with lower waist circumference, triacylglycerol, high-sensitivity c-reactive protein, fibrinogen, and higher HDL-C (p<0.05). Greater adherence to the DASH diet was associated with lower fibrinogen (p<0.05). Adherence to the MDP was inversely associated with diastolic blood pressure (OR, 0.35; 95% CI, 0.14-0.79; P=0.01) and fibrinogen levels (OR, 0.33; 95% CI, 0.20-0.52; P<0.001). Moreover, greater adherence to the DASH diet (second vs first category) was associated with reduced risk of high diastolic blood pressure (OR, 0.11; 95% CI, 0.04-0.34; P<0.001), insulin levels (OR, 0.44; 95% CI, 0.28-0.72; P<0.001), hs-CRP (OR, 0.53; 95% CI, 0.33-0.85; P=0.009), and fibrinogen (OR, 0.37; 95% CI, 0.21-0.64; P<0.001). There was an inverse association between the DASH and MDP with several cardiovascular risk factors. Future, longitudinal study designs are needed to confirm these results.

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 and coagulation dysfunction in adults: A systematic review and meta-analysis.

The outbreak of 2019 novel coronavirus disease (COVID‐19) has posed a grave threat to the global public health. The COVID‐19‐induced infection is closely related to coagulation dysfunction in the affected patients. This paper attempts to conduct a meta‐analysis and systematically review the blood coagulation indicators in patients with severe COVID‐19. A meta‐analysis of eligible studies was performed to compare the blood coagulation indicators in patients with severe and nonsevere COVID‐19. PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies published between 1 December 2019 and 7 May 2020. A total of 13 studies with 1341 adult patients were enrolled in this analysis. Platelet (weighted mean difference [WMD] = −24.83, 95% confidence interval [CI]: −34.12 to −15.54; P < .001), d‐dimer (WMD = 0.19, 95% CI: 0.09‐0.29; P < .001), and fibrinogen (WMD = 1.02, 95% CI: 0.50‐1.54; P < .001) were significantly associated with the severity in patients with COVID‐19. The meta‐analysis revealed that no correlation was evident between an increased severity risk of COVID‐19 and activated partial thromboplastin time (WMD = −1.56, 95% CI: −5.77 to 2.64; P = .468) or prothrombin time (WMD = 0.19, 95% CI: −0.13 to 0.51; P = .243). The single arm meta‐analysis showed that compared with the nonsevere group, the severe group had a lower pooled platelet (165.12 [95% CI: 157.38‐172.85] vs 190.09 [95% CI: 179.45‐200.74]), higher d‐dimer (0.49 [95% CI: 0.33‐0.64] vs 0.27 [95% CI: 0.20‐0.34]), and higher fibrinogen (4.34 [95% CI: 1.98‐6.70] vs 3.19 [95% CI: 1.13‐5.24]). Coagulation dysfunction is closely related to the severity of patients with COVID‐19, in which low platelet, high d‐dimer, and fibrinogen upon admission may serve as risk indicators for increased aggression of the disease. These findings are of great clinical value for timely and effective treatment of the COVID‐19 cases.

Predictive value of combining the level of fibrinogen and antithrombin III for contrast-induced nephropathy in coronary artery disease patients undergoing percutaneous coronary intervention.

Contrast-induced nephropathy (CIN) is a common adverse event in the diagnosis and treatment of coronary intervention. The current study investigated the predictive effect of preoperative fibrinogen (FIB) combined with antithrombin III (AT-III) on CIN following percutaneous coronary intervention (PCI). A total of 394 patients who underwent PCI between October 2018 and May 2019 were selected for the present study. Pre-procedural FIB levels and AT-III activity were measured before PCI. CIN was defined as a 0.5 mg/dl or 25% increase in serum creatinine levels 48 to 72 h after exposure to a radiocontrast agent. Patients were classified into CIN and non-CIN groups. CIN occurred in 48 (12.2%) patients. The serum FIB levels were significantly higher in patients who developed CIN compared with those who did not develop CIN. In addition, AT-III levels ≤89.5% were associated with higher rates of CIN. Logistical regression analysis showed that high FIB, and low AT-III and albumin levels were high-risk factors associated with CIN. For FIB, the area under the receiver operating characteristic curve (AUC) for predicting CIN was 0.653. The optimal cut-off value was 3.48 g/l with a sensitivity of 45.8% and a specificity of 79.7% [95% confidence interval (CI): 0.603-0.701; P=0.0002)]. For AT-III, the AUC was 0.711, and the optimal cut-off value was 89.5%, with a sensitivity of 81.3% and specificity of 58.2% (95% CI: 0.659-0.758; P<0.0001). When combining FIB and AT-III, the AUC was 0.747. The optimal cut-off value was 0.090424, with a diagnostic sensitivity of 93.8% and specificity of 46.6% (95% CI: 0.697-0.792; P<0.0001). The results showed that FIB combined with AT-III resulted in improved predictive accuracy of CIN (FIB vs. AT-III, AUC=0.653 vs. 0.711, P=0.292; FIB vs. FIB + AT-III, AUC=0.653 vs. 0.747, P=0.012; AT-III vs. FIB + AT-III, AUC=0.711 vs. 0.747, P=0.138). Pre-procedural levels of FIB, AT-III and albumin were independently associated with an increased risk of CIN. Furthermore, the results suggested that the combination of FIB and AT-III was a better predictor of CIN after PCI.

Outcome and complications following transrectal and transabdominal large intestinal trocarization in equids with colic: 228 cases (2004-2015).

To describe outcome and complications after large intestinal trocarization in equids with colic and identify factors associated with nonsurvival and clinically relevant peritonitis (CRP). 228 (198 horses, 24 ponies, and 6 donkeys and mules) equids with colic that underwent large intestinal trocarization. Medical records from 2004 through 2015 were reviewed for equids with colic that underwent large intestinal trocarization. Factors associated with nonsurvival in all (ie, surgically and medically treated) equids and with CRP in medically only treated equids were identified. Medically only treated equids with a high peritoneal fluid cell count (ie, > 10,000 cells/μL) after large intestinal trocarization were classified as having CRP if they met ≥ 2 of the following clinical criteria: anorexia, fever, lethargy, abnormal oral mucous membrane color, abnormal WBC count, or high blood fibrinogen concentration (> 5 g/L). Transabdominal large intestinal trocarization was performed in 190 (83%) equids, transrectal trocarization in 17 (7%), and both procedures in 21 (9%). Of 228 equids, 167 (73%) survived to hospital discharge. None died or were euthanized because of complications from large intestinal trocarization. Nonsurvival was associated with an increasing number of trocarization procedures and diagnosis of a large intestinal strangulating lesion. A diagnosis of nephrosplenic ligament entrapment of the large colon decreased the odds of nonsurvival. Twelve of 60 (20%) equids that received medical treatment only had CRP following large intestinal trocarization. Large intestinal trocarization could be considered for equids with colic and large intestinal gas distension. More than one trocarization procedure was associated with an increase in nonsurvival, which should be considered for equids for which consent for surgery has been obtained.

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.