Which injured patients with moderate fibrinogen deficit need fibrinogen supplementation?

Background In severely injured patients, fibrinogen supplementation is recommended when fibrinogenemia is < 1.5 g L−1, but some teams have suggested to use higher thresholds (fibrinogenemia < 2.0 g L−1 or FIBTEM clot amplitude at 5 min (A5) values < 11 mm). The goal of this study was to specify in patients with a moderate fibrinogen deficit (MFD) whether some admission characteristics would be associated with fibrinogen administration at 24 h. Methods Prospective analysis of retrospectively collected data from a trauma registry (01/2011–12/2019). MFD-C was defined by a fibrinogenemia 1.51–1.99 g L−1 or the corresponding FIBTEM-A5 values (MFD-A5) that were determined from linear regression and ROC curve analysis. Administration of fibrinogen were described according to the following admission parameters: shock index (SI) > 1, hemoglobin level < 110 g L−1 (HemoCue®), and base deficit > 5 mEq L−1. Data are expressed as count (%), median [IQR]. Results 1076 patients were included in the study and 266 (27%) had MFD-C, among them, 122/266 (46%) received fibrinogen. Patients with MFD-C who received fibrinogen were more severely injured (ISS: 27 [19–36] vs. 24 [17–29]) and had more impaired vital signs (base deficit: 5.4 [3.6–7.8] vs. 3.8 [2.0–6.0]). Linear regression analysis found a positive correlation between fibrinogen level and FIBTEM-A5 (r: 0.805). For a fibrinogen level < 1.5 g L−1 and < 2.0 g L−1, FIBTEM-A5 thresholds were 6 mm (sensitivity 85%, specificity 83%, AUC: 0.934) and 9 mm (sensitivity 84%, specificity 69%, AUC: 0.874), respectively. MFD-A5 values (185 (27%) patients) were defined as a FIBTEM-A5 between 7 and 9 mm. More than 50% of MFD-C patients presenting a SI > 1, a hemoglobin level < 110 g L−1, or a base deficit > 5.0 mEq L−1 received fibrinogen. The relative risk [95% CI] for fibrinogen administration (SI > 1) were 1.39 [1.06–1.82] for MFD-C, and 2.17 [1.48–3.19] for MFD-A5. Results were not modified after adjustment on the ISS. Conclusions We have shown in this study an association between shock parameters and fibrinogen administration. Further studies are needed to determine how these parameters may be used to guide fibrinogen administration in trauma patients with MFD.

Coagulopathy Following Chimeric Antigen Receptor T Cell Therapy in R/R Adult B Cell Malignancies: A Single Center Experience

Background. Immunotherapy with chimeric antigen receptor T (CAR-T cells) is a new therapeutic approach approved for patients with relapsed/refractory (R/R) B-lymphoproliferative malignancies. Specific toxicities have been described following CAR-T cells therapy, mainly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Coagulation disorders have been described in patients experiencing CRS. However, data is scarce regarding such consequences. Methods. We retrospectively evaluated patients treated with CAR T-cells for R/R B-cell lymphoma in our tertiary hospital between 2019, January 1 st and 2021, March 1 st. Post-infusion coagulation disorders were assessed, as well as factors associated with such anomalies using a multivariate logistic regression model. Results. During the study period, 64 patients received CAR T-cell therapy for R/R diffuse large B-cell lymphoma (n=52, 81%), transformed follicular lymphoma (n=9, 14%) and mantel cell lymphoma (n=3, 5%).The median follow-up was 7.98 months (IQR 4.24; 12.39). All patients had a normal coagulation panel at CAR-T cells infusion. The incidence of CRS was 92% (n=59; grade 3-4 n=2, 3%) and ICANS 38% (n=24; grade 3-4 n=7; 11%). We observed a decrease in fibrinogen level in all patients (grade 3-4 n=44, 69%), occurring at day 11 (median) post-infusion, prolonged prothrombin time (PT) in 27 patients (42%, grade 3-4 n=0), at day 4 (median), and thrombocytopenia in 62 patients (97%, grade 3-4 n=46, 72%) at day 1 (median). By multivariate analysis, fibrinogen below 2 g/L after CAR-T cells infusion was independently associated with CRS grade 2 or greater (OR 58.4; 95%CI [5.8-4212.8] p = 0.009), ICANS grade 2 or greater (OR 2.36; 95%CI [2.2-80.6] p = 0.007) and day-0 lymphocyte count (OR 0.32 per 0.1 G/L; 95%CI [0.10-0.89] p = 0.037). However, it was not associated with comorbidities, disease history, tumor burden, CAR product, or outcomes. Furthermore, by the end of the study, 5 patients (8%) did not recover a normal fibrinogen level and 41 (64%) did not recover a normal platelet count. Others recovered a normal fibrinogen level within a median of 69 days, a normal platelet count within a median of 15 days, and a normal PT within in a median of 7 days. Interestingly, no significant thrombotic or hemorrhagic events were recorded for those patients. Conclusion. A high incidence of asymptomatic coagulation disorders was observed after CAR-T cell therapy, notably prolonged hypofibrinogenemia. Further studies should focus on the mechanisms involved in such abnormalities. Disclosures Lamure: Janssen: Other: miscellaneous support , Research Funding; Gilead: Other: miscellaneous support ; Roche: Other: miscellaneous support ; Abbvie: Other: miscellaneous support ; Sanofi: Other: miscellaneous support ; Novartis: Other: miscellaneous support ; Pfizer: Other: miscellaneous support ; Actelion: Other: miscellaneous support . Paul: NOVARTIS: Other: BOARD; SERVIER: Other: BOARD. Tchernonog: JANSSEN: Consultancy; ABBVIE: Consultancy; ASTRAZENECA: Consultancy. Herbaux: Takeda: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Roche: Honoraria; Janssen: Honoraria. Cartron: Roche, Celgene-BMS: Consultancy; Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda: Honoraria.

The clinical significance of preoperative serum fibrinogen levels and platelet counts in patients with gallbladder carcinoma

Background Gallbladder carcinoma (GBC) was the most common malignancy of biliary tract. Patients with malignancies frequently present with activated coagulation pathways, which might potentially related to tumor progression and prognosis. The purpose of the study was to investigate the clinical significance of preoperative serum fibrinogen levels and platelet counts in GBC patients. Methods The preoperative fasting serum fibrinogen levels and platelet counts of 58 patients with GBC were measured by AUV2700 automatic biochemical analyzer, as well as 60 patients with cholesterol polyps and 60 healthy volunteers. Kaplan–Meier survival analysis was applied to show the correction between fibrinogen levels and outcome after surgery. Results The fibrinogen levels of patients with GBC were significantly higher than healthy gallbladder and cholesterol polyp of gallbladder (p < 0.001 and p < 0.001, respectively). In GBC, fibrinogen levels were associated with tumor depth (p = 0.001), lymph node metastasis (p = 0.002), distant metastasis (p < 0.001) and Tumor Node Metastasis (TNM) stage (p < 0.001). The levels in TNM stage IV disease were significantly higher than stage III or stage I + II disease (p = 0.048 and p < 0.001, respectively), and in TNM stage III disease were significantly higher than stage I + II disease (p = 0.002). Furthermore, the overall survival was better in low fibrinogen level group than in high fibrinogen level group (p < 0.001). However, thrombocytosis was not significantly associated with overall survivals (p > 0.05) in multivariate analysis. Conclusions The preoperative serum fibrinogen levels and platelet counts might be reliable biomarkers for the occurance of disease, tumor depth, lymph node metastasis, distant metastasis and advanced TNM stage in patients with GBC. The serum fibrinogen levels might be a prognostic factor to predict outcome for GBC patients suffering from surgery treatment. Anticoagulation therapy might be considered to control cancer progression in future studies.

Do We Need To Evaluate Patients With Spontaneous Subconjunctival Hemorrhage For Bleeding Disorders?

Aim of the study: Subconjunctival hemorrage (SCH) is a frequent bleeding manifestation and a common cause of visits to the primary care. Trauma in young patients and vascular damage such as hypertension in the elderly are the most common causes of SCH and the prevalence of hematological diseases is less than 1%. We aimed to evaluate the prevalence of congenital or acquired bleeding disorders in patients with once or recurrent SCH. Methods used to conduct the study: It is a retrospective study and included fifty-two patients with SCH whose etiologic factor was not detected. Hemostatic tests were studied in 52 patients (25 male and 27 females). All patients included were evaluated for congenital or acquired bleeding disorder and SCH with once and those with 2 or more were compared for the laboratory results. Results of the study: Type I von Willebrand disease (vWD) was diagnosed in one patient with recurrent SCH and one patient with single SCH (3.8%). The prevalence of patients with type 1 vWD in the study was not statistically significant when compared with the frequency of vWD in the normal population. Fibrinogen level was found to be statistically higher in patients who had SCH once than those who had recurrent SCH. But fibrinogen level was in normal range in all patients. Conclusions drawn from the study and clinical implications: There was no increase in the incidence of congenital or acquired bleeding disorder in SCH compared to normal population. For this reason it was thought that there was no need for evaluation for bleeding disorders in spontaneous SCH.

Elevated Plasma Fibrinogen and the Risk of Stroke: A Hospital Based Prospective Case-Control Study in Uyo, Nigeria

Background: Stroke is one of the leading causes of morbidity and mortality globally. In recent time, there is increasing evidence that suggest that increased plasma fibrinogen is associated with increased risk of stroke with unfavourable clinical outcome. Objectives: To determine the plasma fibrinogen levels in stroke patients and compare with healthy controls. Study Design: The study design was Prospective case- control study. Place and Duration of Study: The study was conducted in the department of Internal Medicine (Neurology Unit) and the department of Haematology between March to August, 2019. Methodology: A case- control study consisting of 41 patients (21M: 19F) diagnosed with stroke in line with WHO definition and confirmed by CT-Scan of the brain were recruited consecutively into the study. 20 (10M: 10F) healthy age and gender matched consenting adults were used as controls. Plasma fibrinogen was determined for both the patients and controls using ELISA method. Also, socio-demographic and clinical data were collected using questionnaire designed for the study. The level of significance was set at P=.05. Results: The mean plasma fibrinogen level of 458.0 ± 89.1 was significantly higher in the stroke patients compared to the controls 307.8 ± 61.5 (P<0.001). An increasing level of plasma fibrinogen was observed with increasing age in both the patients and controls. However, this increase was not statistically significant (P=0.98). Also, the plasma fibrinogen level was significantly higher in the female patients (501.21±83.96) than the males 420.59±77.02 (P=0.003). Conclusion: Plasma fibrinogen was significantly higher in the stroke patients compared to the controls with female patients having a significantly higher levels than males. Also, the plasma fibrinogen levels appear to increase proportionally with increasing age.

Do We Need To Evaluate Patients With Spontaneous Subconjunctival Hemorrhage For Bleeding Disorders?

Aim of the study: Subconjunctival hemorrage (SCH) is a frequent bleeding manifestation and a common cause of visits to the primary care. Trauma in young patients and vascular damage such as hypertension in the elderly are the most common causes of SCH and the prevalence of hematological diseases is less than 1%. We aimed to evaluate the prevalence of congenital or acquired bleeding disorders in patients with once or recurrent SCH. Methods used to conduct the study: It is a retrospective study and included fifty-two patients with SCH whose etiologic factor was not detected. Hemostatic tests were studied in 52 patients (25 male and 27 females) with. All patients included were evaluated for congenital or acquired bleeding disorder and SCH with once and those with 2 or more were compared for the laboratory results. Results of the study: One patient with once and one patient with recurrent SCH (3.8%) were diagnosed a type I von Willebrand disease (vWD). The prevalence of patients with type 1 vWD in the study was not statistically significant when compared with the frequency of von Willebrand favctor (vWF) deficiency in the normal population. Fibrinogen level was found to be statistically higher in patients who had SCH once than those who had recurrent SCH. But fibrinogen level was in normal range in all patients. Conclusions drawn from the study and clinical implications: There was no increase in the incidence of congenital or acquired bleeding disorder in SCH patients compared to normal population. Therefore, it was considered that spontaneous SCH patients do not need to be evaluated for bleeding disorder.