Low Fibrinogen Levels Research Articles

Clinical case of hemophagocytic lymphohistiocytosis: rare or undiagnosed syndrome?

Hemophagocytic lymphohistiocytosis (hemophagocytic syndrome, HLH) is a life-threatening hyperinflammatory condition associated with a high mortality rate; it is characterized by hyperstimulation of histiocytes and cytotoxic T-cells, which leads to cytokine storm and multisystemic injury. Aim. To present our own clinical case of the HLH development at the key aspects of pathogenic mechanisms, differential diagnosis, and therapeutic management of this syndrome. Materials and methods. This article provides information on the HLH development in a 69-year-old man with the onset of this syndrome prior to a diagnosis of the underlying disease – splenic marginal zone lymphoma. The article summarizes the current literature data on clinical manifestations, diagnosis, and treatment of HLH. Results. This article describes a case of secondary HLH from our clinical practice. The most common causes of HLH are malignant neoplasm, infectious factors and rheumatic diseases (when associated with the latest, HLH is called “macrophage activation syndrome”). The main clinical symptoms are prolonged high fever and hepatosplenomegaly, typical laboratory changes such as cytopenia, hyperferritinemia, hypertriglyceridemia, elevated liver enzymes and low fibrinogen levels. Conclusions. Despite typical clinical features, HLH is a condition that often remains unrecognized and it is characterized by a poor prognosis. Prompt prescription of adequate treatment can improve patients’ prognoses and increase the survival rate.

Comparisons of coagulation characteristics between elderly and non-elderly patients with sepsis: A prospective study

BackgroundA blunt host defense response in older patients may contribute to different coagulation responses during sepsis. We aimed to investigate the differences in coagulation parameters between elderly and non-elderly patients with sepsis. MethodsAdult patients diagnosed with sepsis within 24 hours after admission to the intensive care unit between September 2018 and December 2020 were prospectively enrolled. Patients were categorized into the adult (18–64 years) and elderly (age ≥65 years) groups. Conventional coagulation parameters and inflammatory markers were measured on intensive care unit admission and on Days 3 and 7. Thromboelastography was performed on intensive care unit admission. The differences in the coagulation parameters between the 2 groups were evaluated. The adult and elderly patients were matched to adjust for baseline characteristics. Correlations between inflammatory markers and coagulation-related parameters were also analyzed. ResultsOf the 567 patients, 303 (53.4%) were elderly. Compared with adult patients, elderly patients had lower prothrombin time elevation, lower fibrinogen, D-dimer, and fibrin/Fib degradation product levels, and lower proportion of disseminated intravascular coagulation on intensive care unit admission; and, they had lower dynamic platelet, lower fibrinogen, and D-dimer levels during the first week in the intensive care unit. Thromboelastography parameters were generally within the normal range, although elderly patients had lower R and K values and a higher alpha angle. Comparisons of coagulation parameters between the 2 groups revealed similar results in the matched cohort. The inflammatory markers correlated with prothrombin time, activated partial thromboplastin time, and antithrombin III. ConclusionElderly patients had milder coagulation activation, accompanied by a decreased inflammatory response during sepsis, compared to non-elderly patients.

Factors associated with migraine aura mimicking stroke in code stroke.

Migraine with aura (MA) is a frequent stroke simulator that can lead to erroneous diagnosis and subsequent unnecessary acute or secondary prevention treatments. We analyzed clinical and laboratory data of migraine with aura and ischemic stroke patients to detect differences that could help in the diagnosis. Retrospective analysis of a consecutive register of code strokes between January 2005 and June 2020. Diagnosis of ischemic stroke or MA was collected. Multivariable logistic regression analyses were performed to test associations between clinical and blood data with ischemic stroke. Of 3140 code strokes, 2424 (77.2%) were ischemic strokes and 34 (1.1%) were MA. Migraine cases were younger, more frequently females and with lower prevalence of vascular risk factors. Initial NIHSS was lower in MA cases, but no differences were seen in fibrinolysis rate (30%). Blood test showed lower levels of glucose, D-dimer, and fibrinogen in MA cases. Multivariable model showed and independent association for ischemic stroke with age [OR, (95%CI): 1.09, (1.07-1.12, p < 0.001], male sex [OR, (95%CI): 4.47, (3.80-5.13), p < 0.001], initial NIHSS [OR, (95%CI): 1.21, (1.07-1.34), p < 0.01], and fibrinogen levels [OR, (95%CI): 1.01, (1.00-1.01), p < 0.05]. A model including sex male OR: 3.55 [2.882; 4.598], p < 0.001, and cutoff points (age > 65, OR: 7.953 [7.256; 8.649], p < 0.001, NIHSS > 6, OR: 3.740 [2.882; 4.598], p < 0.01, and fibrinogen > 400mg/dL, OR: 2.988 [2.290; 3.686], p < 0.01) showed a good global discrimination capability AUC = 0.89 (95%CI: 0.88-0.94). In code stroke, a model including age, sex, NIHSS, and fibrinogen showed a good discrimination capability to differentiate between MA and Ischemic stroke. Whether these variables can be implemented in a diagnostic rule should be tested in future studies.

Plasma fibrinogen levels and all-cause and cause-specific mortality in an Italian adult population: results from the Moli-sani study

Epidemiological data on the association between fibrinogen levels and mortality are scarse and controversial. Longitudinal analyses were performed, separately by sex, on 17,689 individuals from the Moli-sani study [53% women, ≥35 years, free from cardiovascular disease (CVD) or cancer at enrolment], to evaluate the association between plasma fibrinogen and all-cause and cause-specific mortality. Over a median follow-up of 11.2 years, 1,058 deaths (34.7% CVD, 36.3% cancer) were ascertained. Both in the lowest (1.12-2.64 g/L) and highest (≥3.62 g/L) fibrinogen quintiles, women had an increased all-cause mortality hazard, when compared with third quintile (2.97-3.23 g/L). Dose-response analyses showed a U-shaped relationship in women (P overall &lt;0.0001; P non-linear association &lt;0.0001), but a positive linear association for all-cause mortality in men (P overall 0.0038; P non-linear association 0.76). Similar trends for a U-shaped association were observed for CVD mortality, while no association was observed with cancer deaths. A U-shaped association of fibrinogen levels with other-cause mortality was also found in both sexes. This study shows that not only higher but also lower fibrinogen levels represent hazard for mortality when compared to normal levels; U-shaped curves being prevalently observed in women.

The potential impact of coagulation factor XIII in trauma-induced coagulopathy – a retrospective case series analysis

BackgroundThe role of factor XIII (FXIII) in trauma-induced coagulopathy (TIC) is not fully understood.MethodsWe evaluated FXIII supplementation in severely injured patients with persistent bleeding. This was a retrospective case series analysis.ResultsTwenty-four patients received FXIII concentrate within 24 h of admission for bleeding that continued after transfusion of > 6 U red blood cells (RBCs); control patients (n = 27) did not receive FXIII concentrate. Both study groups were similar regarding injury severity score and global coagulation tests, but FXIII activity levels were significantly higher and lactate levels significantly lower in the control group, respectively. The differences in FXIII activity between the groups could be attributed to a more severe trauma-induced coagulopathy in FXIII-deficient patients, as demonstrated by lower fibrinogen and higher lactate levels. The median dose of FXIII concentrate within 24 h of admission was 2500 IU (IQR: 1250–4375). Median 24-h transfusion of RBCs (primary study endpoint) was significantly higher in the FXIII group versus controls (10.0 U, IQR 5–14 U vs. 2, IQR 0–6 U; p < 0.01). Subsequently, while patients were in the intensive care unit, there was no statistically significant difference regarding RBC transfusion anymore and the overall clinical outcomes were similar in both patient groups.ConclusionsThe substitution of FXIII in patients who were more seriously compromised due to higher lactate levels and who presented with initially more severe bleedings than patients in the control group, resulted in a comparable transfusion necessity after 24 h. Thus, we guess that the substitution of FXIII in severely injured patients with ongoing bleeding might have an impact on their clinical outcome.

Low preoperative serum fibrinogen level is associated with postoperative acute kidney injury in patients with in acute aortic dissection

ObjectiveAcute kidney injury (AKI) after cardiac surgery is associated with serious complication and high risk of mortality. The relationship between hemostatic system and the prognosis of patients with acute type A aortic dissection (ATAAD) has not been evaluated. The purpose of this study was to investigate the association between preoperative serum fibrinogen level and risk of postoperative AKI in patients with ATAAD.MethodsA total of 172 consecutive patients undergoing urgent aortic arch surgery for ATAAD between April 2020 and December 2021 were identified from Beijing Anzhen Hospital aortic surgery database. The primary outcome was postoperative AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The univariate and multivariate logistic regression analysis were done to assess the independent predictors of risk for postoperative AKI. Receiver operating characteristic (ROC) curve was generated to evaluate the predictive probabilities of risk factors for AKI.ResultsIn our study, 51.2% (88/172) patients developed postoperative AKI. Multivariate logistic regression analysis identified low preoperative serum fibrinogen level (OR, 1.492; 95% CI, 1.023 to 2.476; p = 0.021) and increased body mass index (BMI) (OR, 1.153; 95% CI, 1.003 to 1.327; p = 0.046) as independent predictors of postoperative AKI in patients with ATAAD. A mixed effect analysis of variance modeling revealed that obese patients with low preoperative serum fibrinogen level had higher incidence of postoperative AKI (p = 0.04). The ROC curve indicated that low preoperative serum fibrinogen level was a significant predictor of AKI [area under the curve (AUC), 0.771; p < 0.001].ConclusionsLow preoperative serum fibrinogen level and obesity were associated with the risk of postoperative AKI in patients with ATAAD. These data suggested that low preoperative serum fibrinogen level was preferred marker for predicting the postoperative AKI, especially in obese patients with ATAAD.

Investigation of erythrocyte aggregation parameters of blood with low levels of fibrinogen by syllectometry

Investigation of erythrocyte aggregation parameters of blood with low levels of fibrinogen by syllectometry

Risk factors and clinical outcomes associated with acquired hypofibrinogenemia in patients administered hemocoagulase batroxobin for hemoptysis.

Hemocoagulase batroxobin is used to prevent hemostasis or bleeding in surgical and trauma patients; however, the role of batroxobin in patients with hemoptysis is not well understood. We evaluated the risk factors and prognosis of acquired hypofibrinogenemia in hemoptysis patients treated systemically with batroxobin. We retrospectively reviewed the medical charts of hospitalized patients who were administered batroxobin for hemoptysis. Acquired hypofibrinogenemia was defined as a plasma fibrinogen level >150 mg/dL at baseline, decreasing to <150 mg/dL after batroxobin administration. Overall, 183 patients were enrolled, of whom 75 had acquired hypofibrinogenemia after the administration of batroxobin. There was no statistical difference in the median age of the patients in the non-hypofibrinogenemia and hypofibrinogenemia groups (72.0 vs. 74.0 years, respectively). The patients in the hypofibrinogenemia group showed a higher rate of intensive care unit (ICU) admission (11.1% vs. 22.7%; P=0.041) and tended to have more massive hemoptysis than those in the non-hyperfibrinogenemia group (23.1% vs. 36.0%; P=0.068). The patients in the hypofibrinogenemia group further showed a higher requirement for transfusion (10.2% vs. 38.7%; P<0.000) than those in the non-hyperfibrinogenemia group. Low levels of baseline plasma fibrinogen and a prolonged and higher total dose of batroxobin were associated with the development of acquired hypofibrinogenemia. Acquired hypofibrinogenemia was associated with increased 30-day mortality [hazard ratio (HR), 4.164; 95% confidence interval (CI), 1.318-13.157]. The plasma fibrinogen levels in patients who were administered batroxobin for hemoptysis should be monitored, and batroxobin should be discontinued if hypofibrinogenemia occurs.

Evaluation of fibrinogen function by CFF-A10 in cardiac surgery

Fibrinogen function is evaluated as the maximum amplitude (MA) of the citrated functional fibrinogen (CFF) assay in TEG6s®, however, CFF-MA requires a long time to obtain results. CFF-A10 (10-minute value), allowing more rapid decisions, however, no studies have evaluated the correlation between CFF-A10 levels and fibrinogen concentration. This study aimed to assess the correlation between CFF-A10 and blood fibrinogen levels measured using the dry hematology method after cardiopulmonary bypass (CPB). This retrospective study was conducted in a single university hospital and enrolled 192 patients of all ages who underwent cardiovascular surgery with CPB between 01 March 2020, and 05 November 2021. CFF-A10 and CFF-MA levels were measured using the TEG6s® global hemostasis assay, and blood fibrinogen levels were measured using the Fibcare® DRIHEMATO Fib-HSII after CPB. Simple linear regression analysis was used to evaluate the relationship between TEG6s® parameters and fibrinogen concentration. Furthermore, the patients were classified into four groups based on the cut-off values of fibrinogen at 150 mg/dL and CFF-A10, and the background factors for each group were analyzed. CFF-A10 and blood fibrinogen levels were correlated by linear regression (p &lt; 0.0001, R2 = 0.37), similar to CFF-MA and fibrinogen levels (p &lt; 0.0001, R2 = 0.40). The optimal cut-off value, which maximizes the sensitivity and specificity, of CFF-A10 for predicting low fibrinogen levels below 150 mg/dL, was 8.4 mm, with a sensitivity of 80.7% and specificity of 67.9%; that of CFF-MA was 9.2 mm, with a sensitivity of 76.3% and specificity of 69.8%. Despite sufficient blood fibrinogen levels, patients with low CFF-A10 levels experienced more postoperative bleeding. CFF-A10 predicted fibrinogen loss faster and with the same accuracy as CFF-MA did. Low CFF-A10 levels, despite sufficient fibrinogen levels, may be associated with increased blood loss following CPB.

Перебіг СОVID-19 в імуноскомпроментованих пацієнтів

Purpose - to analyze the currently described variants of the course of COVID-19 in immunocompromised patients in order to inform the medical community and focus on this problem. Two clinical cases of different course of COVID-19 in patients with primary immunodeficiencies, both mild, asymptomatic and severe, with a fatal outcome, are presented. In the first case, in a child with Nijmegen breakage syndrome, despite lymphopenia, the course of SARS-CoV-2 was asymptomatic, which may be due to the regular administration of immunoglobulin for replacement purposes. The peculiarity of the second case was a repeated episode of COVID-19 in an immunocompromised child with APECED. The first episode of COVID-19 in September 2020 had a mild course, but led to the manifestation of immunodeficiency symptoms. The present symptoms (retinopathy, hepatitis), except for mild mucosal candidiasis, are not part of the triad of classic APECED symptoms, although along with the reaction to the live vaccine, they made it possible to suspect immunodeficiency. Immunosuppressive therapy contributed to stabilization of hepatitis, but ocular symptoms were without positive dynamics. The second episode of COVID-19 was observed in January 2022. It proceeded with prolonged fever for 2 weeks, which was resistant to treatment, with progressive cytopenia, hypoproteinemia, hypoalbuminemia, signs of active hepatitis, hyperferritinemia, elevated triglycerides; coagulopathy with low fibrinogen levels. Subsequently, signs of pneumonia were added, confirmed by radiology. Another feature of this case was the presence of a mixed infection - COVID-19 and Epstein-Barr virus infection. The cause of death in this case was not only COVID-19 pneumonia, but also progressive macrophage activation syndrome. Conclusions. Thus, the sequence of COVID-19 in patients with inborn errors of immunity can be either asymptomatic and mild or fatal, depending on the type of immune disorders, the therapy received, and concomitant conditions. SARS-CoV-2 in immunocompromised individuals requires close attention for timely diagnosis of life-threatening conditions. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Blood component requirements in liver transplantation: effect of 2 thromboelastometry-guided strategies for bolus fibrinogen infusion—the TROMBOFIB randomized trial

BackgroundA low plasma fibrinogen level influences blood component transfusion. Thromboelastometry provides clinical guidance for fibrinogen replacement in liver transplantation (LT). ObjectivesWe hypothesized that infusions of fibrinogen concentrate to reach an A10FibTem value of 11 mm during LT could reduce red blood cell (RBC) and other component and fluid requirements in comparison to standard care. MethodsThis randomized, blinded, multicenter trial in 3 hospitals enrolled 189 LT-scheduled patients allocated to an intervention target (A10FibTem, 11 mm) or a standard target (A10FibTem, 8 mm); 176 patients underwent LT with fibrinogen replacement. Data were analyzed by intention-to-treat (intervention group, 91; control group, 85). Blood was extracted, and fibrinogen kits were prepared to bring each patient’s fibrinogen level to the assigned target at the start of LT, after portal vein clamping, and after graft reperfusion. The main outcome was the proportion of patients requiring RBC transfusion during LT or within 24 hours. ResultsThe proportion of patients requiring RBCs did not differ between the groups: intervention, 74.7% (95% CI, 65.5%-83.3%); control, 72.9% (95% CI, 62.2%-82.0%); absolute difference, 1.8% (95% CI, −11.1% to 14.78%) (P = .922). Thrombotic events occurred in 4% of the patients in both groups; reoperation and retransplantation rates and mortality did not differ. Nearly 70% of the patients in both groups required fibrinogen concentrate to reach the target. Using an 11-mm A10FibTem target increased the maximum clot firmness without affecting safety. However, this change provided no clinical benefits. ConclusionThe similar low plasma fibrinogen concentrations could explain the lack of significant between-group outcomes.

Dynamic Changes of Hemostasis in Patients with Traumatic Brain Injury Undergoing Craniotomy: Association with in-Hospital Mortality.

Traumatic brain injury (TBI) induces complex systemic hemostatic alterations associated with secondary brain damage and death. We specifically investigated perioperative changes of hemostasis in patients with isolated TBI undergoing major neurosurgery and searched for their influence on outcome. Serial analysis (four time points, T0-T3) of conventional coagulation assay and rotational thromboelastometry data acquired during 72h from admission of 68 patients who underwent craniotomy to remove hematoma and/or to decompress the brain was performed. The primary outcome was in-hospital mortality. Secondary outcomes were the prevalence of hypocoagulation and increased clotting activity, coagulation parameters between survivors and nonsurvivors, and cutoff values of coagulation parameters predictive of mortality. Overall mortality was 22%. The prevalence of hypocoagulation according to rotational thromboelastometry decreased from 35.8% (T0) to 15.9% (T3). Lower fibrinogen levels, hyperfibrinolysis and fibrinolysis shutdown in the early period (T0-T1) following TBI were associated with higher mortality. Optimal cutoff values were identified: fibrin polymerization thromboelastometry (FIBTEM) clot amplitude at 10min after clotting time ≤ 13mm at T0 and FIBTEM clot amplitude at 10min after clotting time ≤ 16.5mm at T1 increased the odds of death by 6.0 (95% confidence interval [CI] 1.54-23.13, p = 0.010) and 9.7 (95% CI 2.06-45.36, p = 0.004), respectively. FIBTEM maximum clot firmness ≤ 14.5mm at T0 and FIBTEM maximum clot firmness ≤ 18.5mm at T1 increased the odds of death by 6.3 (95% CI 1.56-25.69, p = 0.010) and 9.1 (95% CI 1.88-44.39, p = 0.006). Fibrinogen < 3g/L on postoperative day 1 (T1) was associated with a 9.5-fold increase of in-hospital mortality (95% CI 1.72-52.98, p = 0.01). Increased clotting activity was not associated with mortality. Rotational thromboelastometry adds important information for identifying patients with TBI at increased risk of death. Early fibrinogen-related coagulation disorders are associated with mortality of patients with TBI undergoing major neurosurgical procedures. Maintenance of higher fibrinogen levels might be necessary for neurosurgical patients with acute TBI.

The role of fibrinogen in postpartum hemorrhage.

Postpartum hemorrhage (PPH) is the leading cause of maternal death worldwide (WHO), with almost 60000 deaths annually. Pregnancy is a prothrombotic state with increased levels of several coagulation factors to protect the parturient from bleeding problems during delivery. Fibrinogen has a significant role in coagulation and bleeding. Studies have pointed out that lower fibrinogen levels before delivery, but also at the initiation of PPH, are predictive of major hemorrhage. Early, the goal-directed fibrinogen concentrate therapy might be very useful in a subgroup of patients with serious PPH. This review aims to summarize the current literature on fibrinogen during PPH.

Beyond uterine atony: characterizing postpartum hemorrhage coagulopathy

Postpartum hemorrhage is a leading cause of morbidity and mortality worldwide, yet the associated early coagulopathy is not well defined. We hypothesized that women who develop postpartum hemorrhage have a distinct derangement of thrombin generation and coagulation factors compared with postpartum women without postpartum hemorrhage. This prospective study of pregnant patients with postpartum hemorrhage was completed at a single urban hospital. Blood was drawn on postpartum hemorrhage diagnosis and 2 and 4 hours later. Assays of patients with postpartum hemorrhage included thrombelastography, whole blood thrombin generation, coagulation factor activity, tissue factor levels and activity, and tissue factor pathway inhibitor levels, which were compared with that of patients without postpartum hemorrhage. A total of 81 patients were included in this study. Of those patients, 66 had postpartum hemorrhage, and 15 served as controls. Compared with patients without PPH, patients with postpartum hemorrhage had lower fibrinogen levels (469.0 mg/dL vs 411.0 mg/dL; P=.02), increased tissue plasminogen activator resistance (fibrinolysis 30 minutes after maximal clot strength: 8.7% vs 4.2%; P=.02), decreased peak thrombin concentration (150.2 nM vs 40.7 nM; P=.01), and decreased maximal rate of thrombin generation (60.1 nM/minute vs 2.8 nM/minute; P=.02). Furthermore, compared with patients without postpartum hemorrhage, patients with postpartum hemorrhage had decreased tissue factor levels (444.3 pg/mL vs 267.1 pg/mL; P=.02) and increased tissue factor pathway inhibitor levels (0.6 U/mL vs 0.8 U/mL; P=.04), with decreased tissue factor pathway inhibitor ratios (624 vs 299; P=.01). PPH is not only an issue of uterine tone and mechanical bleeding but also a distinct coagulopathy that is characterized by decreased fibrinogen level, clot breakdown resistance, and markedly low thrombin generation. This pathology seemed to be driven by low tissue factor and high tissue factor pathway inhibitor levels.

Association between hypomagnesemia and coagulopathy in sepsis: a retrospective observational study

BackgroundHypomagnesemia reportedly has significant associations with poor clinical outcomes such as increased mortality and septic shock in patients with sepsis. Although the mechanism underlying these outcomes mostly remains unclear, some experimental data suggest that magnesium deficiency could potentiate coagulation activation in sepsis. However, in sepsis, the association between serum magnesium levels and coagulopathy, including disseminated intravascular coagulation (DIC), remains unknown. Thus, we aimed to investigate the relationship between serum magnesium levels and coagulation status and the association between hypomagnesemia and DIC in patients with sepsis.MethodsThis retrospective observational study was conducted at the intensive care unit (ICU) of a university hospital from June 2011 to December 2017. Patients older than 19 years who met the Sepsis-3 definition were included. We categorized patients into three groups according to their serum magnesium levels: hypomagnesemia (< 1.6 mg/dL), normal serum magnesium level (1.6–2.4 mg/dL), and hypermagnesemia (> 2.4 mg/dL). We investigated the association between serum magnesium levels and overt DIC at the time of ICU admission according to the criteria of the International Society on Thrombosis and Haemostasis.ResultsAmong 753 patients included in this study, 181 had DIC, 105 had hypomagnesemia, 552 had normal serum magnesium levels, and 96 had hypermagnesemia. Patients with hypomagnesemia had a more activated coagulation status indicated by lower platelet counts, lower fibrinogen levels, higher prothrombin time-international normalized ratios, higher thrombin-antithrombin complex, and more frequent DIC than those with normal serum magnesium levels and hypermagnesemia (DIC: 41.9% vs. 20.6% vs. 24.0%, P < 0.001). The coagulation status in patients with hypomagnesemia was more augmented toward suppressed fibrinolysis than that in patients with normal serum magnesium levels and hypermagnesemia. Multivariate logistic regression revealed that hypomagnesemia was independently associated with DIC (odds ratio, 1.69; 95% confidence interval, 1.00–2.84; P = 0.048) after adjusting for several confounding variables.ConclusionsPatients with hypomagnesemia had a significantly activated coagulation status and suppressed fibrinolysis. Hypomagnesemia was independently associated with DIC in patients with sepsis. Therefore, the treatment of hypomagnesemia may be a potential therapeutic strategy for the treatment of coagulopathy in sepsis.

494 Low plasma fibrinogen levels are associated with poor prognosis in cutaneous angiosarcoma of the head and neck

Angiosarcomas are malignant vascular tumors that account for 2% of all soft-tissue sarcomas. Due to the rarity of angiosarcomas, the prognostic factors are seldom reported. Here, we investigated plasma fibrinogen levels as a prognostic factor for angiosarcoma of the head and neck (ASHN). This retrospective study reviewed a cohort of patients histologically diagnosed with ASHN at Nagoya University Hospital between April 2006 and July 2019. The 22 patients with ASHN included in the present study. The cutoff value of plasma fibrinogen levels was determined to be 257 mg/dL. The Kaplan–Meier curve showed the OS rate to be significantly higher in the high plasma fibrinogen group than in the low plasma fibrinogen group (p=0.0027). The univariable model showed that patients with low plasma fibrinogen levels had a significantly poor OS [hazard ratio 6.78, 95% confidence interval 1.63 to 28.2, p-value of 0.008503]. Recently, high plasma fibrinogen levels were reported to predict poor prognosis in several malignancies. Unexpectedly, the present study suggests that low plasma fibrinogen levels predict poor prognosis. ASHN is an extremely hemorrhagic tumor. From repeated microbleeds and blood coagulation in ASHN lesions, plasma fibrinogen is considered to be consumed and to decrease in patients with ASHN. Therefore, we speculate that the reduced plasma fibrinogen levels might reflect tumor burden indirectly. In conclusion, the present study suggests that pre-treatment plasma fibrinogen levels are a useful prognostic factor for ASHN that may reflect tumor burden.

The indicators for early blood transfusion in patients with placental abruption with intrauterine fetal death: a retrospective review

BackgroundPlacental abruption (PA) with intrauterine fetal death (IUFD) is associated with a high risk of postpartum hemorrhage (PPH) resulting from severe disseminated intravascular coagulation (DIC). Therefore, blood products that are sufficient for coagulation factor replacement must be prepared, and delivery should occur at referral medical institutions that are equipped with sufficient blood products and emergency transfusion protocols. We retrospectively reviewed the records of patients with PA and IUFD (PA-IUFD) to identify possible factors that may indicate the need for early blood transfusion and investigated whether the Japanese scoring system for PPH can be applied in such cases.MethodsWe used a database of 16,058 pregnant patients who delivered at Yokohama City University Medical Center between January 2000 and February 2016. Thirty-three patients were diagnosed with PA-IUFD before delivery and categorized into two groups–blood transfusion and non-transfusion–to compare the maternal characteristics and pregnancy outcomes.ResultsIn patients with PA-IUFD, the transfusion group exhibited significantly more blood loss; lower fibrinogen levels and platelet counts; higher levels of fibrin degradation products (FDP), D-dimer, and prothrombin time; and a tendency for tachycardia on admission, compared to the non-transfusion group. Many patients in the transfusion group had normal fibrinogen levels on admission but later displayed markedly decreased fibrinogen levels. The Japan Society of Obstetrics and Gynecology (JSOG) DIC score was significantly higher in the transfusion than in the non-transfusion group.ConclusionsIn PA-IUFD, the fibrinogen level, platelet count, D-dimer, FDP, heart rate, and JSOG DIC score on admission may indicate the need for blood transfusion. However, even with normal fibrinogen levels on admission, continuous monitoring is indispensable for identifying progressive fibrinogen reductions in patients with PA-IUFD.

Prognosis of Hyperviscosity Syndrome in Newly Diagnosed Multiple Myeloma in Modern-Era Therapy: A Real-Life Monocentric Study

Introduction Hyperviscosity syndrome (HVS) is a rare and life-threatening complication of multiple myeloma (MM). HVS was a criterion of MM treatment in the previous international recommendation, but it was withdrawn in the IMWG 2014 guidelines. Moreover, studies about the prognosis of HVS in modern-era therapy are missing. Our objective is to describe MM patients with HVS and to evaluate its prognosis impact. Methods Inclusion criteria for the case were patients aged ≥18 years newly diagnosed with MM with HVS in Saint Louis Hospital, Paris, France, between 2011 and 2021. HVS diagnosis was based on presence of neurological signs and/or evaluation by ophthalmologic examination for symptoms or high spike. Two controls were selected for each case in the same period with the best fit set on age, sex, year of diagnosis, and front-line treatment. The primary outcome was overall survival. Results Thirty-nine MM patients with HVS (7 severe forms and 32 ophthalmologic confirmation) were included with a median age of 59 years (IQR 51-68). The main isotype of immunoglobulin was IgG (69%, median 61 g/L), followed by IgA (28%, median 41 g/L). Translocation t(11;14), presented in 37% of the cohort (13 IgG and 1 IgA), was associated with a higher spike level than other patients (for IgG: 71 versus 59 g/L, p=0.0001). HVS clinical presentation was heterogenous: 23% asymptomatic (median spike at 60 and 44 g/L for IgG and IgA), 59% mild (epistaxis, headache, blurry vision) and 18% severe with neurological signs, respectively. Fifteen (38%) patients required ICU admission: severe HVS for 6, association with other complications for 6 and only for therapeutic plasma exchange (TPE) realization for 3. No major ischemic or bleeding was observed at diagnosis. For HVS management, in addition to myeloma therapy, TPE was performed for 35 patients (92%), which was well tolerated, and 3 patients received only steroids. One month after HVS diagnosis and care, no rebound effect of monoclonal spike was observed and 33 (84%) patients had complete clinical recovery. Three patients (8%) died, and three (16%) had an ophthalmic sequela of HVS. All patients had at least one CRAB criterion except one who had two focal lesions on MRI. Most of the patients received bortezomib and high-dose steroids (95%) associated with an immunomodulatory drug (43%) or alkylating agents (42%). Two patients (5%) received Daratumumab. For younger patients (< 65 years), 21 patients (84%) received autologous stem cell transplantation upfront. After the exclusion of one patient with an early loss in follow-up (< 3 months), the global response rate (≥PR) was 92%. The median time to the subsequent treatment was 2.1 years (95%IC 1.4-3.4). At subsequent relapse, 6 patients (3 IgG, 2 IgA and 1 IgM) had HVS recurrence. With a median follow-up of 5.2 years, the median OS for HVS patients was 3.6 years (95%CI 2.7-not reached). Among patients older than 65 years, the early mortality rate (< 3 months) was 21%. Presence of > 5% of blood plasma cell (HR 6.06, p=<.01), high-risk cytogenetics (HR 3, p=0.03), R-ISS3 score (HR 3.3, p=0.04), and LDH above normal level (HR 3.6, p=0.01) shortened the OS. Compared to controls, HVS MM patients had a higher spike level at diagnosis, higher ISS3 rate, higher bone marrow plasma cells and lower fibrinogen levels (Table). HVS myeloma had dismal OS compared to controls (median: 3.6 vs. 7.7 years, p=0.01, Figure). In a multivariate analysis of pooled HVS and control patients, HVS (HR 2.7, 95%CI 1.4-5.4, p=0.004) and high-risk cytogenetics (HR 2.8, 95%CI 1.4-5.7, p=0.005) were two independent adverse factors for OS. HVS remained an independent factor for OS for myeloma with the addition of the ISS score or R-ISS score in the model. Conclusion HVS at myeloma diagnosis is a rare but urgent complication associated with high lethality in older patients. HVS was associated with high tumor burden and dismal survival, independent of principal prognosis scores in modern treatment era. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Inflammatory and Coagulation Biomarkers in Patients with Sars-COV2 Infection Receiving COVID-19 Convalescent Plasma: The Bergamo Registry

INTRODUCTION: Passive immunization therapy with convalescent plasma has been successfully used in prior viral pandemics. For these reasons, from the beginning of the COVID-19 outbreak in March 2020, our hospital has been actively involved in the collection of COVID-19 convalescent plasma (CCP) and its administration to hospitalized COVID-19 patients. We set up a registry to collect prospectively clinical and laboratory data, and blood samples, from CCP donors and CCP recipients (IMMUNOCOVID registry, clinicaltrials.gov identifier #04614012, approved by the local Ethics Committee). In the present study, in a cohort of COVID-19 plasma recipients, we prospectively assessed the effect of CCP treatment on different clinical and laboratory parameters, including anti-SARS-CoV2 IgG antibody (Ab) levels, inflammatory and coagulation biomarkers. METHODS: Hospitalized COVID-19 patients were treated with maximum 3 CCP units (200 ml/unit), each given every other day, and followed-up clinically for 30 days after first CCP infusion. Venous blood samples were collected on days 0 (D0), 3 (D3), and 5 (D5) before each CCP administration, and on day 7 (D7) after the first administration. The following laboratory measurements were performed: IgG anti-SARS-CoV2 Nucleocapsid protein (anti-N) and IgG anti-Spike protein (anti-S) Ab (quantitative assay); fibrinogen, D-dimer, C reactive protein (CRP), procalcitonin, LDH, Hb, blood cell counts, AST, ALT, creatinine, and GFR. Results are expressed as median and 5th-95th percentile range. RESULTS: From May 2020 to April 2022, 334 (103F/231M) hospitalized COVID-19 patients received CCP treatment. The median age of the cohort was 67 (41-86) years; 89 were admitted to the intensive care unit (ICU) and 245 were in the medical general ward (non-ICU patients). Among this cohort, 255 patients received 3 CCP units, 47 patients 2 CCP units, and 32 only 1 CCP unit. The median time from hospital admission to CCP infusion was 2 days (0 - 70) and a total of 890 CCP units were infused with a median value of 153 AU/ml (100-400) anti-S IgG Ab. Treatment with CCP led to a significant (p<0.001) 7.1-fold increase in anti-S and 1.7-fold increase in anti-N Ab at day 7. By multivariate analysis, the percentage increase in anti-S Ab [i.e., delta = (D7-D0/D0)] was significantly (p<0.05) associated with younger age (beta=-0.181) and male gender (beta=-0.195), but not with disease severity (ICU vs non-ICU), with the highest increment occurring in males <60 years (9.8-fold). Regarding inflammatory and coagulation biomarkers, at enrollment, CRP, neutrophil count, LDH, procalcitonin, fibrinogen and D-dimer levels were all significantly elevated, while lymphocytes and Hb were significantly lower than the normal range. Compared to non-ICU patients, the ICU group, at D0, had higher levels (p<0.05) of inflammatory biomarkers and D-dimer, and significantly lower (p<0.05) lymphocyte count, Hb, and fibrinogen level. In the subgroup of 255 patients who received 3 CCP infusions, in parallel to anti-SARS-CoV2 IgG increment, a significant (p<0.001) reduction in CRP, LDH, ferritin, procalcitonin, and fibrinogen levels occurred. This was particularly apparent in the non-ICU subgroup. Among the whole cohort of 334 patients, 66 had cancer (28 hematological tumors, 33 solid tumors, and 5 both hematological and solid tumors). The median age of this subgroup was 70 years (49-88), with 16 of them admitted to ICU. In this category of patients, a significant increase (p<0.01) of both anti-S (4.7-fold) and anti-N (1.3-fold) IgG occurred, not differently from the rest of patients. Four out of 890 CCP infusions were associated with a mild adverse event with a resolution in 24 hours. Regarding overall mortality, 48 patients (14%) died after 30 days follow-up [15F/33M, median age 64 years (40-81)], 16 of them were in ICU. CONCLUSIONS: In our study, CCP treatment leads to an increase in antibody levels in the recipients, particularly in males <60 years. This occurs also in subjects with cancer and those with severe COVID-19. Notably, the increase of humoral immune response is associated with a decrease in inflammatory parameters and fibrinogen levels. The low incidence of adverse events observed supports the safety of CCP administration.

Fibrinogen and antithrombin III are associated with in-hospital mortality among critically ill patients with acute kidney injury

Objectives Coagulation factors participates in the inflammatory cascade, known to play a crucial role in the development of acute kidney injury (AKI). Thus, it’s likely that some factors may be associated with AKI. Among them, low levels of fibrinogen and antithrombin III (ATIII) activity have been proved to increase mortality in patients with sepsis. Moreover, they are also reported to be associated with higher incidence of AKI. However, the association between coagulation parameters, especially fibrinogen and ATIII, and prognosis of AKI has not been examined. Methods Data were acquired from Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV) version 1.0. Cox proportional hazards regression model was used to estimate the relationship between coagulation parameters and in-hospital mortality in critically ill patients with AKI. Subgroup analysis was also conducted to assess the robustness of the association. Restricted cubic spline (RCS) curve was utilized to examine the nonlinear relationships between fibrinogen or ATIII and in-hospital mortality. Kaplan–Meier method was used to estimate cumulative incidence of mortality by fibrinogen or ATIII levels. Receiver-operating characteristic (ROC) curve was plotted and area under curve was calculated to evaluate predictive ability of fibrinogen or ATIII. Results A total of 5914 eligible patients were enrolled in fibrinogen cohort study and 115 patients were eligible for ATIII cohort study. The baseline of low fibrinogen (<150 mg/dL) or ATIII (<80%) activity was associated with significantly higher in-hospital mortality (fibrinogen HR [95% CIs] 2.01 [1.79, 2.27]; ATIII 3.73 [1.11, 12.54]). The HR [95% CIs] of low fibrinogen remained significant 1.29 (1.13, 1.48) in multivariate analysis. The RCS curve showed nearly linear relationship. Subgroup analysis also proved the robustness of the association between fibrinogen and in-hospital mortality. Kaplan–Meier survival curve and ROC demonstrated the predictive capability of fibrinogen and ATIII. Conclusion Low fibrinogen is an independent predictor of in-hospital mortality in critically ill patients with AKI. Low ATIII activity is also likely to impact the risk of in-hospital death.