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Introduction: Pit viper envenomation may cause coagulopathy. The coagulopathy has been treated with crotalidae polyvalent immune fragment antigen-binding (Fab) ovine antivenom for the last few decades in the United States and usually corrects the acute coagulopathy within hours. Days after receiving Fab, coagulopathy may recur in approximately half of the patients. Another divalent antivenom, crotalidae immune F(ab’)2 (equine)–F(ab’)2–was approved by the US Food and Drug Administration for the treatment of pit viper envenomation. F(ab’)2 is composed of two linked antigen-binding fragments of immunoglobulin G. Several studies have demonstrated that F(ab’)2 is less likely to be associated with recurrence. There is no reported case of F(ab’)2-associated late coagulopathy in very young patients. We report the first case of recurrence associated with F(ab’)2 use in a preschool-age child.Case Report: A preschool-age male developed leg swelling and hypofibrinogenemia after rattlesnake envenomation. F(ab’)2 was administered to stabilize the leg edema and to correct the hypofibrinogenemia. The patient improved clinically and was discharged on hospital day five. Seven days after the rattlesnake envenomation, he returned to the emergency department as instructed. Laboratory data revealed recurrent hypofibrinogenemia.Conclusion: There are two antivenoms available in the US to treat crotalid envenomation, Fab and F(ab’)2. F(ab’)2 is less likely to be associated with recurrent coagulopathy in comparison to Fab. We report the first case of recurrence associated with F(ab’)2 in a preschool-age child. It is important that the emergency physician be aware of potential F(ab’)2-associated recurrent coagulopathy. Adult and pediatric patients may need to follow up to be evaluated for hypofibrinogenemia and/or thrombocytopenia after receiving F(ab’)2.

Tocilizumab (TCZ) which is a humanized interleukin (IL)-6 receptor antibody has been increasingly widespread used in rheumatology practice. TCZ-related hypofibrinogenemia is a not well-described side effect, but awareness seems to be incresing as publications on this topic are also becoming more frequent. Our aim in this study was to determine the frequency, timing, and approach to TCZ-related hypofibrinogenemia in rheumatic diseases. We retrospectively screened our patients who received TCZ for inflammatory rheumatic diseases and studied serum fibrinogen at least once before and/or after drug administration. We recorded and analyzed demographic features (age, gender, diagnosis), comorbidities, laboratory parameters, management, and outcome data. 30 patients who received TCZ due to rheumatological diseases and had at least one fibrinogen level were included in this study. 73.3% were female and median age was found to be 65 (42–82) years, with median disease duration of 148 (36–500) months. 90% of the patients received TCZ for RA and 10% for GCA. We examined the fibrogen levels at an average of 24 months (min 1 max 108) following the start of TCZ treatment. The study group was divided into those with normal fibrinogen levels (normal fibrinogen group) and those with low fibrinogen levels (lowfibrinogen group). In total, hypofibrinogenemia was found in 14 (46.6%) patients. Median serum fibrinogen level in the low fibrinogen group after TCZ was calculated to be 151.5 mg/dl (min 92 max 171). Most patients were asymptomatic (71.4%). Ecchymoses were in seen 4 (28,6%) patients. No major bleeding were seen. TCZ was discontinued in 5 out of 14 patients (35.7%), while 9 out of 14 patients (64.3%) were closely followed. Outcomes regarding fibrinogen levels (11 out of 14) were as follows: increase in 4 and not checked in one after cessation of the drug, 3 spontaneous increases under the drug, and 3 persistently low levels on TCZ treatment. We found no difference in terms of gender (p = 0.417), platelets (p = 0.343), ESR (p = 0.448), and CRP (p = 0.660) at the time of TCZ initiation between groups. TCZ-related hypofibrinogenemia is more frequent than expected with occurence in both the early and late stages of treatment. Further research is required to determine whether to regularly measure fibrinogen levels in patients using TCZ and how to treat patients with hypofibrinogenemia. [ABSTRACT FROM AUTHOR]

Background: In clinical practice, the incidence of hypofibrinogenemia (HF) after tigecycline (TGC) treatment significantly exceeds the probability claimed by drug manufacturers. Objective: We aimed to identify the risk factors for TGC-associated HF and develop prediction and survival models for TGC-associated HF and the timing of TGC-associated HF. Methods: This single-center retrospective cohort study included 222 patients who were prescribed TGC. First, we used binary logistic regression to screen the independent factors influencing TGC-associated HF, which were used as predictors to train the extreme gradient boosting (XGBoost) model. Receiver operating characteristic curve (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA) were used to evaluate the performance of the model in the verification cohort. Subsequently, we conducted survival analysis using the random survival forest (RSF) algorithm. A consistency index (C-index) was used to evaluate the accuracy of the RSF model in the verification cohort. Results: Binary logistic regression identified nine independent factors influencing TGC-associated HF, and the XGBoost model was constructed using these nine predictors. The ROC and calibration curves showed that the model had good discrimination (areas under the ROC curves (AUC) = 0.792 [95% confidence interval (CI), 0.668–0.915]) and calibration ability. In addition, DCA and CICA demonstrated good clinical practicability of this model. Notably, the RSF model showed good accuracy (C-index = 0.746 [95%CI, 0.652–0.820]) in the verification cohort. Stratifying patients treated with TGC based on the RSF model revealed a statistically significant difference in the mean survival time between the low- and high-risk groups. Conclusions: The XGBoost model effectively predicts the risk of TGC-associated HF, whereas the RSF model has advantages in risk stratification. These two models have significant clinical practical value, with the potential to reduce the risk of TGC therapy. [ABSTRACT FROM AUTHOR]

Background: Surgery often leads to bleeding associated with hypofibrinogenemia. Supplementation with fibrinogen concentrate appears to be effective and safe, although findings from studies are inconsistent. The primary aim of this study was to assess the safety of fibrinogen concentrate during the perioperative period. Methods: This single-centre, prospective, observational study included adult patients undergoing scheduled or emergency surgery related to bleeding coagulopathy and the administration of fibrinogen concentrate. Patients were followed until their discharge from the institution. Comprehensive data were collected, including age, sex, type of surgery, associated comorbidities, anticoagulant and/or anti-aggregating therapy, and the number of blood transfusions. Laboratory data on plasma fibrinogen concentration, haemoglobin, and platelet count before and after surgery were also collected. The primary outcomes were the mortality rate at discharge and any reported thrombotic or thromboembolic events, including deep vein thrombosis, pulmonary embolism, and myocardial infarction. Results: The study included 91 adult patients who had undergone surgery, with 29 surgeries (32%) conducted in an emergency setting. The mean age was 59.2 years, and 53.8% were male. Major bleeding occurred in 29 cases, mainly in older males and those on anticoagulant therapy. The pre-operative fibrinogen level averaged 161 mg/dL, and the average dosage of fibrinogen concentrate administered was 2.7 g. Eight patients died (8.8%), mostly due to septic or cardiogenic shock, with deaths being more frequent in emergency settings. Thromboembolic events occurred in eight patients, none of whom died. No additional adverse events directly related to the administration of fibrinogen concentrate were reported. Conclusions: Our findings suggest a favourable safety profile for fibrinogen concentrate in surgical patients, as evidenced by a low incidence of deaths and thromboembolic events, which were primarily attributed to other factors. Future research should strive to increase statistical robustness to further illuminate clinically significant patient safety measures. [ABSTRACT FROM AUTHOR]

Abstract Background In clinical practice, the incidence of hypofibrinogenemia (HF) after tigecycline (TGC) treatment significantly exceeds the probability claimed by drug manufacturers. Objective We aimed to identify the risk factors for TGC-associated HF and develop prediction and survival models for TGC-associated HF and the timing of TGC-associated HF. Methods This single-center retrospective cohort study included 222 patients who were prescribed TGC. First, we used binary logistic regression to screen the independent factors influencing TGC-associated HF, which were used as predictors to train the extreme gradient boosting (XGBoost) model. Receiver operating characteristic curve (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve analysis (CICA) were used to evaluate the performance of the model in the verification cohort. Subsequently, we conducted survival analysis using the random survival forest (RSF) algorithm. A consistency index (C-index) was used to evaluate the accuracy of the RSF model in the verification cohort. Results Binary logistic regression identified nine independent factors influencing TGC-associated HF, and the XGBoost model was constructed using these nine predictors. The ROC and calibration curves showed that the model had good discrimination (areas under the ROC curves (AUC) = 0.792 [95% confidence interval (CI), 0.668–0.915]) and calibration ability. In addition, DCA and CICA demonstrated good clinical practicability of this model. Notably, the RSF model showed good accuracy (C-index = 0.746 [95%CI, 0.652–0.820]) in the verification cohort. Stratifying patients treated with TGC based on the RSF model revealed a statistically significant difference in the mean survival time between the low- and high-risk groups. Conclusions The XGBoost model effectively predicts the risk of TGC-associated HF, whereas the RSF model has advantages in risk stratification. These two models have significant clinical practical value, with the potential to reduce the risk of TGC therapy.

Chiari I Malformation and Intramedullary Hemorrhage in a Female Patient with Klippel Trenaunay Syndrome: A Rare Case Report Study

A minority of snake envenomations in the United States involve non-native snakes. In this report, we describe what we believe is the first documented human envenoming from an emerald horned pitviper, Ophryacus smaragdinus. A previously healthy 36-year-old woman was bitten on her left index finger by a captive emerald horned pitviper she was medicating at work. Swelling to the entire hand was present on emergency department arrival. She had no systemic symptoms and her initial laboratory studies were unremarkable. The affected limb was elevated. We administered five vials of Antivipmyn TRIⓇ (Bioclon), which specifically lists Ophryacus among the envenomations for which it is indicated. She developed pruritus and was treated with IV diphenhydramine and famotidine. Her swelling improved, but her repeat laboratory studies were notable for a platelet count of 102 K/µL and a fibrinogen level of 116 mg/dL. She declined additional antivenom because of the previous allergic reaction. She was admitted for further monitoring and pain control. Subsequent laboratory tests were better, but a small hemorrhagic bleb developed at the bite site. She was discharged the next day and followed up as an outpatient. Her swelling had resolved, her bleb had healed, and her laboratory studies continued to improve. Emergency physicians may be required to treat bites from non-native snakes. Many of these bites will warrant treatment with non–U.S. Food and Drug Administration–approved antivenoms. Consultation with a regional poison center or medical toxicologist may be necessary to procure the proper antivenom. [ABSTRACT FROM AUTHOR]

Tigecycline-associated hypofibrinogenemia has been reported as an important adverse effect in recent years, but controlled studies minimizing confounding factors are needed. The objective of our study was to assess changes in fibrinogen levels in patients for hospitalization, comparing two antibiotic episodes (tigecycline and other) within the same patients. The retrospective, self-controlled case series study was conducted at our University Hospitals. The study compared the change in fibrinogen levels during the patient's hospitalization for tigecycline (TigePer) and another antibiotic period (OtherPer). In addition, bleeding events, bleeding risk (determined by the IMPROVE bleeding risk score), as well as 15- and 30-day mortality rates between TigePer and OtherPer were compared. The study enrolled 50 patients with 100 episodes of antibiotic treatment. The median age (interquartile range) of the patients was 68.5 (21.5) years, and 38 % were female. As compared to OtherPer, TigePer had a statistically significant reduction in fibrinogen levels (p < 0.001), with a hypofibrinogenemia rate of 40 % in TigePer as compared to 2 % in OtherPer (p < 0.001). TigePer demonstrated a significantly higher 15-day mortality rate (p = 0.006). No significant differences were observed between the two periods in terms of bleeding risk, rate of bleeding events, and 30-day mortality rate (p > 0.05). Hypofibrinogenemia and other coagulopathies, without associated bleeding events, are more frequently observed in patients receiving tigecycline. Therefore, it is crucial for clinicians to monitor fibrinogen levels during tigecycline use. • Patients undergoing tigecycline treatment are prone to low fibrinogen levels. • High incidence of hypofibrinogenemia is associated with the use of tigecycline. • Tigecycline can elevate INR levels without causing bleeding events or risk. • The 30-day mortality rate did not differ between the groups. [ABSTRACT FROM AUTHOR]

Abstract Congenital fibrinogen disorders are a group of coagulation deficiencies caused by fibrinogen defects and are divided into four types, including afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia. In this study, we collected a family with hypofibrinogenemia, and genetics analysis identify a novel pathogenic variants (c.668G > C, p.Arg223Thr) in the FGG gene. And electron microscope observation revealed significant changes in the ultrastructure of fibrin of the proband. Our research expands the phenotypic and genetic spectrum associated with the FGG gene, which would facilitate in genetic counselling and prenatal genetic diagnosis.

Klippel Trenaunay Syndrome (KTS) is a rare vascular disorder characterized by a triad of symptoms including capillary malformations known as port-wine stains, venous varicosities, and osseous- or soft-tissue hypertrophy of the affected extremity. The etiology remains ambiguous, although genetic factors have been implicated. We present a case of a 27-year-old female with KTS who presented with progressive right sided paresis. An intramedullary hemorrhage and syringomyelia of the cervical spine, along with a Chiari I malformation were identified in brain and cervical spine MRI. Her laboratory tests revealed significant coagulopathy. Our patient was initially treated conservatively before she discharged for both a scheduled neurosurgical procedure and splenectomy. [ABSTRACT FROM AUTHOR]

The Giant cell arteritis (GCA) is the most common form of systemic vasculitis in elderly patients. The treatment includes high doses of steroids and interleukin (IL)-6 inhibitor tocilizumab, especially in refractory or relapsing disease or in cases where there is an increased risk of steroid-related adverse events. This report discusses the case of a patient with giant cell arteritis who underwent treatment with tocilizumab for four years. The treatment was successful and resulted in clinical remission. However, four years after starting the therapy, the patient developed spontaneous hematomas on their extremities. After further investigation, it was discovered that the patient had developed thrombocytopenia and hypofibrinogenemia, which required substitution therapy. Malignancy and immune-mediated causes of hypofibrinogenemia and thrombocytopenia were ruled out. The patient experienced an extended period of hypofibrinogenemia that lasted for two months after the last dose of tocilizumab. During this time, the levels of CRP remained very low. This could be because the continued inhibition of IL-6 caused impaired hepatic synthesis of acute phase response proteins, which led to low fibrinogen and CRP levels in serum. The purpose of this case-based review is to emphasize the necessity of regular fibrinogen check-ups in GCA patients treated with tocilizumab.

Abstract Background Preeclampsia complicated with hypofibrinogenemia is a rare disorder. We report two cases of severe preeclampsia complicated with hypofibrinogenemia followed by postpartum haemorrhage (PPH). Case Two women diagnosed as preeclampsia and hypofibrinogenemia developed severe PPH after undergoing Cesarean sections. Besides supplement with fibrinogen concentrate and supportive treatment, the second patient got administration of heparin after delivery and bleeding was stopped. The haemorrhage in case 1 didn’t disappear until an hysterectomy. The two patients both recovered and were discharged soon. Conclusions Severe preeclampsia patients with hypofibrinogenemia could suffer PPH. It’s necessary to detect and master coagulation function. Heparin could be considered to balance hypercoagulation and hypocoagulation to avoid catastrophic haemorrhage and hysterectomy.

Summary: Congenital fibrinogen disorders or CFDs are heterogenous, both in clinical manifestation and array of culprit molecular lesions. Correlations between phenotype and genotype remain poorly defined. This review examines the genetic landscape discovered to date for this rare condition. The question of a possible oligogenic model of inheritance influencing phenotypic heterogeneity is raised, with discussion of the benefits and challenges of sequencing technology used to enhance discovery in this space. Considerable work lies ahead in order to achieve diagnostic and prognostic precision and subsequently provide targeted management to this complex cohort of patients. [ABSTRACT FROM AUTHOR]

Human fibrinogen concentrate (Fibryga) received temporary approval for fibrinogen replacement therapy in France (2017), with subsequent full approval for congenital and acquired hypofibrinogenemia. We evaluated real‐world use for on‐demand treatment of bleeding and prophylaxis to enhance our knowledge on fibrinogen concentrate as an option for fibrinogen replacement. Data were retrospectively collected from adult and pediatric patients with fibrinogen deficiency. The primary end point was indication for fibrinogen concentrate use; the secondary end point was treatment success for on‐demand treatment/perioperative prophylaxis. The study included 150 adult (median age, 62 years; range, 18‐94 years) and 50 pediatric (median age, 3 years; range, 0.01‐17 years) patients with acquired fibrinogen deficiency. Fibrinogen concentrate was administered to 47.3% for nonsurgical bleeding, 22.7% for surgical bleeding, and 30.0% for perioperative prophylaxis in adult patients, and to 4.0% for surgical bleeding and 96.0% for perioperative prophylaxis in pediatric patients. Cardiac surgeries accounted for 79.5%/75.0% perioperative prophylaxis and 82.4%/100.0% surgical bleeding cases in adult/pediatric patients, respectively. The mean ± standard deviation (SD, median) total fibrinogen doses were 3.06 ± 1.69 g (32.61 mg/kg), 2.09 ± 1.36 g (22.99 mg/kg), and 2.36 ± 1.25 g (29.67 mg/kg) for adult nonsurgical bleeding, surgical bleeding, and perioperative prophylaxis, respectively; doses of 0.75 ± 0.35 g (47.64 mg/kg) and 0.83 ± 0.62 g (55.56 mg/kg) were used for pediatric surgical bleeding and perioperative prophylaxis, respectively. Treatment success was 85.7%/97.1/93.3% in adults and 50.0%/87.5% in pediatrics for nonsurgical bleeding (adults only), surgical bleeding, and perioperative prophylaxis, respectively. Fibrinogen concentrate demonstrated favorable effectiveness and safety across the age groups. This study contributes to evidence supporting fibrinogen concentrate for bleeding control/prevention in real‐world clinical practice, particularly for patients with acquired fibrinogen deficiency. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia complicated with hypofibrinogenemia is a rare disorder. We report two cases of severe preeclampsia complicated with hypofibrinogenemia followed by postpartum haemorrhage (PPH). Case: Two women diagnosed as preeclampsia and hypofibrinogenemia developed severe PPH after undergoing Cesarean sections. Besides supplement with fibrinogen concentrate and supportive treatment, the second patient got administration of heparin after delivery and bleeding was stopped. The haemorrhage in case 1 didn't disappear until an hysterectomy. The two patients both recovered and were discharged soon. Conclusions: Severe preeclampsia patients with hypofibrinogenemia could suffer PPH. It's necessary to detect and master coagulation function. Heparin could be considered to balance hypercoagulation and hypocoagulation to avoid catastrophic haemorrhage and hysterectomy. [ABSTRACT FROM AUTHOR]

Introduction: Uncontrolled hemorrhage accounts for up to 40% of trauma-related mortality. Previous reports demonstrate that decreased fibrinogen levels during traumatic hemorrhage are associated with worse outcomes. Cryoprecipitate is used to replace fibrinogen for patients in hemorrhagic shock undergoing massive transfusion (MT), though the optimal ratio of cryoprecipitate to fresh frozen plasma (FFP), packed red blood cells (PRBCs), and platelets remains undefined. The purpose of this study is to investigate the effect of admission fibrinogen level and the use of cryoprecipitate on outcomes in trauma patients undergoing MT. Methods: A prospective practice management guideline was established to obtain fibrinogen levels on adult trauma patients undergoing MT at a level I trauma center from December 2019 to December 2021. Ten units of cryoprecipitate were administered every other round of MT. Thromboelastography (TEG) was also obtained at the initiation and completion of MT. Patient demographic, injury, transfusion, and outcome data were collected. Hypofibrinogenemic (<200 mg/dL) patients at initiation of MT were compared to patients with a level of 200 mg/dL or greater. Results: A total of 96 out of 130 patients met criteria and underwent MT with a median admission fibrinogen of 170.5 mg/dL. Hypofibrinogenemia was associated with elevated INR (1.26 vs 1.13, P <.001) and abnormal TEG including decreased alpha angle (68.1 vs 73.3, P <.001), increased K time (1.7 vs 1.1, P <.001), and decreased max amplitude (58 vs 66, P <.001). Patients with hypofibrinogenemia received more PRBC (10 vs 7 U, P =.002), FFP (9 vs 6 U, P =.003), and platelets (2 vs 1 U, P =.004) during MT. Hypofibrinogenemic patients demonstrated greater mortality than patients with normal levels (50% vs 23.5%, P =.021). Older age, decreased GCS, and elevated injury severity score (ISS) were risk factors for mortality. Increased fibrinogen was associated with lower odds of mortality (P =.001). Age, ISS, and fibrinogen level remained significantly associated with mortality in a multivariable analysis. Overall, fibrinogen in post-MT survivors showed an increase in median level compared to admission (231 vs 177.5 mg/dL, P <.001). Conclusion: Trauma patients undergoing MT with decreased admission fibrinogen demonstrate increased mortality. Other mortality risk factors include older age, decreased GCS, and higher ISS. Patients with increased fibrinogen levels had lower odds of mortality in a multivariable model. Post-MT survivors demonstrated significantly higher fibrinogen levels than pre-MT patients. Hypofibrinogenemic patients also had worse TEG parameters and required more PRBCs, FFP, and platelets during MT. Further studies are needed to assess the optimal volume of fibrinogen replacement with cryoprecipitate during MT to improve trauma patient mortality. [ABSTRACT FROM AUTHOR]

Introduction: The aims of the study were to investigate the risk factors of tigecycline-induced hypofibrinogenemia and to evaluate the safety of tigecycline with concomitant antithrombotic drugs. Methods: We performed a retrospective analysis of patients who received tigecycline for more than 3 days between January 2015 and June 2019. Clinical and laboratory data were collected including fibrinogen concertation, tigecycline dose, duration of treatment, disease severity, complete blood count, indicators of infection, liver and renal function. Risk factors of hypofibrinogenemia were analyzed by univariate and multivariate analysis. To evaluate the safety of tigecycline and concomitant antithrombotic drugs, bleeding events were assessed by comparing the decline in hemoglobin and the amount of red blood cell transfusion in patients with antithrombotic drugs and those without. Results: This study included a total of 68 cases, 20 of which experienced hypofibrinogenemia while receiving tigecycline treatment. Duration of treatment, cefoperazone/sulbactam combination therapy, and fibrinogen levels prior to initiation of tigecycline were risk factors associated with tigecycline-induced hypofibrinogenemia. There were 26 recorded bleeding incidents, 25 of which happened before the start of tigecycline. Antithrombotic and non-antithrombotic patients did not differ in their hemoglobin decline or need for red blood cell transfusions while taking tigecycline. Conclusion: A longer treatment duration, cefoperazone/sulbactam combination therapy, and a lower level of fibrinogen before tigecycline were associated with an increased risk of tigecycline-induced hypofibrinogenemia. A combination of antithrombotic drugs and tigecycline did not aggravate the bleeding events during tigecycline treatment. [ABSTRACT FROM AUTHOR]

Congenital fibrinogen disorders (CFD) include several types and subtypes of fibrinogen deficiency, resulting from monoallelic or biallelic mutations in one of the three fibrinogen genes. While it is relatively easy to make an accurate diagnosis based on activity and antigen levels of fibrinogen and genotype, prediction of the clinical phenotype is challenging. Even among patients with the same genotype, the clinical features are heterogeneous and unpredictable. The development of next-generation sequencing rises the possibility to integrate genetic modifiers to explain the subtle relationship between genotype and clinical phenotype. A recent development in integrative hemostasis assays can also help in the determination of patients at risk of bleeding or thrombosis. In this short review, we go through these topics and explain why CFD could be considered an oligogenic rather than a monogenic disease. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the thresholds of serum concentration as a predictor of tigecycline (TGC)-induced hypofibrinogenemia (HF) in critically ill patients. Methods: A retrospective cohort study was conducted in intensive care unit patients treated with TGC. The clinical data and serum concentration were extracted from the patients’ electronic medical records. Patients were divided into an HF group and a normal group according to fibrinogen value. The receiver operating characteristic curves and logistic regression were used to derive serum concentration thresholds and quantify the association between exposure thresholds and HF while adjusting for confounders. Results: In total, 100 patients were included. The receiver operating characteristic curves analysis showed that TGC concentration parameters were strongly predictive of HF. Adjusting for duration of TGC, serum concentration at the 6 hours after the dosing (C1/2) ≥ 0.645 mg/l, area under the concentration-time curve over a 24-hour period (AUC 0-24) ≥ 20.76 mg·h/l, and serum concentration of 30 minutes before next dose (Cmin) ≥ 0.455 mg/l were associated with a three- to five-fold increased risk of TGC-induced HF in logistic regression. Conclusion: The findings from this study provide evidence that TGC exposure is highly predictive of HF, with an approximately three- to five-fold increased risk. Serum concentration at the 6 hours after the dosing (C1/2) ≥ 0.645 mg/l with best area under the receiver operating characteristic curve and negative predictive value appears to be the most appropriate toxicity threshold.

Hypofibrinogenemia is often associated with excessive bleeding and requires immediate treatment. The qLabs FIB® is a handheld and easy-to-use point-of-care (POC) device designed for the rapid measurement of functional fibrinogen concentration from a single drop of citrated whole blood. The aim of this study was to evaluate the analytical performances of the qLabs FIB system. Fibrinogen concentrations from 110 citrated whole blood specimen were measured by both the qLabs FIB and the Clauss laboratory reference methods (STA®-Liquid Fib assay on STA-R® Max from Stago). A three-laboratories comparison study was conducted to assess reproducibility and repeatability of the qLabs FIB using plasma quality control material. In addition, single-site assays were conducted to assess the repeatability from citrated whole blood specimen covering the qLabs FIB reportable range. A very strong correlation between the qLabs FIB and the Clauss laboratory reference method was observed (r = 0.95). Using a clinical cut-off value of 2.0 g/L, the area under the receiver operating characteristic curve (ROC) of citrated whole blood was 0.99 and sensibility and specificity were 100 % and 93.5 %, respectively. Percent CVs for reproducibility and repeatability assessed from quality control material, were both <5 %. Repeatability assessed from citrated whole blood specimen showed a CV of 2.6 to 6.5 %. In conclusion, the qLabs FIB system enables a rapid and reliable measurement of functional fibrinogen levels from citrated whole blood and exhibits a strong prediction power at the 2 g/L clinical cut-off when compared to the Clauss laboratory reference. Further clinical studies should demonstrate its ability to quickly confirm the diagnosis of acquired hypofibrinogenemia and help identify patients who may benefit from targeted hemostatic treatment. • qLabs FIB novel point-of-care system • qLabs FIB provides an accurate quantification of functional fibrinogen concentration • qLabs FIB enables a rapid measurement of fibrinogen level from one drop of blood • qLabs FIB provides a fibrinogen level adjusted by an integrated hematocrit estimation • qLabs FIB to guide management of critical bleeding especially postpartum hemorrhage [ABSTRACT FROM AUTHOR]

Background: Coagulopathy is often observed in severe traumatic brain injury (sTBI), and hyperfibrinolysis (HF) is associated with a poor prognosis. Although the efficacy of fibrinogen concentrate (FC) in multiple trauma has been reported, its efficacy in sTBI is unclear. Therefore, we delineated severe HF risk factors despite fresh frozen plasma transfusion. Using these risk factors, we defined high-risk patients and determined whether FC administration to this group improved fibrinogen level. Methods: In the first part of this study, successive adults with sTBI treated at our hospital between April 2016 and March 2019 were reviewed. Patients underwent transfusion as per our conventional protocol and were divided into two groups based on whether fibrinogen levels of ≥ 150 mg/dL were maintained 3–6 h after arrival to delineate the risk factors of severe HF. In the second part of the study, we conducted a before-and-after study in patients with sTBI who were at a higher risk for severe HF (presence of at least one of the risk factors identified in the first part of the study), comparing those treated with FC between April 2019 and March 2021 (FC group) with those treated with conventional transfusion before FC between April 2016 and March 2019. The primary outcome was maintenance of fibrinogen levels, and the secondary outcome was 30-day mortality. Results: In the first part of the study, 78 patients were included. Twenty-three patients did not maintain fibrinogen levels ≥ 150 mg/dL. A D-dimer level on arrival > 50 μg/mL, a fibrinogen level on arrival < 200 mg/dL, depressed skull fracture, and multiple trauma were severe HF risk factors. In the second part, compared with 46 patients who were identified as being at high risk for severe HF but were not administered FC (non-FC group), fibrinogen levels ≥ 150 mg/dL 3–6 h after arrival were maintained in 14 of 15 patients in the FC group (odds ratio: 0.07; 95% confidence interval: 0.01–0.59). Although there were significant differences in fibrinogen levels, no significant differences were observed in terms of 30-day mortality between the groups. Conclusions: Coagulation abnormalities on arrival, severe skull fracture, and multiple trauma are severe HF risk factors. FC administration may contribute to rapid correction of developing hypofibrinogenemia. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary hypofibrinogenemia is a rare fibrinogen disorder characterised by decreased levels of fibrinogen. Pregnant women with hypofibrinogenemia are at risk of adverse obstetrical outcomes, depending on the fibrinogen level. Aim: We investigated how the physiological changes of hemostasis throughout the pregnancy impact the hemostatic balance in a woman with hereditary mild hypofibrinogenemia. Methods: Fibrin clot properties were analyzed by turbidimetry and scanning electron microscopy, clot weight and red blood cells retention were measured by whole clot contraction, and in vitro thrombin generation was assessed by calibrated automated thrombogram and ex vivo by TAT. Results: Throughout the pregnancy, the fibrinogen levels increased reaching normal values in the third trimester (activity 3.1 g/L, antigen 3.2 g/L). In parallel, the fibrin polymerisation increased, the fibrinolysis decreased, the fibrin clot network became denser with thicker fibrin fibers, and the fibrin clot weight and red blood cells retention increased, reaching control's value at the third trimester. Similarly, in vitro and ex vitro thrombin generation increased, reaching maximum values at the delivery. Conclusion: In this case of hereditary mild hypofibrinogenemia we observed a physiological increase of fibrinogen and thrombin generation. Future studies should focus on moderate and severe hypofibrinogenemia, to assess fibrinogen variation and the overall impact of increased TG on the hemostasis balance. [ABSTRACT FROM AUTHOR]

SARS-Cov-2 infection during pregnancy can lead to severe placental lesions characterized by massive perivillous fibrin deposition, histiocytic intervillositis and trophoblast necrosis. Diffuse placental damage of this kind is rare, but can sometimes lead to obstetric complications, such as intrauterine fetal death (IUFD). The objectives of this study were to identify possible predictors of severe placental lesions. We retrospectively studied 96 placentas from SARS-Cov-2 positive pregnant women who gave birth between March 2020 and March 2022. Cases with and without severe placental lesions were compared in terms of clinical and laboratory findings. Twelve of the 96 patients had severe placental lesions. There was no significant association with diabetes, obesity or severe clinical maternal disease. In contrast, presence of severe placental lesions was significantly associated with neonatal intensive care, cesarean section, prematurity, IUFD, intrauterine growth restriction (IUGR), gestational age, maternal hypofibrinogenemia and thrombocytopenia. No cases of severe placental lesions were observed in vaccinated patients or in those with the Omicron variant. In these patients, severe placental lesions due to SARS-Cov-2 were significantly associated with the presence of coagulation abnormalities (hypofibrinogenemia and thrombocytopenia), IUGR and gestational age. These results support laboratory and ultrasound monitoring of these parameters in pregnant women with SARS-Cov-2 infection, especially during the second trimester, to predict potential negative fetal outcomes. • None of the patients with severe placental damage had severe COVID-19. • Severe placental damage was significantly associated with maternal hypofibrinogenemia. • Severe placental damage was significantly associated with maternal thrombocytopenia. • Severe placental damage was associated with poor fetal outcomes. •No cases of severe placental damage in vaccinated or Omicron-infected patients [ABSTRACT FROM AUTHOR]

Hypofibrinogenemia and Factor XI deficiency are rare defects of hemostasis, potentially leading to spontaneous bleeding manifestations and increased bleeding risk during surgery, dentistry, and interventions. Due to the different mode of inheritance, the concomitance of both defects is extremely rare and the clinical management of combined hypofibrinogenemia and factor XI deficiency is not standardized. Here, we report a rare case of concomitant genetically determined hypofibrinogenemia and factor XI deficiency as a cause of increased spontaneous bleeding and bleeding complications during dentistry. The diagnostic procedure including screening assays, single clotting factor determinations, genetic analyses, and also use of thrombin generation assays (TGA) are described. Also, we present our considerations regarding the development of an adequate prophylaxis of bleeding with fibrinogen concentrate in this case. The literature regarding the issue is briefly discussed. [ABSTRACT FROM AUTHOR]

Congenital fibrinogen disorders (CFD) include several types and subtypes of fibrinogen deficiency, resulting from monoallelic or biallelic mutations in one of the three fibrinogen genes. While it is relatively easy to make an accurate diagnosis based on activity and antigen levels of fibrinogen and genotype, prediction of the clinical phenotype is challenging. Even among patients with the same genotype, the clinical features are heterogeneous and unpredictable. The development of next-generation sequencing rises the possibility to integrate genetic modifiers to explain the subtle relationship between genotype and clinical phenotype. A recent development in integrative hemostasis assays can also help in the determination of patients at risk of bleeding or thrombosis. In this short review, we go through these topics and explain why CFD could be considered an oligogenic rather than a monogenic disease.

Objective To evaluate the efficacy of perioperative use of tigecycline in preventing infection and the incidence of hypofibrinogenemia in liver transplant recipients. Methods Clinical data of 40 liver transplant recipients given with tigecycline to prevent infection were retrospectively analyzed. The incidence of infection in recipients and donor-derived infection were analyzed. The changes of clinical indexes in recipients during, upon the completion and (7±2) d after tigecycline treatment were analyzed, respectively. The incidence and treatment of hypofibrinogenemia were summarized. Results Among 40 liver transplant recipients, 2 cases were infected by aspergillus niger and cytomegalovirus, out of the antibacterial spectrum of tigecycline. After adjusting the anti-infection regimen, the infection was properly controlled. Liver allografts were positive for relevant culture in 9 cases, whereas none of them progressed into donor-derived infection. Approximately at postoperative 2 weeks, all 40 recipients restored liver function and were discharged from hospital. Among them, 6 recipients developed hypofibrinogenemia complicated with coagulation disorder at postoperative 2-4 d, whereas transaminase level, bilirubin level and infection-related indexes were gradually decreased after liver transplantation, and albumin level was stable. After supplemented with human fibrinogen and prothrombin complex, coagulation function was improved, but fibrinogen level persistently declined. After terminating use of tigecycline, fibrinogen level was gradually restored to normal range, which might be an adverse drug reaction induced by tigecycline. Conclusions Perioperative anti-infection regimen including tigecycline may reduce the incidence of infection caused by sensitive bacteria in liver transplant recipients. Nevertheless, the incidence of hypofibrinogenemia should be intimately monitored throughout the use of tigecycline. [ABSTRACT FROM AUTHOR]

Intravascular fluids administered to patients may influence hemostasis. In patients undergoing cardiac surgery with cardiopulmonary bypass, the heart-lung machine is primed with 1300 ml of fluid. We assessed postoperative coagulation and platelet function in patients randomized to two different priming solutions, one colloid-based (dextran 40) and one crystalloid-based. Eighty-four elective cardiac surgery patients were randomized to either a dextran-based prime or Ringer's acetate with added mannitol. Blood samples were collected before, and 2 and 24 h after cardiopulmonary bypass. Coagulation was assessed by standard coagulation tests and rotational thromboelastometry. Platelet function was assessed with impedance aggregometry. Bleeding volumes and transfusion requirements were recorded. Comparing the groups 2 h after bypass, the dextran group showed lower hemoglobin concentration, hematocrit, platelet count, and fibrinogen concentration, and higher INR and aPTT, as well as longer clot formation time (+41 ± 21 % vs. +8 ± 18 %, p < 0.001) and a larger reduction in fibrinogen-dependent clot strength (−37 ± 12 % vs. -7 ± 20 %, p < 0.001). Adenosine diphosphate-dependent platelet activation was reduced in the dextran group but not in the crystalloid group 2 h after bypass (−14 ± 29 % vs. -1 ± 41 %, p = 0.041). No significant between-group differences in hemostatic variables remained after 24 h, and no significant differences in perioperative bleeding volumes, re-explorations for bleeding, or transfusion rates were observed. Compared to a crystalloid solution, a dextran-based prime had measurable negative impact on hemostatic variables but no detectable increase in bleeding volume or transfusion requirements in cardiac surgery patients. [Display omitted] • The optimal priming solution for cardiopulmonary bypass is debated. • Dextran-based and crystalloid priming solutions were compared in a randomized study. • Coagulation, platelet function, bleeding volume and transfusions were assessed. • The dextran-based prime had measurable negative impact on hemostatic variables. • There was no detectable increase in bleeding or transfusions with dextran-based prime. [ABSTRACT FROM AUTHOR]

Shock index (a ratio between heart rate and systolic blood pressure) predicts transfusion requirements and the need for haemostatic resuscitation in severe trauma patients. In the present study, we aimed to determine whether prehospital and on-admission shock index values can be used to predict low plasma fibrinogen in trauma patients. Between January 2016 and February 2017, trauma patients admitted from the helicopter emergency medical service into two large trauma centres in the Czech Republic were prospectively assessed for demographic, laboratory and trauma-associated variables and shock index at scene, during transport and at admission to the emergency department. Hypofibrinogenemia defined as fibrinogen plasma level of 1.5 g·L−l was deemed as a cut-off for further analysis. Three hundred and twenty-two patients were screened for eligibility. Of these, 264 (83%) were included for further analysis. The hypofibrinogenemia was predicted by the worst prehospital shock index with the area under the receiver operating characteristics curve (AUROC) of 0.79 (95% CI 0.64–0.91) and by the admission shock index with AUROC of 0.79 (95% CI 0.66–0.91). For predicting hypofibrinogenemia, the prehospital shock index ≥ 1 has 0.5 sensitivity (95% CI 0.19–0.81), 0.88 specificity (95% CI 0.83–0.92) and a negative predictive value of 0.98 (0.96–0.99). The shock index may help to identify trauma patients at risk of hypofibrinogenemia early in the prehospital course. [ABSTRACT FROM AUTHOR]

Rotational Thromboelastometry (ROTEM) Delta has been described in several postpartum hemorrhage algorithms, but this device requires pipetting and careful mixing of reagents to initiate the clotting reaction. In contrast, thromboelastography (TEG 6s) and the Quantra devices operate utilizing an automated pre-mixed cartridge that only requires a blood sample to start the clot strength analysis. We compared the correlation between 3 point of care viscoelastic testing (POCVT) devices to laboratory Clauss fibrinogen and platelets, their inter-device correlation, and the total running time difference between Quantra and ROTEM. A high correlation was noted between the Clauss fibrinogen and the fibrinogen parameters from ROTEM (r = 0.76–0.84, P < 0.0001), TEG6s (r = 0.71, P < 0.0001) and Quantra (r = 0.72, P = 0.0001). A moderate correlation between laboratory platelets and the ROTEM (r = 0.54;0.45, P < 0.0001; P = 0.0013) and Quantra (r = 0.66, P = 0.0001) parameters was noted. The inter-device correlation showed to be high when comparing the fibrinogen parameters of TEG6s and Quantra to that of ROTEM (r = 0.88 and 0.74, P < 0.0001, respectively). In contrast, a moderate correlation was noted between the platelet parameters of Quantra and ROTEM (r = 0.51, p = 0.0036). The Quantra device resulted 20.9 min (95% CI -0.2 to 4.7, P = 0.07) faster than the ROTEM if the warming and pipetting of reagents of the latter were considered. All the POCVT devices demonstrated a high correlation to laboratory Clauss fibrinogen, making each beneficial for the early recognition and management of hypofibrinogenemia. [ABSTRACT FROM AUTHOR]

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. • Pregnancy is a hyperthrombotic state with an increase of several coagulation factors with simultaneously increasing activity in the fibrinolytic system when progressing to the late pregnancy. • Even when there isn't an identification of any risk factor in the parturient, she should be seen as at risk for postpartum hemorrhage. • Plasma fibrinogen is a predictor of progression to postpartum hemorrhage predelivery as well as postdelivery. • Thromboelastography can be used to verify the status of the coagulation system and can be used to replenish insufficient factors, e.g., fibrinogen. • There is no evidence that administration of fibrinogen to all patients with a postpartum hemorrhage without evidence of fibrinogen deficiency will lower blood loss or mortality. In patients with low fibrinogen levels administration of fibrinogen improves outcomes. [ABSTRACT FROM AUTHOR]

Background: Breast angiosarcoma is a rare malignant tumor, accounting for approximately 0.04% of all breast malignancies. Angiosarcoma of the breast with hypofibrinogenemia is even rarer and has not been described in man. Breast angiosarcoma is associated with high metastatic potential and poor prognosis, and there is no specific manifestation in imaging. At present, surgery is considered to be the only effective treatment. There is no unified standard for postoperative adjuvant radiotherapy and chemotherapy. Case Presentation: A 30-year-old female patient underwent left breast mass resection under local anesthesia on May 22, 2014. Postoperative pathology showed a vasogenic tumor. On November 10, 2017, she visited us again due to left breast swelling and pain during lactation, and underwent breast mass puncture. She was diagnosed with breast hematoma and fibrinogen reduction. On November 14, 2017, mastectomy was performed under tracheal intubation and general anesthesia, and the fibrinogen gradually returned to normal after surgery. Pathological examination showed a hemangiosarcoma with hematoma formation in the left breast. According to the pathological findings and after comprehensive evaluation, the patient underwent modified radical mastectomy for left breast cancer and right axillary sentinel lymph node biopsy on December 5, 2017. The patient died on January 28, 2018 due to rupture and hemorrhage of liver cancer and hemorrhagic shock. Conclusion: Breast angiosarcoma with hypofibrinogenemia is a rare and highly aggressive malignancy. Clinicians should be familiar with its clinicopathological features and diagnostic criteria. Multidisciplinary approach is recommended to benefit the patients. [ABSTRACT FROM AUTHOR]

Fibrinogen is a complex protein that plays a key role in the blood clotting process. It is a hexamer composed of two copies of three distinct chains: Aα, Bβ, and γ encoded by three genes, FGA, FGB , and FGG, clustered on the long arm of chromosome 4. Congenital fibrinogen disorders (CFDs) are divided into qualitative deficiencies (dysfibrinogenemia, hypodysfibrinogenemia) in which the mutant fibrinogen molecule is present in the circulation and quantitative deficiencies (afibrinogenemia, hypofibrinogenemia) with no mutant molecule present in the bloodstream. Phenotypic manifestations are variable, patients may be asymptomatic, or suffer from bleeding or thrombosis. Causative mutations can occur in any of the three fibrinogen genes and can affect one or both alleles. Given the large number of studies reporting on novel causative mutations for CFDs since the review on the same topic published in 2016, we performed an extensive search of the literature and list here 120 additional mutations described in both quantitative and qualitative disorders. The visualization of causative single nucleotide variations placed on the coding sequences of FGA, FGB , and FGG r eveals important structure function insight for several domains of the fibrinogen molecule. [ABSTRACT FROM AUTHOR]

Background: Tigecycline was recently found to cause coagulation disorders, especially hypofibrinogenemia, which may interfere with the administration of antimicrobial therapy. This study aimed to investigate the incidence and clinical characteristics of and risk factors for tigecycline-associated hypofibrinogenemia. Methods: In this multicenter retrospective study, patients receiving tigecycline or imipenem-cilastatin to treat Gram-negative bacterial infections in nine Chinese tertiary hospitals between January 2020 and December 2020 were enrolled. Baseline data and coagulation variables were compared using cohort and case-control studies. Results: Totals of 485 patients treated with tigecycline and 490 patients treated with imipenem-cilastatin were included in this study. Compared with imipenem-cilastatin, tigecycline was associated with reduced fibrinogen and prolonged activated partial thromboplastin time and prothrombin time (all p < 0.001), with the most remarkable change in fibrinogen (down by 48.0%). The incidence of hypofibrinogenemia in patients treated with tigecycline was >50%, with propensity score-matched analysis or not. The relative risk of hypofibrinogenemia with tigecycline versus imipenem-cilastatin was 2.947 (95% CI: 2.151-4.039) at baseline balance. Tigecycline-associated hypofibrinogenemia led to a higher incidence (12.1%) of bleeding events. However, none of supplemental therapies after withdrawal had an effect on the normalization of fibrinogen levels. The risk factors for tigecyclineassociated hypofibrinogenemia were treatment duration =6 days (odds ratio [OR] 5.214, 95% confidence interval [CI] 2.957-9.191, p < 0.001), baseline fibrinogen <4 g/L (OR 4.625, 95% CI 2.911-7.346, p < 0.001), cumulative dose =1,000 mg (OR 2.637, 95% CI 1.439-4.832, p = 0.002), receiving CRRT (OR 2.436, 95% CI 1.179-5.031, p = 0.016), baseline PT > 14 s (OR 2.110, 95% CI 1.317-3.380, p = 0.002) and baseline total bilirubin >21 µmol/L (OR 1.867, 95% CI 1.107-3.147, p = 0.019), while the protective factor was skin and soft tissue infection (OR 0.110, 95% CI 0.026-0.473, p = 0.003). Conclusion: The clinical characteristics of and risk factors for tigecyclineassociated hypofibrinogenemia identified in this study can offer practical reference for the clinical management of patients. [ABSTRACT FROM AUTHOR]

• Tigecycline treatment causes a significant decrease in fibrinogen levels. • Tigecycline exposure is highly predictive of hypofibrinogenemia. • Serum concentration at the 6 hours after the dosing (C 1/2) ≥ 0.645 mg/l with best predictive performance may be the optimal toxicity threshold. This study aimed to determine the thresholds of serum concentration as a predictor of tigecycline (TGC)-induced hypofibrinogenemia (HF) in critically ill patients. A retrospective cohort study was conducted in intensive care unit patients treated with TGC. The clinical data and serum concentration were extracted from the patients' electronic medical records. Patients were divided into an HF group and a normal group according to fibrinogen value. The receiver operating characteristic curves and logistic regression were used to derive serum concentration thresholds and quantify the association between exposure thresholds and HF while adjusting for confounders. In total, 100 patients were included. The receiver operating characteristic curves analysis showed that TGC concentration parameters were strongly predictive of HF. Adjusting for duration of TGC, serum concentration at the 6 hours after the dosing (C 1/2) ≥ 0.645 mg/l, area under the concentration-time curve over a 24-hour period (AUC 0-24) ≥ 20.76 mg·h/l, and serum concentration of 30 minutes before next dose (C min) ≥ 0.455 mg/l were associated with a three- to five-fold increased risk of TGC-induced HF in logistic regression. The findings from this study provide evidence that TGC exposure is highly predictive of HF, with an approximately three- to five-fold increased risk. Serum concentration at the 6 hours after the dosing (C 1/2) ≥ 0.645 mg/l with best area under the receiver operating characteristic curve and negative predictive value appears to be the most appropriate toxicity threshold. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: With the widespread use of hemocoagulase in patients with gastrointestinal bleeding, clinicians have become increasingly concerned about coagulation disorders associated with this medication. Risk factors for hypofibrinogenemia associated with hemocoagulase are poorly understood., Aim: To determine risk factors for hemocoagulase-associated hypofibrinogenemia in patients with gastrointestinal bleeding., Methods: We performed a retrospective analysis of the medical documentation of hospitalized patients treated with hemocoagulase for gastrointestinal bleeding. Hypofibrinogenemia was defined as a decrease in plasma fibrinogen concentration to less than 2.0 g/L. The included patients were divided into two groups: acquired hypofibrinogenemia group and non-hypofibrinogenemia group. We used logistic regression analysis to identify potential risk factors and established risk assessment criteria by employing a receiver operating characteristic curve., Results: There were 36 patients in the acquired hypofibrinogenemia group and 73 patients in the non-hypofibrinogenemia group. The hypofibrinogenemia group showed higher rates of intensive care unit admissions ( P = 0.021), more female patients ( P = 0.005), higher in-hospital mortality ( P = 0.027), larger hemocoagulase doses ( P = 0.026), more Packed Red Cells transfusions ( P = 0.024), and lower baseline fibrinogen levels ( P < 0.000). Binary logistic regression was employed to examine the risk factors associated with acquired hypofibrinogenemia. The analysis revealed that baseline fibrinogen [odds ratio (OR) 0.252, 95%CI: 0.137-0.464, P < 0.000], total hemocoagulase doses (OR 1.074, 95%CI: 1.015-1.137, P = 0.014), and female gender (OR 2.856, 95%CI: 1.015-8.037, P = 0.047) were statistically significant risk factors., Conclusion: Higher doses of total hemocoagulase, female gender, and a lower baseline fibrinogen level were risk factors for hemocoagulase-associated hypofibrinogenemia in patients with gastrointestinal bleeding., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

BackgroudPeutz–Jegers syndrome (PJS) is an autosomal dominant hereditary disorder characterized by hamartomatous polyposis of the entire gastrointestinal tract. Fibrinogen (Fbg) is synthesized by the liver, and hypofibrinogenemia is often asymptomatic and manifests with bleeding after trauma or invasive surgical procedures. Here, we present a case of a pediatric patient with PJS and hypofibrinogenemia who manifested with gastrointestinal bleeding after endoscopic mucosal resection (EMR) of small intestinal polyps.Case PresentationAn 11-year-old boy with PJS was referred to our hospital. Since his mother was diagnosed with PJS, with black pigments being observed on his lips, mouth, and limbs, he underwent upper and lower gastrointestinal endoscopy at the age of 8 years at a previous hospital. EMR for duodenal polyp was performed, and the pathological findings were consistent with hamartoma. His Fbg level was 117 mg/dl at the time, with no post-bleeding being detected after EMR. The small intestine was not assessed at the prior facility and was left neglected for three years. At our hospital, small intestine fluoroscopy was performed and revealed a polyp in the jejunum, and abdominal computed tomography showed two polyps and intussusception. On double-balloon enteroscopy, the resected polyps were hamartoma with diameters of 20 and 30 mm. The patient’s Fbg level was 107 mg/dl. The day after EMR, he had melena and black stools. He was diagnosed with post-EMR bleeding and started to stop eating, and hemostatic agents were given. His hemoglobin level dropped to 9.2 g/dl the next day. Genetic testing for congenital Fbg deficiency revealed a heterozygous pathogenic variant in fibrinogen gamma chain Exon 10. Therefore, he was diagnosed with concurrent hypofibrinogenemia and PJS.ConclusionTo the best of our knowledge, this is the first reported case with concurrent PJS and hypofibrinogenemia. In patients with PJS, hypofibrinogenemia should be considered as one of the risk factors of postoperative bleeding during polypectomy, and appropriate prophylactic measures should be taken.

Intravenous thrombolysis (IVT) for acute brain infarctions caused by aortic dissection (AD) may lead to fatal outcomes; thus, it should be ruled out, especially if hypofibrinogenemia occurs after IVT. Successful management of AD-related acute brain infarction with hypofibrinogenemia after IVT has not been reported previously. An 84-year-old woman developed sudden left limb weakness and aphasia for almost 4 h. Alteplase was administered intravenously immediately after cerebral hemorrhage was ruled out by emergent head computed tomography (CT). An anomaly suspected to be AD was detected during subsequent routine chest CT, which was confirmed by CT angiography to be a thoracoabdominal aortic dissecting aneurysm (DeBakey type I). Severe hypofibrinogenemia was also noted. After effective blood pressure control, intramuscular injection of vitamin K, and rehydration therapy, her brain cell metabolism improved, hemiplegia improved slightly, and hypofibrinogenemia recovered gradually. The patient's cerebral hemorrhage did not progress, there was no chest pain or no aggravation of hemiplegia, and the fibrinogen level gradually returned to normal. The condition was stable during hospitalization. At 1.5 months after discharge, the patient showed minimal change in condition. The symptoms of AD may be nonspecific and latent. IVT may be allowed to perform for some patients with AD related ischemical stroke, And IVT can improve the neural symptoms of AD-related ischemic stroke, but close monitoring is needed to avoid aneurysm rupture. Fibrinogen levels should also be monitored periodically after IVT for early detection of hypofibrinogenemia. [ABSTRACT FROM AUTHOR]

Adrenocorticotropic hormone (ACTH) therapy is a first-line treatment for infantile spasms, which may rarely cause intracranial hemorrhage. However, the changes in blood coagulation during ACTH therapy are poorly understood, with little description in the management guidelines. To assess the changes in blood coagulation during ACTH therapy. This retrospective study reviewed the medical records of 10 patients diagnosed with infantile spasms and treated with ACTH therapy, between January 2015 and March 2021. The underlying diseases included intracranial hemorrhage, hypoxic-ischemic encephalopathy, tuberous sclerosis, and cerebral infarction. Antiepileptic drugs administered were valproic acid (VPA), vitamin B6, zonisamide, topiramate, clobazam, clonazepam, and phenobarbital. The 10 patients had a median age of 8 months (4–17 months) and included eight males. The median fibrinogen (Fbg) level before ACTH therapy was 202 mg/dL (125–392 mg/dL); however, this significantly decreased to 108.5 mg/dL (65–135 mg/dL) during treatment at a median of 12 days after (days 8–17) (p < 0.01). Decreased Fbg levels were observed with and without VPA. This suggests the possible influence of ACTH therapy on Fbg levels, irrespective of the VPA combination. Additionally, prothrombin time and activated partial thromboplastin time were significantly shortened when compared to those before ACTH therapy and at the lowest of Fbg levels. Careful coagulation monitoring, especially during the second week of treatment, is necessary for the safe completion of ACTH therapy, with or without concomitant VPA. [ABSTRACT FROM AUTHOR]

Disorders of fibrinogen have been reported to be associated not only with bleeding and thrombosis but also with miscarriage. Here, we report the case of a woman with genetically determined hypofibrinogenemia and recurrent miscarriages who had a first successful pregnancy under fibrinogen substitution. Current knowledge on fibrinogen disorders and recurrent miscarriages is briefly summarized and discussed. [ABSTRACT FROM AUTHOR]

• The current study was conducted to evaluate both efficacy and safety of fibrinogen administration in severe traumatic head injury (TBI), and concurrent hypofibrinogenemia. • Fibrinogen administration controls hematoma expansion and improves GCS recovery and GOSE in severe TBI. This study was conducted to evaluate clinical outcomes after fibrinogen administration in hypofibrinogenemia following severe traumatic brain injury. Post traumatic coagulopathy (PTC) is a common but devastating medical condition in patients with severe head injury. Hypofibrinogenemia is considered as an indicator for poor clinical outcomes in traumatic brain injury (TBI). In this randomized clinical trial (RCT), primarily 137 patients with severe traumatic brain injury (Glasgow coma scale score: GCS < 9) were enrolled. Thereafter, their plasma fibrinogen level was measured. The patients with primary hypofibrinogenemia (<200 mg/dL) with no concurrent coagulopathy were randomly allocated into fibrinogen-receiving (n = 50) and control (n = 54) groups. P-value < 0.05 was considered as statistically significant. Seventy-one patients were analyzed in the final step of the study. The mean value for age in fibrinogen and control groups was 25.64 ± 10.71 and 28.91 ± 12.25 years old, respectively. Male – female patients in both groups were equally distributed. In the fibrinogen receiving group, GCS scores were significantly higher after 24, 48, and 72 h compared to the control group (p = 0.000). Hematoma expansion was better controlled in the fibrinogen receiving group (p = 0.000). Notably, the number needed to treat (NNT) for fibrinogen infusion and hematoma expansion control was 2.3. Glasgow outcome scale-extended (GOSE) was significantly better in the fibrinogen group (p = 0.25). Multiple regression tests showed intracerebral hematoma (ICH) and severe brain edema had the most detrimental effect on GOSE outcomes. The need for cranial surgery, hospital stay duration, mechanical ventilator dependency, in hospital and 90-day post discharge mortality rates were similar in both study groups. In severe TBI, hypofibrinogenemia correction (>200 mg/dL) could improve GOSE, GCS score progression within 3 days after primary head injury and hematoma expansion controllability. [ABSTRACT FROM AUTHOR]

Jia Liu,1 Yingying Yan,2 Fan Zhang1 1Department of Geriatrics, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Pharmacy, Peking University Third Hospital, Beijing, People’s Republic of ChinaCorrespondence: Fan ZhangDepartment of Geriatrics, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, People’s Republic of ChinaTel +86-010-82265685Email zhangfan_puh3@yeah.netBackground: With the widespread use of tigecycline, especially in elderly people infected with multidrug-resistant bacteria, the associated coagulation disorders are attracting the attention of clinicians. The risk factors of tigecycline-associated hypofibrinogenemia are still controversial.Purpose: The aims of our study were to explore the related factors of hypofibrinogenemia caused by tigecycline, and to establish the risk assessment criteria for tigecycline-associated hypofibrinogenemia.Patients and Methods: This was an observational retrospective cohort study of patients treated for at least 3 days with tigecycline. Hypofibrinogenemia was defined as plasma fibrinogen < 2.0 g/L. Risk factors were determined using logistic regression analysis, and the risk assessment criteria were identified by using receiver operating characteristic curves.Results: In total, 148 patients were included in the analysis, mean age was 77.09± 15.11 years old. Ninety patients who developed hypofibrinogenemia during tigecycline treatment with mean plasma fibrinogen of 1.42 g/L were included in the hypofibrinogenemia group, the other 58 patients with mean plasma fibrinogen of 2.68 g/L were included in the normal group. In the multivariate analysis, age (p = 0.035), tigecycline treatment duration (p = 0.044), and baseline fibrinogen level (p = 0.002) were independently associated with hypofibrinogenemia. An age of ≥ 82 years, ≥ 9 days of medication, and a baseline fibrinogen level of ≤ 3.5 g/L were selected for predicting hypofibrinogenemia. Hypofibrinogenemia was independently associated with bleeding (OR 8.96, 95% CI [1.132– 70.946], p = 0.038).Conclusion: Hypofibrinogenemia is a common adverse effect of tigecycline in our study. Elderly patients are more prone to developing hypofibrinogenemia after the administration of tigecycline. It is independently associated with bleeding but not death. The risk assessment criteria can help in the identification of patients with high risk of hypofibrinogenemia.Keywords: tigecycline, hypofibrinogenemia, coagulation disorders, risk factors

• The fibrinogen variant γ p.Gly310Glu accounts for decreased fibrinogen levels. • The fibrin clot structure: decreased fibrin density and large pores, are explained by the low fibrinogen level. • The fibrin clot architecture and degradation profile correspond to "bleeding clot phenotype". [ABSTRACT FROM AUTHOR]