Machine learning-based prediction model for hypofibrinogenemia after tigecycline therapy.

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.

Evaluation of tocilizumab-induced hypofibrinogenemia in rheumatology practice: a retrospective, real-life, single-center experience.

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.

Incidence, characteristics, and risk factors of hypofibrinogenemia induced by generic tigecycline: a retrospective study.

The objective of this study was to evaluate the incidence, clinical features, and risk factors of generic tigecycline-associated hypofibrinogenemia. A single-center retrospective study was conducted in adult patients treated with generic tigecycline. Clinical data were extracted from the electronic medical records. The endpoint was tigecycline-related hypofibrinogenemia, defined as a condition with no abnormality in fibrinogen before tigecycline application, but developing hypofibrinogenemia upon prescription. The risk factors were determined by logistic regression analysis, and the ROC curve was subsequently established. A total of 240 adults prescribed generic tigecycline from May 1st to November 30th 2023 were included. It was shown that hypofibrinogenemia is a frequent side effect of generic tigecycline, with an adverse reaction rate of 42.9% (103/240). However, the incidence of adverse reactions to generic drugs was lower than in previous studies. The cumulative dose of tigecycline (OR:1.002, 95%CI 1.001-1.002, P < 0.001), baseline FIB (OR:0.995, 95%CI 0.992-0.997, P < 0.001), baseline PT (OR:1.247, 95%CI 1.071-1.452, P = 0.004) and baseline ALB (OR:0.931, 95%CI 0.879-0.986, P = 0.025) were identified as independent prognostic factors of tigecycline-related hypofibrinogenemia. We recommend intensive monitoring of coagulation function in patients exhibiting the aforementioned risk factors for generic tigecycline-associated hypofibrinogenemia to ensure patients safety.

Dysfibrinogenemia and hypofibrinogenemia - Spectrum of pathogenic variants in Slovak patients.

INTRODUCTION: Congenital hypofibrinogenemia (CH) and congenital dysfibrinogenemia (CD) are rare coagulation disorders caused by quantitative or qualitative defects in the fibrinogen gene. The aim of this study was to characterize the genetic background and the clinical manifestations of congenital fibrinogen disorders in the patients from Slovakia registered at the National Haemophilia Centre. MATERIALS AND METHODS: Results of genetic analysis of the fibrinogen genes FGA, FGB and FGG using polymerase chain reaction followed by direct sequencing were evaluated in 36 patients. RESULTS: Molecular-genetic analysis revealed six novel variants - FGA c.923_968dup p.(Gly324Lysfs*44) and FGG c.1105C>T p.(His369Tyr) were identified in CD patients. In CH patients, in the FGG gene c.8G>A p.(Trp3*), c.823G>T p.(Glu275*) and c.323C>A p.(Ala108Asp) variants were detected. In the FGB gene c.1427C>T p.(Ser476Leu) was identified. CONCLUSION: This study is a positive contribution towards expanding knowledge about genetic variants in patients with congenital fibrinogen disorders.

Clinical phenotype and laboratory characteristics of 93 patients with congenital fibrinogen disorders from unrelated 36 families.

Background: Congenital fibrinogen disorders (CFDs) are rare bleeding disorders (RBDs) caused by mutations in 1 of the 3 fibrinogen genes (FGA, FGB, and FGG). Objectives: To investigate the clinical phenotype, laboratory features, diagnosis, treatment, and prognosis of CFDs. Methods: Clinical data of 93 subjects with CFDs identified from June 2018 to December 2023 were retrospectively analyzed. Results: Among the 93 patients, there were 46 males (49.5%) and 47 females (50.5%), with a median age of 23 years. Fifty-three of 93 (57%) subjects experienced bleeding, 3/93 (3.2%) experienced thrombosis, and 37/93 (39.8%) were asymptomatic. Females were more prone to experience bleeding (P < .0001). The 93 patients exhibited prolonged thrombin time, significantly decreased fibrinogen activity (Fg:C), and normal or decreased fibrinogen antigen. The 93 patients included 3 with hypofibrinogenemia, 16 with hypodysfibrinogenemia, and 74 with dysfibrinogenemia. Among the 53 patients with bleeding, bleeding episodes were identified in 3.8% (2/53), 20.8% (11/53), and 75.5% (40/53) patients with hypofibrinogenemia, hypodysfibrinogenemia, and dysfibrinogenemia, respectively. Genetic analysis was performed on 22 cases from 8 pedigrees, revealing 10 mutations, including 1 novel splice mutation. Twenty-eight (30.1%) subjects received replacement therapy to treat or prevent bleeding, consisting of 8 fresh frozen plasma transfusions, 3 packing and suture treatment, and 61 fibrinogen infusions. Conclusion: Most patients with CFDs have mild or no bleeding symptoms. Fg:C combined with fibrinogen antigen and pedigree investigation can improve the feasibility and accuracy of diagnosis of CFDs. The severity of bleeding symptoms was negatively correlated with Fg:C.

Transient Hematotoxicity After Emerald Horned Pitviper (Ophryacus smaragdinus) Envenomation: A Case Report.

BACKGROUND: 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. CASE REPORT: 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. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: 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.

Clinical observation of hypofibrinogenemia induced by the treatment of tocilizumab in rheumatic diseases and exploration of risk factor for hypofibrinogenemia.

OBJECTIVE: The objective of this study was to analyze the changes in plasma fibrinogen (FIB) levels during tocilizumab (TCZ) treatment in patients with rheumatic diseases, to clarify the incidence of hypofibrinogenemia and its possible risk factors, and to establish a nomogram model for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ. METHODS: Clinical data of patients treated with TCZ at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to October 2021 were retrospectively analyzed to observe the incidence of hypofibrinogenemia in several rheumatic diseases at different time points. The risk factor of hypofibrinogenemia in RA patients treated with TCZ was determined by using Cox regression analysis. Based on the results of Cox regression analysis, a nomogram for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ was established and validated through RStudio software. RESULTS: A total of 83 TCZ-treated patients were enrolled in this study, and 32 (38.55%) patients developed hypofibrinogenemia during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with an average age of 44.88 ± 18.39 years. Hypofibrinogenemia was most common in TCZ-treated patients with takayasu arteritis (TA) and RA. Hypofibrinogenemia typically occured within 3 months after TCZ treatment. In RA patients treated with TCZ, platelet distribution width, parathyroid hormone, bone mineral density, tender joint count, and swollen joint count were independent risk factors for the occurrence of hypofibrinogenemia. The nomogram based on the above risk factors could effectively predict the probability of hypofibrinogenemia in RA patients receiving TCZ. CONCLUSION: Although bleeding symptoms were not observed in this study, the incidence of hypofibrinogenemia remained high after TCZ treatment, usually occurring within 3 months of treatment. Therefore, it is necessary to monitor FIB levels during TCZ treatment. In addition, clinicians can use the nomogram model developed from this study to predict the incidence of hypofibrinogenemia after TCZ treatment in RA patients. Key Points • Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases. • PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia. • It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency.

Tigecycline-associated hypofibrinogenemia: A single center, retrospective, controlled study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

A novel mutation in the FGG gene causes hypofibrinogenemia in a Chinese family.

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.

Management of pregnancy and delivery in congenital fibrinogen disorders: communication from the ISTH SSC Subcommittee on Factor XIII and Fibrinogen.

Congenital fibrinogen disorders (CFDs) are a heterogeneous group of rare congenital quantitative and/or qualitative fibrinogen deficiencies. The spectrum of molecular anomalies is broad, leading to several subtypes of fibrinogen disorders (ie, afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia). Pregnancy in women with CFDs is a high-risk clinical situation, with an increased tendency for miscarriages, bleeding, and thrombosis. Even though it is well established that management of such pregnancies requires a multidisciplinary approach involving specialists (hematologists and maternal/fetal medicine experts with expertise in the management of inherited bleeding disorders), specific guidelines are lacking. In this International Society on Thrombosis and Haemostasis (ISTH) Scientific and Standardization Committee communication, we aim to propose an expert consensus opinion with literature evidence where available on the strategy for management of pregnancy, delivery, and puerperium in CFDs.

Safety of Tigecycline in Patients on Antithrombotic Therapy: A Single-Center Retrospective Study.

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.

Preeclampsia complicated with hypofibrinogenemia: 2 case reports and review of the literature.

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.

Congenital fibrinogen disorders: Strengthening genotype-phenotype correlations through novel genetic diagnostic tools.

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.

Concomitant hypofibrinogenemia and factor XI deficiency as rare cause of bleeding during urgent dentistry: case report and short review of the literature.

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.

Real-World Experience with a Human Fibrinogen Concentrate: Clinical Data from Adult and Pediatric Patients Requiring Fibrinogen for Bleeding Control and Prevention.

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.

[Placenta percreta management in a patient with a severe congenital hypofibrinogenemia]. / Gestion d'un placenta percreta chez une patiente atteinte d'une hypofibrinogénémie congénitale sévère.

The obstetrical follow-up of patients with a severe hypofibrinogenemia requires a multidisciplinary collaboration because of potential maternal-fetal complications (recurrent miscarriages, intrauterine fetal demise, post-partum hemorrhage, thrombosis). We report the obstetrical management of a multiparous patient with a severe congenital hypofibrinogenemia associated with a platelet disorder (abnormal phospholipid externalization). A therapeutic strategy based on a biweekly administration of fibrinogen concentrates associated with enoxaparin and aspirin allowed the maintenance of pregnancy. But this last one got complicated by a placenta percreta requiring a salvage hysterectomy with an appropriate hemorrhage prophylaxis.

The qLabs® FIB system, a novel point-of-care technology for a rapid and accurate quantification of functional fibrinogen concentration from a single drop of citrated whole blood.

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.

Obstetrical complications in hereditary fibrinogen disorders: the Fibrinogest study.

BACKGROUND: Women with hereditary fibrinogen disorders (HFDs) seem to be at an increased risk of adverse obstetrical outcomes, but epidemiologic data are limited. OBJECTIVES: We aimed to determine the prevalence of pregnancy complications; the modalities and management of delivery; and the postpartum events in women with hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia. METHODS: We conducted a retrospective and prospective multicentric international study. RESULTS: A total of 425 pregnancies were investigated from 159 women (49, 95, and 15 cases of hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia, respectively). Overall, only 55 (12.9%) pregnancies resulted in an early miscarriage, 3 (0.7%) resulted in a late miscarriage, and 4 (0.9%) resulted in an intrauterine fetal death. The prevalence of live birth was similar among the types of HFDs (P = .31). Obstetrical complications were observed in 54 (17.3%) live birth pregnancies, including vaginal bleeding (14, 4.4%), retroplacental hematoma (13, 4.1%), and thrombosis (4, 1.3%). Most deliveries were spontaneous (218, 74.1%) with a vaginal noninstrumental delivery (195, 63.3%). A neuraxial anesthesia was performed in 116 (40.4%) pregnancies, whereas general or no anesthesia was performed in 71 (16.6%) and 129 (44.9%) pregnancies, respectively. A fibrinogen infusion was administered in 28 (8.9%) deliveries. Postpartum hemorrhages were observed in 62 (19.9%) pregnancies. Postpartum venous thrombotic events occurred in 5 (1.6%) pregnancies. Women with hypofibrinogenemia were at an increased risk of bleeding during the pregnancy (P = .04). CONCLUSION: Compared with European epidemiologic data, we did not observe a greater frequency of miscarriage, while retroplacental hematoma, postpartum hemorrhage, and thrombosis were more frequent. Delivery was often performed without locoregional anesthesia. Our findings highlight the urgent need for guidance on the management of pregnancy in HFDs.

Hypofibrinogenemic Massive Transfusion Trauma Patients Experience Worse Outcomes.

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.