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).
CONCLUSIONS: 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.

BACKGROUND: 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.
CONCLUSIONS: 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.

Women with hereditary fibrinogen disorders (HFDs) seem to be at an increased risk of adverse obstetrical outcomes, but epidemiologic data are limited.
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.
We conducted a retrospective and prospective multicentric international study.
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).
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.

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.

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.

UNASSIGNED: Hypofibrinogenemia is a serious adverse reaction related to tigecycline administered against multidrug-resistant (MDR) bacteria and can lead to therapy termination. High dose and prolonged tigecycline therapy, renal failure, and base level of fibrinogen (FIB) were reported risk factors of tigecycline-associated FIB reduction. But results are unknown in patients with renal transplantation.
UNASSIGNED: A single-center and a case-control study involving renal transplantation patients was conducted. From January, 2017 to January, 2020, patients with a tigecycline course more than 2 days and a baseline FIB level greater than 2 g/L were enrolled. Hypofibrinogenemia was defined as plasma FIB <2.0 g/L. The extent of FIB reduction was calculated based on the baseline of FIB level before tigecycline administration. FIBRO was defined as the extent of FIB reduction over 50%, and FIBRB referred to the extent of FIB reduction below 50%. Univariate and multivariate analyses were performed by logistic regression models to identify independent risk factors of tigecycline-associated FIB reduction.
UNASSIGNED: In total, 120 patients were enrolled. A total of 114 patients (95.00%) developed with hypofibrinogenaemia. Hypofibrinogenemia mainly occurred 3 days after tigecycline administration. Of them, 79 (65.83%) developed FIBRO with a median occurrence of 3 [2-4] days after initiation of tigecycline. Multivariable regression analysis demonstrated that the FIB level before tigecycline use [odds ratio (OR): 3.225, 95% confidence interval (CI): 1.801-5.772] and total tigecycline dose (OR: 4.930, 95% CI: 1.433-16.959) were risk factors for FIBRO.
UNASSIGNED: The FIB level before tigecycline use and total tigecycline dose were significantly associated with FIBRO, suggesting that FIB level and coagulation-related indicators should be closely monitored during tigecycline treatment to avoid life-threatening bleeding events.

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.
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.
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.
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.

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 tigecycline-associated 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 tigecycline-associated hypofibrinogenemia identified in this study can offer practical reference for the clinical management of patients.

Early recognition of hypofibrinogenemia and prompt initiation of transfusion therapy in patients with massive obstetrical hemorrhage can improve prognosis. There are reports on the usefulness of point-of-care testing, which provides quicker test results compared with fibrinogen measurements using the conventional Clauss method.
This study aimed to compare and investigate the diagnostic accuracy of dry hematology and thromboelastography in point-of-care testing for the diagnosis of hypofibrinogenemia.
A single-center, retrospective study of 126 massive obstetrical hemorrhage cases with point-of-care testing before treatment was initiated. The correlation of fibrinogen values with the Clauss method and the diagnostic accuracy for hypofibrinogenemia were compared between dry hematology and thromboelastography.
Fibrinogen value in dry hematology showed a strong positive correlation with values measured by the Clauss method, and the diagnostic accuracy for hypofibrinogenemia was high, but there were many residuals above 100 mg/dL, and the distribution of these residuals was not uniform. Although thromboelastography cannot be used to directly measure fibrinogen values, maximum amplitude citrated functional fibrinogen, amplitude-10 citrated rapid thromboelastography, and amplitude-10 citrated functional fibrinogen showed a strong positive correlation with fibrinogen values using the Clauss method, and no significant difference in correlation or diagnostic accuracy was observed relative to dry hematology.
Dry hematology and thromboelastography were equally accurate in diagnosing hypofibrinogenemia, with results correlating well with fibrinogen values measured by the Clauss method.

OBJECTIVE: 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.
CONCLUSIONS: 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.