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Pharmacology 2023The aims of the study were to investigate the risk factors of tigecycline-induced hypofibrinogenemia and to evaluate the safety of tigecycline with concomitant...
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.
Topics: Humans; Tigecycline; Anti-Bacterial Agents; Retrospective Studies; Fibrinolytic Agents; Cefoperazone; Sulbactam; Afibrinogenemia; Hemorrhage; Fibrinogen; Hemoglobins
PubMed: 37751720
DOI: 10.1159/000532001 -
Cureus Mar 2023We present a case of bleeding from circumcision in a full-term newborn male resulting from a rare coagulopathy, congenital afibrinogenemia, and a review of the...
We present a case of bleeding from circumcision in a full-term newborn male resulting from a rare coagulopathy, congenital afibrinogenemia, and a review of the literature regarding the management of bleeding after circumcision. Bleeding was managed with silver nitrate, suturing, thrombin powder, Arista AH (absorbable hemostatic particles; Becton, Dickinson and Company, Franklin Lakes, USA), FFP (fresh frozen plasma), and cryoprecipitate. The Fibrinogen level was less than 30 mg/dl (ref 150-430 mg/dl). The diagnosis of congenital afibrinogenemia was confirmed by a gene test. The baby was found to have a heterozygous pathogenic variant (c.510+1G>T) and a heterozygous likely pathogenic variant (c.1037del) in the gene.
PubMed: 36950719
DOI: 10.7759/cureus.36459 -
Journal of Thrombosis and Haemostasis :... Jul 2007Fibrinogen, the soluble precursor of fibrin, which is the main protein constituent of the blood clot, is synthesized in hepatocytes in the form of a hexamer composed of... (Review)
Review
Fibrinogen, the soluble precursor of fibrin, which is the main protein constituent of the blood clot, is synthesized in hepatocytes in the form of a hexamer composed of two sets of three polypeptides (Aalpha, Bbeta, and gamma). Each polypeptide is encoded by a distinct gene, FGA, FGB and FGG, all three clustered in a region of 50 kb on 4q32. Congenital afibrinogenemia is characterized by the complete absence of fibrinogen. The first causative mutation for this disease was identified in Geneva in a non-consanguineous Swiss family in 1999: the four patients were homozygous for a large deletion in the fibrinogen cluster, which eliminated almost the entire FGA genomic sequence. Mutations in the fibrinogen genes may lead to deficiency of fibrinogen by several mechanisms: acting at the DNA level, at the RNA level by affecting mRNA splicing or stability, or at the protein level by affecting protein synthesis, assembly or secretion. Recent reviews have provided helpful updates for the rapidly growing number of causative mutations identified in patients with fibrinogen deficiencies, either afibrinogenemia or hypofibrinogenemia. The aim of this review is to highlight specifically the subset of mutations that allow fibrinogen chain synthesis and hexamer assembly but impair secretion. Indeed, functional studies of these mutations have shed light on the specific sequences and structures in the fibrinogen molecule involved in the quality control of fibrinogen secretion.
Topics: Fibrinogen; Humans; Mutation; Protein Folding; RNA, Messenger; Sequence Deletion
PubMed: 17635718
DOI: 10.1111/j.1538-7836.2007.02465.x -
Anesthesiology 1966
Topics: Afibrinogenemia; Fibrinolysis; Hemorrhagic Disorders; Humans
PubMed: 5946526
DOI: 10.1097/00000542-196607000-00012 -
Transfusion Sep 2022Congenital fibrinogen deficiency (CFD) is a rare coagulation disorder placing patients at increased bleeding risk. Human fibrinogen concentrate (HFC) represents current...
Efficacy and safety of fibrinogen concentrate for perioperative prophylaxis of bleeding in adult, adolescent, and pediatric patients with congenital fibrinogen deficiency: FORMA-02 and FORMA-04 clinical trials.
BACKGROUND
Congenital fibrinogen deficiency (CFD) is a rare coagulation disorder placing patients at increased bleeding risk. Human fibrinogen concentrate (HFC) represents current standard of care for fibrinogen replacement in CFD, however, limited data are available on HFC for prophylactic administration before/during surgery. Here, we report results and dosing considerations for HFC treatment in perioperative bleeding management in adult, adolescent, and pediatric patients with CFD.
STUDY DESIGN AND METHODS
FORMA-02/FORMA-04 were multinational, prospective, open-label, uncontrolled Phase 3 HFC efficacy/safety studies for surgical bleeding prophylaxis in adult/adolescent (≥12 years) and pediatric patients (<12 years) respectively. HFC dosing was calculated to achieve pre-established target fibrinogen plasma levels. Overall hemostatic efficacy was assessed as success/failure by an Independent Data Monitoring and Endpoint Adjudication Committee (IDMEAC) according to objective criteria.
RESULTS
Twelve patients (≥12 years, N = 9; <12 years, N = 3) received HFC for surgical prophylaxis (15 surgeries; 13 minor, 2 major). Eleven minor surgeries in patients aged ≥12 years required a median of 1 infusion (range; 1-5), with a mean (±SD) dose of 93.50 mg/kg [±41.43] and two minor surgeries in patients <12 years required 1 infusion (91.55 mg/kg [±23.40]). The major surgery in an adult patient required eight infusions (225.3 mg/kg total dose). The major surgery in a pediatric patient required six infusions (450.4 mg/kg). All surgeries were rated successful by the IDMEAC.
DISCUSSION
In adults/adolescents and pediatric patients with fibrinogen deficiency, HFC treatment for hemostatic management during/after minor and major surgery was successful, with efficacy comparable across the different age groups.
Topics: Adolescent; Adult; Afibrinogenemia; Blood Loss, Surgical; Child; Fibrinogen; Hemostatics; Humans; Prospective Studies
PubMed: 35932202
DOI: 10.1111/trf.17029 -
Research and Practice in Thrombosis and... Dec 2021Afibrinogenemia and congenital dysfibrinogenemia (CD) are rare conditions with limited information available for appropriate management. Previous case reports have...
Afibrinogenemia and congenital dysfibrinogenemia (CD) are rare conditions with limited information available for appropriate management. Previous case reports have demonstrated the safe and efficacious use of fibrinogen replacement therapy (FRT) as a therapeutic approach to prevent hemorrhage and fetal loss in pregnant women with CD. In this case report, we present a 28-year-old pregnant woman who sought testing for CD given her family history. She denied any current or previous bleeding symptoms. Laboratory testing confirmed the diagnosis of CD. She was treated with FRT and prophylactic anticoagulation starting in her third trimester. She had preterm labor that prompted an urgent cesarean section with FRT support. This case adds to the sparse literature about fibrinogen disorders in pregnancy, and highlights the benefits, safety, and tolerability of FRT and prophylactic anticoagulation in pregnant women with CD. Finally, it emphasizes the importance of a multidisciplinary team approach for an uneventful delivery.
PubMed: 34816075
DOI: 10.1002/rth2.12619 -
Scandinavian Journal of Trauma,... Dec 2021In severely injured patients, fibrinogen supplementation is recommended when fibrinogenemia is < 1.5 g L, but some teams have suggested to use higher thresholds...
BACKGROUND
In severely injured patients, fibrinogen supplementation is recommended when fibrinogenemia is < 1.5 g L, but some teams have suggested to use higher thresholds (fibrinogenemia < 2.0 g L or FIBTEM clot amplitude at 5 min (A5) values < 11 mm). The goal of this study was to specify in patients with a moderate fibrinogen deficit (MFD) whether some admission characteristics would be associated with fibrinogen administration at 24 h.
METHODS
Prospective analysis of retrospectively collected data from a trauma registry (01/2011-12/2019). MFD-C was defined by a fibrinogenemia 1.51-1.99 g L or the corresponding FIBTEM-A5 values (MFD-A5) that were determined from linear regression and ROC curve analysis. Administration of fibrinogen were described according to the following admission parameters: shock index (SI) > 1, hemoglobin level < 110 g L (HemoCue®), and base deficit > 5 mEq L. Data are expressed as count (%), median [IQR].
RESULTS
1076 patients were included in the study and 266 (27%) had MFD-C, among them, 122/266 (46%) received fibrinogen. Patients with MFD-C who received fibrinogen were more severely injured (ISS: 27 [19-36] vs. 24 [17-29]) and had more impaired vital signs (base deficit: 5.4 [3.6-7.8] vs. 3.8 [2.0-6.0]). Linear regression analysis found a positive correlation between fibrinogen level and FIBTEM-A5 (r: 0.805). For a fibrinogen level < 1.5 g L and < 2.0 g L, FIBTEM-A5 thresholds were 6 mm (sensitivity 85%, specificity 83%, AUC: 0.934) and 9 mm (sensitivity 84%, specificity 69%, AUC: 0.874), respectively. MFD-A5 values (185 (27%) patients) were defined as a FIBTEM-A5 between 7 and 9 mm. More than 50% of MFD-C patients presenting a SI > 1, a hemoglobin level < 110 g L, or a base deficit > 5.0 mEq L received fibrinogen. The relative risk [95% CI] for fibrinogen administration (SI > 1) were 1.39 [1.06-1.82] for MFD-C, and 2.17 [1.48-3.19] for MFD-A5. Results were not modified after adjustment on the ISS.
CONCLUSIONS
We have shown in this study an association between shock parameters and fibrinogen administration. Further studies are needed to determine how these parameters may be used to guide fibrinogen administration in trauma patients with MFD.
Topics: Afibrinogenemia; Blood Coagulation Disorders; Fibrinogen; Humans; Retrospective Studies; Thrombelastography; Wounds and Injuries
PubMed: 34952618
DOI: 10.1186/s13049-021-00988-x -
Medicine Oct 2020Extensive off-label use may affect the safety profile of tigecycline. Tigecycline-associated hypofibrinogenemia is potentially life threatening, although the frequency... (Review)
Review
RATIONALE
Extensive off-label use may affect the safety profile of tigecycline. Tigecycline-associated hypofibrinogenemia is potentially life threatening, although the frequency of life-threatening reactions is unknown and their incidence is easily overlooked. We report a case of 2 instances of treatment with high-dose tigecycline, each of which presented with hypofibrinogenemia.
PATIENT CONCERNS
An 86-year-old male patient was treated twice with high-dose tigecycline and presented with hypofibrinogenemia both times. The decrease in fibrinogen occurred within 3 to 7 days of tigecycline treatment. Other coagulation parameters had slightly prolonged values.
DIAGNOSES
Coagulopathy and hypofibrinogenemia.
INTERVENTIONS
We discontinued the tigecycline.
OUTCOMES
The fibrinogen level normalized within 5 days after the withdrawal of tigecycline. Following 80 days of hospitalization, the patient was transferred to the rehabilitation hospital for further treatment.
LESSONS
We suggest routine strict monitoring of coagulation parameters, particularly fibrinogen. Attention should be paid to below-normal fibrinogen levels due to increased bleeding risk and severity of reaction at fibrinogen levels below 1 g/L.
Topics: Adult; Afibrinogenemia; Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Fibrinogen; Humans; Male; Middle Aged; Off-Label Use; Tigecycline
PubMed: 33120753
DOI: 10.1097/MD.0000000000022638 -
Journal of Clinical Laboratory Analysis Sep 2022We reported a patient with congenital dysfibrinogenemia who was misdiagnosed and reviewed relevant literature, in order to discuss the methods to reduce misdiagnosis. (Review)
Review
BACKGROUND
We reported a patient with congenital dysfibrinogenemia who was misdiagnosed and reviewed relevant literature, in order to discuss the methods to reduce misdiagnosis.
METHODS
A 23-year-old pregnant woman was found to be with low fibrinogen in antenatal examination at another province teaching hospital, who was misdiagnosed to have hypofibrinogenemia. Fibrinogen infusion or cryoprecipitation was recommended if necessary. The patient came to our hospital for further diagnosis and treatment considering the safety of herself and the fetus. We examined the coagulation function and gene sequencing of the pregnant woman and her family members.
RESULTS
Fibrinogen (Clauss method) was significantly reduced in the patient and her mother, while the level of fibrinogen (PT-derived method) was normal. Thrombin time was prolonged. Heterozygous mutation site was found in exon 2 of the FGA gene, c.104G > A(p.Arg35His).
CONCLUSION
When the fibrinogen (Clauss method) is significantly reduced and the thrombin time is prolonged, PT-derived method and the investigation of family coagulation function should be added, which can be used to diagnose and distinguish congenital dysfibrinogenemia from hypofibrinogenemia.
Topics: Adult; Afibrinogenemia; Diagnostic Errors; Exons; Female; Fibrinogen; Humans; Pregnancy; Young Adult
PubMed: 35949040
DOI: 10.1002/jcla.24624 -
The Pan African Medical Journal 2016Afibrinogenemia is a rare dyscrasia characterized by a congenital fibrinogen deficiency It is transmitted in an autosomal recessive manner. Hemorrhagic manifestations...
Afibrinogenemia is a rare dyscrasia characterized by a congenital fibrinogen deficiency It is transmitted in an autosomal recessive manner. Hemorrhagic manifestations are variable and can be life-threatening. A little more than 250 cases have been published up till now. We here report a new case of congenital afibrinogenemia in a 3 1/2-year old child hospitalized for medium abundance hematemesis. This case study aims to highlight numerous aspects of this condition from a clinical, biological, genetic and therapeutic points of view.
Topics: Afibrinogenemia; Child, Preschool; Female; Hematemesis; Hospitalization; Humans
PubMed: 28293349
DOI: 10.11604/pamj.2016.25.233.10754