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Annals of Clinical Biochemistry Jun 2024The presence of latent fibrin clots is a recognised pre-analytical factor that causes inaccurate immunoassay results. This report details a case of a patient with...
The presence of latent fibrin clots is a recognised pre-analytical factor that causes inaccurate immunoassay results. This report details a case of a patient with Graves' disease and congenital dysfibrinogenemia (CD) that had serum thyroid function test results (TFTs) that were not in keeping with clinical signs or symptoms. Analysis of plasma samples taken from the patient was shown to provide more accurate results than those obtained using serum samples. Further cases of patients with CD, all sharing the same genetic mutation of fibrinogen, and discordant TFTs are described, where TFTs measurement in serum samples proved to be unreliable. Despite evidence of fibrin effecting immunoassays, this is the first report of its kind linking CD to erroneous immunoassay results. The mechanism is postulated to be related to atypical forms of fibrinogen resulting in latent fibrin in serum samples blocking the antigen binding site and leading to incorrect results. Congenital dysfibrinogenemia is asymptomatic in most patients and therefore abnormal, albeit inaccurate, TFTs may be the first finding. Recognition of CD as a cause of discordant results is important when interpreting TFTs to avoid unnecessary investigations and inappropriate clinical interventions to those with the disorder and potentially identify undiagnosed cases.
PubMed: 38844473
DOI: 10.1177/00045632241263494 -
Clinica Chimica Acta; International... Apr 2024Congenital dysfibrinogenemia (CD) is characterized by dysfunction induced by an abnormal fibrinogen molecule structure that results in blood coagulation dysfunction. The... (Review)
Review
INTRODUCTION
Congenital dysfibrinogenemia (CD) is characterized by dysfunction induced by an abnormal fibrinogen molecule structure that results in blood coagulation dysfunction. The clinical manifestations of CD patients are asymptomatic, bleeding and thrombosis. The majority of patient are asymptomatic. However, the single fibrinogen detection method is easy to cause missed diagnosis or misdiagnosis of CD patients. The treatment strategies of CD patients with different clinical manifestations are also different.
METHODS
Combing the existing experimental diagnosis technology, literature and our research results, a simple and practical CD diagnostic criteria was proposed. And based on the relevant literature and existing treatment guidelines, more comprehensive treatment recommendations are summarized.
RESULTS
In this new criteria, combination Clauss method and PT derived method was proposed to detect fibrinogen and its ratio was used to diagnose for CD. Diagnosis also needs to be combined the clinical manifestations, family investigation and genetic testing. According to different clinical manifestation (bleeding, thrombosis or asymptomatic), treatment methods and strategies are different. The treatment of CD patients should consider the patient's personal and family history of bleeding or thrombosis. Treatment of thrombosis and pregnancy may be more challenging. The risk of bleeding and thrombosis should be evaluated and balanced at all times during clinical treatment. These detailed treatment recommendations can provide reference for patients with different clinical manifestations of CD.
CONCLUSIONS
The new CD diagnosis criteria and comprehensive treatment recommendations can effectively improve the diagnosis and treatment of CD.
PubMed: 38642629
DOI: 10.1016/j.cca.2024.119680 -
British Journal of Haematology Jun 2024
Topics: Humans; Afibrinogenemia; Fibrinogen; Hemorrhage; Thrombosis; Female; Male; Arginine
PubMed: 38607668
DOI: 10.1111/bjh.19431 -
British Journal of Haematology Jun 2024
Topics: Humans; Afibrinogenemia; Fibrinogen; Hemorrhage; Thrombosis; Male; Female; Adult; Middle Aged; Arginine
PubMed: 38607667
DOI: 10.1111/bjh.19430 -
Acta Obstetricia Et Gynecologica... Jul 2024Pregnant women with a fibrinogen level <2 g/L represent a high-risk group that is associated with severe postpartum hemorrhage and other complications. Women who would...
INTRODUCTION
Pregnant women with a fibrinogen level <2 g/L represent a high-risk group that is associated with severe postpartum hemorrhage and other complications. Women who would qualify for fibrinogen therapy are not yet identified.
MATERIAL AND METHODS
A population-based cross-sectional study was conducted using the UK Obstetric Surveillance System between November 2017 and October 2018 in any UK hospital with a consultant-led maternity unit. Any woman pregnant or immediately postpartum with a fibrinogen <2 g/L was included. Our aims were to determine the incidence of fibrinogen <2 g/L in pregnancy, and to describe its causes, management and outcomes.
RESULTS
Over the study period 124 women with fibrinogen <2 g/L were identified (1.7 per 10 000 maternities; 95% confidence interval 1.4-2.0 per 10 000 maternities). Less than 5% of cases of low fibrinogen were due to preexisting inherited dysfibrinogenemia or hypofibrinogenemia. Sixty percent of cases were due to postpartum hemorrhage caused by placental abruption, atony, or trauma. Amniotic fluid embolism and placental causes other than abruption (previa, accreta, retention) were associated with the highest estimated blood loss (median 4400 mL) and lowest levels of fibrinogen. Mortality was high with two maternal deaths due to massive postpartum hemorrhage, 27 stillbirths, and two neonatal deaths.
CONCLUSIONS
Fibrinogen <2 g/L often, but not exclusively, affected women with postpartum hemorrhage due to placental abruption, atony, or trauma. Other more rare and catastrophic obstetrical events such as amniotic fluid embolism and placenta accreta also led to low levels of fibrinogen. Maternal and perinatal mortality was extremely high in our cohort.
Topics: Humans; Female; Pregnancy; United Kingdom; Adult; Cross-Sectional Studies; Postpartum Hemorrhage; Fibrinogen; Cohort Studies; Afibrinogenemia; Pregnancy Outcome; Infant, Newborn; Postpartum Period
PubMed: 38519441
DOI: 10.1111/aogs.14828 -
Haemophilia : the Official Journal of... Apr 2024Inherited factor coagulation deficiencies and vascular bleeding disorders, associated with bleeding of various severity, are often classified as rare bleeding disorders...
Inherited factor coagulation deficiencies and vascular bleeding disorders, associated with bleeding of various severity, are often classified as rare bleeding disorders (RBDs). These include inherited fibrinogen disorders, inherited platelet function disorders (IPFD) and hereditary haemorrhagic telangiectasia (HHT). In the last decades, there have been large increases in knowledge on the epidemiology, genetics, physiopathology, clinical features, and diagnosis of RBDs, but improvements in management have been more limited and remain challenging. The treatment mainstay of RBDs is based only on replacement of a few available coagulation factor concentrates or cryoprecipitates. There is growing interest in therapeutic agents that enhance coagulation or inhibiting anticoagulant pathways in RBDs. In severe IPFD, the optimal platelet transfusion strategy is not yet established. Moreover, data is scarce on the effectiveness and safety of desmopressin and/or antifibrinolytic drugs often used for milder IPFD treatment. The best fibrinogen replacement strategy (prophylaxis vs. on demand) in afibrinogenemia is still debated. Similarly, the optimal trough fibrinogen target level for treatment of acute bleeding, and the role of fibrinogen replacement during pregnancy in mild hypofibrinogenemia and dysfibrinogenemia, have not been properly evaluated. The therapeutic arsenal in HHT includes antifibrinolytics and a series of antiangiogenic agents whose potential efficacy has been tested in small studies or are under investigation for treatment of bleeding. However, there is need to address several issues, including the optimal dosing strategies, the potential emergent toxicity of longer-term use, and the impact of systemic antiangiogenic treatment on visceral arteriovenous malformations.
Topics: Pregnancy; Female; Humans; Blood Coagulation Disorders; Hemorrhage; Fibrinogen; Blood Coagulation Factors; Afibrinogenemia; Antifibrinolytic Agents
PubMed: 38494995
DOI: 10.1111/hae.14986 -
Hereditas Feb 2024Congenital fibrinogen disorders are a group of coagulation deficiencies caused by fibrinogen defects and are divided into four types, including afibrinogenemia,...
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.
Topics: Humans; Afibrinogenemia; Asian People; China; Fibrinogen; Mutation
PubMed: 38374144
DOI: 10.1186/s41065-024-00313-3 -
Blood Coagulation & Fibrinolysis : An... Apr 2024An elderly woman with light chain myeloma presented with prolonged epistaxis and extensive cutaneous haematomas: her kappa/lambda ratio was high at 395, her coagulation...
An elderly woman with light chain myeloma presented with prolonged epistaxis and extensive cutaneous haematomas: her kappa/lambda ratio was high at 395, her coagulation screen, thrombin and reptilase times were abnormal, her FV and FX were in the low range in the absence of specific inhibitors, her Clauss fibrinogen was low at 0.95 g/l but antigenic FNG was 1.58 g/l. The patient denied treatment and died of progressive renal failure. We wish to describe the unusual association of FX and FV deficiency co-existing with an acquired dysfibrinogenaemia.
Topics: Aged; Female; Humans; Afibrinogenemia; Factor V; Factor X Deficiency; Fibrinogen; Multiple Myeloma
PubMed: 38358896
DOI: 10.1097/MBC.0000000000001280 -
Frontiers in Neurology 2024Congenital dysfibrinogenemia (CD) is a rare hereditary coagulation disorder resulting from mutations in fibrinogen genes. CD primarily presents with bleeding symptoms,...
BACKGROUND
Congenital dysfibrinogenemia (CD) is a rare hereditary coagulation disorder resulting from mutations in fibrinogen genes. CD primarily presents with bleeding symptoms, but it can also lead to thrombotic events, including ischemic stroke.
CASE PRESENTATION
This report describes the case of a 52-year-old Chinese man who was admitted to the hospital twice due to recurrent cerebral infarction, characterized by sudden speech impairment and weakness in the right upper extremity. Brain MRI revealed multiple ischemic changes, predominantly in the left frontal and parietal lobes. Coagulation tests demonstrated reduced plasma fibrinogen (Clauss method), prolonged prothrombin time and thrombin time, and an elevated international normalized ratio. However, the ELISA assay indicated elevated levels of fibrinogen γ-chain protein. Despite a 2-month-old treatment regimen with aspirin, clopidogrel, and atorvastatin after the first hospitalization, the patient experienced a second ischemic stroke. Genetic analysis using whole-exome sequencing (WES) and Sanger sequencing identified a rare heterozygous missense variation, c.952G>A (rs267606810), in both the stroke patient and his asymptomatic sister. Both individuals exhibited the same alterations in fibrinogen, characterized by reduced functional levels but increased antigenic protein. Subsequently, the patient was diagnosed with ischemic stroke associated with congenital dysfibrinogenemia.
CONCLUSION
This case report expands the clinical phenotype spectrum associated with c.952G>A (rs267606810) and underscores the significance of considering CD as a potential etiology for unexplained ischemic stroke, particularly in patients with a family history of coagulation disorders.
PubMed: 38327620
DOI: 10.3389/fneur.2024.1272802 -
Blood Advances Mar 2024Congenital fibrinogen deficiency (CFD) is a rare bleeding disorder caused by mutations in FGA, FGB, and FGG. We sought to comprehensively characterize patients with CFD...
Congenital fibrinogen deficiency (CFD) is a rare bleeding disorder caused by mutations in FGA, FGB, and FGG. We sought to comprehensively characterize patients with CFD using PRO-RBDD (Prospective Rare Bleeding Disorders Database). Clinical phenotypes, laboratory, and genetic features were investigated using retrospective data from the PRO-RBDD. Patients were classified from asymptomatic to grade 3 based on their bleeding severity. In addition, FGA, FGB, and FGG were sequenced to find causative variants. A total of 166 CFD cases from 16 countries were included, of whom 123 (30 afibrinogenemia, 33 hypofibrinogenemia, 55 dysfibrinogenemia, and 5 hypodysfibrinogenemia) were well characterized. Considering the previously established factor activity and antigen level thresholds, bleeding severity was correctly identified in 58% of the cases. The rates of thrombotic events among afibrinogenemic and hypofibrinogenemic patients were relatively similar (11% and 10%, respectively) and surprisingly higher than in dysfibrinogenemic cases. The rate of spontaneous abortions among 68 pregnancies was 31%, including 86% in dysfibrinogenemic women and 14% with hypofibrinogenemia. Eighty-six patients received treatment (69 on-demand and/or 17 on prophylaxis), with fibrinogen concentrates being the most frequently used product. Genetic analysis was available for 91 cases and 41 distinct variants were identified. Hotspot variants (FGG, p.Arg301Cys/His and FGA, p.Arg35Cys/His) were present in 51% of dysfibrinogenemia. Obstetric complications were commonly observed in dysfibrinogenemia. This large multicenter study provided a comprehensive insight into the clinical, laboratory, and genetic history of patients with CFDs. We conclude that bleeding severity grades were in agreement with the established factor activity threshold in nearly half of the cases with quantitative defects.
Topics: Humans; Female; Fibrinogen; Afibrinogenemia; Prospective Studies; Retrospective Studies; Hemorrhage; Hemostatics
PubMed: 38286442
DOI: 10.1182/bloodadvances.2023012186