497 results match your criteria Dysfibrinogenemia

Fibrinogen Longmont: A Clinically Heterogeneous Dysfibrinogenemia with Discrepant Fibrinogen Results Influenced by Clot Detection Method and Reagent.

TH Open 2022 Jan 24;6(1):e18-e20. Epub 2022 Jan 24.

Department of Haematology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia.

View Article and Full-Text PDF
January 2022

Mutations Accounting for Congenital Fibrinogen Disorders: An Update.

Semin Thromb Hemost 2022 Jan 24. Epub 2022 Jan 24.

Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

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, , and 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. Read More

View Article and Full-Text PDF
January 2022

Development and validation of a novel qualitative test for plasma fibrinogen utilizing clot waveform analysis.

Sci Rep 2022 01 21;12(1):434. Epub 2022 Jan 21.

Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Aichi, Japan.

Plasma fibrinogen is commonly examined by Clauss fibrinogen assay, which cannot distinguish between quantitative and qualitative fibrinogen anomalies. However, our previously reported Clauss fibrinogen assay utilizing clot waveform analysis (Clauss-CWA) provides additional information that contributes to the classification of fibrinogen anomalies. In this study, we adopted the Clauss-CWA method for an autoanalyzer to automatically measure the antigenic estimate (eAg) of fibrinogen in addition to the functional amount (Ac), and to thus provide the Ac/eAg ratio as a qualitative indicator. Read More

View Article and Full-Text PDF
January 2022

Congenital dysfibrinogenemia in major surgery: A description of four cases and review of the literature.

Clin Chim Acta 2022 Mar 19;528:1-5. Epub 2022 Jan 19.

Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. Electronic address:

Background: Congenital dysfibrinogenemia is characterized by qualitatively abnormal fibrinogens with resultant blood coagulation dysfunction. The clinical manifestations are high heterogeneity. Treatment for dysfibrinogenemia should be personalized. Read More

View Article and Full-Text PDF

Structural and Functional Characterization of Four Novel Fibrinogen Mutations in Causing Congenital Fibrinogen Disorder.

Int J Mol Sci 2022 Jan 10;23(2). Epub 2022 Jan 10.

Department of Biochemistry, Institute of Hematology and Blood Transfusion, U Nemocnice 2094/1, 12800 Prague, Czech Republic.

Congenital fibrinogen disorders are caused by mutations in genes coding for fibrinogen and may lead to various clinical phenotypes. Here, we present a functional and structural analysis of 4 novel variants located in the gene coding for fibrinogen Bβ chain-heterozygous missense BβY416C and BβA68S, homozygous nonsense BβY345*, and heterozygous nonsense BβW403* mutations. The cases were identified by coagulation screening tests and further investigated by various methods. Read More

View Article and Full-Text PDF
January 2022

[Pedigree Analysis and Diagnosis of Congenital Dysfibrinogenemia: A Case Report].

Sichuan Da Xue Xue Bao Yi Xue Ban 2022 Jan;53(1):171-174

Department of Neonatology, West China Second University Hospital, Key Laboratory of Birth Defects and Related Disease of Women and Children of the Ministry of Education, Sichuan University, Chengdu 610041, China.

Objective: To improve the understanding and diagnosis and treatment of congenital dysfibrinogenemia (CD) through analyzing the clinical data of a pediatric patient and his pedigree.

Methods: The clinical manifestations, laboratory findings and treatment of a case of CD diagnosed at West China Second University Hospital, Sichuan University and those of its pedigree members were analyzed, and genetic tracing and follow-up were conducted on the patient and its pedigree.

Results: The child has no clinical manifestations at the time of admission. Read More

View Article and Full-Text PDF
January 2022

Extension of the Human Fibrinogen Database with Detailed Clinical Information-The αC-Connector Segment.

Int J Mol Sci 2021 Dec 23;23(1). Epub 2021 Dec 23.

Department of Biochemistry, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 12800 Prague, Czech Republic.

Fibrinogen, an abundant plasma glycoprotein, is involved in the final stage of blood coagulation. Decreased fibrinogen levels, which may be caused by mutations, are manifested mainly in bleeding and thrombotic disorders. Clinically relevant mutations of fibrinogen are listed in the Human Fibrinogen Database. Read More

View Article and Full-Text PDF
December 2021

Congenital Afibrinogenemia and Hypofibrinogenemia: Laboratory and Genetic Testing in Rare Bleeding Disorders with Life-Threatening Clinical Manifestations and Challenging Management.

Diagnostics (Basel) 2021 Nov 19;11(11). Epub 2021 Nov 19.

National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, Slovakia.

Congenital fibrinogen disorders are rare pathologies of the hemostasis, comprising quantitative (afibrinogenemia, hypofibrinogenemia) and qualitative (dysfibrinogenemia and hypodysfibrinogenemia) disorders. The clinical phenotype is highly heterogeneous, being associated with bleeding, thrombosis, or absence of symptoms. Afibrinogenemia and hypofibrinogenemia are the consequence of mutations in the homozygous, heterozygous, or compound heterozygous state in one of three genes encoding the fibrinogen chains, which can affect the synthesis, assembly, intracellular processing, stability, or secretion of fibrinogen. Read More

View Article and Full-Text PDF
November 2021

Percutaneous left atrial appendage closure in patients with primary hemostasis disorders and atrial fibrillation.

J Interv Card Electrophysiol 2021 Nov 25. Epub 2021 Nov 25.

Service de Cardiologie, Institut Universitaire de Cardiologie Et de Pneumologie de Québec, 2725 Chemin de Sainte-Foy, Québec City, Québec, G1V 4G5, Canada.

Background Or Purpose: We report our single-center experience with percutaneous left atrial appendage closure (LAAC) in patients with non-valvular atrial fibrillation (NVAF) and primary hemostasis disorders (HD).

Methods: Consecutive patients with primary HD who underwent a percutaneous LAAC were included. Baseline characteristics, procedural data, and clinical outcomes were prospectively collected and compared with the overall LAAC cohort without HD. Read More

View Article and Full-Text PDF
November 2021

Management of congenital dysfibrinogenemia in pregnancy: A challenging patient case.

Res Pract Thromb Haemost 2021 Dec 16;5(8):e12619. Epub 2021 Nov 16.

Division of Hematology and Cellular Therapy Allegheny Health Network Cancer Institute Pittsburgh Pennsylvania USA.

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. Read More

View Article and Full-Text PDF
December 2021

Clinical features and genetic defect in six index patients with congenital fibrinogen disorders: Three novel mutations with one common mutation in Taiwan's population.

Haemophilia 2021 Nov 30;27(6):1022-1027. Epub 2021 Aug 30.

Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Introduction: Congenital fibrinogen disorders (CFDs) are caused by mutations in fibrinogen-encoding genes, FGA, FGB, and FGG, which lead to quantitative or qualitative abnormalities of fibrinogen. Although the diagnosis of CFDs is based on antigenic and functional level of fibrinogen, few genotypes are clearly correlated with phenotype.

Methods: In this study, we investigated all of the referred patients diagnosed as CFDs in Taiwan's population between 1995 and 2020. Read More

View Article and Full-Text PDF
November 2021

Pseudohomozygous dysfibrinogenemia.

Res Pract Thromb Haemost 2021 Aug 21;5(6):e12568. Epub 2021 Aug 21.

School of Cellular and Molecular Medicine University of Bristol Bristol UK.

Hypodysfibrinogenemia (HD) is a heterogeneous disorder in which plasma fibrinogen antigen and function are both reduced but discordant. This report addresses the key clinical question of whether genetic analysis enables clinically useful subclassification of patients with HD. We report a new case and identify a further eight previously documented cases that have the laboratory features of HD but biallelic inheritance of quantitative and qualitative fibrinogen gene variants. Read More

View Article and Full-Text PDF

[Analysis of gene mutation spectrum and pharmacokinetics of fibrinogen infusion in 146 cases of congenital fibrinogen disorders].

Zhonghua Xue Ye Xue Za Zhi 2021 Jul;42(7):555-562

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Tianjin Laboratory of Blood Disease Gene Therapy, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.

To investigate the clinical type and gene mutations, clinical manifestations, laboratory tests, diagnosis, and fibrinogen replacement therapy of congenital fibrinogen disorders. Clinical data of 146 patients with congenital fibrinogen disorders diagnosed from April 2000 to November 2020 were retrospectively analyzed. Among the 146 patients, 61 (41. Read More

View Article and Full-Text PDF

Disorders of Fibrinogen and Fibrinolysis.

Hematol Oncol Clin North Am 2021 12 14;35(6):1197-1217. Epub 2021 Aug 14.

Department of Internal Medicine, Division of Hematology and Hematologic Malignancies, University of Utah, 2000 Circle Hope Drive, Room 4126, Salt Lake City, UT 84112, USA. Electronic address:

Fibrinogen plays a fundamental role in coagulation through its support for platelet aggregation and its conversion to fibrin. Fibrin stabilizes clots and serves as a scaffold and immune effector before being broken down by the fibrinolytic system. Given its importance, abnormalities in fibrin(ogen) and fibrinolysis result in a variety of disorders with hemorrhagic and thrombotic manifestations. Read More

View Article and Full-Text PDF
December 2021

Laboratory Methods in the Assessment of Hereditary Hemostatic Disorders.

Hematol Oncol Clin North Am 2021 12 12;35(6):1051-1068. Epub 2021 Aug 12.

Coagulation and Transfusion Medicine, Rhode Island Hospital and Warren Alpert School of Medicine at Brown University, 593 Eddy Street, Providence, RI 02903, USA. Electronic address:

In patients presenting with a suspect hereditary bleeding disorder a detailed bleeding history is first obtained. Testing proceeds in a tiered manner with platelet count, platelet morphology, platelet histogram, PFA-100, fibrinogen, prothrombin time, and activated partial thromboplastin time. More detailed testing includes von Willebrand factor, individual clotting factor assays, and platelet function testing. Read More

View Article and Full-Text PDF
December 2021

A novel variant fibrinogen, AαE11del, demonstrating the importance of AαE11 residue in thrombin binding.

Int J Hematol 2021 Nov 31;114(5):591-598. Epub 2021 Jul 31.

Department of Clinical Laboratory Investigation, Graduate School of Medicine, Shinshu University, Matsumoto, Japan.

Introduction: We identified a novel heterozygous AαE11del variant in a patient with congenital dysfibrinogenemia. This mutation is located in fibrinopeptide A (FpA). We analyzed the effect of AαE11del on the catalyzation of thrombin and batroxobin and simulated the stability of the complex structure between the FpA fragment (AαG6-V20) peptide and thrombin. Read More

View Article and Full-Text PDF
November 2021

Clinical and molecular characterization of Iranian patients with congenital fibrinogen disorders.

Transfus Apher Sci 2021 Dec 1;60(6):103203. Epub 2021 Jul 1.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran. Electronic address:

Introduction: Congenital fibrinogen disorders (CFDs) are caused by mutations in the FGA, FGB and FGG genes and are classified as quantitative and qualitative fibrinogen defects. This study sought to determine the genetic background of CFDs in Iran and to examine the genotype-phenotype correlation.

Methods: Fourteen patients with a CFD diagnosis were included. Read More

View Article and Full-Text PDF
December 2021

Automated screening procedure for the phenotypes of congenital fibrinogen disorders using novel parameters, |min1|c and Ac/|min1|c, obtained from clot waveform analysis using the Clauss method.

Clin Chim Acta 2021 Oct 15;521:170-176. Epub 2021 Jul 15.

Department of Clinical Laboratory Investigation, Graduate School of Medicine, Shinshu University, Matsumoto, Japan; Laboratory of Clinical Chemistry and Immunology, Department of Biomedical Laboratory Sciences, School of Health Sciences, Shinshu University, Matsumoto, Japan.

Introduction: Fibrinogen activity (Ac) is widely measured, but fibrinogen antigen (Ag) is measured only in specialized laboratories, so it is difficult to discriminate congenital fibrinogen disorders (CFDs) from acquired hypofibrinogenemia (aHypo). In this study, to screen for CFD phenotypes we adopted novel parameters, |min1|c and Ac/ |min1|c, and compared these with validated Ac, Ag, and Ac/Ag, and previously proposed Ac/dH and Ac/|min1|.

Materials And Methods: We calibrated |min1| using a CN-6000 instrument and investigated the correlation between Ag and |min1|c for aHypo (n = 131) and CFD [18 dysfibrinogenemia (Dys), two hypodysfibrinogenemia (Hypodys) and four hypofibrinpogenemia (Hypo)]. Read More

View Article and Full-Text PDF
October 2021

Dysfibrinogenemia-Potential Impact of Genotype on Thrombosis or Bleeding.

Semin Thromb Hemost 2022 Mar 14;48(2):161-173. Epub 2021 Jul 14.

Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.

The congenital dysfibrinogenemias, most often associated with bleeding disorders, encompass mutations in the amino-terminal end of fibrinogen α-chain consisting of Gly17-Pro18-Arg19-Val20, known as knob A, which is a critical site for fibrin polymerization. Here we review the studies reporting dysfibrinogenemia due to mutations affecting fibrinogen knob A and identified 29 papers. The number of reports on dysfibrinogenemias related to residues Gly17, Pro18, Arg19, and Val20 is 5, 4, 18, and 2, respectively. Read More

View Article and Full-Text PDF

Pembrolizumab-induced hypothyreosis and subcutaneous bleeding.

Vnitr Lek 2021 ;67(3):175-179

Pembrolizumab belongs to so called immune checkpoint inhibitors. Frequent adverse event of this therapy is hypothyroidism. The authors present a case report of patient treated with pembrolizumab for non-small cell lung carcinoma, in whom severe hypothyroidism followed quite rapidly after transient phase of subclinical hyperthyroidism - at this time point new and spontaneous onset of large subcutaneous hematomas was observed. Read More

View Article and Full-Text PDF

Identification of a recurrent missense mutation in the FGA gene likely causing a congenital fibrinogen disorder.

Blood Coagul Fibrinolysis 2021 09;32(6):424-426

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

View Article and Full-Text PDF
September 2021

Congenital Fibrinogen Deficiency in India and Role of Human Fibrinogen Concentrate.

Acta Haematol 2021 4;144(6):595-602. Epub 2021 Jun 4.

Department of Clinical Haematology, Haemato-Oncology and Bone Marrow (Stem Cell) Transplantation, Christian Medical College, Ludhiana, India.

Congenital fibrinogen deficiency is an inherited disorder due to genetic mutations with diverse presentations arising from reduced fibrinogen levels (hypofibrinogenemia), absence of fibrinogen in circulation (afibrinogenemia), abnormal functioning (dysfibrinogenemia) or both reduced levels and abnormal functioning (hypodysfibrinogenemia) of fibrinogen. The decreased fibrinogen concentration in congenital fibrinogen deficiency necessitates fibrinogen replacement therapy with fresh frozen plasma, cryoprecipitate, or human fibrinogen concentrate. However, the use of fresh frozen plasma and cryoprecipitate is limited owing to their longer transfusion time, requirement of high doses, volume overload, risk of viral transmission, and other safety concerns. Read More

View Article and Full-Text PDF
December 2021

How I treat dysfibrinogenemia.

Blood 2021 11;138(21):2021-2030

Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Congenital dysfibrinogenemia (CD) is caused by structural changes in fibrinogen that modify its function. Diagnosis is based on discrepancy between decreased fibrinogen activity and normal fibrinogen antigen levels and is confirmed by genetic testing. CD is caused by monoallelic mutations in fibrinogen genes that lead to clinically heterogenous disorders. Read More

View Article and Full-Text PDF
November 2021

Bleeding Diathesis in Multiple Myeloma: A Rare Presentation of a Dreadful Emergency With Management Nightmare.

Cureus 2021 Mar 19;13(3):e13990. Epub 2021 Mar 19.

Hematology and Oncology, Saint Michael's Medical Center, Newark, USA.

Multiple myeloma is a neoplastic disorder of plasma cells. An abnormal coagulation profile, though commonly seen in multiple myeloma, can rarely manifest as life-threatening hemorrhagic complications. Bleeding tendencies in multiple myeloma can be explained by a variety of mechanisms such as dysfibrinogenemia, paraprotein-induced platelet dysfunction, shortened platelet survival, damage to the vascular endothelium, and acquired von-Willebrand syndrome. Read More

View Article and Full-Text PDF

Hiding in plain sight: Diagnosing congenital dysfibrinogenemia in a child presenting with acute myeloid leukemia.

Pediatr Blood Cancer 2021 07 6;68(7):e29050. Epub 2021 Apr 6.

Department of Pediatrics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.

View Article and Full-Text PDF

Resolving Differential Diagnostic Problems in von Willebrand Disease, in Fibrinogen Disorders, in Prekallikrein Deficiency and in Hereditary Hemorrhagic Telangiectasia by Next-Generation Sequencing.

Life (Basel) 2021 Mar 5;11(3). Epub 2021 Mar 5.

Division of Clinical Laboratory Science and Specialist Clinical Hemostasis Laboratory, Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.

Diagnosis of rare bleeding disorders is challenging and there are several differential diagnostics issues. Next-generation sequencing (NGS) is a useful tool to overcome these problems. The aim of this study was to demonstrate the usefulness of molecular genetic investigations by summarizing the diagnostic work on cases with certain bleeding disorders. Read More

View Article and Full-Text PDF

Effects of pathogen reduction technology and storage duration on the ability of cryoprecipitate to rescue induced coagulopathies in vitro.

Transfusion 2021 06 23;61(6):1943-1954. Epub 2021 Mar 23.

Department of Pediatrics, Division of Critical Care, Washington University School of Medicine, St. Louis, Missouri, USA.

Background: Fibrinogen concentrates and cryoprecipitate are currently used for fibrinogen supplementation in bleeding patients with dysfibrinogenemia. Both products provide an abundant source of fibrinogen but take greater than 10 min to prepare for administration. Fibrinogen concentrates lack coagulation factors (i. Read More

View Article and Full-Text PDF

Whole Blood Thromboelastometry by ROTEM and Thrombin Generation by Genesia According to the Genotype and Clinical Phenotype in Congenital Fibrinogen Disorders.

Int J Mol Sci 2021 Feb 25;22(5). Epub 2021 Feb 25.

Division of Angiology and Hemostasis, University Hospitals of Geneva, 1211 Geneva, Switzerland.

The outcome of congenital fibrinogen defects (CFD) is often unpredictable. Standard coagulation assays fail to predict the clinical phenotype. We aimed to assess the pheno- and genotypic associations of thrombin generation (TG) and ROTEM in CFD. Read More

View Article and Full-Text PDF
February 2021

Congenital dysfibrinogenemia caused by γAla327Val mutation: structural abnormality of D region.

Hematology 2021 Dec;26(1):305-311

Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China.

Background: : Congenital dysfibrinogenemia (CD) is a coagulation disorder caused by mutations in the fibrinogen genes, which result in abnormal fibrinogen function. However, the precise pathogenesis underlying it remains unclear.

Methods: : In this study, we identified a novel heterozygous mutation in an asymptomatic patient with CD caused by γ Ala327Val mutation. Read More

View Article and Full-Text PDF
December 2021