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Annales de Biologie Clinique Aug 2016Congenital fibrinogen disorders comprise quantitative disorders defined by a complete absence (afibrinogenemia) or by a decreased level (hypofibrinogenemia) of... (Review)
Review
Congenital fibrinogen disorders comprise quantitative disorders defined by a complete absence (afibrinogenemia) or by a decreased level (hypofibrinogenemia) of circulating fibrinogen and qualitative disorders characterized by a discrepancy between the activity and the antigenic levels of fibrinogen (dysfibrinogenemia and hypodysfibrinogenemia). The biological diagnosis is based on a standard haemostasis assessment. All the coagulation tests that depend on the formation of fibrin as the end point are affected; although in dysfibrinogenemia the specificity and sensitivity of routine test depend on reagent and techniques. A genetic exploration permits to confirm the diagnosis and may enhance the prediction of the patient's phenotype. Homozygous or composite heterozygous null mutations are most often responsible for afibrinogenemia while hypofibrinogenemic patients are mainly heterozygous carrier of an afibrinogenemic allele. Heterozygous missense mutations are prevalent in dysfibrinogenemia, with two hot spot localized in exon 2 of the FGA and in the exon 8 of the FGG. The correlation between phenotype and genotype has been identified in some fibrinogen variants, including six mutations clustered in exons 8 and 9 of the FGG leading to hypofibrinogenemia with hepatic inclusions of abnormal fibrinogen aggregates as well as a few mutations associated with an increase risk of thrombotic events. A familial screening and additional functional assays should be carried out when possible.
Topics: Afibrinogenemia; Blood Coagulation; Blood Coagulation Disorders, Inherited; Clinical Laboratory Techniques; Diagnosis, Differential; Fibrinogen; Fibrinogens, Abnormal; Humans; Molecular Diagnostic Techniques
PubMed: 27492693
DOI: 10.1684/abc.2016.1167 -
Thrombosis and Haemostasis Sep 2009
Topics: Blood Platelets; Coagulation Protein Disorders; Crystallography, X-Ray; Dimerization; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Heterozygote; Humans; Models, Genetic; Mutation; Phosphorylation; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex; Protein Binding
PubMed: 19718461
DOI: 10.1160/TH09-07-0432 -
American Journal of Hematology Dec 1997
Topics: Adult; Afibrinogenemia; Blood Coagulation; Bone Marrow Transplantation; Female; Fibrinogen; Humans; Liver Diseases; Liver Function Tests; Transplantation, Homologous
PubMed: 9395195
DOI: 10.1002/(sici)1096-8652(199712)56:4<294::aid-ajh17>3.0.co;2-9 -
Indian Journal of Hematology & Blood... Sep 2017Congenital dysfibrinogenemia is a rare autosomal recessive bleeding disorder, which is characterized by the absence of functional fibrinogen. Patients may have bleeding...
Congenital dysfibrinogenemia is a rare autosomal recessive bleeding disorder, which is characterized by the absence of functional fibrinogen. Patients may have bleeding and paradoxical arterial and venous thrombotic problems from early childhood. The optimal antithrombotic therapy in these patients hasn't been determined yet. In this report we present a dysfibrogenemic patient, who has suffered recurrent arterial thrombosis under aspirin treatment. Intravenous fibrinogen concentrates (fc) along with reduced doses of rivaroxaban (10 mg daily), cilostazol (50 mg bid) and aspirin (100 mg daily) were given as antithrombotic treatment. The pain and the cyanosis clinically recovered within 6 weeks. This is, to our knowledge, the first time in which a new oral anticoagulant, rivaroxaban and cilostazol combination was used in a dysfibrinogenemic patient with thrombotic episodes. We determined the type, the dosage and the duration of antithrombotic treatment according to the clinical progress of the symptoms. Rivaroxaban, cilostazol and fibrinogen concentrate replacement; combination may represent a useful alternative for the antithrombotic treatment in dysfibrinogenemic patients.
PubMed: 28824252
DOI: 10.1007/s12288-016-0751-2 -
The New England Journal of Medicine Aug 1978Abnormal coagulation studies indicative of a dysfibrinogen were found in the plasma of four of seven patients with malignant hepatoma. The abnormal fibrinogen was...
Abnormal coagulation studies indicative of a dysfibrinogen were found in the plasma of four of seven patients with malignant hepatoma. The abnormal fibrinogen was characterized by prolonged prothrombin, thrombin and reptilase times and inhibition of the coagulation of normal plasma. Purified fibrinogen revealed abnormalities similar to those in plasma. The functional defect was one of delayed polymerization of the fibrin monomer. The carbohydrate content of the abnormal fibrinogen was increased, and this change was related to the abnormal fibrinogen function. Enzymatic cleavage of sialic acid from the abnormal fibrinogen restored fibrinogen function to normal. This hepatoma-associated dysfibrinogen (acquired dysfibrinogenemia) is similar in many respects to fetal fibrinogen and may represent the presence of a fetal form of fibrinogen in hepatoma.
Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Carbohydrates; Carcinoma, Hepatocellular; Fetal Blood; Fibrinogen; Humans; Liver Neoplasms; Neuraminidase; Sialic Acids
PubMed: 207986
DOI: 10.1056/NEJM197808032990503 -
Pediatric Blood & Cancer Jul 2021
Topics: Afibrinogenemia; Child; Family; Humans; Leukemia, Myeloid, Acute
PubMed: 33822462
DOI: 10.1002/pbc.29050 -
Journal of Clinical Pathology Feb 2017A novel heterozygous variant, FGA c.169_180+2 del (designated fibrinogen Shanghai), was identified in a patient with dysfibrinogenemia with antiphospholipid antibody...
Dysfibrinogenemia-associated novel heterozygous mutation, Shanghai (FGA c.169_180+2 del), leads to N-terminal truncation of fibrinogen Aα chain and impairs fibrin polymerization.
AIMS
A novel heterozygous variant, FGA c.169_180+2 del (designated fibrinogen Shanghai), was identified in a patient with dysfibrinogenemia with antiphospholipid antibody syndrome (APS) and recurrent venous thrombosis, and in his asymptomatic father. We aimed to reveal the functional implication of structural change caused by this variant.
METHODS
Transcription analysis was performed with FGA minigene transfection assay to evaluate the impact of nucleosides deletion on mRNA editing. The fibrinogen isolated from propositus' plasma was used to characterise its functional defects. Fibrin polymerization and clot lysis experiments were performed by optical measurement of turbidity. Thrombin-catalysed fibrinopeptide release was analysed by the reversed-phase, high-performance liquid chromatography. The ultrastructures of fibrin clots were visualised by scanning electron microscopy.
RESULTS
FGA c.169_180+2 del led to an aberrant mRNA with exon 2 skipping and encoded an shortened Aα chain with 42 amino acids truncation at its N-terminal. The propositus' fibrinogen had an impaired release of fibrinopeptide A and abnormal polymerization with a significantly prolonged lag time, a slower maximum slope and reduced final turbidity. The fibrin clot formed with propositus' fibrinogen showed thicker fibres with looser network structure. Clot lysis was normal using the purified fibrinogen but was significantly impaired using the plasma sample from propositus, compared with that from his father.
CONCLUSIONS
Fibrinogen Shanghai results in N-terminal truncation of Aα chain, which does not interfere with synthesis, assembly or secretion of fibrinogen, but compromises fibrin polymerization and clot formation. APS at least partially contributes to the development of thrombosis in the propositus.
Topics: Afibrinogenemia; Antiphospholipid Syndrome; China; Fibrin; Fibrinogen; Humans; Male; Mutation; Venous Thrombosis; Young Adult
PubMed: 27555433
DOI: 10.1136/jclinpath-2016-203862 -
The Canadian Veterinary Journal = La... Jul 1997Hereditary fibrinogen deficiency is a rare condition in all species. Measurement of plasma fibrinogen should indicate low levels. Specific factor assays and pedigree...
Hereditary fibrinogen deficiency is a rare condition in all species. Measurement of plasma fibrinogen should indicate low levels. Specific factor assays and pedigree analysis are essential in establishing a definitive diagnosis of the hereditary deficiency. Differentiation between afibrinogenemia, hypofibrinogenemia, and dysfibrinogenemia requires sophisticated techniques and assistance from a specialized laboratory.
Topics: Afibrinogenemia; Animals; Diagnosis, Differential; Female; Sheep; Sheep Diseases
PubMed: 9220135
DOI: No ID Found -
Journal of Neurosurgical Anesthesiology Oct 2016
Topics: Afibrinogenemia; Brain; Hematoma, Subdural; Humans; Infant; Male; Tomography, X-Ray Computed
PubMed: 26524418
DOI: 10.1097/ANA.0000000000000244 -
BMJ Case Reports Jul 2019Patients with multiple myeloma (MM) are at risk for acquired dysfibrinogenemia resulting in laboratory abnormalities and/or bleeding complications. We describe a...
Patients with multiple myeloma (MM) are at risk for acquired dysfibrinogenemia resulting in laboratory abnormalities and/or bleeding complications. We describe a 63-year-old man who presented with bleeding diathesis in the presence of a low fibrinogen activity level with a normal fibrinogen antigen level. Further studies revealed elevated levels of lambda free light chains, and he was diagnosed with MM. Despite initiating treatment with bortezomib/dexamethasone, he continued to have recurrent bleeds along with hypofibrinogenaemia, prompting a switch to carfilzomib/dexamethasone. The patient responded with improvement in bleeding symptoms, normalisation of fibrinogen activity and a decrease in serum free light chains.
Topics: Afibrinogenemia; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Drug Substitution; Hemorrhage; Humans; Immunoglobulin lambda-Chains; Male; Middle Aged; Multiple Myeloma; Oligopeptides
PubMed: 31320370
DOI: 10.1136/bcr-2019-229312