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Clinical Chemistry Apr 1985Inherited qualitative abnormalities of fibrinogen have been documented in more than 100 families. These dysfibrinogenemias usually are clinically silent, but in some...
Inherited qualitative abnormalities of fibrinogen have been documented in more than 100 families. These dysfibrinogenemias usually are clinically silent, but in some cases are associated with bleeding, thrombosis, or defective wound healing. Abnormalities of the fibrinogen molecule may impair any of the major steps involved in the conversion of fibrinogen into stabilized fibrin; i.e., cleavage of the fibrinopeptides by thrombin, polymerization, and cross-linking of fibrin. Biochemical studies of several abnormal fibrinogens have demonstrated that the functional defects are the result of single amino acid substitutions. The hereditary dysfibrinogenemias are the first coagulation disorder in which the pathophysiology has been elucidated on a molecular level. Studies of these "experiments of nature" have important implications in such diverse processes as wound healing and thrombosis.
Topics: Biopolymers; Blood Coagulation Disorders; Chemical Phenomena; Chemistry; Fibrin; Fibrinogen; Heterozygote; Humans; Protein Binding; Thrombin; Thrombosis; Wound Healing
PubMed: 3978780
DOI: No ID Found -
TH Open : Companion Journal To... Jan 2022
PubMed: 35088022
DOI: 10.1055/s-0041-1740644 -
British Journal of Haematology Aug 2001
Review
Topics: Afibrinogenemia; Blood Coagulation Tests; Carcinoma, Hepatocellular; Fibrinogen; Hemorrhage; Humans; Liver Cirrhosis; Liver Neoplasms; Mutation; Thrombosis
PubMed: 11529842
DOI: 10.1046/j.1365-2141.2001.02892.x -
Indian Journal of Hematology & Blood... Jun 2016
PubMed: 27408401
DOI: 10.1007/s12288-015-0606-2 -
Rinsho Byori. the Japanese Journal of... May 1987
Review
Topics: Afibrinogenemia; Antithrombins; Fibrinogen; Humans; Thrombosis
PubMed: 3302409
DOI: No ID Found -
International Journal of Hematology Jul 2020We report a case of acquired dysfibrinogenemia with monoclonal gammopathy of undetermined significance presenting λ-type IgA M protein. The patient showed lower...
We report a case of acquired dysfibrinogenemia with monoclonal gammopathy of undetermined significance presenting λ-type IgA M protein. The patient showed lower functional (0.4 g/dL) and normal immunological fibrinogen (2.9 g/dL). To examine the cause of the false lower value of fibrinogen, we performed experiments using the patient's purified fibrinogen and IgA. Fibrinogen was purified from the patient's plasma; IgA was purified from plasma or serum by immunoaffinity chromatography. We performed thrombin-catalyzed fibrin polymerization, scanning electron microscopy (SEM), immunoblotting analysis, and enzyme-linked immunosorbent assays (ELISAs). Fibrin polymerization in the patient's plasma was markedly reduced and SEM showed no fiber bundles or sponge-like structures. Purified IgA did not influence polymerization, whereas immunoprecipitated plasma with an anti-IgA (α-chain) antibody indicated normalization of polymerization and clot structure. Western blotting analysis revealed the presence of monoclonal λ-type IgA-bound fibrinogen, the proportion of which was significantly higher than normal control plasma using ELISA. Our results suggest that IgA M protein-bound fibrinogen is not normally converted into fibrin, but rather leads to formation of an aberrantly structured fragile clot. The patient's reduced plasma fibrinogen level was caused by the presence of IgA M protein-bound fibrinogen, not by IgA M protein alone.
Topics: Adult; Blood Coagulation Disorders; Fibrinogen; Humans; Immunoglobulin A; Male; Polymerization; Thrombin; Thrombosis
PubMed: 32253663
DOI: 10.1007/s12185-020-02874-1 -
La Tunisie Medicale Oct 2010Congenital dysfibrinogenemia is a functional disorder of the fibrinogen that represents a rare cause of thrombophilia.
BACKGROUND
Congenital dysfibrinogenemia is a functional disorder of the fibrinogen that represents a rare cause of thrombophilia.
AIM
To report a Tunisian case of the association dysfibrinogenemia and thrombosis.
CASE
A woman with inherited dysfibrinogenemia associated with mild tendency to bleeding experienced a deep vein thrombosis of the lower-extremity at 26 years of age and a fatal pulmonary embolism a few years later. Paradoxically coagulation function of fibrinogen was markedly altered in vitro with a significantly prolonged prothrombin time, activated partial thromboplastin time and thrombin time, a functional fibrinogen level that was undetected and a severely impaired fibrin polymerisation. The thromboembolic events in the patient could be related to dysfibrinogenemia since the main causes of thrombophilia were excluded.
CONCLUSION
Although it is rare, this cause of thrombophilia must not be misdiagnosed, systematic measuring of prothrombin time, activated partial thromboplastin time and functional fibrinogen might be helpful.
Topics: Adult; Afibrinogenemia; Fatal Outcome; Female; Fibrinogens, Abnormal; Humans; Pulmonary Embolism; Thrombophilia; Venous Thrombosis
PubMed: 20890827
DOI: No ID Found -
Journal of Blood Medicine 2016Acquired hypofibrinogenemia is most frequently caused by hemodilution and consumption of clotting factors. The aggressive replacement of fibrinogen has become one of the... (Review)
Review
Acquired hypofibrinogenemia is most frequently caused by hemodilution and consumption of clotting factors. The aggressive replacement of fibrinogen has become one of the core principles of modern management of massive hemorrhage. The best method for determining the patient's fibrinogen level remains controversial, and particularly in acquired dysfibrinogenemia, could have major therapeutic implications depending on which quantification method is chosen. This review introduces the available laboratory and point-of-care methods and discusses the relative advantages and limitations. It also discusses current strategies for the correction of hypofibrinogenemia.
PubMed: 27713652
DOI: 10.2147/JBM.S90693 -
Blood Coagulation & Fibrinolysis : An... Oct 2010A 2-year-old asymptomatic boy and his relatives were investigated for a suspected fibrinogen mutation after coagulation tests revealed a decreased functional fibrinogen...
A 2-year-old asymptomatic boy and his relatives were investigated for a suspected fibrinogen mutation after coagulation tests revealed a decreased functional fibrinogen level (family A). Eight-year-old and 1-year-old asymptomatic brothers were investigated for a suspected fibrinogen mutation after coagulation tests revealed a decreased functional fibrinogen level and prolonged thrombin time (family B). To identify whether genetic mutations were responsible for these dysfibrinogens, DNA extracted from the blood was analyzed. Fibrin polymerization and fibrinolysis were measured by a turbidimetric method at 450 nm. DNA analysis was performed by the Sanger method. Mass spectroscopy was performed on a Biflex IV mass spectrometer. DNA sequencing showed the heterozygous point mutation Aα Arg16His in the fibrinogen of family A and the heterozygous point mutation Aα Arg16Cys in the fibrinogen of family B. Kinetics of fibrinopeptide release, fibrinolysis, and fibrin polymerization were impaired in the carriers of the mutations in both families. Mass spectroscopy showed the presence of mutant fibrinogen chains in circulation. Scanning electron microscopy revealed thicker fibrin fibers, differing significantly from the normal control in both cases. Two cases of asymptomatic dysfibrinogenemias, found by routine coagulation testing, were genetically identified as new cases of fibrinogen variants Aα Arg16His and Aα Arg16Cys.
Topics: Afibrinogenemia; Child; DNA Mutational Analysis; Fibrin; Fibrinogen; Heterozygote; Humans; Infant; Male; Point Mutation; Siblings; Thrombin Time
PubMed: 20829681
DOI: 10.1097/MBC.0b013e32833e4284 -
The American Journal of the Medical... Jul 1986A 58-year-old black woman with IgD multiple myeloma developed a hemorrhagic diathesis within 48 hours after receiving mithramycin (20 micrograms/kg/day) for therapy of...
A 58-year-old black woman with IgD multiple myeloma developed a hemorrhagic diathesis within 48 hours after receiving mithramycin (20 micrograms/kg/day) for therapy of hypercalcemia. Her coagulation studies were characterized by prolonged prothrombin, partial thromboplastin, thrombin, and reptilase clotting times. Her plasma and partially purified fibrinogen were inhibitory to the clotting of normal plasma and fibrinogen. The patient's isolated fibrinogen showed a normal rate of fibrinopeptide release, but her fibrin monomer aggregation was markedly abnormal. These studies document the development of a dysfibrinogenemia secondary to mithramycin toxicity.
Topics: Afibrinogenemia; Blood Coagulation Tests; Female; Hemorrhagic Disorders; Humans; Hypercalcemia; Middle Aged; Multiple Myeloma; Plicamycin
PubMed: 2940861
DOI: 10.1097/00000441-198607000-00011