Acquired Circulating Anticoagulants Other than Lupus Anticoagulants
E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson in Phospholipid-Binding Antibodies, 2020
As with other patients having deficiencies of individual clotting factors, patients with hereditary afibrinogenemia have been reported to develop inhibitors or antibodies to normal fibrinogen following transfusion.114 Many of these “antifibrin(ogen) autoantibodies” have been described as IgM in nature and it is believed that the high molecular weight proteins interfere with the polymerization of the fibrin monomers simply through a physical interaction. However, there have been some cases of specific immunoglobulins, IgGs directed against components of the fibrinogen-converting mechanism. Galanakis and colleagues found two such patients with monoclonal antibodies that reacted with different parts of the fibrinogen molecule.115 Most of these cases have been relatively asymptomatic with no bleeding complications, even following surgery.
Inflammation
George Feuer, Felix A. de la Iglesia in Molecular Biochemistry of Human Disease, 2020
Coagulation disorders include abnormalities of fibrinogen production and metabolism. There are two types: afibrinogenemia or impaired conversion of fibrinogen to fibrin.376 Subjects with congenital absence of fibrinogen have a severe bleeding tendency. These patients are not able to synthesize any fibrinogen-like material. There are a number of individuals whose plasma contains fibrinogen-like substance that coagulate upon the effects of thrombin, but it is abnormally slow. These individuals have a mild bleeding tendency, and some have impaired wound healing or cerebrovascular disease.50 Investigations on these fibrinogens revealed an abnormality in the amino acid sequence of the protein stucture, which is probably responsible for the delayed response to thrombin. In some patients with afibrinogenemia, ADP-induced platelet aggregation is decreased.326
Platelet Disorders Douglas Triplett
Genesio Murano, Rodger L. Bick in Basic Concepts of Hemostasis and Thrombosis, 2019
Most deficiencies of coagulation proteins are associated with a normal bleeding time; however, afibrinogenemia is usually found to have a prolonged bleeding time. In patients with hereditary afibrinogenemia, platelet function studies in vitro are also abnormal.143 There is a deficiency in platelet aggregation with low concentrations of ADP, and retention of platelets in glass-bead columns is decreased. Variable abnormalities in platelet factor 3 activity have also been reported.144 The prolonged bleeding time as well as the platelet abnormalities demonstrable in the laboratory can be corrected by the addition of fibrinogen to the test system.
Hereditary afibrinogenemia and pulmonary-renal hydralazine-induced vasculitis
Published in Baylor University Medical Center Proceedings, 2019
Ginger Tsai-Nguyen, Ariel M. Modrykamien, Arthur Bredeweg
The presented patient had a diagnosis of afibrinogenemia, which may be mistakenly considered the cause of hemoptysis and hematuria. Congenital fibrinogen disorders are of two types. Type I disorders (afibrinogenemia and hypofibrinogenemia) affect the quantity of circulating fibrinogen, and type II disorders (dysfibrinogenemia) affect the quality of circulating fibrinogen.7 Hereditary afibrinogenemia is a very rare bleeding disorder, with a prevalence of 1:1,000,000 live births, and has autosomal recessive genetic transmission.8 Bleeding in the adult population is not unusual9 and most commonly presents as muscle hematoma, easy bruising, menorrhagia, hemarthrosis, or oozing in the oral cavity. Though afibrinogenemia is associated with a bleeding tendency, hemoptysis is a very rare manifestation and should trigger investigation of other lung bleeding causes.9
Fibrinogen alpha amyloidosis: insights from proteomics
Published in Expert Review of Proteomics, 2019
Mutations, both autosomal dominant and recessive, in the fibrinogen chain genes can cause a series of disorders most of which are related to clotting [10,14,15]. Congenital afibrinogenemia is a rare autosomal recessive inherited disorder which usually involves a non-functional mutation in both the maternal and paternal copies of either the FGA, FGB, or FBG genes [16,17]. These individuals experience frequent and sometimes life-threatening episodes of bleeding and/or thrombosis due to a lack of fibrinogen. Congenital hypofibrinogenemia is also a rare inherited disorder, but individuals only have a non-functional mutation in one of the two parental FGA, FGB, or FBG genes [18]. Blood may not clot normally due to a reduced level of fibrinogen and the lower the fibrinogen levels the more symptomatic. Congenital dysfibrinogenemia is an autosomal dominant inherited disorder in which fibrinogen is composed of a dysfunctional protein made by a mutated gene plus a normal fibrinogen made by a normal gene [19]. Fibrinogen levels appear normal by immunological measurements, but when measured by clot formation methods levels are approximately 50%. This disorder has a reduced penetrance and only some individuals show symptoms of abnormal bleeding or thrombosis.
Evolution of viscoelastic coagulation testing
Published in Expert Review of Hematology, 2020
Kenichi A. Tanaka, Reney A. Henderson, Erik R. Strauss
The utility of FIBTEM in monitoring fibrinogen replacement was previously demonstrated in patients with afibrinogenemia [94]. In an observational study of 16 patients, human fibrinogen concentrate (RiaStap, CSL Behring, Marburg, Germany) was intravenously dosed at 70 mg/kg. The pre-treatment FIBTEMMCF was zero, which increased by 8.9 (6.5–16.5) mm in 1 hour after the fibrinogen infusion. VCTs reflect fibrin polymerizing activity of factor XIII (FXIII), and thus TEG and ROTEM may be used to monitor FXIII replacement therapy in hereditary FXIII deficiency. [95] However, there is a paucity of data to support the use of TEG/ROTEM in determining the need for replacement in mild–moderate FXIII deficiency [96].