Fibrinogen New Orleans: Hereditary dysfibrinogenemia with an Aα chain abnormality

Wa, Andes; Chavin, Stephen I.; Beltran, German; Stuckey, W. J.

doi:10.1016/0049-3848(82)90213-4

Cited by 10 publications

(5 citation statements)

References 12 publications

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“…This supports the conclusion (Martinelli & Scheraga, 1980) that the chains behave independently in their competition for thrombin. The independence of the Aa and B/3 chains, in their competition for thrombin, is also supported by the report of Andes et al (1982) that FpB is released (at a slightly lower than normal rate) before the complete release of FpA in fibrinogen New Orleans (an abnormal fibrinogen). Henschen et al (1983) divide abnormal fibrinogens into several categories according to the number of moles of FpA and FpB released per mole of F. Two categories of interest here are those in which 2 mol of FpB and 0 mol of FpA are released per mol of F (e.g., fibrinogen Metz) and those in which 2 mol of FpB and 1 mol of FpA are released per mol of F (e.g., fibrinogens Amsterdam, Frankfurt II and III, London III, and Zurich I).…”

Section: Discussionsupporting

confidence: 62%

Comparison of structures of various human fibrinogens and a derivative thereof by a study of the kinetics of release of fibrinopeptides

Hanna¹,

Scheraga²,

Francis³

et al. 1984

Biochemistry

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The kinetics of the thrombin-induced release of fibrinopeptides from several variants of human fibrinogen, and from the plasmin digestion fragment E thereof, have been studied by using an HPLC technique to separate the reaction products. The data were analyzed in terms of a Michaelis-Menten mechanism in which the A alpha and B beta chains compete for thrombin. Phosphorylation of Ser-3 of the A alpha chain appears to increase the rate of release of the corresponding phosphorylated peptide A from fibrinogen, due to enhanced binding of thrombin (lower value of the Michaelis-Menten constant KM). However, phosphorylation does not affect the rate of release of the unphosphorylated A or B peptides. Increase in the length of the gamma chain (at the C-terminus) does not affect the rate of release of any of the fibrinopeptides. The rate of release of the A peptide from fragment E (which is devoid of the B peptide) is similar to that for the complete fibrinogen molecule. These results are in agreement with an earlier conclusion [Martinelli, R. A., & Scheraga, H. A. (1980) Biochemistry 19, 2343] that the A alpha and B beta chains behave independently in their competition for thrombin; i.e., the hydrolyzable Arg-Gly bonds of the A alpha and B beta chains are both accessible to thrombin.

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Section: Discussionsupporting

confidence: 62%

Comparison of structures of various human fibrinogens and a derivative thereof by a study of the kinetics of release of fibrinopeptides

Hanna¹,

Scheraga²,

Francis³

et al. 1984

Biochemistry

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“…Kotlin et al [23] showed another point of view that some FpB were released from the fibrinogen molecules without any prior release of FpA. Andes et al [28] also suggested that the cleavage and release of FpB are in some way dependent upon the prior release of FpA and the polymerization of fibrinogen. On the basis of these observations, Blomback et al [29] proposed that removal of FpA leads to change in conformation of the fibrinogen molecule and that these conformational changes in turn increase the cleavability of FpB.…”

Section: Discussionmentioning

confidence: 99%

Three cases of congenital dysfibrinogenemia in unrelated Chinese families

Luo¹,

Deng

Xiang³

et al. 2016

Medicine

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Congenital dysfibrinogenemia (CD) is a qualitative fibrinogen disorder caused by an abnormal fibrinogen molecule structure, leading to dysfunctional blood coagulation. This study describes 3 cases of dysfibrinogenemia identified in the unrelated Chinese pedigrees.Routine coagulation screening tests were performed on the probands and their families. The antigens and functionality of fibrinogen was measured using an immunoturbidimetry assay and the Clauss method, respectively. To identify the genetic mutation responsible for these dysfibrinogens, genomic DNA extracted from the blood was analyzed using PCR amplification and direct sequencing. The presence of the mutant chains was determined using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectroscopy. Purified plasma fibrinogen of 3 probands was analyzed using SDS–PAGE, fibrinogen clottability, fibrin polymerization, fibrinopeptide release, and scanning electron microscopy (SEM).The 3 probands had a long thrombin time. Levels of functional fibrinogen were found to be very low, while the fibrinogen antigen was within the normal range. DNA sequencing revealed a heterozygous Arg16His substitution in the fibrinogen Aα chain (FGA). The mutant chains were found to be expressed using MALDI-TOF mass spectroscopy. SDS–PAGE did not reveal any difference in the molecular weights of 3 polypeptide chains between normal and abnormal fibrinogens. Fibrinogen clottability showed a slower fibrin clot formation than the healthy control. Fibrin polymerization, after addition of thrombin, showed a prolonged lag phase and decreased final turbidity. The kinetics of fibrinopeptides release revealed a decreased amount of the released fibrinopeptide A. SEM of the patient's fibrin clot was found to be abnormal.Results indicate that the 3 probands with dysfibrinogenemia were caused by mutations of Aα chain Arg16His. Mutation of this fibrinogen induced dysfunction of plasma fibrinogen.

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“…Release of this peptide from abnormal fibrinogen molecules has been studied by several investigators. 2,16,25,27,29 For example, modification of the Ace chain results in delayed FPA release. Also, FPA content has been proposed as a criteria of quality control for plasma products, such as the Factor VIII concentrates.…”

Section: Clinical Applications Of Fpamentioning

confidence: 99%

Development and Performance Characteristics of a Competitive Enzyme Immunoassay for Fibrinopeptide A

Amiral¹,

Walenga²,

Fareed³

1984

Semin Thromb Hemost

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A simple nonisotopic method for the quantitation of FPA in biologic samples has been developed utilizing a competitive enzyme immunoassay technique. The performance characteristics of these assays have been investigated in both the experimental and clinical settings and were found to be satisfactory for the routine clinical application. This method is comparable to a commercially available RIA kit (Mallinckrodt, St. Louis, MO) in both the clinical and normal samples. This assay can be used in the diagnosis of hypercoagulable states associated with various diseases. Subclinical activation of coagulation can be readily assessed when the global tests, such as the prothrombin time, partial thromboplastin time, and thrombin time, have no value. This test is of value in the monitoring of the newer antithrombotic agents, such as the low molecular weight heparin fractions that do not effect the global assays, such as the partial thromboplastin time. Similarly, the risk of thrombosis associated with the use of procoagulant therapy, such as the activated prothrombin complex concentrates, can be readily assessed using this assay. It is proposed that the FPA measurement may also provide useful information on the quality control of various plasma-based therapeutic products, such as plasma concentrates or activated prothrombin complex concentrates. FPA generation tests are currently proposed for the screening of antithrombotic and prohemostatic agents.

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Fibrinogen New Orleans: Hereditary dysfibrinogenemia with an Aα chain abnormality

Cited by 10 publications

References 12 publications

Comparison of structures of various human fibrinogens and a derivative thereof by a study of the kinetics of release of fibrinopeptides

Comparison of structures of various human fibrinogens and a derivative thereof by a study of the kinetics of release of fibrinopeptides

Three cases of congenital dysfibrinogenemia in unrelated Chinese families

Development and Performance Characteristics of a Competitive Enzyme Immunoassay for Fibrinopeptide A

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