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Published in:

01-10-2018

Abnormal fibrinogen with an Aα 16Arg → Cys substitution is associated with multiple cerebral infarctions

Authors: Meiling Luo, Aiqiu Wei, Liqun Xiang, Jie Yan, Lin Liao, Xuelian Deng, Donghong Deng, Peng Cheng, Faquan Lin

Published in: Journal of Thrombosis and Thrombolysis | Issue 3/2018

Abstract

We found a heterozygous dysfibrinogenemia caused by a substitution of AαArg16Cys. The proband suffered multiple cerebral infarctions. Routine coagulation tests revealed a prolonged thrombin time. The fibrinogen levels in the functional assays were considerably lower than the levels in the immunological assays. The polymerization of the purified fibrinogen was strongly impaired in the presence of calcium. As previously observed in other heterozygous Aα R16C variants, the release rate and amount of fibrinopeptide A (FPA) were lower in the proband than those in normal controls. Additionally, the release of fibrinopeptide B (FpB) was delayed. The immunoblotting analysis using antibodies against human serum albumin indicated that albumin is bound to Aα R16C. The mass spectrometry analysis showed that the Aα R16C fibrinogen chains appeared in the patient’s circulation. The clot structure analysis using scanning electron microscopy (SEM) revealed that the fibrin network was dense and consisted of thin and highly branched fibres. Using overlaid fibrinolytic enzymes in a clot lysis experiment, clot degradation was observed to be delayed. These results indicated that the thrombotic tendency may be ascribed to a fibrinolytic resistance caused by an abnormal clot structure with thin fibres and fibrinogen–albumin complexes.

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Title: Abnormal fibrinogen with an Aα 16Arg → Cys substitution is associated with multiple cerebral infarctions
Authors: Meiling Luo
Aiqiu Wei
Liqun Xiang
Jie Yan
Lin Liao
Xuelian Deng
Donghong Deng
Peng Cheng
Faquan Lin
Publication date: 01-10-2018
Publisher: Springer US
Published in: Journal of Thrombosis and Thrombolysis / Issue 3/2018
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI: https://doi.org/10.1007/s11239-018-1689-z

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Abnormal fibrinogen with an Aα 16Arg → Cys substitution is associated with multiple cerebral infarctions

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