Demonstration of heterodimeric fibrinogen molecules partially conjugated with albumin in a novel dysfibrinogen: Fibrinogen Mannheim V

Carl-Erik Dempfle; Peter M.George; Martin Borggrefe; Michael Neumaier; Stephen O. Brennan

doi:10.1160/TH08-09-0559

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2009; 102(01): 29-34
DOI: 10.1160/TH08-09-0559

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Demonstration of heterodimeric fibrinogen molecules partially conjugated with albumin in a novel dysfibrinogen: Fibrinogen Mannheim V

Carl-Erik Dempfle

¹University Hospital of Mannheim, I. Department of Medicine, Mannheim, Germany

,

Peter M.George

²Molecular Pathology Laboratory, Canterbury Health Laboratories, Christchurch Hospital, Christchurch, New Zealand

,

Martin Borggrefe

¹University Hospital of Mannheim, I. Department of Medicine, Mannheim, Germany

,

Michael Neumaier

³University Hospital of Mannheim, Department of Clinical Chemistry, Mannheim, Germany

,

Stephen O. Brennan

²Molecular Pathology Laboratory, Canterbury Health Laboratories, Christchurch Hospital, Christchurch, New Zealand

› Institutsangaben

Abstract

Summary

A 30-year-old female experienced three miscarriages in early pregnancy. Extensive laboratory screening showed a low plasma fibrinogen level of approximately 1 g/l detected by PT-derived fibrinogen assay.The fibrinogen level in the immunological assay was 3 g/l.The functional Clauss assay yielded an intermediate result of 1.78 g/l. During her fourth and fifth pregnancy, the patient received fibrinogen concentrates (Haemocomplettan, CLS Behring, Marburg, Germany), starting with 4 grams of human fibrinogen, followed by 2 grams every second day until the 15th week of pregnancy.The further course of these pregnancies was uneventful. SDS-PAGE and immunoblotting showed doublet bands in the positions of the high-molecular weight (HMW)-and lowmolecular-weight (LMW)-fibrinogen, a single LMW’ fibrinogen band, plus additional bands with higher molecular weight than HMW-fibrinogen, which were also reactive with anti-human serum albumin (HSA) antiserum. These bands correspond to variant fibrinogen conjugated with albumin. Reduced SDS-PAGE and immunoblotting using polyclonal anti-fibrinopeptide A antiserum disclosed one additional Aα-chain band with lower molecular weight. Amplification and sequencing of exon 5 of the α gene indicated heterozygosity for a novel single nucleotide deletion at codon Aα494 (C1537delA). His494 is replaced by Pro and this is followed by 23 (LMKLPSSTLPQLEKHSQ VSSHLC) new amino acids before premature truncation after Cys517, yielding a free C-terminal cysteine, which may link with albumin.This new fibrinogen mutation, leads to a balanced array of homo- and heterodimeric fibrinogen molecules, some of which are conjugated to albumin.

Keywords

Fibrinogen - dysfibrinogenemia - pregnancy complications - recurrent abortions

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Referenzen

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