Related Experiment Video
Updated: Oct 1, 2026

Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States
Published on: April 1, 2015
Fibrinogen Hillsborough: a novel gammaGly309Asp dysfibrinogen with impaired clotting
Jennifer L Mullin1, Stephen O Brennan, Peter S Ganly
1Molecular Pathology Laboratory, Canterbury Health Laboratories, Christchurch Hospital, Christchurch, New Zealand. jennifer.mullin@chmeds.ac.nz
Abstract:
We present a novel gamma-chain dysfibrinogen that was discovered in a 32-year-old asymptomatic man admitted to the hospital after a car accident. He presented with a low fibrinogen concentration, 0.5 mg/mL, and a prolonged thrombin clotting time, 58 seconds. Analysis of purified fibrinogen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a gamma-chain variant with an apparently higher molecular weight. Isoelectric focusing (IEF) demonstrated an anodal shift in the banding pattern of the chains and electrospray ionization mass spectrometry (ESIMS) showed a 27-Da increase in the average mass of the unresolved variant and normal gamma chains. DNA sequence analysis showed a heterozygous mutation of GGC (Gly)-->GAC (Asp) at codon 309 of the gamma chain gene. This Gly--> Asp substitution was consistent with the charge change shown by IEF as well as the mass change identified by ESIMS. Functional analysis revealed that thrombin-catalyzed polymerization occurred with a longer lag time, lower rate of lateral aggregation, and similar final turbidity compared to normal and that factor XIII cross-linking was normal. The polymerization results suggest that residue gamma309 is necessary for proper alignment of fibrinogen molecules, specifically in protofibril formation and D:D interactions. gammaGly309 is highly conserved and x-ray structures support the conclusion that the lack of a side chain at this position helps facilitate the close contact between abutting gammaD domains of condensing fibrin monomers during polymerization.
Related Concept Videos
Clot Retraction and Fibrinolysis
Disorders of Hemostasis
Thromboembolic Disorders
Two factors primarily cause thromboembolic conditions.
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Blood Transfusion and Agglutination
History
The history of blood transfusion dates back to the 17th century, when early attempts were made in animals. In 1818 James Blundell, a British doctor, performed the first successful human blood transfusion. Later in 1900, Karl...
Anticoagulant Drugs: Low-Molecular-Weight Heparins
