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Analysis of β-Amyloid-induced Abnormalities on Fibrin Clot Structure by Spectroscopy and Scanning Electron Microscopy
Published on: November 30, 2018
Structural changes in the fibrin network of a pretoria family with dysfibrinogenemia: a scanning electron
E Pretorius1, S Briedenhann, J Marx
1Department of Anatomy, School of Health Sciences, Medical Faculty of the University of Pretoria, Pretoria, South Africa. resia.pretorius@up.ac.za
Insights
Congenital dysfibrinogenemias cause abnormal fibrin structure. This study found a specific fibrinogen defect leads to a dense, tight fibrin network, increasing thrombosis risk, though bleeding may also occur due to platelet interaction issues.
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- Inborn errors of fibrinogen structure define congenital dysfibrinogenemias.
- These genetic defects impact fibrin clot formation and function.
- Understanding fibrin network morphology is crucial for diagnosing and managing bleeding or clotting disorders.
Purpose of the Study:
- To characterize the fibrin network morphology in a family with a specific gamma-chain fibrinogen defect.
- To correlate fibrin ultrastructure with clinical manifestations of thrombosis and bleeding.
- To investigate the impact of this defect on fibrin polymerization and platelet interactions.
Main Methods:
- Scanning electron microscopy (SEM) was used to analyze fibrin network morphology.
- Fibrin clot analysis was performed on four family members with the identified genetic defect.
- Clinical data regarding bleeding and thrombosis history were collected.
Main Results:
- A consistent tighter fibrin network with increased density and reduced pore size was observed in all affected family members.
- Fibrin fibers exhibited a "stellate" appearance and longitudinal fusion, forming "matted" sheets.
- Platelets were conspicuously absent in the fibrin clots, suggesting impaired platelet binding.
- The study identified an amino-acid substitution (Cys to Tyr at position 139) on the gamma chain, disrupting disulfide bonds and fibrin polymerization.
Conclusions:
- The identified fibrinogen defect leads to abnormal fibrin polymerization and a rigid, dense fibrin network.
- This altered fibrin structure is independently associated with thrombotic disease.
- Bleeding tendencies may arise from defective fibrin binding to activated platelets, impairing thrombin generation.
- Congenital dysfibrinogenemias present with diverse clinical phenotypes, including thrombosis and bleeding, linked to specific fibrin network abnormalities.
Abstract:
Inborn errors of fibrinogen structure are by definition congenital dysfibrinogenemias. The present study assesses the scanning electron microscope characteristics in the fibrin network morphology in a Pretoria family with an amino-acid substitution defect at position 139 on the gamma chain where the cystein residue is replaced by tyrosine. This anomaly results in a disturbance of the interchain disulfide bond, an ultrastructural defect that interferes with fibrin polymerization. Clinical manifestations showed that 2 of the family members presented with thrombosis, as well as a bleeding tendency, while 2 were asymptomatic. Fibrin clot analysis revealed that in all 4 family members a tighter fibrin network with increased fibrin density and reduced pore size was present. The fibers showed a "stellate" appearance where they converge and some were fused longitudinally to form sheets of "matted" fibrin. Furthermore, there was a conspicuous absence of platelets. Fibrin dysfunction is associated with the development of vascular complications, while proneness to the formation of tight and rigid fibrin networks is independently associated with thrombotic disease. Although this does not explain the proneness of some family members who present with excess bleeding, bleeding might be related to the defective binding of fibrin to activated platelets, resulting in inadequate prothrombotic stimulus that is normally enhanced by the second wave of thrombin generation, which occurs on the platelet surface.
