Determinants of fibrin formation, structure, and function

  title={Determinants of fibrin formation, structure, and function},
  author={Alisa S. Wolberg},
  journal={Current Opinion in Hematology},
  • A. Wolberg
  • Published 1 September 2012
  • Biology, Medicine
  • Current Opinion in Hematology
Purpose of reviewFibrinogen is the protein substrate of the multifaceted procoagulant and proinflammatory enzyme, thrombin. Fibrin, the product of thrombin's proteolytic cleavage of fibrinogen, provides biophysical and biochemical support to blood clots, and subsequent degradation of fibrin by plasmin is a critical inflammatory mediator and essential step in wound healing. As such, fibrin(ogen) lies at the nexus of vascular injury and repair. Herein, we review aspects of fibrin(ogen) formation… 

Fibrin Formation, Structure and Properties.

The X-ray crystallographic structure of major parts of fibrin(ogen), together with computational reconstructions of missing portions and numerous biochemical and biophysical studies, have provided a wealth of data to interpret molecular mechanisms offibrin formation, its organization, and properties.

Mechanisms of fibrin polymerization and clinical implications.

Research on all stages of fibrin polymerization, using a variety of approaches, has revealed aspects of the molecular mechanisms involved that are relevant for the pathogenesis of diseases, prophylaxis, diagnosis, and treatment.

Fibrin clot structure - pro-fibrinolytic effect of oral contraceptives in apparently healthy women.

The effect of OCs on the coagulation system is balanced by alterations in fibrin structure, facilitating clot lysis and contributing to the fibrinolytic susceptibility already present in women treated with OC.

Effect of Ascorbate on Coagulation and Fibrinolytic Factors in the Septic Microvasculature

It is observed that sepsis-induced increases in bacterial count, PAI-1 expression and myeloperoxidase content in various organs were not affected by ascorbate, suggesting that the lack of effect of asCorbate on PAi-1 in the tissue may maintain PAI’1’s beneficial role insepsis.

Batroxobin Binds Fibrin with Higher Affinity and Promotes Clot Expansion to a Greater Extent than Thrombin*

The capacity of batroxobin to promote fibrin accretion is 18-fold greater than that of thrombin, a finding that may explain the microvascular thrombosis that complicates envenomation by B. atrox moojeni.

Lipopolysaccharide-binding protein (LBP) can reverse the amyloid state of fibrin seen or induced in Parkinson's disease

It is hypothesised, and here show, that this unusual clotting in the blood of patients with Parkinson’s Disease can be prevented by LBP, and this adds further evidence implicating inflammatory microbial cell wall products as an accompaniment to the disease, and may be part of its aetiology.

Thrombin and fibrinogen γ' impact clot structure by marked effects on intrafibrillar structure and protofibril packing.

It is concluded that regulation of protofibril content of fibers is an important mechanism by which thrombin and fibrinogen γ' modulatefibrin clot structure and strength and that protein density within fibers correlates with strength of the fibrIn network.

Impact of γ'γ' fibrinogen interaction with red blood cells on fibrin clots.

AFM shows that the recombinant human (rh)γ'γ' fibrinogen increases the binding force and the frequency of the binding to RBCs compared with rhγAγA, promoting cell aggregation.

THROMBOSIS AND HEMOSTASIS Thrombin and fi brinogen g9 impact clot structure by marked effects on intra fi brillar structure and proto fi bril packing

It is demonstrated that, in fully hydrated conditions, thrombin and fibrinogen g9 have dramatic effects on protofibril content and that protein density within fibers correlates with strength of the fibr in network.



Molecular Mechanisms Affecting Fibrin Structure and Stability

  • S. Lord
  • Biology
    Arteriosclerosis, thrombosis, and vascular biology
  • 2011
In insights are provided that might allow the development of pharmaceuticals and treatments to modulate fibrin structure and stability in vivo and thereby prevent or limit thrombotic disease.

Cellular Procoagulant Activity Dictates Clot Structure and Stability as a Function of Distance From the Cell Surface

Thrombus formation in vivo may reflect the ability of the local cell population to support thrombin generation and, therefore, the three-dimensional structure and stability of the fibrin network.

Factor XIIa regulates the structure of the fibrin clot independently of thrombin generation through direct interaction with fibrin.

Modification of fibrin structure by FXIIa represents a novel physiologic role for the contact pathway that may contribute to the pathophysiology of thrombosis.

Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability.

Findings indicate fibrin structure and stability reflect the procoagulant phenotype of the endogenous cells, and suggest abnormal fibr in structure is a novel link between inflammation and thrombosis.

Fibrin(ogen)-alpha M beta 2 interactions regulate leukocyte function and innate immunity in vivo.

Findings have positively established the physiological importance of fibrin(ogen) as a ligand for alpha(M)beta(2) and illustrate that the fibr inogen) gamma chain residues 390-396 constitute a critical feature of the alpha( M) beta( 2) binding motif.

Disaggregation of In Vitro Preformed Platelet-Rich Clots by Abciximab Increases Fibrin Exposure and Promotes Fibrinolysis

The superiority of abciximab over aspirin in accelerating fibrinolysis of forming and preformed PRCs is related to its ability to modulate the interactions of fibr inogen and fibrin with platelets.

Polyphosphate modifies the fibrin network and down-regulates fibrinolysis by attenuating binding of tPA and plasminogen to fibrin.

Data show that polyP directly influences fibrin architecture and attenuates fibrinolysis through reduced binding of fibrinelytic proteins, and that changes induced by polyP occur at the level of conversion offibrinogen to fibrIn.

Alterations of fibrinogen structure in human disease.

  • M. Hoffman
  • Biology
    Cardiovascular & hematological agents in medicinal chemistry
  • 2008
Good evidence exists that fibrinogen modification affects clot stability in vivo, however, direct evidence is still lacking that these modifications contribute to the increased atherothrombotic risk associated with hyperhomocysteinemia and diabetes.

Rheological properties of fibrin clots. Effects of fibrinogen concentration, Factor XIII deficiency, and Factor XIII inhibition.

The effect of fibrinogen concentration, Factor XIII deficiency, and Factor XIII inhibition, utilizing hydroxylamine, on the formation of clot structure in vitro was studied in human platelet-free

Dusart syndrome: a new concept of the relationship between fibrin clot architecture and fibrin clot degradability: hypofibrinolysis related to an abnormal clot structure.

Clot architecture is crucial for the propensity of blood clot to be degraded and that abnormal clot structure can be highly thrombogenic in vivo.