Related Experiment Video
Updated: Jul 29, 2026
10:37
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
The conformational basis of thrombosis
R W Carrell1, J A Huntington, A Mushunje
1Department of Haematology, University of Cambridge, Wellcome Trust Centre for Molecular Mechanisms in Disease, UK. rwc1000@cam.ac.uk
Thrombosis and Haemostasis
|August 7, 2001
Summary
Plasma antithrombin spontaneously transitions to an inactive form. This conversion accelerates with heat and can trigger severe thromboembolism in individuals with unstable antithrombin variants.
Area of Science:
- Biochemistry
- Molecular Biology
- Hematology
Background:
- Antithrombin (AT) naturally transitions from an active five-stranded conformation to an inactive six-stranded latent form.
- Detecting latent AT in plasma is challenging due to its rapid dimerization with active AT, creating a confusing electrophoretic profile.
Purpose of the Study:
- To develop a method for unequivocally identifying latent antithrombin in plasma.
- To investigate the temperature-dependent conversion rate of active to latent antithrombin.
- To explore the clinical implications of AT conformational changes, particularly in relation to thromboembolism.
Main Methods:
- Development of a novel micromethod for unequivocal latent antithrombin identification in whole plasma.
- Incubation of plasma at 37°C and elevated temperatures to assess AT transition rates.
- Analysis of AT conformational changes in relation to temperature and potential genetic variants.
Main Results:
- At 37°C, approximately 10% of plasma antithrombin converts to the latent form within 24 hours.
- Increased temperatures significantly accelerate the conversion rate of active to latent antithrombin.
- Conformationally unstable antithrombin variants exhibit accelerated transition, potentially triggered by fever.
Conclusions:
- Latent antithrombin formation is a significant process in plasma, influenced by temperature.
- Plasma concentrate pasteurization efficacy requires reassessment due to accelerated AT transition.
- Fever-induced AT transition in unstable variants may precipitate thromboembolic events, offering insights into conformational diseases.
Related Concept Videos
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
01:09Coagulation
The coagulation phase is a critical part of the body's process to prevent blood loss following injury to blood vessels. It involves chemical reactions that form a clot to seal the injured area. The clotting process begins shortly after injury, within 15-20 seconds for severe damage and 1-2 minutes for minor injuries.
During the coagulation phase, clotting factors, or procoagulants, play a vital role in initiating and progressing the coagulation cascade. This cascade is a series of reactions...
During the coagulation phase, clotting factors, or procoagulants, play a vital role in initiating and progressing the coagulation cascade. This cascade is a series of reactions...
01:20Extrinsic and Intrinsic Pathways of Hemostasis
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
01:16Clot Retraction and Fibrinolysis
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
01:30Venous Thrombosis I: Introduction
Venous thrombosis, the most common disorder of the veins, involves the formation of a thrombus or blood clot associated with vein inflammation. It can be classified as either superficial vein thrombosis or deep vein thrombosis.Superficial Vein Thrombosis: This involves the formation of a thrombus in a superficial vein, usually the greater or lesser saphenous vein. Though less severe than deep vein thrombosis (DVT), SVT can lead to complications if untreated.Deep Vein Thrombosis (DVT): This...