Related Experiment Video
Updated: Jul 4, 2025
A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
Published on: June 4, 2021
Thrombin as target for prevention of recurrent events after acute coronary syndromes
M Cecilia Bahit1, C Michael Gibson2
1INECO Neurociencias, Rosario, Provincia de Santa Fe, Argentina.
Insights
Thrombin plays a key role in acute coronary syndrome (ACS) thrombus formation and recurrent events. Targeting thrombin, like with factor XI inhibition, may reduce cardiovascular events post-ACS while preserving hemostasis.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Thrombosis Research
Background:
- Thrombus formation in acute coronary syndrome (ACS) involves platelets and thrombin.
- Platelet inhibition is common in chronic ACS care, but thrombin is crucial for platelet activation and fibrin formation.
- ACS patients exhibit persistent chronic thrombin generation, linked to adverse events.
Purpose of the Study:
- To review evidence on thrombin generation in recurrent post-ACS events.
- To evaluate thrombin as a therapeutic target in ACS management.
- To explore factor XI inhibition as a potential strategy.
Main Methods:
- Literature review of studies on thrombin generation and ACS pathophysiology.
- Analysis of clinical trial data for antithrombotic therapies in post-ACS care.
- Examination of the role of factor XI in thrombin generation and hemostasis.
Main Results:
- Thrombin generation is implicated in recurrent cardiovascular events post-ACS.
- Targeting thrombin with agents like rivaroxaban or vorapaxar reduced events but increased bleeding.
- Factor XI inhibition is a potential target for reducing thrombin generation while preserving hemostasis.
Conclusions:
- Thrombin generation is a significant factor in recurrent events after ACS.
- Targeting thrombin pathways offers potential benefits but requires careful risk-benefit assessment.
- Factor XI inhibition presents a promising therapeutic strategy for managing ACS by modulating thrombin generation with potentially preserved hemostasis.
Abstract:
The mechanism underlying thrombus formation in acute coronary syndrome (ACS) involves both platelets and thrombin. While both pathways are targeted in acute care, platelet inhibition has been predominantly administered in the chronic phase, yet thrombin plays a key role in platelet activation and fibrin formation. Among ACS patients, there is also a persistent chronic increase in thrombin generation, which is associated with a higher rate of adverse events. In the setting of post-ACS care with rivaroxaban or vorapaxar, targeting thrombin has been associated with decreased thrombin generation and reduced cardiovascular events, but has been associated with increased bleeding risk. We explored the evidence supporting thrombin generation in the pathophysiology of recurrent events post-ACS and the role of thrombin as a viable therapeutic target. One specific target is factor XI inhibition, which is involved in thrombin generation, but may also allow for the preservation of normal hemostasis.
Related Concept Videos
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:16Clot Retraction and Fibrinolysis
01:18Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:20Extrinsic and Intrinsic Pathways of Hemostasis
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...
01:22Formation of the Platelet Plug
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...