Related Experiment Video
Updated: Mar 23, 2026
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
The Role of Complement Inhibition in Thrombotic Angiopathies and Antiphospholipid Syndrome
1Hospital for Special Surgery, Weill Cornell Medicine, New York, United States. Phone : +90 212 774 22 91
Insights
Antiphospholipid syndrome (APS) involves thrombosis and pregnancy issues. Complement activation contributes to APS, and blocking complement C5 or C5aR shows promise in preventing APS complications in mouse models.
Area of Science:
- Immunology
- Hematology
- Obstetrics
Background:
- Antiphospholipid syndrome (APS) is defined by thrombosis and/or pregnancy morbidity in patients with antiphospholipid antibodies (aPL).
- Catastrophic APS (CAPS) presents as rapid, multi-organ thrombosis, often with thrombotic microangiopathy (TMA).
- Complement activation on endothelial cells is implicated in hypercoagulability in aPL-positive patients, similar to TMA seen in complement regulatory gene mutations.
Purpose of the Study:
- To investigate the role of complement activation in antiphospholipid syndrome (APS).
- To evaluate the therapeutic potential of complement inhibition in experimental models of APS.
Main Methods:
- Utilized mouse models of APS to study complement activation pathways.
- Administered anti-C5 antibody and C5a receptor (C5aR) antagonist peptides in experimental models.
Main Results:
- Complement activation, specifically the C5a-C5aR interaction, was found to be essential for aPL-induced inflammation, placental insufficiency, and thrombosis in mouse models.
- Treatment with anti-C5 antibody and C5aR antagonist peptides successfully prevented pregnancy loss and thrombosis in these experimental APS models.
Conclusions:
- Complement activation plays a critical role in the pathogenesis of APS.
- Targeting the complement cascade, particularly C5 or C5aR, offers a potential therapeutic strategy for APS complications.
- Further clinical studies are warranted to assess the efficacy of complement inhibitors in managing APS patients.
Abstract:
Antiphospholipid syndrome (APS) is characterized by thrombosis (arterial, venous, small vessel) and/or pregnancy morbidity occurring in patients with persistently positive antiphospholipid antibodies (aPL). Catastrophic APS is the most severe form of the disease, characterized by multiple organ thromboses occurring in a short period and commonly associated with thrombotic microangiopathy (TMA). Similar to patients with complement regulatory gene mutations developing TMA, increased complement activation on endothelial cells plays a role in hypercoagulability in aPL-positive patients. In mouse models of APS, activation of the complement is required and interaction of complement (C) 5a with its receptor C5aR leads to aPL-induced inflammation, placental insufficiency, and thrombosis. Anti-C5 antibody and C5aR antagonist peptides prevent aPL-mediated pregnancy loss and thrombosis in these experimental models. Clinical studies of anti-C5 monoclonal antibody in aPL-positive patients are limited to a small number of case reports. Ongoing and future clinical studies of complement inhibitors will help determine the role of complement inhibition in the management of aPL-positive patients.
More Related Videos
Related Concept Videos
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:27Complement System
01:29Venous Thrombosis III: Interprofessional Care
01:16Clot Retraction and Fibrinolysis
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...
01:18Anticoagulant 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...