ArticleBlood advances2023
Complement and platelets: prothrombotic cell activation requires membrane attack complex-induced release of danger signals.
Article in Blood advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- Sepsis-associated endothelial dysfunction: clinical phenotypes, biomarkers, bedside evidence, and translational implications.The Journal of clinical investigation · 2026Review
- Platelets link coagulation and complement in regulating murine placental vascular development.The Journal of clinical investigation · 2026Article
- Gelatin 4% and hydroxyethyl starch (130/0.42) impair clot formation in a human ex vivo whole-blood resuscitation model.Scandinavian journal of trauma, resuscitation and emergency medicine · 2026Article
- Design of a modified platelet immunofluorescence test to assess platelet-reactive antibody burden and its association with platelet functional exhaustion and clinical features in chronic immune thrombocytopenia.British journal of haematology · 2026Article
- In vivo evidence of effective complement modulation by TriFu in comparison to C5 inhibition and complement depletion.Blood advances · 2026Article
- Porcine kidney xenotransplantation: From primate models to clinical reality.Animal models and experimental medicine · 2026Review
- Thrombosis in paroxysmal nocturnal hemoglobinuria in the complement inhibitor era: mechanisms, risk stratification, and clinical management.International journal of hematology · 2026Review
- Thrombosis in paroxysmal nocturnal hemoglobinuria in the complement inhibitor era: mechanisms, risk stratification, and clinical management.International journal of hematology · 2026Review
- Complement C5 inhibition in generalized myasthenia gravis is associated with improved survival and increased cardiovascular risk.Frontiers in immunology · 2026Article
- The hidden battlefield: platelet function in the wake of severe trauma.Frontiers in immunology · 2026Review
- MUC4 mutations promote a thrombotic phenotype in patients with paroxysmal nocturnal haemoglobinuria by increasing the deposition of terminal complement.Clinical and translational medicine · 2026Article
- Pathophysiological changes in patients during hemodialysis and blood reinfusion predict potential development of hemodialysis reactions.Renal failure · 2025Article
- Diabetes Mellitus and Cardiopulmonary Bypass (CPB): Pathophysiological Mechanisms Related to Inflammation and Cardiovascular Disease.Current issues in molecular biology · 2025Review
- Complement activation in a phase Ib study of fordadistrogene movaparvovec for Duchenne muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Histone-driven hypercoagulation contributes to the lethal triad of acute trauma-induced coagulopathy.Scientific reports · 2025Article
- Action of the Terminal Complement Pathway on Cell Membranes.The Journal of membrane biology · 2025Review
- Genetic association of preeclampsia to von Willebrand factor and its size-regulator ADAMTS13.Research square · 2025Article
- Prevention and Management of Thromboembolism in Patients with Paroxysmal Nocturnal Hemoglobinuria in Asia: A Narrative Review.International journal of molecular sciences · 2025Review
- Beneath the surface in autoimmune hemolytic anemia: pathogenetic networks, therapeutic advancements and open questions.Frontiers in immunology · 2025Review
- Thrombosis in Paroxysmal Nocturnal Hemoglobinuria (PNH): From Pathogenesis to Treatment.International journal of molecular sciences · 2024Review
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Complement activation in the diseases paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) results in cytolysis and fatal thrombotic events, which are largely refractory to anticoagulation and/or antiplatelet therapy. Anticomplement therapy, however, efficiently prevents thrombotic events in PNH and aHUS, but the underlying mechanisms remain unresolved. We show that complement-mediated hemolysis in whole blood induces platelet activation similarly to activation by adenosine 5'-diphosphate (ADP). Blockage of C3 or C5 abolished platelet activation. We found that human platelets failed to respond functionally to the anaphylatoxins C3a and C5a. Instead, complement activation did lead to prothrombotic cell activation in the whole blood when membrane attack complex (MAC)-mediated cytolysis occurred. Consequently, we demonstrate that ADP receptor antagonists efficiently inhibited platelet activation, although full complement activation, which causes hemolysis, occurred. By using an established model of mismatched erythrocyte transfusions in rats, we crossvalidated these findings in vivo using the complement inhibitor OmCI and cobra venom factor. Consumptive complement activation in this animal model only led to a thrombotic phenotype when MAC-mediated cytolysis occurred. In conclusion, complement activation only induces substantial prothrombotic cell activation if terminal pathway activation culminates in MAC-mediated release of intracellular ADP. These results explain why anticomplement therapy efficiently prevents thromboembolisms without interfering negatively with hemostasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.