ArticleBlood2013
Loss of endothelial protein C receptors links coagulation and inflammation to parasite sequestration in cerebral malaria in African children.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
146 citing papers in PubMed, 2 syntheses or guidelines pooled it, 208 citations in OpenAlex.
- Alteration of prothrombin time in Plasmodium falciparum and Plasmodium vivax infections with different levels of severity: a systematic review and meta-analysis.Scientific reports · 2024Pooled it
- Retinal imaging technologies in cerebral malaria: a systematic review.Malaria journal · 2023Pooled it
- Aberrant stromal tissue factor localisation and mycolactone-driven vascular dysfunction, exacerbated by IL-1β, are linked to fibrin formation in Buruli ulcer lesions.PLoS pathogens · 2022Trial
- Alterations of blood coagulation in controlled human malaria infection.Malaria journal · 2016Trial
- Protein C system defects inflicted by the malaria parasite protein PfEMP1 can be overcome by a soluble EPCR variant.Thrombosis and haemostasis · 2015Trial
- Bradykinin contributes to vasogenic edema in murine experimental cerebral malaria.The Journal of clinical investigation · 2026Article
- CCL5 and CD11b-fibrin interactions regulate microglia migration and morphology in hyperinflammatory experimental cerebral malaria.Journal of neuroinflammation · 2026Article
- Plant-food components at the microbiota-neuroinflammation interface: human evidence, translational limits, and sustainable dietary translation.Frontiers in nutrition · 2026Review
- Prolonged dysregulation of gene expression and biomarkers of coagulation, fibrinolysis, and endothelium in pediatric central nervous system malaria.BMC infectious diseases · 2025Article
- Intravenous Fluid Bolus Resuscitation Increases Mortality Risk in Malawian Children with Cerebral Malaria.The American journal of tropical medicine and hygiene · 2025Article
- Anticoagulant therapy and altered tissue factor expression protect against experimental placental and cerebral malaria.PLoS pathogens · 2025Article
- Nilotinib attenuates vascular pathology in experimental cerebral malaria.Blood advances · 2025Article
- Infection with Toxoplasma gondii triggers coagulation at the blood-brain barrier and a reduction in cerebral blood flow.Journal of neuroinflammation · 2025Article
- Article
- Exploring the association between circulating endothelial protein C receptor and disease activity of rheumatoid arthritis in a pilot study.Rheumatology advances in practice · 2024Article
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- Review
- Dynamic intravital imaging reveals reactive vessel-associated microglia play a protective role in cerebral malaria coagulopathy.Scientific reports · 2023Article
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- Probing cerebral malaria inflammation in 3D human brain microvessels.Cell reports · 2023Article
86 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
Cerebral malaria (CM) is a major cause of mortality in African children and the mechanisms underlying its development, namely how malaria-infected erythrocytes (IEs) cause disease and why the brain is preferentially affected, remain unclear. Brain microhemorrhages in CM suggest a clotting disorder, but whether this phenomenon is important in pathogenesis is debated. We hypothesized that localized cerebral microvascular thrombosis in CM is caused by a decreased expression of the anticoagulant and protective receptors thrombomodulin (TM) and endothelial protein C receptor (EPCR) and that low constitutive expression of these regulatory molecules in the brain make it particularly vulnerable. Autopsies from Malawian children with CM showed cerebral fibrin clots and loss of EPCR, colocalized with sequestered IEs. Using a novel assay to examine endothelial phenotype ex vivo using subcutaneous microvessels, we demonstrated that loss of EPCR and TM at sites of IE cytoadherence is detectible in nonfatal CM. In contrast, although clotting factor activation was seen in the blood of CM patients, this was compensated and did not disseminate. Because of the pleiotropic nature of EPCR and TM, these data implicate disruption of the endothelial protective properties at vulnerable sites and particularly in the brain, linking coagulation and inflammation with IE sequestration.
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Registered trials
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.