ArticleBlood advances2026
Heme and hemozoin induce platelet cell death through UPR-induced apoptosis and ferroptosis in vivax malaria.
Article in Blood advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Afebrile falciparum malaria with severe hemolytic anemia in a returning traveler: a case report.Tropical diseases, travel medicine and vaccines · 2026Article
- Decoding ferroptosis in intracerebral hemorrhage: multidimensional monitoring and integrative perspectives beyond single biomarkers.Frontiers in neurology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors.
Funding
Abstract
abstractMalaria is a highly prevalent infectious disease caused by Plasmodium parasites. Plasmodium intraerythrocytic replication leads to hemolysis-driven intermittent febrile crises in patients. In addition, the lysis of unparasitized red blood cells contributes to anemia and endotoxemia. Because thrombocytopenia is an important feature of vivax and severe falciparum malaria, we hypothesized that increased hemolysis in malaria contributes to severe thrombocytopenia by releasing endogenous and parasite toxins (ie, heme and hemozoin) capable of inducing programmed cell death in platelets. Using complementary biochemical, ultrastructural, pharmacological, and molecular approaches, we examined response to stress and cell death pathways that were elevated in the transcriptome of platelets during vivax malaria and evaluated markers of hemolysis that correlated with thrombocytopenia. We found that heme in plasma from thrombocytopenic vivax malaria, but not nonthrombocytopenic vivax or falciparum malaria, induced platelet cell death ex vivo. Platelet stimulation with heme and hemozoin induced apoptotic and necrotic cell death features, with stronger necrosis triggered by hemozoin. Heme and hemozoin activated apoptotic caspases, but only heme induced calpain-dependent BcL-xL degradation, which was not required for platelet apoptosis. We unmasked a caspase-independent intrinsic apoptosis program mechanism depending on the endoplasmic reticulum stress sensor and unfolded protein response trigger IRE1α. Regarding necrosis, we observed inflammasome activation but not pyroptosis. Instead, we distinguished a necrotic cell death feature consistent with ferroptosis, dependent on lipid peroxidation and regulated by DGAT1/2 enzymes, which was the main pathway for hemozoin-induced thrombocytopenia in vitro. Our results identify novel pathways of regulated cell death in platelets that were associated with thrombocytopenia in malaria and may have potential implications for other hemolytic disorders.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.