Intravascular Hemolysis: A Disease Mechanism Not to Be Ignored

Conran, Nicola

doi:10.1159/000356836

Cited by 15 publications

(12 citation statements)

References 16 publications

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“…In the absence of malaria parasites, free iron bioactivation of the endoperoxide bridge of artemisinin drugs can be used to modulate its effects (Conran, 2014;Krishna et al, 2004;Meshnick et al, 1989;Meshnick et al, 1993;Muhia et al, 1994;Tangnitipong et al, 2012). Delayed hemolysis in AS group follows a pattern similar to that reported in malaria infected persons (Arguin, 2014;Boillat et al, 2015;Chavada et al, 2015;Conran, 2014;Jauréguiberry et al, 2014;Kurth et al, 2016;Lee et al, 2015;Rehman et al, 2014;Rolling et al, 2015;WHO, 2013), although no anemia was recorded throughout this study.…”

Section: Discussionsupporting

confidence: 67%

Artemisinin-induced delayed hemolysis after administration of artesunate and artesunate-amodiaquine in malaria-free Wistar rats

et al. 2017

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Background: Hemolysis is common in malaria infection and during the course of treatment. Previous studies have reported delayed post-artemisinin hemolysis occurring in naïve and immune individuals treated with parenteral or oral artemisinin-derivatives. This study aims to understand if delayed hemolysis occurs in the absence of malaria parasites and the underlying mechanisms for the hemolytic effects after administration of two antimalarial drugs to malaria-free Wistar rats. Methods: Forty animals were randomized into 5 groups of eight animals each; they received 4 mg/kg artesunate for 7 days (AS), 4 mg/kg artesunate plus 10mg/kg amodiaquine for 3 days (ASQ), 10mg/kg amodiaquine for 3 days (AQ), distilled water [normal control], (Control) and 1mg/kg phenylhydrazine for 1 day to induce hemolysis (PHZ) groups respectively. Packed cell volume (PCV), white blood cell differential count and serum haptoglobin (Hpt) levels were determined in all groups on day 4 and 18 to detect hemolysis. Mean values were compared using t-test and ANOVA with p values <0.05 taken to be significantly different. Results: Post-treatment mean PCV on day 4 was significantly lower than day 18 in all groups except AS group which had similar PCV all through evaluation. Although AQ had lowest mean PCV on day 4, by day 18, mean PCV returned to normal and hpt levels was significantly higher than AS and ASQ groups (p<0.001). Hpt level (mean ± sem) for AS, ASQ, AQ, and control on day 18 were: 18.67 ± 0.004, 50.66 ± 0.014, 73.06 ± 0.003, and 74.13 ± 0.032 mg/dl respectively (p < 0.0001). On day 18, AS and ASQ had significantly lower Hpt level compared to day 4 (p <0.001). No neutropenia was observed during the study. Conclusion: Artesunate induces delayed hemolysis in malaria-free animals possibly through an oxidative toxic effect on the red blood cell membrane. Delayed post-treatment hemolysis was not observed with artesunateamodiaquine or amodiaquine alone.

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Section: Discussionsupporting

confidence: 67%

Artemisinin-induced delayed hemolysis after administration of artesunate and artesunate-amodiaquine in malaria-free Wistar rats

et al. 2017

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“…12 Thus, hemolysis constitutes a major disease mechanism, and failure to neutralize CFHb can cause vascular and organ dysfunction, leading to the adverse clinical effects that have been associated with hemolytic diseases, including leg ulcers, pulmonary hypertension, and priapism. 13 Hydroxyurea (HU) is a cytostatic drug, frequently used in the treatment of hematologic diseases such as SCD, beta thalassemia, polycythemia vera, essential thrombocythemia, and myelofibrosis, as well as nonhematologic diseases such as HIV/AIDS. [14][15][16] In SCD, HU modifies the disease process, improving hematologic parameters and reducing hospitalization and mortality.…”

Section: Introductionmentioning

confidence: 99%

Acute hemolytic vascular inflammatory processes are prevented by nitric oxide replacement or a single dose of hydroxyurea

Almeida

Souza

Leonardo

et al. 2015

Blood

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“…Procedures such as mismatched transfusions and hemodialysis can induce intravascular hemolysis, and red cell destruction is a characteristic of a number of diseases including malaria, sepsis, preeclampsia, and hemolytic anemias, such as sickle cell anemia (SCA) and paroxysmal nocturnal hemoglobinuria, all of which are associated with inflammatory states that contribute to some degree to these pathologies . In the hemolytic anemias, for example, clinical manifestations associated with hemolysis include leg ulcers, pulmonary hypertension, and priapism …”

Section: Introductionmentioning

confidence: 99%

S100A8 acts as an autocrine priming signal for heme-induced human Mϕ pro-inflammatory responses in hemolytic inflammation

Silveira

Mahon

Cunningham

et al. 2019

Journal of Leukocyte Biology

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Intravascular hemolysis, in addition to reducing red cell counts, incurs extensive vascular inflammation and oxidative stress. One product of hemolysis, heme, is a potent danger associated molecular pattern (DAMP), activating leukocytes and inducing cytokine expression and processing, among other pro-inflammatory effects. We explored pathways by which heme-induced inflammation may be amplified under sterile conditions. Incubation of human M s, differentiated from CD14 + cells, with heme induced time-and concentration-dependent gene and protein expression of S100A8, a myeloid cell-derived alarmin. Human M stimulation with recombinant S100A8, in turn, induced robust pro-IL-1 expression that was dependent upon NF-B activation, gene transcription, and partially dependent upon TLR4-mediated signaling. Moreover, heme itself stimulated significant M pro-IL-1 gene and protein expression via an S100A8-mediated mechanism and greatly amplified S100A8-driven NLRP3 inflammasome-mediated IL-1 secretion. In vivo, induction of acute intravascular hemolysis in mice induced a rapid elevation of plasma S100A8 that could be abolished by hemopexin, a heme scavenger. Finally, plasma S100A8 levels were found to be significantly elevated in patients with the inherited hemolytic anemia, sickle cell anemia, when compared with levels in healthy individuals. In conclusion, we demonstrate that hemolytic processes are associated with S100A8 generation and that some of the inflammatory effects of heme may be amplified by autocrine S100A8 production. Findings suggest a mechanism by which hemolytic inflammation could be propagated via leukocyte priming by endogenous proteins, even in sterile inflammatory environments such as those that occur in the hemolytic diseases. S100A8 may represent a therapeutic target for reducing inflammation in hemolytic disorders.

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Intravascular Hemolysis: A Disease Mechanism Not to Be Ignored

Cited by 15 publications

References 16 publications

Artemisinin-induced delayed hemolysis after administration of artesunate and artesunate-amodiaquine in malaria-free Wistar rats

Artemisinin-induced delayed hemolysis after administration of artesunate and artesunate-amodiaquine in malaria-free Wistar rats

Acute hemolytic vascular inflammatory processes are prevented by nitric oxide replacement or a single dose of hydroxyurea

S100A8 acts as an autocrine priming signal for heme-induced human Mϕ pro-inflammatory responses in hemolytic inflammation

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