Abstract Number: PB0759
Meeting: ISTH 2021 Congress
Background: Low platelet count is a common clinical finding during early stages of malaria infection in humans. Despite growing evidence of platelets playing a crucial role in malaria pathophysiology, mechanisms leading to the decreased platelet numbers in malaria infections are still poorly understood.
Aims: In this study, we utilized a controlled human malaria infection (CHMI) model established for vaccine clinical trial to investigate several platelet parameters during early stages of Plasmodium falciparum (Pf) infection.
Methods: We used flow cytometry to analyze circulating platelets in healthy, malaria-naïve, adult volunteers undergoing CHMI using infectious Pf sporozoites. Volunteers were followed daily until parasites were detected in the circulation by RT-qPCR. The following parameter were analyzed: Platelet count, mean platelet volume (MPV), platelet desialylation, the expression of CD62P as α-granule and CD63 as a δ-granule marker, respectively. The platelet responsiveness was investigated by determining the platelet activation markers after incubation with the agonist adenosine diphosphate (ADP), or thrombin receptor-activating peptide (TRAP).
Results: We found a significant drop in platelet count of all malaria positive participants 10 days after Pf-inoculation. Interestingly, MPV was found to be lower in malaria positive subjects and relatively decreased from day 8 onwards. On the other hand, increased platelet desialylation was observed in malaria positive subjects. Flow cytometry analysis showed that platelets of a subgroup of participants were pre-activated as indicated by the higher CD62P expression compared to control blood donors. No significance differences were observed in platelet markers CD42a, CD63 as well as in cell viability and apoptosis.
Conclusions: In conclusion, our study shows that early malaria infection leads to a significant thrombocytopenia in infected patients during CHMI. The higher incidence of desialylated platelets and decreased MPV among infected participants indicate that the cleavage of sialic acid on platelets, and probably megakaryocytes, might be involved in the pathophysiology of malaria-induced thrombocytopenia.
To cite this abstract in AMA style:Singh A, Witzemann A, Pelzl L, Marini I, Rigoni F, Zlamal J, Kreidenweiss A, Mordmüller B, Kremsner P, Bakchoul T. Platelets Show a Distinct Response in a Controlled Human Malaria Infection (CHMI) Model [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/platelets-show-a-distinct-response-in-a-controlled-human-malaria-infection-chmi-model/. Accessed September 27, 2023.
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