Platelets are pre-activated during thrombocytopenia in a subset of early malaria infections

Introduction Human malaria infections with Plasmodium falciparum are commonly accompanied by a reduction of platelet counts and thrombocytopenia. Usually, platelet counts drop within 10 to 15 days after the initial infection and do not fully recover up until the malaria infection is cleared. Previously, a variety of mechanisms for thrombocytopenia in Malaria have been proposed, including the removal of activated platelets from circulation or anti-Platelet Factor 4 (PF4) antibody-mediated platelet clearance. However, these mechanisms have commonly been studied in natural malaria infection and thus the observation periods are restricted to the symptomatic phase of the disease. Here, we report platelet phenotypes of a cohort of P. falciparum infected vaccine trial participants, covering the initial phase of infection and thrombocytopenia up to two weeks after challenge with malaria parasites.

Method Blood parameters were recruited from malaria-infected and control volunteers enrolled in an anti-Plasmodium falciparum vaccine clinical trial. Participants were challenged with fully-infectious P. falciparum on day one of the observation period. The observation period covered the first two weeks of malaria infection, until parasitemia was detected in blood smear or by PCR. Platelet counts and mean platelet volume were followed daily by peripheral blood counts Platelet activation status was determined by flow cytometry, measuring the expression of CD62P as α-granule, or CD63 as a δ-granule marker. The platelet responsiveness to agonists was quantified after incubation with adenosine triphosphate (ADP) and thrombin receptor-activating peptide (TRAP).

Results In our study cohorts, the malaria infected participants experienced a significant reduction of platelet count between day 11 and 13 post-infection. Platelet count nadir (PLT mean: 104.100/ µL, range: 55.800-138.000/ µL) was accompanied by a statistically significant increase of mean platelet volume (MPV mean: 9.5 fL, range: 7.2-15.9 fL). We found that a subgroup of participants shows pre-activated platelets, as indicated by higher expression of CD62P before stimulation with agonists. Pre-activation did not correlate with platelet count reduction and thrombocytopenia was observed independently of pre-activation in some individuals. Upon challenge with the platelet agonists ADP and TRAP-6, both disease-free and infected participant platelets displayed similar increases of CD62P and CD63 expression.

Conclusion Challenge with malaria parasites could cause a remarkable drop in platelet counts. Our data suggests that pre-activation of platelets co-occurs with thrombocytopenia in a subset of malaria infections. The causal association between circulating activated platelets and thrombocytopenia needs further investigation.

Conflict of Interest

The author does not report any conflict of interest.

Publication History

Article published online:
20 February 2023