Functional changes in hemostasis during asexual and sexual parasitemia in a controlled human malaria infection

Abstract

Decreased platelet count is an early phenomenon in asexual Plasmodium falciparum parasitemia, but its association with acute or long-term functional changes in platelets and coagulation is unknown. Moreover, the impact of gametocytemia on platelets and coagulation remains unclear. We investigated the changes in platelet number and function during early asexual parasitemia, gametocytemia and convalescence in 16 individuals participating in a controlled human malaria infection study, and studied its relationship with changes in total and active von Willebrand factor levels (VWF) and the coagulation system. Platelet activation and reactivity were determined by flow cytometry, and the coagulation system was assessed using different representative assays including antigen assays, activity assays and global functional assays. Platelet count was decreased during asexual blood stage infection but normalized during gametocytemia. Platelet P-selectin expression was slightly increased during asexual parasitemia, gametocytemia and at day 64. In contrast, platelet reactivity to different agonists remained unchanged, except a marked decrease in reactivity to low dose collagen-related peptide-XL. Thrombin generation and antigen assays did not show a clear activation of the coagulation during asexual parasitemia, whereas total and active VWF levels were markedly increased. During gametocytemia and on day 64, the endogenous thrombin potential, thrombin peak and velocity index were increased and prothrombin conversion and plasma prothrombin levels were decreased. We conclude that the decreased platelet count during asexual parasitemia is associated with increased active VWF levels (i.e. endothelial activation), but not platelet hyperreactivity or hypercoagulability, and that the increased platelet clearance in asexual parasitemia could cause spontaneous VWF-platelet complexes formation.

Mosquito Salivary Antigens and Their Relationship to Dengue and P. vivax Malaria

“…Yet, previous studies have described a significantly lower platelet count in males with malaria during the high transmission season [77], suggesting a sex-dependent association. In general, thrombocytopenia in malaria has been associated with an increase in endothelial activation [78] and with a widespread activation of platelets by an interaction between the parasite PfEMP1 and the platelet's CD36 and other receptors [79], but the sex-dependent relationships are still under investigation. Several anticoagulants in mosquito saliva are known to interact directly with platelets and other modulate endothelial responses [80,81], but the significance of the levels of antibodies against the An.…”