Alterations of blood coagulation in controlled human malaria infection

Julia Riedl, Benjamin Mordmüller, Silvia Koder, Ingrid Pabinger, Peter G. Kremsner, Stephen L. Hoffman, Michael Ramharter, Cihan Ay

Alterations of blood coagulation are thought to be involved in malaria pathogenesis. This study had the aim to investigate changes of blood coagulation under the standardized conditions of controlled human malaria infection. In a clinical trial aseptic, purified, cryopreserved Plasmodium falciparum sporozoites were intravenously (n = 24) or intradermally (n = 6) injected into 30 healthy volunteers. Twenty-two participants developed parasitaemia. Serial blood samples before and during prepatent period and at parasitaemia, diagnosed by microscopic assessment of thick blood smear, were obtained. Biomarkers of blood coagulation (thrombin generation potential, D-dimer, prothrombin fragment 1 + 2, von Willebrand factor, ADAMTS13 activity and soluble P-selectin) were determined. At first detection of P. falciparum parasitaemia, 72.7 % of volunteers had peak thrombin generation 10 % above their baseline. Overall, peak thrombin generation was 17.7 % higher at parasitaemia compared to baseline [median (25th-75th percentile): 225.4 nM (168.1-295.6) vs. 191.5 nM (138.2-231.9); p = 0.026]. There were no significant changes of other coagulation parameters. The thrombin generation potential, an in vitro blood coagulation test, which reflects an individual´s global coagulation status, was increased by 17.7 % at very early stages of P. falciparum malaria, suggesting a hypercoagulable state may be induced, even when parasite density is low.