title: Alterations of blood coagulation in controlled human malaria infection.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. julia.riedl@meduniwien.ac.at.
authors.forename: Julia
authors.initials: J
authors.lastname: Riedl
authors.affiliation: Institute of Tropical Medicine and German Center for Infection Research, University of Tübingen, Tübingen, Germany. benjamin.mordmueller@uni-tuebingen.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mordmüller
authors.affiliation: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. silvia.koder@meduniwien.ac.at.
authors.forename: Silvia
authors.initials: S
authors.lastname: Koder
authors.affiliation: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. ingrid.pabinger@meduniwien.ac.at.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger
authors.affiliation: Institute of Tropical Medicine and German Center for Infection Research, University of Tübingen, Tübingen, Germany. peter.kremsner@uni-tuebingen.de.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.affiliation: Sanaria Inc., Rockville, MD, 20850, USA. slhoffman@sanaria.com.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
authors.affiliation: Clinical Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Vienna, Austria. michael.ramharter@meduniwien.ac.at.
authors.forename: Michael
authors.initials: M
authors.lastname: Ramharter
authors.affiliation: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. cihan.ay@meduniwien.ac.at.
authors.forename: Cihan
authors.initials: C
authors.lastname: Ay
mesh_terms: D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation / Q000502:physiology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D018512:Parasitemia / Q000097:blood* / Q000469:parasitology*; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D034101:Sporozoites / Q000502:physiology*; D055815:Young Adult