Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria.
The pathogenesis of fatal cerebral malaria (CM) is not well understood, in part because data from patients in whom a clinical diagnosis was established prior to death are rare. In a murine CM model, platelets accumulate in brain microvasculature, and antiplatelet therapy can improve outcome. We determined whether platelets are also found in cerebral vessels in human CM, and we performed immunohistopathology for platelet-specific glycoprotein, GPIIb-IIIa, on tissue from multiple brain sites in Malawian children whose fatal illness was severe malarial anemia, CM, or nonmalarial encephalopathy. Platelets were observed in 3 locations within microvessels: between malaria pigment and leukocytes, associated with malaria pigment, or alone. The mean surface area of platelet staining and the proportion of vessels showing platelet accumulation were significantly higher in patients with CM than in those without it. Platelet accumulation occurs in the microvasculature of patients with CM and may play a role in the pathogenesis of the disease.
Grau
Georges E
GE
Experimental Parasitology Unit, IFR48, Université de la Méditerranée, Marseille, France. georges.grau@medecine.univ-mrs.fr
Mackenzie
Charles D
CD
Carr
Richard A
RA
Redard
Mireille
M
Pizzolato
Giampaolo
G
Allasia
Claude
C
Cataldo
Claude
C
Taylor
Terrie E
TE
Molyneux
Malcolm E
ME
D000740:Anemia; D001792:Blood Platelets / Q000502:physiology*; D001921:Brain / Q000098:blood supply*; D002536:Cerebral Arteries / Q000503:physiopathology; D002550:Cerebral Veins / Q000503:physiopathology; D002648:Child; D006420:Hemeproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes; D016779:Malaria, Cerebral / Q000097:blood* / Q000401:mortality; D008296:Malaysia; D008833:Microcirculation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis
D006420:Hemeproteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C020753:hemozoin