Thrombocytopenia in early malaria is associated with GP1b shedding in absence of systemic platelet activation and consumptive coagulopathy.
Thrombocytopenia develops early in malaria, but the underlying mechanisms remain incompletely understood. We studied the aetiology of malaria-associated thrombocytopenia in volunteers experimentally infected with Plasmodium falciparum malaria, in Indonesian malaria patients and in ex vivo studies. In experimental human malaria, the decrease in platelet counts was associated with a concurrent rise in young platelets (immature platelet fraction) and thrombopoietin. D-dimer concentrations were moderately elevated without a prolongation in the activated partial thromboplastin time or decrease in fibrinogen. There was no increase in expression of the platelet surface markers CD62P, PAC-1 and CD63 and in plasma concentrations of the platelet factors P-selectin, CXCR4, CXCL7, RANTES and CD40L. In contrast, concentrations of soluble glycoprotein-1b (sGP1b), the external domain of the platelet receptor for von Willebrand factor (VWF), increased early. Indonesian malaria patients also had elevated concentrations of sGP1b, which correlated with VWF concentrations. Finally, incubation of platelets with parasitized erythrocytes in vitro failed to induce platelet aggregation or activation. We concluded that neither compromised platelet production nor platelet activation or consumptive coagulopathy were responsible for the early thrombocytopenia in malaria. We hypothesize that the increase in sGP1b concentrations results from VWF-mediated GP1b shedding; a process that may prevent excessive adhesion of platelets and parasitized erythrocytes.
Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. q.demast@aig.umcn.nl
Quirijn
Q
de Mast
Philip G
PG
de Groot
Waander L
WL
van Heerde
Meta
M
Roestenberg
Jeroen F
JF
van Velzen
Bert
B
Verbruggen
Mark
M
Roest
Matthew
M
McCall
An-Emmie
AE
Nieman
Josien
J
Westendorp
Din
D
Syafruddin
Rob
R
Fijnheer
Edmee C
EC
van Dongen-Lases
Robert W
RW
Sauerwein
Andre J
AJ
van der Ven
D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000469:parasitology*; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000150:complications*; D015539:Platelet Activation; D010974:Platelet Aggregation; D010979:Platelet Function Tests / Q000379:methods; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D013921:Thrombocytopenia / Q000097:blood / Q000469:parasitology*; D014841:von Willebrand Factor / Q000378:metabolism
D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor