Thrombocytopenia in early malaria is associated with GP1b shedding in absence of systemic platelet activation and consumptive coagulopathy

Autor: De Mast, Quirijn, De Groot, Philip G., Van Heerde, Waander, Roestenberg, Meta, Van Velzen, Jeroen F, Verbruggen, Bert, Roest, Mark, McCall, Matthew, Nieman, An-Emmie, Westendorp, Josien, Syafruddin, Din, Fijnheer, Rob, Van Dongen-Lases, Edmee C, R, Sauerwein, Van Der Ven, Andre J.
Přispěvatelé: General Internal Medicine, Radboud University Medical Center [Nijmegen], Clinical Chemistry and Hematology, University Medical Center [Utrecht], Laboratory Medicine, Medical Microbiology, Malaria research, Eijkman Institute for Molecular Biology [Jakarta]
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: British Journal of Haematology
British Journal of Haematology, Wiley, 2010, 151 (5), pp.495. ⟨10.1111/j.1365-2141.2010.08399.x⟩
ISSN: 0007-1048
1365-2141
DOI: 10.1111/j.1365-2141.2010.08399.x⟩
Popis: International audience; Thrombocytopenia develops early in malaria, but the underlying mechanisms remain incompletely understood. We studied the etiology 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 numbers was associated with a concurrent rise in young platelets (immature platelet fraction) and thrombopoietin. D-dimer concentrations were moderately elevated without a prolongation in APTT 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 conclude that neither a compromised platelet production nor platelet activation or consumptive coagulopathy are 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
Databáze: OpenAIRE
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