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

Quirijn de Mast (1) , Philip G. de Groot (2) , Waander van Heerde (3) , Meta Roestenberg (4) , Jeroen F van Velzen (3) , Bert Verbruggen (3) , Mark Roest (2) , Matthew Mccall (4) , An-Emmie Nieman (4) , Josien Westendorp (5) , Din Syafruddin (6) , Rob Fijnheer (2) , Edmee C van Dongen-Lases (3) , Sauerwein R (4) , Andre J. van Der Ven (5)

1 General Internal Medicine
2 Clinical Chemistry and Hematology
3 Laboratory Medicine
4 Medical Microbiology
5 General Internal Medicine
6 Malaria research

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

Mots clés: Medicine

Quirijn de Mast, Philip G. de Groot, Waander van Heerde, Meta Roestenberg, Jeroen F van Velzen, et al.. Thrombocytopenia in early malaria is associated with GP1b shedding in absence of systemic platelet activation and consumptive coagulopathy. British Journal of Haematology, 2010, 151 (5), pp.495. ⟨10.1111/j.1365-2141.2010.08399.x⟩. ⟨hal-00586985⟩