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Thrombocytopenia in early malaria is associated with GP1b shedding in absence of systemic platelet activation and consumptive coagulopathy
Author(s) -
De Mast Quirijn,
De Groot Philip G.,
Van Heerde Waander L.,
Roestenberg Meta,
Van Velzen Jeroen F.,
Verbruggen Bert,
Roest Mark,
McCall Matthew,
Nieman AnEmmie,
Westendorp Josien,
Syafruddin Din,
Fijnheer Rob,
Van DongenLases Edmee C.,
Sauerwein Robert W.,
Van Der Ven Andre J.
Publication year - 2010
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2010.08399.x
Subject(s) - platelet , von willebrand factor , immunology , platelet activation , coagulopathy , partial thromboplastin time , malaria , endothelial activation , fibrinogen , platelet transfusion , p selectin , medicine , biology , inflammation
Summary 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.