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

Abstract

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.

Thrombocytopenia and Altered Platelet indices as potential Marker in complicated malaria caused by Plasmodium vivax: cross sectional descriptive study

“…[27,28] Pathogenesis of thrombocytopenia in malaria is due to peripheral destruction, splenic pooling or consumption coagulopathy but mast et al study has suggested thrombocytopenia in early malaria associated with Gplb shedding in absence of platelet activation and coagulopathy and is not at all due to reduction in megakaryocytes in marrow which are usually normal. [29] An inverse relationship was seen between parasite density and platelet counts and platelet counts returned to normal with treatment as similar to other studies. [30] Platelet indices show increase in mean platelet volume and platelet distribution width as platelet count decreases due to platelet aggregation leads to platelet dysfunction [30] .…”

“…Platelet distribution width was also increased due to variation in size of platelets (giant platelets) and also due to platelet aggregation. [29,34,35] Post treatment follow up was done in 47 cases out of which 41 patient showed almost normal to mild leucocytosis and platelet also returns to near normal MPV and PDW were also normal in range but Plateletcrit was not showed much difference from previous value. This suggested that malaria was the most likely cause which alters the studied platelet parameters.…”

Mortality in virulent canine babesiosis is associated with a consumptive coagulopathy

“…A similar severe thrombocytopenia is seen in B. rossi with platelet counts reported as low as 14×10 9 /L being a common finding without any associated clinical signs of hemorrhage (Kettner et al, 2003). As with canine babesiosis, thrombocytopenia develops early in falciparum malaria in people but the underlying mechanisms remain unresolved (de Mast et al, 2010).…”

Plasmodium coatneyi in Rhesus Macaques Replicates the Multisystemic Dysfunction of Severe Malaria in Humans

“…NAP-2 induces neutrophil adhesion to endothelial cells and transendothelial migration and has been involved in regeneration of vascular integrity after injury. Studies with malaria-naïve volunteers experimentally infected with P. falciparum have shown that levels of CXCL7 are elevated in the early stages of the infection (99). Given the evidence of thrombocytopenia and coagulopathy described here for P. coatneyi infections, and as we have reported for a severe case of disseminated intravascular coagulation (DIC) with P. coatneyi (25), high levels of NAP-2 in plasma could indicate massive platelet activation.…”