The role of platelets in the pathogenesis of cerebral malaria

Cox, Dermot; McConkey, Samuel

doi:10.1007/s00018-009-0211-3

Cited by 73 publications

(83 citation statements)

References 119 publications

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“…12,66 The mechanisms responsible for this thrombocytopenia have not been fully elucidated, but a number of putative mechanisms have been proposed. 66,67 In addition, a series of studies dating back to the 1960s have shown that coagulation cascade activation is also common in both children and adults with P falciparum infection.…”

Section: Coagulation Cascade Activation In Malariamentioning

confidence: 99%

Emerging roles for hemostatic dysfunction in malaria pathogenesis

O’Sullivan

Preston

O’Regan

et al. 2016

Blood

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Severe Plasmodium falciparum malaria remains a leading cause of mortality, particularly in sub-Saharan Africa where it accounts for up to 1 million deaths per annum. In spite of the significant mortality and morbidity associated with cerebral malaria (CM), the molecular mechanisms involved in the pathophysiology of severe malaria remain surprisingly poorly understood. Previous studies have demonstrated that sequestration of P falciparum–infected erythrocytes within the microvasculature of the brain plays a key role in the development of CM. In addition, there is convincing evidence that both endothelial cell activation and platelets play critical roles in the modulating the pathogenesis of severe P falciparum malaria. In this review, we provide an overview of recent studies that have identified novel roles through which hemostatic dysfunction may directly influence malaria pathogenesis. In particular, we focus on emerging data suggesting that von Willebrand factor, coagulation cascade activation, and dysfunction of the protein C pathway may be of specific importance in this context. These collective insights underscore a growing appreciation of the important, but poorly understood, role of hemostatic dysfunction in malaria progression and, importantly, illuminate potential approaches for novel therapeutic strategies. Given that the mortality rate associated with CM remains on the order of 20% despite the availability of effective antimalarial therapy, development of adjunctive therapies that can attenuate CM progression clearly represents a major unmet need. These emerging data are thus not only of basic scientific interest, but also of direct clinical significance.

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Section: Coagulation Cascade Activation In Malariamentioning

confidence: 99%

Emerging roles for hemostatic dysfunction in malaria pathogenesis

O’Sullivan

Preston

O’Regan

et al. 2016

Blood

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“…CD36, a platelet receptor for infected erythrocytes, is also present in brain endothelium and may play a role in platelet activation. However, the exact mechanism for thrombocytopenia is not known [24].…”

Section: Discussionmentioning

confidence: 99%

Plasmodium falciparum malaria, bilateral sixth cranial nerve palsy and delayed cerebellar ataxia

Duque

Seixas

Ventura

et al. 2011

J Infect Dev Ctries

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We describe the case of a 14-year-old Caucasian male, a resident in the Democratic Republic of the Congo, who was observed in Portugal with severe Plasmodium falciparum malaria with high-level parasitemia and severe thrombocytopenia. The course was complicated by bilateral sixth cranial nerve palsy during acute malaria, followed by the appearance of delayed cerebellar ataxia during the recovery phase. This occurred after successful treatment with quinine plus doxycycline over seven days. Different levels of thrombocytopenia and C-reactive protein were observed during both neurologic events in the presence of HRP-2 positive tests for Plasmodium falciparum antigen. The patient recovered completely after three months.

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“…Rosetting pRBCs bind to the endothelial cells and occlude microvessels in the brain (Cox and McConkey 2010). Therefore, it is not surprising that thrombocytopenia is a common feature in both murine ECM and human CM (Wassmer, Combes et al 2003;Combes, ElAssaad et al 2010).…”

Section: Plateletsmentioning

confidence: 99%

“…Interactions between PfEMP1 on Plasmodium and CD36 on platelets possibly lead to platelet activation. The platelet activation aggregates pRBCs and platelets resulting in occlusion of microcirculation and activation of the endothelial cells (Cox and McConkey 2010). gC1qR/HABP/p32 interacts with both pRBCs and platelets potentiating clumping of pRBCs (Biswas, Hafiz et al 2007).…”

Section: Plateletsmentioning

confidence: 99%

“…Both permeability and trans-endothelial electrical resistance (TEER) are strongly affected, and the apoptosis rate of HBVEC cells dramatically increase. Inhibition of platelet adherence to brain microvessels protects against severe P. berghei malaria (Sun, Chang et al 2003;van der Heyde, Gramaglia et al 2005); third, studies evaluating interactions of platelet-RBC-endothelium suggest that pathogenic effects of platelets are not caused by adherence to the endothelial cells but result from the regulation of cytokine production (van der Heyde, Gramaglia et al 2005;Cox and McConkey 2010). It has also been reported that there are more than 300 biologically active proteins in platelet extracts (Coppinger, Cagney et al 2004), which play a crucial role in activation of endothelial cells (Coppinger, Cagney et al 2004).…”

Section: Plateletsmentioning

confidence: 99%

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