Influence of Platelet Membrane Sialic Acid and Platelet-Associated IgG on Ageing and Sequestration of Blood Platelets in Baboons

Kotzé, Harry F.; Wyk, Van; Badenhorst, P. N.; Heyns, A. du P.; Roodt, Jan; Mg, Lötter

doi:10.1055/s-0038-1649648

Cited by 40 publications

(30 citation statements)

References 12 publications

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“…Moreover, an exponential correlation was showed between the shortening of platelet life span in the circulation and the content of sialic acid removed by neuraminidases in vitro [39]. In addition, direct injection of neuraminidases to mammals markedly accelerated the clearance and shorted the life span of platelets [40, 41].…”

Section: Discussionmentioning

confidence: 99%

Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial

Fan

et al. 2017

J Hematol Oncol

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BackgroundStudies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis.MethodsFirst, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the association between platelet desialylation and thrombocytopenia in patients with sepsis, severe sepsis, and septic shock. Gender- and age-matched healthy adults were selected as normal controls in analysis of the platelet desialylation levels (study I). Next, we conducted an open-label randomized controlled trial (RCT) in which the patients who had severe sepsis with thrombocytopenia (platelet counts ≤50 × 109/L) were randomly assigned to receive antimicrobial therapy alone (control group) or antimicrobial therapy plus oseltamivir (oseltamivir group) in a 1:1 ratio (study II). The primary outcomes were platelet desialylation level at study entry, overall platelet response rate within 14 days post-randomization, and all-cause mortality within 28 days post-randomization. Secondary outcomes included platelet recovery time, the occurrence of bleeding events, and the amount of platelets transfused within 14 days post-randomization.ResultsThe platelet desialylation levels increased significantly in the 127 septic patients with thrombocytopenia compared to the 134 patients without thrombocytopenia. A platelet response was achieved in 45 of the 54 patients in the oseltamivir group (83.3%) compared with 34 of the 52 patients in the control group (65.4%; P = 0.045). The median platelet recovery time was 5 days (interquartile range 4–6) in the oseltamivir group compared with 7 days (interquartile range 5–10) in the control group (P = 0.003). The amount of platelets transfused decreased significantly in the oseltamivir group compared to the control group (P = 0.044). There was no difference in the overall 28-day mortality regardless of whether oseltamivir was used. The Sequential Organ Failure Assessment score and platelet recovery time were independent indicators of oseltamivir therapy. The main reason for all of the mortalities was multiple-organ failure.ConclusionsThrombocytopenia was associated with increased platelet desialylation in septic patients. The addition of oseltamivir could significantly increase the platelet response rate, shorten platelet recovery time, and reduce platelet transfusion.Trial registrationChinese Clinical Trial Registry, ChiCTR-IPR-16008542.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0476-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial

Fan

et al. 2017

J Hematol Oncol

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“…It is responsible for thrombocytopenia in many diseases and pathological situations1719212739. However, its role in autoimmune diseases remains not well elucidated.…”

Section: Discussionmentioning

confidence: 99%

CD8+ T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia

Qiu

Liu

et al. 2016

Sci Rep

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In addition to antiplatelet autoantibodies, CD8+ cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8+ T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8+ T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8+ T cells than those without cytotoxicity and controls. In vitro, CD8+ T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8+ splenocytes were used. Platelets co-cultured with these CD8+ splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8+ splenocytes. These findings suggest that CD8+ T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP.

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“…Therefore, it is not surprising that in vivo loss of sialic acid would influence platelet lifespan by the same mechanism. 32 Platelets lose sialic acid during storage at room temperature, 33 and sialic acid loss has been correlated with reduced platelet recovery and survival. 10,31,34 It is tempting to speculate that platelets lose sialic acid from membrane glycoproteins during aging in the circulation by up-regulating surface sialidase activity.…”

Section: Platelet Sialidase and Mp Cross Talkmentioning

confidence: 99%

Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice

Jansen

Josefsson

Rumjantseva

et al. 2012

Blood

183

188

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Influence of Platelet Membrane Sialic Acid and Platelet-Associated IgG on Ageing and Sequestration of Blood Platelets in Baboons

Cited by 40 publications

References 12 publications

Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial

Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial

CD8+ T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia

Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice

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