Platelet hyperactivation, apoptosis and hypercoagulability in patients with acute pulmonary embolism

Samin Rezania, Michael A. Puskarich, Daniela Petrusca, Evandro M. Neto-Neves, Matthew T. Rondina, Jeffrey Kline

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Changes in systemic redox balance can alter platelet activation and aggregation. Acute pulmonary embolism (PE) is a systematic inflammatory disease associated with mechanical shear stress, increased thrombin, catecholamines, serotonin and hemolysis, which cumulatively can hyperactivate platelets and accelerate their turnover. We tested the hypothesis that platelets from patients with moderately severe PE will show hyperstimulation and a pre-apoptotic phenotype associated with microparticles (MPs) in plasma. Blood for platelet respiration and thromboelastography (TEG) was obtained at diagnosis and 24 h later from patients (n = 76) with image-proven PE, SBP > 90 mm Hg and right ventricular dysfunction demonstrated by echocardiogram or elevated biomarkers. Controls (n = 12) were healthy volunteers. At diagnosis, platelets from PE patients had significantly elevated baseline oxygen consumption compared with controls, explained primarily by accelerated electron transport and oxygen wasting with no measurable extramitochondrial oxygen consumption. On thromboelastography, unstimulated thrombin-independent maximum amplitude was increased with PE, 19 ± 14.1 vs.10.5 ± 7.8 mm in controls (p = 0.002). Compared with controls, platelets from PE patients showed elevated mitochondrial reactive oxygen species with decreased mitochondrial Bcl-2 protein content and increased cytosolic cytochrome C, coincident with strong annexin V binding, P selectin release from lysed platelets and in plasma MPs compared to controls (p < 0.05). These results show evidence of platelet hyperactivation and apoptosis in patients with acute PE, and provide preliminary theoretical basis for further exploration of platelet inhibition in patients with more severe PE.

Original languageEnglish (US)
Pages (from-to)106-115
Number of pages10
JournalThrombosis Research
Volume155
DOIs
StatePublished - Jul 1 2017

Keywords

  • Apoptosis
  • Oxidative stress
  • Platelet
  • Thromboembolism

ASJC Scopus subject areas

  • Hematology

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