title: Platelet mitochondrial membrane depolarization reflects disease severity in patients with sepsis and correlates with clinical outcome.
abstract: BACKGROUND
  Sepsis is still a leading cause of morbidity and mortality, even in modern times, and thrombocytopenia has been closely associated with unfavorable disease outcome. Decreases in mitochondrial membrane potential (depolarization) were found in different tissues during sepsis. Previous work suggests that mitochondrial dysfunction of platelets correlates with clinical disease activity in sepsis. However, platelet mitochondrial membrane potential (Mmp) has not been investigated in a clinical follow-up design and not with regard to disease outcome.
  
  
  METHODS
  In this study, platelet mitochondrial membrane depolarization was assessed by means of a fluorescent Mmp-Index with flow cytometry in 26 patients with sepsis compared with control patients. Platelet Mmp-Index on admission was correlated with the clinical disease scores Acute Physiology and Chronic Health Evaluation Score II (APACHE II), Sequential Organ Failure Score (SOFA), and Simplified Acute Physiology Score II (SAPS II). Finally, platelet Mmp-Index on admission and follow-up were compared in the group of sepsis survivors and nonsurvivors. Expression of the prosurvival protein Bcl-xL in platelets was quantified by immunoblotting.
  
  
  RESULTS
  Platelet mitochondrial membrane depolarization correlated significantly with the simultaneously assessed clinical disease severity by APACHE II (r = -0.867; P < 0.0001), SOFA (r = -0.857; P <0.0001), and SAPS II score (r = -0.839; P < 0.0001). Patients with severe sepsis showed a significant reduction in platelet Mmp-Index compared with sepsis without organ failure (0.18 (0.12 to 0.25) versus 0.79 (0.49 to 0.85), P < 0.0006) or with the control group (0.18 (0.12 to 0.25) versus 0.89 (0.68 to 1.00), P < 0.0001). Platelet Mmp-Index remained persistently low in sepsis nonsurvivors (0.269 (0.230 to 0.305)), whereas we observed recovery of platelet Mmp-Index in the survivor group (0.9 (0.713 to 1.017)). Furthermore, the level of prosurvival protein Bcl-xL decreased in platelets during severe sepsis.
  
  
  CONCLUSIONS
  In this study, we demonstrated that mitochondrial membrane depolarization in platelets correlates with clinical disease severity in patients with sepsis during the disease course and may be a valuable adjunct parameter to aid in the assessment of disease severity, risk stratification, and clinical outcome.
authors: Katharina
authors: K
authors: Gründler
authors: Matthias
authors: M
authors: Angstwurm
authors: Robert
authors: R
authors: Hilge
authors: Philipp
authors: P
authors: Baumann
authors: Thorsten
authors: T
authors: Annecke
authors: Alexander
authors: A
authors: Crispin
authors: Hae-Young
authors: HY
authors: Sohn
authors: Steffen
authors: S
authors: Massberg
authors: Bjoern F
authors: BF
authors: Kraemer
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000502:physiology*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology*; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000401:mortality; D011379:Prognosis; D018805:Sepsis / Q000145:classification* / Q000401:mortality; D012720:Severity of Illness Index