Reduced Mannose-Binding Lectin-Associated Serine Protease (MASP)-1 is Associated with Disturbed Coagulation in Septic Shock

Thromb Haemost. 2019 Jun;119(6):952-961. doi: 10.1055/s-0039-1685140. Epub 2019 Apr 15.

Abstract

Background: Activation of the complement system is part of the dysregulated immune response in sepsis. The mannose-binding lectin-associated serine proteases (MASP)-1 and -2 activate the lectin pathway of the complement system. Besides, these proteins can activate coagulation in vitro. However, the role of the lectin pathway proteins in the development of sepsis-related disseminated intravascular coagulation (DIC) is only sparsely investigated.

Aim: This article investigates the association between lectin pathway proteins and coagulation disturbances in septic shock patients.

Materials and methods: We included 36 septic shock patients from the intensive care unit, Aarhus University Hospital, Denmark. Blood samples were obtained within 24 hours after admission (day 1), and subsequently on day 2 and day 3. Plasma concentrations of mannose-binding lectin (MBL), H-ficolin, M-ficolin, CL-L1, CL-K1, MASP-1, -2 and -3, MBL-associated proteins of 19 and 44 kDa as well as complement factor C3dg were assessed. Standard coagulation parameters, thrombin generation, thrombin-anti-thrombin (TAT) complex and pro-thrombin fragment 1 + 2 were measured. Sequential Organ Failure Assessment (SOFA) score, DIC score and 30-day mortality were assessed.

Results: Reduced MASP-1 plasma concentration was associated with DIC score ≥5 (p = 0.02), impaired thrombin generation (p = 0.03) and lower plasma TAT complex levels (p = 0.03). No association was found between lectin pathway proteins and SOFA score or 30-day mortality.

Conclusion: Reduced MASP-1 concentrations were associated with impaired coagulation in septic shock patients. This indicates that increased MASP-1 activation and consumption is associated with the more severe coagulation disturbances in sepsis and points to a possible role for MASP-1 in sepsis-related DIC.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood Circulation
  • Complement Activation
  • Denmark / epidemiology
  • Down-Regulation
  • Female
  • Humans
  • Male
  • Mannose-Binding Protein-Associated Serine Proteases / genetics
  • Mannose-Binding Protein-Associated Serine Proteases / metabolism*
  • Middle Aged
  • Shock, Septic / epidemiology
  • Shock, Septic / metabolism*
  • Shock, Septic / mortality
  • Signal Transduction
  • Survival Analysis
  • Thrombin / metabolism

Substances

  • MASP1 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases
  • Thrombin