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.

Disseminated intravascular coagulation (DIC) has a well-examined pathophysiology, yet some essential elements remain undetermined. During DIC, platelets play an important role in the development of micro thrombosis, but changes in platelet function parameters and their association with development of DIC have not been established. The present systematic review investigated reported associations between platelet function (activation, aggregation, and adhesion) and DIC. We performed a literature search in Embase and PubMed, following the Preferred Reporting Items for Systematic and Meta-Analyses (PRISMA) guidelines. In total, 22 articles were included; 14 human studies, seven animal studies, and one with both human and animal subjects. Platelet activation markers were generally reported to be higher in both DIC patients and animals with DIC than healthy controls, and higher among patients with DIC than patients without DIC. Six human and six animal studies investigated platelet aggregation, which were overall reported to be lower in DIC than in non-DIC or in healthy controls in both human and animal studies. Platelet aggregation was deemed to be confounded by low platelet counts, which are known to affect platelet aggregation analyses even within the reference interval. In conclusion, platelet activation analyses showed promise in diagnosis of DIC, but semi-automatization and standardization are warranted before these can be implemented in daily clinical practice. Changes in platelet aggregation analyses during DIC remain inconclusive, and further studies including adjustment for low platelet count are needed to clarify the role of platelet aggregation in DIC.

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