Disseminated intravascular coagulation in critically ill patients

Disseminated intravascular coagulation (DIC) is common in critically ill patients. Patients with disturbed coagulation develop more organ dysfunction and have higher mortality. The pathophysiology behind the increased morbidity and mortality remains unclear. This study assessed the applicability of diagnostic tools for DIC: a modified score for overt DIC and thromboelastometry (TEM), a viscoelastic coagulation monitor. A further aim was to evaluate matrix metalloproteinase-8 (MMP-8), tissue inhibitor of metalloproteinase-1 (TIMP-1), nucleosomal histone-complexed DNA (hcDNA) and high-mobility group box 1 (HMGB1) protein levels in severe sepsis with disturbed coagulation and to assess their association with organ dysfunctions and outcome. Studies I-IV comprised 769 patients. Study I included 494 unselected critically ill patients in whom the incidence of DIC was studied by a modified score for overt DIC. Study II was a prospective pilot study with 28 patients with severe sepsis and ten healthy controls. TEM analyses were performed on admission to intensive care unit (ICU). Study III contained 22 patients with severe sepsis, in whom serum MMP-8 and TIMP-1 concentrations were measured repeatedly. Study IV was a sub-study of a large, prospective, observational, multicentre study conducted in 17 Finnish ICUs (FINNAKI Study). Admission levels of hcDNA and HMGB1 were analysed from 225 consecutive patients. In the university hospital ICU, incidence of DIC ranged from 31% (I) to over 40% (II, III). A multicentre study revealed a lower incidence (33%) of thrombocytopenia in severe sepsis patients. Components of the score discriminated patients with DIC well; only fibrinogen proved useless. Discriminative power of antithrombin was comparable to D-dimer and prothrombin time ratio. TEM trace was hypocoagulable in DIC patients as compared with other sepsis patients and healthy controls. Clot strength and clot formation parameters discriminated DIC patients well from those without DIC. In all patients fibrinolysis was inhibited. The markers speculated to contribute to coagulation disturbance and organ dysfunction, MMP-8, TIMP-1, hcDNA and HMGB1, were higher in patients with disturbed coagulation. HcDNA and HMGB1 were also elevated in patients with acute kidney injury and adverse outcome. HcDNA was an independent predictor of thrombocytopenia.