Abstract
Two phenotypes of disseminated intravascular coagulation (DIC) are systematically
reviewed. DIC is classified into thrombotic and fibrinolytic phenotypes characterized
by thrombosis and hemorrhage, respectively. Major pathology of DIC with thrombotic
phenotype is the activation of coagulation, insufficient anticoagulation with endothelial
injury, and plasminogen activator inhibitor-1-mediated inhibition of fibrinolysis,
leading to microvascular fibrin thrombosis and organ dysfunction. DIC with fibrinolytic
phenotype is defined as massive thrombin generation commonly observed in any type
of DIC, combined with systemic pathologic hyperfibrinogenolysis caused by underlying
disorder that results in severe bleeding due to excessive plasmin formation. Three
major pathomechanisms of systemic hyperfibrinogenolysis have been considered: (1)
acceleration of tissue-type plasminogen activator (t-PA) release from hypoxic endothelial
cells and t-PA-rich storage pools, (2) enhancement of the conversion of plasminogen
to plasmin due to specific proteins and receptors that are expressed on cancer cells
and endothelial cells, and (3) alternative pathways of fibrinolysis. DIC with fibrinolytic
phenotype can be diagnosed by DIC diagnosis followed by the recognition of systemic
pathologic hyperfibrin(ogen)olysis. Low fibrinogen levels, high fibrinogen and fibrin
degradation products (FDPs), and the FDP/D-dimer ratio are important for the diagnosis
of systemic pathologic hyperfibrin(ogen)olysis. Currently, evidence-based treatment
strategies for DIC with fibrinolytic phenotypes are lacking. Tranexamic acid appears
to be one of the few methods to be effective in the treatment of systemic pathologic
hyperfibrin(ogen)olysis. International cooperation for the elucidation of pathomechanisms,
establishment of diagnostic criteria, and treatment strategies for DIC with fibrinolytic
phenotype are urgent issues in the field of thrombosis and hemostasis.
Keywords disseminated intravascular coagulation (DIC) - fibrinolysis - phenotype - plasmin
- thrombin