Plasma and plasma components in the management of disseminated intravascular coagulation Marcel Levi* Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands Best Practice & Research Clinical Haematology Vol. 19, No. 1, pp. 127–142, 2006

Disseminated intravascular coagulation (DIC) Not a disease entity on itself but is always associated to an underlying disease Syndrome characterized by systemic intravascular activation of coagulation leading to widespread deposition of fibrin in the circulation Microvascular dysfunction and contributes to organ failure Bleeding from various sites

Clinical conditions associated with DIC Sepsis/severe infection (any microorganism). Trauma (e.g. polytrauma, neurotrauma, fat embolism). Organ destruction (e.g. severe pancreatitis). Malignancy: solid tumours myeloproliferative/lymphoproliferative malignancies. Obstetrical calamities: amniotic fluid embolism, abruptio placentae. Vascular abnormalities: Kasabach–Merrit syndrome, large vascular aneurysms Severe hepatic failure. Severe toxic or immunological reactions: snake bites, recreational drugs transfusion reactions transplant rejection.

Pathogenesis of DIC Anti-thrombin Protein C system TF pathway inhibitor

Diagnosis of DIC

Management of DIC Cornerstone treatment : treatment of the underlying disorder Supportive treatment directed towards the coagulation system may be essential in restoring microvascular failure and reducing organ dysfunction

Plasma and platelet substitution therapy Anticoagulants Restoration of anticoagulant pathways Therapeutic consequences

Plasma and platelet substitution therapy Patients with active bleeding Those requiring an invasive procedure or otherwise at risk for bleeding complications Fresh frozen plasma & platelets vs whole blood exchange  no specific motality change Large volumes of plasma : correct coagulation defect : Factor V defect by prothrombin complex concentrate : Fibrinogen by purified coagulation factor concentrates or cryoprecipitate

Vitamin K: repeated monitoring PT, aPTT Platelet transfusion: DIC and severe thrombocytopenia (particular bleeding sign) Bleeding & platelet count <5 만 Non-bleeding patients : a much lower threshold (usually <1-2 만 )

Anticoagulants Heparin treatment :can at least partly inhibit the activation of coagulation in sepsis and other causes of DIC : debatable in DIC patients who are prone to bleeding : overt thromboembolism or extensive fibrin deposition (ex) purpura fulminans or acral ischaemia

TFPI (tissue factor pathway inhibitor) treatment : directed against TF activity  theoretically, the most logical anticoagulant agent to use in DIC : recombinant TFPI, inactivated factor VIIa, a potent and specific inhibitor of the ternary complex between TF-factor VIIa and factor Xa etc. : more favorable outcome.

Restoration of anticoagulant pathways Antithrombin III (AT III) : one of the most important physiological coagulation inhibitors : benefect in improvement of laboratory parameters, shortening of the duration of DIC, improvement organ function : being used very high doses of AT concentrate (to supraphysiological plasma levels)

Antithrombin III (AT III) : modest reduction in mortality in AT-treated patients. (not reach statistical significance in any of the trials) : A large-scale, multicentre, randomized controlled trial to address this issue directly showed no significant reduction in mortality of septic patients

Activated protein C (recombinant human activated protein C) : depression of the protein C system in DIC : lowering duration of mechanical ventilation, shock and length of stay in ICU, days free of systemic inflammatory response. : reduction in D-dimer, Median IL-6  the potential anti-inflammatory effect in patients with sepsis.

Activated protein C : shown the highest benefit of activated protein C treatment : effective in patients with normal protein C  administering activated protein C rather the zymogen protein C in septic patients : decreased mortality, coagulation and inflammation, organ function scores