Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition, 8th ed.
DIC – The Pathophysiology 1. Paroxysmal or insidious onset of widespread fibrin thrombi in the microcirculation 2. Widespread thrombi formation results in platelet and coagulation protein consumption 3. Simultaneous activation of fibrinolytic mechanism 4. Thrombotic disorder -> Bleeding catastrophe Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition, 8th ed.
Purpura Fulminans “Purpura fulminans is characterized by the rapid progression of ecchymotic skin lesions, especially of the extremities, that may progress to gangrene, ultimately resulting in amputation.” Rare and more often seen in children Post infection: scarlett fever, varicella, URI (meningococcus) Appears 0-90 days post infection Hoffman: Hematology: Basic Principles and Practice, 5th ed.
Purpura Fulminans - Pathophysiology Most Accepted Explanation: Deficiency of Anticoaggulants Acquired Protein S def, Anti-Protein S Antibody Low levels Activated Protein C -> low levels Protein C, protein S, and antithrombin (thrombomodulin-PrC pathway) Hoffman: Hematology: Basic Principles and Practice, 5th ed.
DIC - Treatment FFP to keep the INR <2 Cryoprecipitate to keep the Fibrinogen level >100 ATIII Concentrates - KyberSept trial, a double-blind placebo-controlled trial of the use of ATIII concentrates in 2300 adults with sepsis, found no difference in mortality at day 28 after diagnosis. Heparin low dose – Controversial. Ad hoc retrospective analysis shows benefit equal to “treatment” arms of study.
DIC / Purpura Fulminans - Treatment APC concentrates – Very Controversial. phase II trial: protein C concentrate for Tx of sepsis and purpura fulminans in children. Dose-dependent activation of protein C and normalization of coagulation imbalances. Not powered to detect mortality differences, none seen. PROWESS vs ADDRESS trials for sepsis Summary: 24hrs onset, multiorgan failure (SOFA scale etc), APACHE II >25
References Toussaint S, Gerlach H. Activated protein C for sepsis. N Engl J Med. 2009 Dec 31;361(27):2646-52. Hoffman: Hematology: Basic Principles and Practice, 5th ed. Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition, 8th ed. Osler W. Principles and Practice of Medicine. 4 th Edition. D. Aplleton and Company. New York. 1901. Dr Elizabeth Bengston. Assistance Professor of Medicine, Hematology/Oncology. Dartmouth Medical School. Medical Student Lectures 2005. Cornet AD, Smit EG, Beishuizen A, Groeneveld AB. The role of heparin and allied compounds in the treatment of sepsis. Thromb Haemost. 2007 Sep;98(3):579-86.