Disseminated Intravascular Coaggulation and Purpura Fulminans

Robert Lampman, MDMorning Report May 2010

Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition , 8th ed.

DIC – The Pathophysiology1. 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.

DIC - 2 Pathways of Activation1. Tissue Factor or thromboplastic

substance release into circulation.obstetrics, malignancy, trauma, surgery, tissue

necrosis

2. Endothelial Injury - collagen exposureendotoxin, bacteria, virus, burns

4th Edition 1901

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 childrenPost 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 <2Cryoprecipitate 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

ReferencesToussaint 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. 4th 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.