Disseminated Intravascular Coagulation

Amanda Tipton Gyn/Onc November 2006

Mechanism

Levi, Marcel MD and Cate, Hugo MD. NEJM ³Disseminated Intravascular Coagulation´ Aug 19, 1999. Vol 341:586-592.

Multiple co-existing factors
1.

Increased generation of thrombin
Predominantly via extrinsic pathway and tissue factor Secondary generation of thrombin through intrinsic pathway

2.

Suppressed anti-coagulation
Reduced antithrombin III Suppressed Protein C system Insufficient action of tissue factor pathway inhibitor (TFPI)

3.
‡ ‡ ‡

Increased availability of negatively charged phospholipid surface facilitating assembly and propagation of coagulation
Externalization of inner leaflet of cell membranes Microparticle formation secondary to cell damage Circulating lipoproteins

4. 5.
‡

Impaired fibrinolysis Inflammation
Cytokines, serine proteases

Frachini, Massimo. Thrombosis Journal ³Recent acquisitions in the pathophysiology, diagnosis and treatment of disseminated intravascular coagulation´ Feb 2006, 4:4. Toh, Cheng Hock. BMJ. ³Disseminated Intravascular Coagulation: Old disease, new hope´ 2003:327:974-77.

In a Little More Detail

PAI-1 = plasminogen activator inhibitor type 1 TFPI = tissue factor pathway inhibitor

Levi, Marcel MD and Cate, Hugo MD. NEJM ³Disseminated Intravascular Coagulation´ Aug 19, 1999. Vol 341:586-592.

Toh, Cheng Hock. BMJ. 2003:327:974-77.

Causes 

Infection/septicemia
± ±

Any microorganism ± bacterial, viral, parasitic, rickettsial, mycotic Triggered by membrane components of microorganism, i.e. endotoxin, exotoxin, LPS Soft tissue injury, fat embolism, head injury Combination of triggers: fat, phospholipids, hemolysis, endothelial injury, activation of cytokines Solid tumors, especially metastatic tumors and hematologic Tissue factor involved in mechanism Abruptio placentae, amniotic fluid embolism, retained deceased fetus, 2nd trimester abortion Due to leakage of thromboplastin-like material Degree of placental separation correlates with severity of DIC Usually short-lived and self-limited 

Trauma & Burns
± ± 

Malignancy
± ± 

Obstetrical complications
± ± ± ±

More Causes 

Vascular disorders
± ±

Hemangioma (Kasabach-Merritt syndrome), aortic aneurysm Local activation of coagulation leads to systemic depletion of factors; activated factors reach systemic circulation, causing DIC Pancreatitis, hepatic failure Snake bite, drugs Transfusion reaction, transplant rejection 

 

Organ destruction
±

Toxins
±

Immunologic mediators
±

Levi, Marcel MD and Cate, Hugo MD. NEJM ³Disseminated Intravascular Coagulation´ Aug 19, 1999. Vol 341:586-592. Toh, Cheng Hock. BMJ. ³Disseminated Intravascular Coagulation: Old disease, new hope´ 2003:327:974-77.

Incidence 

Varies depending on underlying cause
±

± ± ± ± ± ±

Gram negative or gram positive sepsis: 30-50% develop clinically overt DIC Severe trauma + SIRS: 50-70% Metastatic tumors, acute leukemia: ~15% Placental abruption, amniotic fluid embolism: >50% Severe preeclampsia: 7% Giant hemangioma: 25% Large aortic aneurysm: 0.5-1%
Levi, Marcel MD and Cate, Hugo MD. NEJM ³Disseminated Intravascular Coagulation´ Aug 19, 1999. Vol 341:586-592.

Signs & Symptoms 

Diverse range of clinical manifestations
± ± ± ±

Bleeding Thrombosis Acrocyanosis Organ failure Diffuse bleeding Hemorrhagic tissue necrosis Thrombi of small and larger vessels Fibrin deposition in organs, leading to organ failure
Toh, Cheng Hock. BMJ. ³Disseminated Intravascular Coagulation: Old disease, new hope´ 2003:327:974-77. 

Autopsy findings
± ± ± ±

Diagnostic Work-up 

Clinical manifestations of bleeding, thrombosis and/or organ failure
PT o aPTT o Platelets q Initial level <100,000 or rapid decline
± ± ± ± ±

Laboratory findings

Fibrin degradation products (D-dimer) o Fibrinogen* nl/q Protein C q Antithrombin q Coagulation factors q

*An acute phase reactant, low sensitivity
Frachini, Massimo. Thrombosis Journal ³Recent acquisitions in the pathophysiology, diagnosis and treatment of disseminated intravascular coagulation´ Feb 2006, 4:4.

Treatment 


TREAT THE UNDERLYING DISEASE!! Replacement therapy
± ±

Fresh frozen plasma **preferred Platelets, fibrinogen concentrates, cryoprecipitates Heparin or LMWH± contradictory results 
  

Anticoagulants
±

Safety in patients prone to bleeding? Low dose 300-500U/hr Likely of benefit in patients with extensive thromboemboli and fibrin deposition

± ± ±

Danaproid sodium, recombinant hirudin TFPI 

Blocks tissue factor activity in endotoxin-induced DIC

Recombinant nematode anticoagulant protein c2 (NaPc2) ± inhibits complex between TF/VIIa and Xa
Frachini, Massimo. Thrombosis Journal ³Recent acquisitions in the pathophysiology, diagnosis and treatment of disseminated intravascular coagulation´ Feb 2006, 4:4.

Treatment (cont.) 

Restore anticoagulation pathway
±

Antithrombin III 

Might be of benefit in sepsis with improvement of DIC and organ function

± ±

Recombinant tissue plasminogen activator Activated protein C 
  

Also has anti-inflammatory and anti-apoptotic properties Only anti-coagulant shown to be efficacious in trials with sepsistriggered DIC Given as 96 hr infusion Must use caution with thrombocytopenia increased risk of intracerebral hemorrhage

Frachini, Massimo. Thrombosis Journal ³Recent acquisitions in the pathophysiology, diagnosis and treatment of disseminated intravascular coagulation´ Feb 2006, 4:4. Davis-Jackson, Rachel. Thrombosis Journal ³Antithrombin III and R-TPA used singly and in combination vs. supportive care for treatment of endotoxin-induce DIC in the neonatal pig´ May 18, 2006, 4:7.

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