Disseminated intravascular coagulation
(DIC)
Dr. Edmond S. K. Ma
Division of Haematology
Department of Pathology
The University of Hong Kong
Bachelor of Chinese Medicine
Disseminated intravascular coagulation
• Systemic thrombo-haemorrhagic disorder
• Characteristic features:
– activation of coagulation system
– activation of fibrinolytic system
– consumption of clotting factors
– consumption of natural inhibitors
– thrombocytopenia
Bachelor of Chinese Medicine
Disseminated intravascular coagulation:
characteristics
• Widespread activation of coagulation
intravascular formation of fibrin
thrombotic occlusion of small vessels
contributes to multiple organ failure in
conjunction with haemodynamic and metabolic
consequences
• Depletion of platelets and clotting factors
severe bleeding
Bachelor of Chinese Medicine
Bachelor of Chinese Medicine
Systemic activation
of coagulation
Intravascular Depletion of platelets
deposition of fibrin and coagulation factors
Thrombosis of small
and midsize vessels
Bleeding
and organ failure
Bachelor of Chinese Medicine
Skin Bruises
Bachelor of Chinese Medicine
Associated Clinical Conditions
• Sepsis • Vascular
• Trauma – Giant haemangioma
– Serious tissue injury – Aortic aneurysm
– Fat embolism • Reaction to toxins
• Cancer • Immunological
• Obstetrical disorders
complications – Haemolytic transfusion
reaction
– Transplant rejection
Bachelor of Chinese Medicine
DIC and Infectious Disease
• Severe sepsis is the most common clinical
condition associated with DIC
• Bacterial infection
• Occurs in 30 - 50% of Gram -ve sepsis
– Lipopolysaccharide (endotoxin)
• Gram positive sepsis
– exotoxin (e.g. staphylococcal -haemolysin)
Bachelor of Chinese Medicine
DIC and severe trauma
• Especially seen after brain trauma
– release of fat and phospholipid
• Cytokine activation
– similar pattern to severe sepsis
• “Systemic inflammatory response
syndrome” after trauma
– 50 - 70% associated with DIC
Bachelor of Chinese Medicine
DIC and Cancer
• Solid tumours
– metastatic cancer 10 - 15%
• Haematological cancer
– acute leukaemia 15%
• ‘Cancer pro-coagulant’: tissue factor
• Acute promyelocytic leukaemia
– DIC and hyperfibrinolytic state
Bachelor of Chinese Medicine
DIC and Obstetrical Disorders
• Abruptio placentae, amniotic fluid
embolism, fetal death in utero, septic
abortion
• 50% of cases
• Release of thromboplastin-like material
• Usually short-lived and self-limiting
• Pre-eclampsia (7%)
Bachelor of Chinese Medicine
DIC and Giant Haemangioma
• Local activation of coagulation system
systemic depletion of locally consumed
clotting factors and platelets
• Activated coagulation factors reach
systemic circulation DIC
• Giant haemangioma 25%
• Large aortic aneurysm 0.5 - 1%
Bachelor of Chinese Medicine
Microangiopathic haemolytic anaemia
• Peripheral blood picture:
– Anaemia
– Thrombocytopenia
– Fragmented red cells (schistocytes)
• A feature common to several conditions:
– DIC
– Thrombotic thrombocytopenic purpura
– Haemolytic Uraemic Syndrome
Bachelor of Chinese Medicine
Disseminated intravascular coagulation
Bachelor of Chinese Medicine
Pathogenesis of DIC
• Increased thrombin generation
• Depression of physiologic anticoagulation
mechanism
• Delayed removal of fibrin due to impaired
fibrinolysis
Bachelor of Chinese Medicine
Thrombin generation
• Extrinsic pathway
• Tissue factor and factor VIIa
Bachelor of Chinese Medicine
Defects in coagulation inhibitors
antithrombin
– ongoing coagulation
– degradation by neutrophil elastase
– impaired antithrombin synthesis
• Impairment of protein C system
– impaired synthesis
– cytokine mediated endothelial thrombomodulin
free protein S
• Insufficient tissue factor pathway inhibitor activity
Bachelor of Chinese Medicine
Fibrinolytic defect
plasminogen activator inhibitor type I
Bachelor of Chinese Medicine
Bachelor of Chinese Medicine
Pathogenesis of DIC
Bachelor of Chinese Medicine
Systemic activation
of coagulation
Intravascular Depletion of platelets
deposition of fibrin and coagulation factors
Thrombosis of small
and midsize vessels
Bleeding
and organ failure
Bachelor of Chinese Medicine
Diagnosis of DIC
• Clinical setting
• Laboratory tests
• Criteria
– Underlying disease known to be associated
– Initial platelet count < 100 X 10 9/L, or rapid decline in platelet
count
– Prolongation of clotting times (PT & APTT)
– Presence of fibrin degradation products
– Low levels of coagulation inhibitors (e.g. antithrombin)
– Low fibrinogen level in severe cases
Bachelor of Chinese Medicine
Disseminated intravascular coagulation
• Laboratory results:
– Prolonged PT, APTT and TT
– Reduced fibrinogen level
– Increased D-Dimers
– Thrombocytopenia
– Microangiopathic changes in blood film
Bachelor of Chinese Medicine
Bachelor of Chinese Medicine
Management of DIC
• Treatment of underlying disorder
• Anticoagulants
– low dose heparin
– low molecular weight heparin
– new thrombin inhibitors (ATIII independent)
– useful for clinically overt thromboembolism or
extensive deposition of fibrin
Bachelor of Chinese Medicine
Management of DIC
• Platelets and Plasma
– to treat bleeding tendency
– to cover an invasive procedure for patients with a
high risk of bleeding
• Clotting factor concentrates
– overcomes large volumes of plasma
– but not advocated because: 1) contains small amount
of activated factors, and 2) DIC results in deficiency
of multiple factors
Bachelor of Chinese Medicine
Concentrates of coagulation inhibitors
• Antithrombin concentrate
– reduces sepsis related mortality
– improvement of DIC and organ function
• Supportive therapeutic option in severe DIC
• Drawback: expensive
Bachelor of Chinese Medicine
Antifibrinolytic agents
• Generally not recommended
– fibrinolysis is already impaired in DIC
– may enhance fibrin deposition
• For bleeding in DIC associated with
primary or secondary hyperfibrinolysis
– e.g. acute promyelocytic leukaemia
Bachelor of Chinese Medicine
New therapeutic options
• Nematode anticoagulant protein c2
– specific inhibitor of tissue factor-VIIa-Xa
complex
• Recombinant TFPI
• Protein C concentrate
Bachelor of Chinese Medicine
Reference
• Levi M & Ten Cate H. Disseminated intravascular
coagulation. N Engl J Med 341: 586 - 592, 1999.
Bachelor of Chinese Medicine
Acquired bleeding disorders
• Vitamin K deficiency and antagonism
• Liver disease
• Chronic renal failure (uraemia)
• Disseminated intravascular coagulation
Bachelor of Chinese Medicine
Vitamin K metabolism
Bachelor of Chinese Medicine
Vitamin K deficiency
• Clinical scenario:
– Obstructive jaundice
– Fat mal-absorption
– Broad spectrum antibiotics
– Haemorrhagic disease of newborn
• prophylactic vitamin K injection at birth
• Coagulation tests:
– Prolongation of PT and APTT, normal TT
Bachelor of Chinese Medicine
Conventional model of coagulation
Bachelor of Chinese Medicine
Vitamin K antagonism
• Oral anticoagulants (warfarin)
• Prolongation of both PT and APTT
• PT system chosen for monitoring
– due to shortest half life of factor VII
• INR system
– to standardize monitoring of oral anticoagulant therapy
• Important: INR should not be used in other
clinical context
Bachelor of Chinese Medicine
Bleeding in Liver disease
• Causes
– Reduced synthesis of clotting factors
– Vitamin K mal-absorption
– Acquired functional defect of fibrinogen
– Failure to clear activated products of coagulation and
fibrinolysis
– Thrombocytopenia
• hypersplenism
• Coagulation tests
– Prolongation of PT and APTT, TT
Bachelor of Chinese Medicine
Uraemia bleeding
• Causes
– Platelet dysfunction
– Abnormal platelet-vessel wall interaction due to low Hb
(altered blood rheology)
• Clinical feature
– mucocutaneous bleeding
• Coagulation tests
– Normal PT and APTT
– Prolonged skin bleeding time
Bachelor of Chinese Medicine
