1 - Disseminated Intravascular Coagulation

Question 1

Definition of DIC

Answer 1

Acquired syndrome
Intravascular activation of coagulation
Loss of localisation arising from different causes
May produce organ dysfunction

Question 2

Causes of DIC

Answer 2

1. Sepsis - bacterial, viral, mycotic, parasitic, rickettsial
2. Immunologic - acute haemolytic transfusion reaction, transplant rejection, immunotherapy, GVHD
3. Trauma/injury - brain, extensive burns, fat embolism, rhabdomyolysis
4. Drugs - fibrinolytic agents, aprotinin, warfarin, PCC, amphetamines
5. Vascular - giant haemangioma, large vessel aneurysm
6. Evenomation - snake, insects
7. Obstetrical - abruptio, AF embolism, dead fetus syndrome, septic abortion
8. Liver - fulminant hepatic failure, cirrhosis, fatty liver of pregnancy
9. Malignancy
10. Others - shock, ARDS, massive transfusion

Question 3

Pathogenesis of DIC

Answer 3

1. Thrombo-inflammation
   - Activation of inflammatory pathways in response
   to pathogens
   > increased expression of tissue factor,
   activation of neutrophils and monocytes
   > release of cytokines and development of neutrophil extracellular traps
   > release of polyphosphates cross-reacts with coagulation system -> thrombosis formation
2. Damage to vascular endothelial cells
   - loss of native antithrombotic properties
3. +/- Protein C deficiency
   - Development of purpura fulminans
4. Uncontrolled generation of thrombin
   A. Fibrin deposits in microcirculation
   - Ishcaemic tissue damage -> multiorgan failure
   - RBC haemolysis
   - Secondary fibrinolysis

B. Platelet and coagulation factor consumption
- Diffuse bleeding

Question 4

Clinical manifestation of DIC

Answer 4

Acute DIC
1. Cutaneous bleed - petechiae, ecchymoses, oozing from puncture sites
2. Organ haemorrhage - GI tract, lung, CNS
3. Vessel occlusion, microcirculatory and organ failure
4. Thrombosis of large vessel
5. Cerebral embolism
6. Shock
(Mortality 30-80%)

Chronic DIC - discrete and restricted to skin or mucosa
- D-dimer elevated, but APTT, PT and fibrinogen may be normal or high. Normal to mild thrombocytopenia

Question 5

Investigations of DIC

Answer 5

1. FBC - thrombocytopenia, anaemia
2. PBF - schistocytes, red cell fragmentation
3. DIC screen - PT/INR, APTT, PT, D-dimer, fibrinogen
4. LFT and bilirubin
5. ADAMTS13 level - TRO TTP

Question 6

ISTH Criteria for Overt DIC

Answer 6

Question 7

Management of DIC

Answer 7

Mainly supportive management

1. Blood transfusion for anaemia
2. Assess indication for platelet / factor transfusion
   - High risk bleeding or active bleeding
   - Platelet < 20,000
   - Fibrinogen < 150mg/dL
   - PT > 3s above normal
   > Platelet, FFP, cryoprecipitate or fibrinogen concentrate
   > Protein C infusion in protein C deficiency
3. Vitamin K
4. Assess indications for low dose heparin infusion
   - Low grade DIC
   - Disease: solid tumours, APML, thrombosis, purpura fulminans, giant haemangiomas, dead fetus syndrome
   - Contraindicated in acute bleeding