Disseminated Intravascular Coagulation

Acquired syndrome of extreme systemic intravascular activation of coagulation with loss of localisation that:

• Occurs secondary to an underlying condition
• Causes consumption of platelets and coagulation factors
  With subsequent:
  • Coagulopathy and bleeding.
  • Microvascular damage due to fibrin thrombi
    Leading to tissue ischaemia and multiorgan dysfunction.
• May be acute or chronic
  • Acute DIC is:
    • Generally more familiar
    • Characterised by microvascular thrombosis and bleeding
      • Bruising
      • Bleeding
        Venepuncture sites, surgical wounds.
  • Chronic DIC is:
    • Associated with disease where thrombin formation is occurring over a prolonged period
      e.g. Malignancy, IUFD, aneurysms, wound healing.
    • Partially compensated
      Upregulation of:
      • Platelet and factor production
        Assays may be normal or only slightly abnormal.
      • Hepatic FDP clearance
    • Characterised by thrombosis without bleeding

Epidemiology and Risk Factors

Conditions which lead to the development of DIC include:

• Septic shock
  Occurs in ~35% of cases of severe sepsis.
• Trauma
  • Exsanguination
  • Burns
• Obstetrics
  • Abruptio placentae
  • Haemorrhage
  • AFE
• Vascular malformations
• Malignancy
  • Solid organ tumours
    Primarily thrombosis.
  • Acute promyelocytic leukaemia

Pathophysiology

Normal coagulation involves:

• Vascular constriction
  • ↓ Bleeding
  • Provides time for haemostasis
• Platelet plugging
• Fibrin clot formation
  • Coagulation cascade initiated predominantly via the extrinsic pathway by exposed tissue factor

Pathological coagulation occurs through a series of steps:

• Activation of coagulation system
  • Release of tissue thromboplastins
    • Trauma
    • Surgery
    • Malignancy
    • Intravascular haemolysis
  • Vessel wall endothelial injury
    • Platelet activation
      • Gram negative endotoxin
      • Viral infections
      • Burns
      • Dysoxia
      • Acidosis
    • Trauma
    • Thrombi
  • Primary induction of platelet activation
    • Sepsis
• Excessive thrombin generation
• Thrombin load overcomes anticoagulant control mechanisms
  Including:
  • Protein C
  • Antithrombin
  • Tissue factor pathway inhibitor
• Thrombosis occurring throughout the vasculature

Aetiology

Triggering conditions include:

• Major haemorrhage
  • Trauma
  • Obstetric
• Inflammation
  • AFE
  • Fat embolism
  • Transfusion reaction
  • GVHD
  • Snake bite
• Infection
  • Sepsis
  • Haemorrhagic fevers
  • Gram negative bacteraemia
• Malignancy

Assessment

Diagnostic Approach and DDx

Diagnosis based on a combination of:

• Clinical features
• Laboratory testing

The International Society for Thrombosis and Haemostasis scoring system:

• Requires presence of a DIC-associated disease
• Suggests DIC if score ⩾5

ISTH DIC Scoring System

Category	2 Points	1 Point	0 Points
Platelet count (×109/L)	<50	<100	>100
↑ FDP	High	Moderate	No
↑ PT (s)	>6	6-3	<3
Fibrinogen (g/L)		<1.0	>1.0

Investigations

Laboratory investigations:

• Are not accurate to provide diagnosis on their own
• Can be used to score likelihood for DIC

Laboratory:

• Blood:
  • FBE
    • Anaemia
      Microangiopathic haemolytic anaemia.
    • Thrombocytopaenia
      Low or rapidly ↓ .* Coagulation
    • Assays (PT, APTT)
      Prolonged, but this may be minimal.
    • Fibrinogen
      May be either reduced or ↑.
      • Reduced to consumption
      • ↑ Due to role as acute phase reactant
  • D-Dimer
    ↑ FDP due to fibrinolysis.
  • Blood film
    Schistocyte formation.
  • Haemolysis screen

Coagulation assays may be normal in chronic DIC due to ↑ production, which compensates for ↑ consumption.

Haemolysis screen consists of:

• Reticulocyte count
  ↑ Due to ↑ marrow turnover.
• Blood film
  • Schistocytes
    Mechanically fragmented erythrocyte, favours intravascular mechanical haemolysis.
• LDH
  Present in many cells and so not specific for haemolysis (as opoposed to other cellular destruction). Substantial ↑ (4-5× ULN) favours intravascular over extravascular haemolysis.
• Haptoglobin
  Binds free haemoglobin, and is non-specific for intravascular vs. extravascular haemolysis. Acute phase reactant and so result may be equivocal in inflammatory states.
• Free Hb
  ↑ Due to cellular destruction.
• Bilirubin
  ↑ Due to haemoglobin metabolism. Classically ↑ conjugated bilirubin, although unconjugated may ↑ in concurrent hepatic impairment.

Management

• Treat the underlying condition
• If bleeding: Judicious use of blood products
• If clotting: Cautious anticoagulation

Specific therapy:

• Pharmacological
  Three strategies:
  • Active bleeding
    Transfuse to keep:
    • Platelets >30-50
    • PT <3s
    • Fibrinogen >1.5g/L
    • Consider vitamin K
    • Consider antifibrinolytic
  • No major bleeding or thrombosis
    Prophylactic LMWH.
  • Overt thromboembolism or organ failure
    
    • Therapeutic anticoagulation
      Usually UFH.

Anaesthetic Considerations

Marginal and Ineffective Therapies

Complications

Include:

• Microangiopathic haemolytic anaemia
• Organ failures
  • 15% of malignancy
  • 40% of sepsis

Prognosis

Strong independent predictor of mortality in critically ill patients.

Key Studies

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References

1. Levi M, Scully M. How I treat disseminated intravascular coagulation. Blood. 2018 Feb 22;131(8):845–54.