FRCA Notes

Disseminated Intravascular Coagulation

DIC isn't explicitly mentioned in the curriculum, but falls broadly under the category: 'Haemostasis and coagulation, fibrinolysis – including abnormalities, congenital and acquired'

Resources

  • DIC is defined as:

    • 'an acquired syndrome characterized by intravascular activation of coagulation with loss of localization arising from different causes that can originate from and cause damage to the microvasculature, which if sufficiently severe, can produce organ dysfunction'


  • It is different from, and often more severe than, sepsis-induced coagulopathy

Pro-coagulant activation

  • There is systemic exposure of pro-coagulant molecules such as:
    • Tissue factor on vascular endothelial surfaces, due to endothelial damage/dysfunction which is itself secondary to the inciting (often inflammatory) aetiology
    • Tissue factor on immune cells, particularly macrophages and monocytes, which also secrete pro-inflammatory cytokines thus exacerbating the above process
    • Phosphatidylserine, on the surface of damaged cells
  • This causes widespread activation of the clotting cascade, and thus clotting factor consumption and platelet activation
  • Microthrombi are generated

Anti-coagulant inhibition

  • There is inactivation of the body's anti-coagulant systems through depletion of:
    • Circulating antithrombin, causing acquired antithrombin deficiency
    • Endogenous heparins and antithrombin, owing to damage of the endothelial glycocalyx
    • Thrombomodulin
    • Factors in the protein C system
  • One is left with both excessive activation of the clotting cascade, but also gross dysfunction of the anticoagulant mechanisms

Failure of fibrinolysis

  • Fibrinolysis is also impaired owing to increased secretion of soluble plasminogen activator inhibitor-1
  • This inhibits plasminogen and consequently prevents fibrin degradation by plasmin

  • Microvascular thrombi thus persist, lodging in the microvascular circulation and impairing regional blood flow
  • This microvascular shunting leads to organ dysfunction

Organ consequences of microthrombi

  • Respiratory: ARDS
  • Cardiovascular: DVT or PE
  • Neurological: delirium, coma or seizure
  • Renal: AKI (the most common)
  • Metabolic: adrenal failure due to adrenal haemorrhage (Waterhouse-Friedrichsen syndrome)
  • Dermatological: purpura fulminans

Infectious Traumatic Inflammatory Neoplastic Vascular Hepatic Reactions
Bacterial sepsis
(particularly Gram-negatives such as meningococcus)		 Head injury Pancreatitis Solid tumours
(esp. AdenoCa and GI tumours) 		AAA Cirrhosis Transfusion reactions
Viral (e.g. viral haemorrhagic fever) Burns or heat stroke Severe inflammatory pathology Haematological malignancy
(acute promyelocytic leukaemia)		 Vasculitides Acute hepatic necrosis CPB
Malaria Fat embolism Tissue necrosis GVHD
Rickettsia Other severe tissue injury inc. surgery Snake bites


Bloods

  • FBC:
    • Anaemia
    • Falling platelets or outright but moderate thrombocytopaenia
      • Highly sensitive but poorly specific to DIC
      • Rarely <30x109/L
  • Blood film: fragmented RBCs

  • Clotting studies
    • Prolonged APTTr and INR (PT)
    • Low fibrinogen (25%)
  • Raised D-dimer
    • Invariably raised; a normal D-dimer excludes DIC

  • Low levels of plasma clotting factors if one were to test them

Viscoelastic haemostatic assays

  • The results of TEG or ROTEM in DIC somewhat depend on the aetiology, phenotype (hyper- vs. normo- vs. hypo-coagulable) and stage of the process one is at
  • In overt DIC, characterised by a hypo-coagulable state, patients will tend to have a prolonged R time and reduced maximum amplitude
  • Conversely, those with hyper-coagulable DIC, e.g. that induced by sepsis, may have a short or normal R time, and an increased maximum amplitude
  • In short, it is likely to be deranged but the nature of that derangement isn't consistent

Scoring systems

  • The Taylor scoring system (2001) benefitted from being simple, using standard components of a clotting screen
    • It had high sensitivity (93%) and specificity (98%)
    • A score of ≥5 points indicated overt DIC, and was a strong independent predictor of mortality in those with sepsis

  • The International Society of Thrombosis and Haemostasis DIC Score is a similar score
    • Once again, a score of ≥5 points indicates overt DIC
    • A score of <5 points may still indicate 'non-overt' (?covert) DIC which may progress
Item Score 1 Score 2 Score 3
Platelets (x109/L) 50 - 100 <50
D-dimer (ng/ml) 400 - 4,000 >4,000
INR
[or PT(s)]		 1.3 - 1.7
[3-6]		 >1.7
[≥6]
Fibrinogen (g/L) 1


  • Treat the underlying cause!
    • There is specific management of DIC from purpura fulminans or acute promyelocytic leukaemia

Blood products

  • There is debate about whether replacement of clotting factors is beneficial
  • Some theorise that provision of exogenous clotting factors adds fuel to the pro-coagulant fire, exacerbating microthrombi formation and organ dysfunction
  • This has not, however, been robustly demonstrated in vivo
  • Conversely, one must treat the serious bleeding which can occur, be it that from trauma, surgery or other interventions such as invasive lines
Abnormality Intervention
Raised APTTr/INR FFP
Hypofibrinogenaemia Cryoprecipitate (aim >1)
Thrombocytopaenia Platelets (aim >10)

Theoretical strategies which aren't widely adopted

  • Antithrombin-III concentrate, particularly in meningococcal infection
  • Activate protein C, particularly in paediatrics
  • Thrombomodulin
  • Tifacogin (a tissue factor pathway inhibitor)
  • Heparin (for chronic or slow-onset DIC)