Disseminated Intravascular Coagulation
Life-threatening consumptive coagulopathy with simultaneous widespread thrombosis and haemorrhage, always secondary to an underlying condition such as sepsis or malignancy.
Key Facts
DIC is always secondary to an underlying condition – most commonly sepsis, trauma, obstetric emergencies, and malignancy Characterised by simultaneous activation of coagulation and fibrinolysis → consumption of clotting factors and platelets Key lab findings: prolonged PT/APTT, low fibrinogen (<1.5 g/L), raised D-dimer, thrombocytopenia, schistocytes on film ISTH DIC scoring system: platelets, D-dimer, fibrinogen, PT prolongation – score ≥5 indicates overt DIC Management is primarily treating the underlying cause Cryoprecipitate (target fibrinogen >1.5 g/L), FFP (if PT ratio >1.5), platelets (if <50 and bleeding or <30 × 10⁹/L) Mortality depends on underlying cause but is 30-50% overall in overt DIC
Overview
Key Facts
DIC is a complex, acquired coagulopathy characterised by systemic intravascular activation of coagulation, leading to fibrin deposition, microvascular thrombosis, and consumption of clotting factors and platelets, resulting in simultaneous thrombosis and haemorrhage.
Epidemiology
- Occurs in ~1% of hospitalised patients (higher in ICU)
- Most common precipitant: sepsis (30-50% of cases)
- Affects all ages, no sex predominance
Aetiology
- Sepsis/infection: Gram-negative (endotoxin) > Gram-positive, meningococcal, malaria
- Trauma/surgery: major trauma, burns, head injury, fat embolism
- Obstetric: amniotic fluid embolism, placental abruption, HELLP, eclampsia, septic abortion
- Malignancy: acute promyelocytic leukaemia (APL, M3), pancreatic cancer, mucin-secreting adenocarcinomas
- Vascular: aortic aneurysm, giant haemangioma (Kasabach-Merritt)
- Other: transfusion reactions, envenomation, liver failure
Pathophysiology
- Underlying trigger causes massive tissue factor release → activation of extrinsic coagulation cascade
- Widespread thrombin generation → fibrin deposition in microcirculation → microthrombi → organ damage
- Consumption of clotting factors (II, V, VIII, fibrinogen) and platelets → coagulopathy and bleeding
- Secondary fibrinolysis (plasmin activation) → elevated D-dimers and FDPs
- RBCs sheared through fibrin strands → microangiopathic haemolytic anaemia (schistocytes)
- Can be acute (fulminant, bleeding dominant – sepsis, trauma) or chronic (thrombosis dominant – malignancy)
Clinical Presentation
Acute DIC (Bleeding Predominant)
- Bleeding from multiple sites: venepuncture sites, surgical wounds, catheters
- Petechiae, purpura, ecchymoses
- Mucosal bleeding: epistaxis, gingival bleeding, haematuria, GI bleeding
- Organ dysfunction: renal failure, ARDS, hepatic dysfunction
- Shock: from blood loss and underlying condition
Chronic DIC (Thrombosis Predominant)
- Venous thromboembolism: DVT, PE
- Arterial thrombosis: digital gangrene, stroke
- Trousseau syndrome: migratory thrombophlebitis (associated with malignancy)
- Purpura fulminans: severe skin necrosis with microvascular thrombosis
Red Flags
- Purpura fulminans (meningococcal sepsis) → emergency resuscitation
- Oozing from all puncture sites → suspect DIC in critically ill patient
- Acute promyelocytic leukaemia → DIC at presentation requiring immediate ATRA and factor replacement
- Massive obstetric haemorrhage → DIC likely, activate major haemorrhage protocol
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| TTP/HUS | Normal coagulation, severe MAHA | ADAMTS13, coagulation normal |
| Severe liver disease | Coagulopathy but often no MAHA | LFTs, no schistocytes |
| Heparin-induced thrombocytopenia | Platelet drop + thrombosis, heparin exposure | 4T score, anti-PF4 |
| Primary fibrinolysis | Low fibrinogen but normal/mildly abnormal PT | Euglobulin clot lysis time |
| Massive transfusion coagulopathy | Dilutional coagulopathy, trauma setting | Clinical context |
| Vitamin K deficiency | Prolonged PT, normal platelets and fibrinogen | Response to vitamin K |
Diagnosis / Investigation
Bedside
- Clinical assessment: bleeding from multiple sites, signs of underlying cause
- Observations: signs of shock, organ dysfunction
Bloods
- Coagulation screen: prolonged PT and APTT
- Fibrinogen: low (<1.5 g/L, often <1.0 g/L in severe DIC)
- D-dimer: markedly elevated (most sensitive but least specific)
- FBC: thrombocytopenia (or rapidly falling platelet count)
- Blood film: schistocytes (fragmented RBCs)
- FDP (fibrin degradation products): elevated
- LDH: elevated (haemolysis and tissue damage)
- Haptoglobin: low (haemolysis)
- Thrombin time: prolonged
Imaging
- As directed by underlying cause (CT for trauma, obstetric assessment)
Special Tests
- ISTH DIC scoring system (repeated serially to monitor trend)
- Thromboelastography (TEG/ROTEM): point-of-care assessment of coagulation status
- Serial coagulation monitoring: every 4-6 hours in acute DIC
Management
Non-pharmacological
- Treat the underlying cause – this is the MOST IMPORTANT intervention
- Sepsis: antibiotics, source control
- Obstetric: delivery of placenta/fetus
- APL: all-trans retinoic acid (ATRA)
- Activate major haemorrhage protocol if severe bleeding
Pharmacological
Replacement therapy (for bleeding or prior to invasive procedures):
- Cryoprecipitate: 2 pools (10 units) – target fibrinogen >1.5 g/L (>2.0 g/L in obstetric DIC)
- Fresh frozen plasma (FFP): 15-20 mL/kg – if PT ratio >1.5 and bleeding
- Platelet transfusion: target >50 × 10⁹/L if bleeding; >30 if not bleeding; >100 if CNS bleeding
- Tranexamic acid 1g IV: consider as adjunct for hyperfibrinolysis (CRASH-2 trial supports in trauma)
Anticoagulation (chronic/thrombotic DIC):
- Unfractionated heparin infusion in select cases (thrombosis-dominant DIC, e.g., malignancy)
- Low-dose LMWH prophylaxis in non-bleeding patients
Specific treatments:
- All-trans retinoic acid (ATRA) for APL-associated DIC
- Protein C concentrate – historically studied but not widely used
Referral Criteria
- All patients with DIC → critical care/haematology
- Obstetric DIC → obstetric emergency team
- Haematological malignancy with DIC → specialist haematology centre
Prognosis
- Overall mortality: 30-50% in overt DIC (depends on underlying cause)
- Sepsis-associated DIC: mortality 40-60%
- Obstetric DIC: generally good prognosis if underlying cause treated promptly (mortality <5%)
- Malignancy-associated DIC: prognosis linked to underlying cancer
- APL with DIC: good prognosis with ATRA treatment (cure rate >85%)
- Serial DIC score monitoring: improving score predicts better outcome
Other Relevant Information
ISTH DIC Scoring System
| Parameter | Score 0 | Score 1 | Score 2 | Score 3 |
|---|---|---|---|---|
| Platelets (×10⁹/L) | >100 | 50-100 | <50 | - |
| D-dimer | Normal | Moderate ↑ | Strong ↑ | - |
| Fibrinogen (g/L) | >1.0 | - | ≤1.0 | - |
| PT prolongation (s) | <3 | 3-6 | >6 | - |
Score ≥5 = Overt DIC; <5 = Non-overt (repeat in 24h)
Acute vs Chronic DIC
| Feature | Acute DIC | Chronic DIC |
|---|---|---|
| Onset | Hours | Weeks-months |
| Dominant feature | Bleeding | Thrombosis |
| Cause | Sepsis, trauma, obstetric | Malignancy |
| Fibrinogen | Very low | Normal/raised |
| Platelets | Very low | Low-normal |