Disseminated Intravascular Coagulation

Disseminated Intravascular Coagulation (DIC) is a complex disorder characterized by widespread coagulation system activation, resulting in microvascular thrombi formation, consumption of coagulation factors and platelets, and secondary hyperfibrinolysis. Laboratory tests are critical for diagnosing, monitoring, and differentiating DIC from other coagulopathies.

Pathophysiology of DIC

1. Triggers of DIC:
   • Infections (e.g., sepsis, especially caused by Gram-negative bacteria).
   • Malignancies (e.g., acute promyelocytic leukemia, metastatic cancers).
   • Obstetric complications (e.g., placental abruption, amniotic fluid embolism).
   • Trauma, burns, or surgery.
   • Vascular disorders (e.g., aortic aneurysm, giant hemangiomas).
2. Phases of DIC:
   • Prothrombotic Phase: Widespread clot formation and microvascular thrombosis.
   • Consumptive Coagulopathy Phase: Depletion of coagulation factors and platelets.
   • Fibrinolytic Phase: Excessive fibrin degradation leads to hemorrhage.

 

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Role of Laboratory Investigations

Laboratory findings in DIC reflect the balance between coagulation activation, consumption of clotting factors, platelet depletion, and secondary fibrinolysis. The following tests are systematically used:

Essential Laboratory Investigations

1. Complete Blood Count (CBC) and Peripheral Smear

• Findings:
  • Thrombocytopenia:
    • Platelet count < 100,000/µL is common, often dropping further in severe cases.
    • Indicates increased platelet consumption.
  • Peripheral Smear Findings:
    • Schistocytes (fragmented red blood cells) indicate microangiopathic hemolytic anemia due to shear stress in microthrombi.

2. Prothrombin Time (PT)

• Purpose: Evaluate the extrinsic and common coagulation pathways.
• Findings:
  • Prolonged PT (> 14 seconds or INR > 1.2): Suggests depletion of factors (e.g., factor II, V, VII, and X) due to consumption.

3. Activated Partial Thromboplastin Time (aPTT)

• Purpose: Assesses intrinsic and common coagulation pathways.
• Findings:
  • Prolonged aPTT (> 35 seconds): Indicates consumption of intrinsic clotting factors (VIII, IX, XI, XII).

4. Thrombin Time (TT)

• Purpose: Measures the conversion of fibrinogen to fibrin.
• Findings:
  • Prolonged TT (> 21 seconds): Reflects depleted or dysfunctional fibrinogen.

5. Fibrinogen Levels

• Purpose: Determines the level of circulating fibrinogen, a critical coagulation factor.
• Findings:
  • Low Fibrinogen (< 100–150 mg/dL): Reflects consumption in fibrin clot formation.
  • In early DIC, fibrinogen may remain normal or elevated (acute-phase reactant).

6. D-dimer and Fibrin Degradation Products (FDPs)

• Purpose: Indicates fibrinolysis and fibrin degradation.
• Findings:
  • Elevated D-dimer (> 0.5 µg/mL): Sensitive marker for ongoing fibrin degradation.
  • Elevated FDPs: Confirms excess fibrin clot breakdown.
  • Note: These markers are elevated in other conditions, such as venous thromboembolism, trauma, or inflammation, so they are not specific to DIC.

7. Platelet Function Tests

• Findings:
  • Platelet dysfunction (qualitative defects) may contribute to the bleeding tendency in DIC.

 

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Additional and Specialized Tests

1. Antithrombin (AT) Levels

• Purpose: Assesses natural anticoagulant activity.
• Findings:
  • Reduced AT levels: Reflect consumption of antithrombin during excessive thrombin generation.

2. Protein C and Protein S Levels

• Purpose: Measures anticoagulant proteins.
• Findings:
  • Both may be reduced due to consumption or impaired production, especially in sepsis-related DIC.

3. Fibrin Monomers

• Purpose: Detects circulating fibrin monomers formed during coagulation activation.
• Findings:
  • Elevated fibrin monomers are indicative of fibrin formation and DIC.

4. Soluble Fibrin Complexes (SFC)

• Purpose: Measures soluble fibrin clots in plasma.
• Findings:
  • Elevated levels suggest active fibrin clot formation.

5. Peripheral Blood Smear Analysis

• Schistocytes, polychromasia, and thrombocytopenia are typical findings in DIC.

6. Reticulocyte Count

• Elevated due to hemolytic anemia in severe DIC.

 

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Diagnostic Scoring for DIC

The International Society on Thrombosis and Hemostasis (ISTH) scoring system is widely used to diagnose and classify DIC:

ISTH Scoring System

Parameter	Score
Platelet Count: >100 x 10⁹/L = 0, 50–100 x 10⁹/L = 1, <50 x 10⁹/L = 2	0–2
Fibrinogen Level: >1 g/L = 0, ≤1 g/L = 1	0–1
Elevated FDP/D-dimer: None = 0, Moderate = 2, Strong = 3	0–3
PT Prolongation: ≤3 sec = 0, 3–6 sec = 1, >6 sec = 2	0–2

• Interpretation:
  • Score ≥ 5: Overt DIC (repeat daily).
  • Score < 5: Non-overt DIC (repeat in 1–2 days).

 

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Monitoring Laboratory Changes in DIC

• DIC is dynamic; serial testing is crucial.
• Improvement in platelet count, normalization of PT/aPTT, and decreasing D-dimer suggest resolution.
• Worsening thrombocytopenia or persistent abnormalities indicate progression.

Summary of Key Laboratory Features in DIC

Test	Expected Result in DIC
Platelet Count	Low (<100,000/µL)
Prothrombin Time (PT)	Prolonged
Activated Partial Thromboplastin Time (aPTT)	Prolonged
Fibrinogen	Low (<100–150 mg/dL), normal in early DIC
D-dimer/FDPs	Elevated (indicative of fibrinolysis)
Thrombin Time (TT)	Prolonged
Peripheral Smear	Schistocytes, fragmented RBCs

 

Differential Diagnosis

The laboratory findings in DIC may overlap with other conditions:

1. Thrombotic Thrombocytopenic Purpura (TTP):
   • Thrombocytopenia and schistocytes, but normal PT/aPTT and fibrinogen.
2. Severe Liver Disease:
   • Coagulopathy with prolonged PT/aPTT but normal or mildly elevated D-dimer.
3. Primary Fibrinolysis:
   • Elevated FDPs but normal D-dimer and no thrombocytopenia.