Laboratory Investigations for Disseminated Intravascular Coagulation

Laboratory Investigations for 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:

 

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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.

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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.

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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).

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4. Thrombin Time (TT)

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

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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).

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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.

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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 a resolution.
• Worsening thrombocytopenia or persistent abnormalities indicate progression.

 

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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.