Disseminated Intravascular Coagulation (DIC)

One-line definition

DIC is not a primary disease. It is always secondary to an underlying condition.
Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 625.

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Core concept: “clotting everywhere, then bleeding everywhere”

Triggering disease
       ↓
Systemic coagulation activation
       ↓
Excess thrombin generation
       ↓
Fibrin thrombi in small vessels
       ↓
┌────────────────────────────────────┐
│ 1. Microvascular occlusion          │
│    → ischemia, organ dysfunction    │
│                                    │
│ 2. Consumption of platelets and     │
│    clotting factors                 │
│    → bleeding                        │
│                                    │
│ 3. Fibrinolysis                     │
│    → FDPs/D-dimer ↑                 │
│    → bleeding worsens                │
└────────────────────────────────────┘

Why does DIC cause both thrombosis and hemorrhage?

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Etiology

Important causes of DIC

DIC
 ├─ Sepsis, especially Gram-negative sepsis
 ├─ Obstetric complications
 ├─ Malignancy
 └─ Major tissue injury

High-yield mnemonic: STOP

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Pathogenesis according to Robbins and Cotran

Two major mechanisms

                   DIC
                    │
     ┌──────────────┴──────────────┐
     ↓                             ↓
1. Release of tissue factor   2. Widespread endothelial injury
   or other procoagulants

1. Release of tissue factor / procoagulants

Placental tissue / trauma / burns / tumor mucin
                         ↓
Tissue factor enters blood
                         ↓
Factor VII activation
                         ↓
Factor X activation
                         ↓
Thrombin generation
                         ↓
Fibrin formation + platelet activation
                         ↓
Widespread microthrombi

• Placental tissue in abruptio placentae or amniotic fluid embolism
• Damaged tissues in trauma and burns
• Mucin from adenocarcinomas can directly activate factor X

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2. Widespread endothelial injury or activation

Sepsis / TNF / immune complexes / burns / microorganisms
                           ↓
Endothelial injury or activation
                           ↓
┌───────────────────────────────────────────────────────┐
│ ↑ Tissue factor expression                             │
│ ↓ Thrombomodulin expression                            │
│ ↑ Leukocyte adhesion and endothelial damage            │
│ Exposure of subendothelial matrix                      │
└───────────────────────────────────────────────────────┘
                           ↓
Platelet activation + coagulation cascade activation
                           ↓
Excess thrombin and fibrin microthrombi

Sepsis-induced DIC: very important flowchart

Bacterial endotoxin
       ↓
Macrophage activation
       ↓
TNF and other cytokines
       ↓
Endothelium becomes procoagulant
       ↓
↑ Tissue factor expression
↓ Thrombomodulin expression
       ↓
Less activation of protein C
       ↓
Less inhibition of factors Va and VIIIa
       ↓
Uncontrolled thrombin generation
       ↓
DIC

Normal anticoagulant control versus DIC

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Complete pathogenetic sequence

Underlying disorder
(sepsis / obstetric event / malignancy / trauma)
                         ↓
Tissue factor release and/or endothelial injury
                         ↓
Generalized activation of coagulation cascade
                         ↓
Thrombin ↑↑
                         ↓
Fibrin deposition in microcirculation
                         ↓
Microthrombi in kidneys, brain, lungs, heart, adrenals
                         ↓
Tissue ischemia and organ dysfunction
                         ↓
Meanwhile:
                         ↓
Platelet consumption + factor consumption
                         ↓
Thrombocytopenia + fibrinogen ↓ + factors V/VIII ↓
                         ↓
Activation of fibrinolysis
                         ↓
Plasmin formation
                         ↓
Fibrin degradation products (FDP) / D-dimer ↑
                         ↓
Bleeding tendency

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Morphology

Microscopy

Small vessel lumen
      ↓
Eosinophilic fibrin thrombi
      ↓
Partial or complete vascular occlusion
      ↓
Ischemia, infarction, tissue damage

Sites affected

Peripheral smear

Fibrin strands in microcirculation
         ↓
RBCs are mechanically fragmented
         ↓
Schistocytes / helmet cells
         ↓
Microangiopathic hemolytic anemia

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Clinical features

DIC can present in two ways

Clinical manifestations flowchart

DIC
 ├─ Microthrombi
 │    ├─ Renal failure
 │    ├─ Respiratory distress
 │    ├─ Confusion/coma
 │    └─ Skin ischemia/necrosis
 │
 └─ Consumption coagulopathy
      ├─ Petechiae
      ├─ Ecchymoses
      ├─ Oozing from IV/venepuncture sites
      ├─ Hematuria
      ├─ GI bleeding
      └─ Postoperative/postpartum hemorrhage

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Laboratory findings

Typical acute DIC profile

Pattern to remember

DIC laboratory triad

Platelets ↓
PT/aPTT ↑
D-dimer ↑

Plus:
Fibrinogen ↓
Schistocytes present

Why do FDPs worsen bleeding?

Fibrin clot
   ↓
Plasmin breaks fibrin
   ↓
FDPs formed
   ↓
FDPs inhibit:
   • platelet aggregation
   • fibrin polymerization
   • thrombin activity
   ↓
Bleeding increases

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Acute versus chronic DIC

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DIC versus TTP: common exam comparison

Shortcut

Schistocytes + low platelets can occur in both.

If PT and aPTT are prolonged → think DIC.
If PT and aPTT are normal → think TTP/HUS.

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Management principles

This is mainly a pathology answer. Clinically, the cornerstone is treatment of the cause.

Recognize DIC
      ↓
Treat the underlying cause urgently
      ↓
Supportive blood-component replacement if bleeding
      ↓
Monitor platelets, PT, aPTT, fibrinogen, D-dimer and organ function

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Exam-ready answer in 5 lines

DIC is an acquired secondary coagulopathy characterized by widespread
activation of coagulation. Tissue factor release or endothelial injury
causes excess thrombin generation and fibrin microthrombi. This produces
organ ischemia and consumes platelets and coagulation factors. Secondary
fibrinolysis generates FDPs, causing severe bleeding.

Final memory diagram

        DIC = THROMBOSIS + BLEEDING

Trigger
  ↓
Tissue factor / endothelial injury
  ↓
Thrombin ↑
  ↓
Fibrin microthrombi
  ├─ Organ ischemia
  └─ Consumption of platelets + factors
                         ↓
                  Secondary fibrinolysis
                         ↓
            FDP/D-dimer ↑ + bleeding