Disseminated Intravascular Coagulation (DIC)

Pathogenesis of DIC

Initiating mechanisms

1. Release of tissue factor or other procoagulants into the circulation
   • Obstetric complications: placental tissue, amniotic fluid, retained dead fetus
   • Major trauma, burns, extensive surgery: damaged tissue releases tissue factor
   • Malignancy: especially mucin-producing adenocarcinomas, in which mucin may activate factor X; acute promyelocytic leukemia is also a classic association.
2. Widespread endothelial injury or activation
   • Especially important in sepsis
   • Endothelial damage exposes subendothelial matrix, activates platelets and coagulation cascade.
   • In sepsis, endotoxin and cytokines, particularly TNF, induce endothelial tissue-factor expression and reduce thrombomodulin expression.
   • Reduced thrombomodulin means reduced activation of protein C, so inhibition of factors Va and VIIIa is impaired, favoring coagulation.

Sequence of events

Underlying disorder
(sepsis / obstetric catastrophe / trauma / malignancy)
                    ↓
Tissue factor release and/or diffuse endothelial injury
                    ↓
Widespread thrombin generation
                    ↓
Fibrin deposition in small vessels + platelet activation
                    ↓
Microvascular thrombi
                    ↓
Tissue ischemia, infarction, multiorgan dysfunction
                    ↓
Consumption of platelets, fibrinogen, and clotting factors
                    ↓
Secondary fibrinolysis with plasmin formation
                    ↓
Fibrin degradation products + depletion of hemostatic factors
                    ↓
Bleeding tendency

Consequences

1. Microvascular thrombosis

• Fibrin thrombi form in small vessels, particularly in the brain, lungs, heart, kidneys, adrenals, spleen, and liver.
• Causes tissue hypoxia, ischemia, infarction, and organ dysfunction.
• Red cells passing through fibrin strands are fragmented, producing microangiopathic hemolytic anemia with schistocytes.

2. Hemorrhagic diathesis

• Consumption of platelets
• Consumption of coagulation factors, including fibrinogen
• Plasmin-mediated degradation of fibrin and factors V and VIII
• Fibrin degradation products that inhibit platelet aggregation, fibrin polymerization, and thrombin activity.

Important causes of DIC

Laboratory Investigations in DIC

Peripheral smear

• May show microangiopathic hemolytic anemia
• Schistocytes and helmet cells support the diagnosis
• Their absence does not exclude DIC.

Important qualification

• In early DIC, aPTT may be normal or even shortened due to circulating activated clotting factors and increased factor VIII as an acute-phase reactant.
• Fibrinogen can be normal in sepsis or chronic DIC because it is an acute-phase protein. Therefore, a falling trend is often more useful than one isolated value.

ISTH scoring system for overt DIC

Exam conclusion

DIC: One-Page Exam Revision Sheet

Definition

Causes: “SOMT”

• Sepsis, especially severe bacterial sepsis
• Obstetric catastrophes: abruptio placentae, retained dead fetus, amniotic-fluid embolism
• Malignancy: acute promyelocytic leukemia; mucinous adenocarcinoma
• Trauma/tissue injury: burns, shock, major surgery

Pathogenesis

Two major initiating mechanisms

1. Tissue-factor/procoagulant release
   • Trauma/burns/surgery
   • Placental or amniotic-fluid material
   • Tumor mucin can directly activate factor X
2. Diffuse endothelial injury/activation
   • Sepsis: endotoxin and TNF
   • TNF causes:
     • ↑ endothelial tissue factor
     • ↓ thrombomodulin expression
     • ↓ protein C anticoagulant pathway
     • leukocyte adhesion and endothelial damage

Flowchart

Trigger (sepsis / obstetric event / trauma / cancer)
                       ↓
Tissue factor release + endothelial injury
                       ↓
Systemic thrombin generation
                       ↓
Widespread fibrin microthrombi + platelet consumption
                       ↓
Ischemia / infarction / multiorgan dysfunction
                       ↓
Consumption of platelets + fibrinogen + clotting factors
                       ↓
Secondary plasmin activation and fibrinolysis
                       ↓
FDPs increase + factors V and VIII degraded
                       ↓
BLEEDING

Why both clotting and bleeding?

Clinical Features

• Oozing from venepuncture, wound, catheter, or surgical sites
• Petechiae, ecchymoses, mucosal bleeding
• Hematuria, GI bleeding, postpartum hemorrhage
• Shock
• Renal failure, respiratory distress, altered sensorium
• Microthrombi may cause ischemia in brain, lungs, heart, kidneys, adrenals, liver, and spleen

Laboratory Investigations

Classic laboratory pattern

Low platelets + prolonged PT/aPTT + low fibrinogen + high D-dimer/FDPs

ISTH Overt DIC Score

• Platelets: low count gives 1-2 points
• Elevated fibrin markers/D-dimer: 2-3 points
• Prolonged PT: 1-2 points
• Fibrinogen <100 mg/dL: 1 point

Interpretation

• Score ≥5: overt DIC
• Score <5: possible non-overt DIC, repeat testing in 1-2 days

One-Line Answer for Viva

Disseminated Intravascular Coagulation (DIC)

Definition

• Widespread fibrin thrombi in the microcirculation
• Consumption of platelets, fibrinogen, and clotting factors
• Secondary activation of fibrinolysis

Etiology

Main settings

1. Sepsis
   • Especially severe bacterial sepsis
   • Endotoxin and cytokines, particularly TNF, activate endothelium and coagulation.
2. Obstetric complications
   • Abruptio placentae
   • Amniotic fluid embolism
   • Retained dead fetus
   • Placental tissue entering circulation
3. Malignancy
   • Acute promyelocytic leukemia
   • Mucin-secreting adenocarcinomas, especially pancreas, lung, stomach, and colon
4. Major tissue injury
   • Trauma
   • Burns
   • Extensive surgery
   • Shock

Pathogenesis

Two initiating mechanisms

In sepsis

• Increased endothelial expression of tissue factor
• Reduced expression of thrombomodulin
• Less thrombin-thrombomodulin complex formation
• Reduced activation of protein C, which normally inhibits factors Va and VIIIa
• Endothelial activation and leukocyte-mediated damage

Flowchart

Sepsis / trauma / obstetric event / malignancy
                         ↓
Tissue factor release and/or endothelial injury
                         ↓
Systemic activation of coagulation
                         ↓
Excess thrombin generation
                         ↓
Widespread fibrin deposition in microcirculation
                         ↓
Microthrombi → ischemia, infarction, organ dysfunction
                         ↓
Consumption of platelets + fibrinogen + coagulation factors
                         ↓
Secondary fibrinolysis with plasmin activation
                         ↓
FDPs/D-dimer rise + factors V and VIII reduced
                         ↓
BLEEDING

Consequences

1. Thrombotic consequences

• Microvascular fibrin thrombi impair tissue perfusion.
• May cause ischemia and dysfunction of:
  • Brain
  • Lungs
  • Heart
  • Kidneys
  • Adrenals
  • Liver and spleen
• RBC fragmentation in narrowed fibrin-lined vessels causes microangiopathic hemolytic anemia.

2. Hemorrhagic consequences

• Consumption of platelets
• Consumption of fibrinogen and clotting factors
• Plasmin-mediated cleavage of fibrin and factors V and VIII
• Fibrin degradation products inhibiting:
  • platelet aggregation
  • fibrin polymerization
  • thrombin activity

Morphology

• Fibrin thrombi occur mainly in small vessels.
• Kidneys: glomerular thrombi, microinfarcts, sometimes bilateral cortical necrosis.
• Lungs: fibrin thrombi in alveolar capillaries; may be associated with pulmonary edema and hyaline membranes.
• Brain: microinfarcts with possible hemorrhage.
• Adrenals: adrenal hemorrhage in meningococcemia, as in Waterhouse-Friderichsen syndrome.

Clinical Features

• Bleeding from venepuncture, wound, catheter, or surgical sites
• Petechiae, ecchymoses, mucosal bleeding
• Hematuria and gastrointestinal bleeding
• Dyspnea, cyanosis, respiratory failure
• Oliguria and acute renal failure
• Confusion, seizures, coma
• Shock and multiorgan dysfunction

Laboratory Diagnosis

Classic DIC pattern

↓ Platelets + ↑ PT/aPTT + ↓ fibrinogen + ↑ D-dimer/FDPs

High-Yield Viva Answer