Introduction to Disseminated Intravascular Coagulation (DIC) in Children

Disseminated Intravascular Coagulation (DIC) is a complex and potentially life-threatening condition characterized by the systemic activation of coagulation pathways. In children, DIC presents unique challenges due to their developing hemostatic systems and varied etiologies. DIC results in the formation of widespread blood clots in small blood vessels throughout the body, leading to organ dysfunction and simultaneously depleting clotting factors and platelets, which can cause severe bleeding.

Key points:

• DIC is not a primary disease but a secondary process resulting from an underlying condition
• It can occur in both acute and chronic forms
• The pediatric population is particularly vulnerable due to their immature coagulation systems
• Early recognition and prompt management are crucial for improving outcomes

Pathophysiology of DIC in Children

The pathophysiology of DIC in children involves a complex interplay of coagulation activation, fibrinolysis, and inflammatory processes:

1. Initiation: Tissue factor exposure triggers the extrinsic coagulation pathway
2. Thrombin generation: Excessive thrombin production leads to widespread fibrin deposition
3. Consumption of clotting factors: Ongoing coagulation depletes clotting factors and platelets
4. Fibrinolysis activation: Initially increased to counteract clot formation, but may become impaired
5. Microvascular thrombosis: Leads to organ ischemia and dysfunction
6. Bleeding: Results from consumption of clotting factors and platelets

In children, the immature hemostatic system can lead to a more rapid progression and severe manifestations of DIC compared to adults. The balance between pro-coagulant and anti-coagulant factors is particularly delicate in neonates and young infants, making them more susceptible to DIC in various clinical scenarios.

Etiology of DIC in Children

DIC in children can be triggered by various underlying conditions:

• Infections:
  • Sepsis (bacterial, viral, fungal)
  • Meningococcemia
  • Severe viral infections (e.g., dengue hemorrhagic fever)
• Trauma:
  • Severe tissue injury
  • Burns
  • Head trauma
• Malignancies:
  • Acute leukemias
  • Solid tumors
• Obstetric complications:
  • Placental abruption
  • Amniotic fluid embolism
• Vascular disorders:
  • Kasabach-Merritt syndrome
  • Large vascular malformations
• Severe hepatic failure
• Toxic reactions:
  • Snake bites
  • Drug reactions
• Massive transfusions

In neonates, additional causes include:

• Perinatal asphyxia
• Respiratory distress syndrome
• Necrotizing enterocolitis

Clinical Presentation of DIC in Children

The clinical manifestations of DIC in children can vary widely depending on the underlying cause, the child's age, and the stage of DIC. Common presentations include:

• Bleeding:
  • Petechiae and purpura
  • Mucosal bleeding (e.g., gums, nose)
  • Gastrointestinal hemorrhage
  • Excessive bleeding from venipuncture sites
• Thrombosis:
  • Acral cyanosis
  • Organ dysfunction due to microvascular thrombosis
  • Skin necrosis
• Signs of underlying condition:
  • Fever, tachycardia, and hypotension in sepsis
  • Specific signs related to the primary disease

In neonates, additional signs may include:

• Respiratory distress
• Poor feeding
• Lethargy
• Seizures

It's important to note that the clinical presentation can range from subtle abnormalities in laboratory values to fulminant multi-organ failure. A high index of suspicion is necessary, especially in high-risk patients.

Diagnosis of DIC in Children

Diagnosing DIC in children requires a combination of clinical assessment and laboratory investigations:

Laboratory Tests:

• Complete Blood Count (CBC):
  • Thrombocytopenia
  • Schistocytes on peripheral blood smear
• Coagulation Studies:
  • Prolonged Prothrombin Time (PT)
  • Prolonged Activated Partial Thromboplastin Time (aPTT)
  • Decreased fibrinogen levels
• D-dimer: Elevated levels indicate active fibrinolysis
• Fibrin Degradation Products (FDPs): Elevated
• Antithrombin III levels: Often decreased

Diagnostic Criteria:

The International Society on Thrombosis and Haemostasis (ISTH) DIC score can be used, but it's important to note that it's not specifically validated for children:

Test	Result	Score
Platelet count	>100 x 10^9/L 50-100 x 10^9/L <50 x 10^9/L	0 1 2
D-dimer	No increase Moderate increase Strong increase	0 2 3
Fibrinogen	>1 g/L <1 g/L	0 1
Prolonged PT	<3 seconds 3-6 seconds >6 seconds	0 1 2

A score ≥5 is compatible with overt DIC. Scores should be calculated daily to monitor progression.

It's crucial to consider age-specific normal values when interpreting laboratory results in children, especially in neonates and infants.

Management of DIC in Children

The management of DIC in children focuses on treating the underlying condition and supporting the coagulation system:

1. Treat the Underlying Cause:

• Antibiotics for sepsis
• Surgical intervention for trauma or obstetric complications
• Specific treatments for malignancies or other primary conditions

2. Supportive Care:

• Maintain adequate tissue perfusion and oxygenation
• Correct electrolyte imbalances and metabolic abnormalities
• Provide appropriate fluid resuscitation

3. Blood Product Replacement:

• Platelets: Transfuse if <50,000/μL or active bleeding
• Fresh Frozen Plasma (FFP): To replace coagulation factors
• Cryoprecipitate: If fibrinogen <100 mg/dL
• Packed Red Blood Cells: For significant anemia or ongoing blood loss

4. Anticoagulation:

In cases of predominant thrombosis:

• Heparin: Low-dose unfractionated heparin (10-15 units/kg/hr) may be considered
• Antithrombin concentrate: May be beneficial, especially in sepsis-induced DIC

5. Other Therapies:

• Recombinant activated Factor VII: May be used in life-threatening bleeding unresponsive to other measures
• Tranexamic acid: In cases of hyperfibrinolysis

Close monitoring of clinical status and laboratory parameters is essential to guide therapy and assess response. The balance between pro-coagulant and anticoagulant therapies is delicate and should be tailored to each patient's specific needs.

Prognosis of DIC in Children

The prognosis of DIC in children varies widely and depends on several factors:

• Underlying cause: The nature and severity of the primary condition significantly impact outcomes
• Timing of diagnosis and intervention: Early recognition and prompt treatment improve prognosis
• Severity of organ dysfunction: Multi-organ failure is associated with poorer outcomes
• Age of the child: Neonates may have more severe courses due to their immature coagulation systems

Mortality rates in pediatric DIC can range from 10% to 50%, depending on the underlying cause and severity. Sepsis-induced DIC tends to have higher mortality rates compared to trauma-induced DIC.

Long-term Complications:

• Chronic organ dysfunction due to microvascular thrombosis
• Neurological sequelae in cases of CNS involvement
• Venous thromboembolism
• Post-thrombotic syndrome

Follow-up care and monitoring are essential, even after the acute phase of DIC has resolved. This includes assessing for potential long-term complications and addressing any persistent coagulation abnormalities.