Acute hematology - thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, disseminated intravascular coagulopathy

Acute Hematology – Thrombotic Thrombocytopenic Purpura, Hemolytic Uremic Syndrome, and DIC

Thrombotic microangiopathies (TMAs) are a group of acute hematologic disorders characterized by:

• Microangiopathic hemolytic anemia (MAHA)
• Thrombocytopenia
• Microvascular thrombosis

The two most important TMAs for exams are:

• Thrombotic thrombocytopenic purpura (TTP)
• Hemolytic uremic syndrome (HUS)

General Pathophysiology

Core Mechanism

• Endothelial injury or dysfunction → Platelet aggregation in small vessels → Formation of microthrombi

Consequences

• RBC fragmentation → schistocytes → hemolytic anemia
• Platelet consumption → thrombocytopenia
• Organ ischemia (brain, kidney)

Thrombotic Thrombocytopenic Purpura (TTP)

Acute, life-threatening TMA caused by ADAMTS13 deficiency → accumulation of large vWF multimers → platelet aggregation

Pathogenesis

• ADAMTS13 normally cleaves large vWF multimers
• Deficiency → large vWF multimers persist → ↑ platelet adhesion → microthrombi

Causes

• Acquired (most common): autoantibodies against ADAMTS13
• Inherited: rare (Upshaw–Schulman syndrome)

Clinical Features

Classically described pentad (but not always complete):

• Thrombocytopenia → petechiae, purpura
• MAHA → fatigue, pallor
• Neurologic symptoms (prominent)→ confusion, headache, seizures
• Renal dysfunction (mild–moderate)
• Fever
• Untreated → high mortality

Laboratory Findings

• ↓ platelets
• ↑ LDH, ↑ indirect bilirubin
• ↓ haptoglobin
• Schistocytes on smear
• Normal coagulation tests (important distinction from DIC)

Hemolytic Uremic Syndrome (HUS)TMA characterized by:

• MAHA
• Thrombocytopenia
• Severe acute kidney injury

Types

1. Typical HUS (Shiga toxin–associated)

• Caused by E. coli O157:H7 (or Shigella)
• Often follows bloody diarrhea
• Common in children

2. Atypical HUS

• Due to complement dysregulation
• Genetic or acquired
• More severe, recurrent

Pathogenesis

Typical HUS

• Shiga toxin → endothelial damage (especially kidney) → platelet activation → microthrombi

Atypical HUS

• Uncontrolled complement activation → endothelial injury

Clinical Features

• Acute kidney injury (dominant) → oliguria, ↑ creatinine
• MAHA → fatigue
• Thrombocytopenia → bleeding
• Often preceded by diarrhea (typical HUS)

Laboratory Findings

• Same TMA pattern:
  • Schistocytes
  • ↑ LDH, ↑ bilirubin
  • ↓ platelets
• Renal failure markers ↑ (creatinine, urea)

Diagnosis

• Clinical + history (diarrhea in typical HUS)
• ADAMTS13 usually normal (helps distinguish from TTP)

• Renal failure dominant
• Neurologic symptoms less prominent than TTP
• Common in children (typical HUS)

Disseminated Intravascular Coagulation (DIC)

Systemic activation of coagulation → widespread fibrin deposition + consumption of clotting factors and platelets

Pathogenesis

Trigger (e.g., sepsis, trauma, malignancy, obstetric complications) → Massive activation of coagulation cascade → Formation of fibrin microthrombi → Consumption of platelets + clotting factors → bleeding + thrombosis simultaneously

Clinical Features

• Bleeding (most prominent):
  • petechiae, ecchymoses
  • mucosal bleeding
• Thrombosis → organ dysfunction

Laboratory Findings

·        ↓ platelets

• ↑ PT, ↑ aPTT
• ↑ D-dimer
• ↓ fibrinogen
• Schistocytes may be present

Diagnosis

Based on clinical context + coagulation abnormalities

Treatment

• Treat underlying cause (most important)
• Supportive:
  • Platelets
  • Fresh frozen plasma
  • Cryoprecipitate (for fibrinogen)

References

1. Robbins & Cotran Pathologic Basis of Disease (10th ed.)
2. AMBOSS – Thrombotic Microangiopathies (TTP, HUS)
3. Harrison’s Principles of Internal Medicine
4. StatPearls (NCBI) – TTP and HUS
5. UpToDate (reviewed concepts for pathophysiology and management)