What are the differences in diagnosis and treatment between Thrombotic Thrombocytopenic Purpura (TTP) and Immune Thrombocytopenic Purpura (ITP)?

Differences Between TTP and ITP: Diagnosis and Treatment

The key difference between TTP and ITP is that TTP is a life-threatening emergency requiring immediate plasma exchange therapy, while ITP is typically managed with observation or immunosuppression depending on bleeding severity.

Diagnostic Differences

TTP (Thrombotic Thrombocytopenic Purpura)

• Clinical Presentation:

  • Pentad of symptoms (not all required): thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities (39-80%), fever, and renal dysfunction 1
  • Abdominal pain (35-39%) 1
  • Typically affects adults more than children 1
  • Higher incidence in females and Black individuals 1

• Laboratory Findings:

  • Severe ADAMTS13 deficiency (<10% activity) 1, 2
  • Microangiopathic hemolytic anemia with schistocytes on peripheral smear 1, 2
  • Elevated LDH, decreased hemoglobin and haptoglobin 2
  • Thrombocytopenia (often <30 × 10^9/L) 1
  • Creatinine typically <2.0 mg/dL 1

ITP (Immune Thrombocytopenic Purpura)

• Clinical Presentation:

  • Isolated thrombocytopenia without other cytopenias 3, 4
  • Mucocutaneous bleeding (petechiae, purpura) 3, 4
  • No neurological symptoms
  • In children: typically ages 2-6 years 5
  • In adults: chronic course, rarely remits spontaneously 3, 6

• Laboratory Findings:

  • Normal red blood cell morphology 3, 5
  • Normal white blood cell morphology 3, 5
  • Thrombocytopenia with normal-sized or slightly larger platelets 3, 5
  • No schistocytes 3
  • Normal LDH and haptoglobin

Treatment Differences

TTP Treatment

• First-line:

  • Immediate therapeutic plasma exchange - lifesaving intervention that must be started promptly 1, 2, 7
  • Corticosteroids 1
  • Rituximab 1

• Additional Therapies:

  • Caplacizumab (nanobody that blocks platelet-VWF binding) 1
  • Monitoring ADAMTS13 activity in remission 1
  • Rituximab when ADAMTS13 activity <20% to prevent relapse 1

• Prognosis:

  • Without treatment: nearly 100% mortality 1
  • With prompt treatment: 93% survival 1
  • 16% relapse rate after clinical remission 1

ITP Treatment

Children:

• First-line:

  • Observation alone for no bleeding or mild bleeding (skin manifestations only) 3, 5
  • 75-80% resolve spontaneously within 6 months 5
  • For significant bleeding: IVIg, anti-D (in appropriate patients), or corticosteroids 3

• Second-line:

  • Splenectomy for chronic ITP (>12 months) with significant bleeding unresponsive to other therapies 3
  • High-dose dexamethasone as alternative to splenectomy 3

Adults:

• First-line:

  • Treatment recommended for platelet count <30 × 10^9/L 3
  • Longer courses of corticosteroids preferred over shorter courses 3
  • IVIg when rapid platelet increase needed 3

• Second-line:

  • Splenectomy for those failing corticosteroid therapy 3
  • Thrombopoietin receptor agonists for those who relapse after splenectomy 3
  • Rituximab may be considered after failure of first-line therapy 3

Key Diagnostic Pitfalls

1. Misdiagnosis risk: TTP is often misdiagnosed initially as ITP, delaying life-saving plasma exchange 1, 2

2. Testing requirements:

   • TTP: ADAMTS13 activity testing is essential 1, 2
   • ITP: Diagnosis of exclusion; requires HIV and HCV testing 3

3. Peripheral smear examination:

   • TTP: Schistocytes are present 1, 2
   • ITP: No schistocytes; normal RBC morphology 3, 5

4. Bone marrow examination:

   • Not necessary for typical ITP presentation 3
   • May be needed to rule out other causes of thrombocytopenia like MDS 4

Treatment Algorithm

1. For suspected thrombocytopenia:

   • Check complete blood count with peripheral smear
   • If schistocytes present + neurological symptoms → Treat as TTP until proven otherwise
   • If isolated thrombocytopenia without schistocytes → Consider ITP

2. For suspected TTP:

   • Start plasma exchange immediately
   • Add corticosteroids and rituximab
   • Consider caplacizumab
   • Monitor ADAMTS13 activity

3. For suspected ITP:

   • In children with mild symptoms: observation
   • In adults or children with significant bleeding:
     • Start corticosteroids
     • Add IVIg if rapid platelet increase needed
     • Consider splenectomy or TPO agonists for refractory cases

Remember that TTP is a medical emergency requiring immediate intervention, while ITP management can often be more measured and depends on bleeding severity rather than platelet count alone.