Jan

31

2025

Immune TTP – Clinical Presentation

By William Aird

Clinical presentation of TTP is highly variable, ranging from minimal symptoms to critical illness, but typically includes a combination of:

  • Microangiopathic hemolytic anemia (MAHA) (median hemoglobin 8-10 g/dL)
  • Thrombocytopenia (median platelet count 10-30 × 109/L)
  • Organ dysfunction

The historic pentad is present in only 5% of patients, and includes:1

  • Thrombocytopenia
  • Microangiopathic hemolytic anemia
  • Neurologic symptoms
  • Kidney impairment
  • Fever

Symptoms may include those of:

  • Anemia:
    • Weakness
    • Fatigue
    • Jaundice
    • Pallor
  • Thrombocytopenia:
    • Petechiae/Purpura
    • Bleeding, for example:
      • Epistaxis
      • Gingival
      • Gastrointestinal
      • Hematuria
      • Menorrhagia
      • Hemoptysis
      • Retinal hemorrhage
  • Organ dysfunction, including:2
    • Neurologic (about 60% of cases), including:3
      • Confusion
      • Headaches
      • Stroke
      • Coma
      • Seizures
      • Visual changes
      • Altered speech
      • Paresthesia
    • Cardiovascular (heart ischemia in about 25% of cases), including:4
      • Chest pain
      • Arrhythmias
      • Symptoms of heart failure, for example:
        • Paroxysmal nocturnal dyspnea
        • Orthopnea
        • Dyspnea on exertion
        • Fatigue and weight gain
        • Cough
      • Hypotension
      • Myocardial infarction
      • Acute cardiac arrest
    • The gastrointestinal tract:
      • Mesenteric ischemia (about 35% of cases), which may present with:
        • Abdominal pain
        • Nausea
        • Vomiting
        • Diarrhea
      • Patients may also present with pancreatitis1
    • The kidney:
      • Hematuria and proteinuria
      • Rena failure rare
  • Conditions associated with secondary TTP such as those related to:
    • Autoimmune diseases, especially SLE
    • Pregnancy
    • Drugs
    • HIV infection
    • Pancreatitis
    • Cancer
    • Organ transplantation
  • Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies: “Acute TTP presentations may include bleeding symptoms such as bruising or hematuria, or thrombotic symptoms associated with neurologic or cardiac involvement.”5

Lab tests

  • Thrombocytopenia:6
    • Caused by consumption of platelets in platelet-rich thrombi.
    • Median platelet count typically 10–30 × 10 9 /L at presentation.
  • MAHA:7
    • Caused by mechanical fragmentation of erythrocytes during flow through partially occluded, high-shear small vessels.
    • Median hemoglobin levels on admission are typically 80–100 g/L.
    • Evidence of hemolysis:
      • Elevated LDH, caused by:
        • Hemolysis
        • Tissue ischemia
      • Low haptoglobin
      • Increased indirect bilirubin
    • Evidence of schistocytes on peripheral smear
  • PT, aPTT typically normal
  • Elevated troponin levels:
    • In > 50% of cases
  • Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies: “Anemia may not be immediately obvious. Thrombocytopenia is generally severe (platelet count of < 30 9 10 9 L1), but higher platelet numbers do not exclude the diagnosis”.8

Cohort studies

  • Scully et al, 2019
    • 145 patients with TTP
    • Median platelet count (range) – 24,000 (3,000-133,000)
    • Median LDH (range) – 422 (120-3343)
  • Page et al, 2017
    • 78 patients with TTP (defined as ADAMTS13 activity <10%)
    • Fever 10%
    • Neurologic changes:
      • Severe 53%
      • Mild 27%
      • None 20%
    • Thrombocytopenia 100%:
      • Median platelet count 10,000
      • Platelet count
        • > 20,000 in 14%
        • > 30,000 in 4%
    • MAHA 100%
      • Median Hct 21%
      • Hct > 30 in 3%
    • Only 14% had serum creatinine concentrations ≥2.5 mg/dL
  • Blombery et al, 2016
    • 57 patients with TTP (defined as ADAMTS13 activity <10%), accounting for 72 episodes
    • Neurological 71% of episodes
    • Hemorrhagic manifestations 46% of episodes
    • GI manifestations in 39% of episodes
    • Fever 28% of episodes
    • Renal manifestations in 10% of episodes
    • TTP pentad 7% of episodes

Clinical practice guidelines