Immune TTP – Clinical Presentation

Clinical presentation

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

Symptoms may include those of:

• Anemia:
  • Weakness
  • Fatigue
  • Jaundice
  • Pallor
• Thrombocytopenia:
  • Petechiae/purpura
  • Bleeding, for example:
    • Epistaxis
    • Gingival bleeding
    • Gastrointestinal bleeding
    • 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 acquired/immune 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

Physical findings

• Look for:
  • Vitals:
    • Fever
    • Hypotension
  • Skin:
    • Petechiae 
    • Echymoses
    • Jaundice from hemolysis
    • Pallor
  • Neurological:
    • Confusion
    • Paresthesia
    • Paresis
    • Aphasia or dysarthria
    • Visual changes
    • Seizures
    • Encephalopathy
    • Fluctuating levels or consciousness
    • Coma, which has been reported in 10% of patients with acute TTP

Lab tests

• Thrombocytopenia:⁶
  • Caused by consumption of platelets in platelet-rich thrombi.
  • Median platelet count typically 10–30 × 10⁹/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 8-10 g/dL.
  • Evidence of hemolysis:
    • Elevated LDH, caused by:
      • Hemolysis
      • Tissue ischemia
    • Low haptoglobin
    • Increased indirect bilirubin
  • Evidence of schistocytes on peripheral smear
• PT, aPTT are typically normal.
• Elevated troponin levels (>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 × 10⁹/L), but higher platelet numbers do not exclude the diagnosis”.⁸

Cohort studies

• Scully et al, 2019
  • 145 patients with TTP (ADAMTS13 activity at baseline was below 10% in 123 patients [85%])
  • Median platelet count (range) – 24 × 10⁹/L (3 × 10⁹/L – 133 × 10⁹/L)
  • Median LDH (range) – 422 (120-3343)
• Page et al, 2017
  • 78 patients with TTP (defined as ADAMTS13 activity <10%)
  • Fever in 10% of patients
  • Neurologic changes:
    • Severe in 53% of patients
    • Mild in 27%
    • None in 20%
  • Thrombocytopenia in100%:
    • Median platelet count 10,000
    • Platelet count:
      • > 20 × 10⁹/L in 14%
      • > 30 × 10⁹/L in 4%
  • MAHA 100%:
    • Median Hct 21%
    • Hct >30 in 3%
  • Only 14% of patients 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 manifestations in 71% of episodes
  • Hemorrhagic manifestations in 46% of episodes
  • GI manifestations in 39% of episodes
  • Fever in 28% of episodes
  • Renal manifestations in 10% of episodes
  • TTP pentad in 7% of episodes

Clinical practice guidelines

• A British Society for Haematology Guideline: Diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies.
  

Want to explore this further?

Check out the related sections in our TTP module:

• TTP – History
• TTP – Physical examination
• TTP Clinical Presentation – Quiz