What is the appropriate management for an adult patient suspected of having Thrombotic Thrombocytopenic Purpura (TTP) with a history of easy bruising or bleeding?

Thrombotic Thrombocytopenic Purpura (TTP) Management

Immediate Emergency Management

If TTP is suspected in an adult with easy bruising or bleeding, initiate therapeutic plasma exchange (TPE) immediately—within hours of clinical suspicion—without waiting for ADAMTS13 results, as delay increases mortality dramatically. 1, 2, 3, 4, 5

Critical First Steps (Within 1-2 Hours)

• Start daily therapeutic plasma exchange at 1-1.5 times plasma volume using fresh frozen plasma as replacement fluid 1, 5
• Perform TPE daily until platelet count >150,000/μL AND lactate dehydrogenase (LDH) normalizes, then taper slowly 5
• Add high-dose corticosteroids (prednisone 1-2 mg/kg/day or methylprednisolone 1g IV daily × 3 days) immediately 2, 3, 4
• Add rituximab 375 mg/m² weekly × 4 doses to front-line therapy—this is now standard of care for immune-mediated TTP 2, 3, 4
• If available, add caplacizumab (anti-VWF nanobody) to front-line therapy to rapidly reduce platelet consumption 3, 4

Diagnostic Confirmation (Send Urgently But Do Not Delay Treatment)

• ADAMTS13 activity level (severe deficiency <10% confirms TTP) 2, 3, 4
• Anti-ADAMTS13 antibodies (positive in acquired/immune TTP) 2, 3, 4
• Complete blood count with peripheral smear showing schistocytes and severe thrombocytopenia 3, 4, 5
• Elevated LDH, elevated indirect bilirubin, low haptoglobin (hemolysis markers) 5
• Elevated creatinine and urinalysis (renal involvement assessment) 5
• Direct antiglobulin test (negative in TTP, distinguishes from autoimmune hemolytic anemia) 3, 4

The classic pentad (thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms, renal dysfunction, fever) occurs in only 6% of patients—do not wait for all five features before treating. 5 Thrombocytopenia plus microangiopathic hemolytic anemia alone mandates immediate TPE. 5

Treatment Algorithm by Clinical Scenario

Newly Diagnosed Acute TTP

Front-line therapy (all components started simultaneously):

• Daily TPE with FFP replacement (1-1.5 plasma volumes) 1, 5
• High-dose corticosteroids (prednisone 1-2 mg/kg/day or methylprednisolone pulses) 2, 3, 4
• Rituximab 375 mg/m² weekly × 4 doses 2, 3, 4
• Caplacizumab if available (10 mg IV bolus before first TPE, then 10 mg SC daily) 3, 4

Expected response: Complete remission achieved in 85% of patients with median 13-15 TPE sessions 5

Refractory TTP (No Response After 5-7 Days of Standard Therapy)

Escalate to intensive therapy:

• Increase TPE frequency to twice daily 4
• Add cyclosporine A, cyclophosphamide pulses, vincristine, or bortezomib 2, 3, 4
• Consider N-acetylcysteine 3, 4
• Salvage splenectomy if medical therapy fails 2, 4

Relapsing TTP (Recurrence After Initial Remission)

• Reinitiate daily TPE immediately 4
• Restart corticosteroids 4
• Give rituximab if not previously used, or repeat if >6 months since last dose 2, 4
• Consider maintenance rituximab or other immunosuppression for relapse prevention 4

Critical Pitfalls to Avoid

Do not withhold TPE while awaiting ADAMTS13 results—mortality without treatment approaches 90%, versus 10-20% with prompt TPE. 3, 4 Clinical suspicion (thrombocytopenia + microangiopathic hemolytic anemia + elevated LDH) is sufficient to start treatment. 5

Do not use platelet transfusions in TTP—they worsen microvascular thrombosis and increase mortality unless life-threatening bleeding occurs. 3, 4

Do not confuse TTP with immune thrombocytopenia (ITP)—ITP lacks hemolysis, schistocytes, and elevated LDH. 3, 4 The presence of hemolytic anemia distinguishes TTP and mandates TPE, not corticosteroids alone. 5

Do not use high-dose plasma infusion (25-30 mL/kg/day) as definitive therapy—while it may temporize when TPE is unavailable, 42% (8/19) of patients required conversion to TPE due to fluid overload or treatment failure. 1 Plasma infusion is only acceptable as a bridge until TPE can be arranged. 1

Do not stop TPE prematurely—continue daily until platelet count >150,000/μL AND LDH normalizes, then taper gradually over 1-2 weeks. 5 Abrupt cessation causes relapse. 4

Monitoring During Treatment

• Daily platelet count and LDH until both normalize 5
• Daily hemoglobin, creatinine, neurological examination 5
• ADAMTS13 activity weekly to guide therapy duration 3, 4
• Monitor for TPE complications: central line infection/thrombosis, hypocalcemia, citrate toxicity 5
• Monitor for fluid overload if plasma infusion used 1

Long-Term Follow-Up After Remission

• Monitor ADAMTS13 activity every 3-6 months indefinitely to detect impending relapse 3, 4
• Screen for other autoimmune diseases (lupus, antiphospholipid syndrome) 4
• Assess for cognitive and psychological sequelae of TTP 3, 4
• Preemptive rituximab may be considered if ADAMTS13 activity declines <10-20% while asymptomatic 2

Relapse occurs in 30-50% of patients with immune-mediated TTP, most commonly within the first year. 4 Vigilant monitoring with ADAMTS13 activity allows preemptive treatment before clinical relapse. 2