Are corticosteroids indicated in thrombotic microangiopathy, and if so, in which forms such as immune‑mediated thrombotic thrombocytopenic purpura, and what dosing regimen should be used?

Corticosteroids in Thrombotic Microangiopathy: Indication and Dosing

Corticosteroids are indicated specifically for immune-mediated thrombotic thrombocytopenic purpura (TTP), not for other forms of thrombotic microangiopathy, and should be initiated immediately alongside plasma exchange while awaiting ADAMTS13 results. 1, 2

Diagnostic Algorithm for TMA with Suspected TTP

When encountering thrombotic microangiopathy with thrombocytopenia and microangiopathic hemolytic anemia:

• Start plasma exchange AND corticosteroids immediately while awaiting ADAMTS13 activity results, particularly if the PLASMIC score is moderate-to-high risk (>5 points) 1
• Send ADAMTS13 activity and anti-ADAMTS13 antibodies urgently 2, 3
• Test for antiphospholipid antibodies to rule out APS-related TMA 1
• Evaluate for complement-mediated TMA, drug-induced TMA, and infection-related causes 1

Corticosteroid Regimens for Immune TTP

Standard Dosing Protocol

Prednisone 1 mg/kg/day orally is the standard corticosteroid regimen used as adjunct to plasma exchange in immune TTP, demonstrating superior suppression of anti-ADAMTS13 antibodies compared to cyclosporine 4. This regimen should be:

• Continued throughout the acute phase until platelet normalization and ADAMTS13 recovery 2, 5
• Tapered gradually after achieving clinical remission 4

High-Dose Methylprednisolone Alternative

For emergency situations with severe organ ischemia:

• Methylprednisolone 30 mg/kg/day IV for 7 days can be used for rapid response 6
• Achieves response in approximately 4.7 days 6
• Particularly useful for active CNS, GI, or genitourinary bleeding 6

Triple Therapy: Current Standard of Care

The contemporary standard for acute immune TTP is triple therapy: plasma exchange + corticosteroids + rituximab, with caplacizumab added upfront 2, 7. This combination:

• Improves 30-day survival to >90% (from nearly zero without treatment) 2
• Reduces time to platelet normalization when caplacizumab is included 2, 5
• Decreases early recurrence risk by 29% with caplacizumab (though bleeding risk increases by 17%) 2

Rituximab Integration

• Rituximab should be added to frontline therapy, not reserved only for refractory cases 3, 5, 7
• Dosing: 375 mg/m² weekly for 4 weeks 5
• Significantly improves ADAMTS13 remission rates and prevents relapse 5, 7

Forms of TMA Where Corticosteroids Are NOT Indicated

Do not use corticosteroids as primary therapy for:

• Complement-mediated TMA (primary or secondary) - requires eculizumab or other complement inhibitors 1
• Antiphospholipid syndrome nephropathy - requires anticoagulation as primary treatment 1
• Shiga-toxin hemolytic uremic syndrome - supportive care only; immunosuppression contraindicated 1

Critical Monitoring and Pitfalls

ADAMTS13 Monitoring Strategy

• Check ADAMTS13 activity regularly during remission 2, 5
• If ADAMTS13 activity drops below 20% during remission, administer preemptive rituximab to prevent clinical relapse (reduces relapse odds ratio to 0.09) 2
• Monitor for anti-ADAMTS13 antibody persistence 4, 5

Common Pitfalls to Avoid

• Never delay plasma exchange and corticosteroids while waiting for ADAMTS13 results - empiric treatment must start immediately based on clinical suspicion 1, 2
• Do not use corticosteroids alone without plasma exchange in suspected immune TTP - mortality remains unacceptably high 2, 7
• Avoid abrupt corticosteroid discontinuation before ADAMTS13 recovery, as this increases exacerbation risk 4, 5
• Do not continue corticosteroids beyond 6-8 weeks without clear indication, given cumulative toxicity risk 8, 6

Steroid-Related Adverse Effects Requiring Monitoring

• Hyperglycemia, hypertension, and fluid retention (monitor closely) 8, 6
• Mood disturbances, insomnia, and psychiatric symptoms 8, 6
• Opportunistic infections due to immunosuppression 8
• Avascular necrosis with prolonged use 8, 6

Distinguishing Immune TTP from ITP

This is NOT immune thrombocytopenic purpura (ITP) - the evidence regarding ITP treatment with corticosteroids 1, 8, 9 does not apply to thrombotic microangiopathy. Key distinguishing features:

• TTP presents with microangiopathic hemolytic anemia (schistocytes on smear), elevated LDH, and organ ischemia 2, 5
• ITP has isolated thrombocytopenia without hemolysis or organ dysfunction 1
• TTP requires urgent plasma exchange; ITP does not [2 vs 1]