What is the treatment approach for thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS)?

Treatment Approach for Thrombotic Microangiopathy

Immediate plasma exchange with high-dose glucocorticoids and rituximab is the first-line treatment for suspected TTP, while aggressive blood pressure control is the primary intervention for malignant hypertension-associated TMA, and eculizumab is indicated for atypical HUS. 1, 2

Immediate Diagnostic Workup

The critical first step is distinguishing between TMA subtypes, as treatment differs dramatically and delays increase mortality 1:

• Obtain ADAMTS13 activity and inhibitor levels immediately to differentiate TTP from other forms—do not wait for results before initiating treatment if TTP is suspected 1
• Examine peripheral blood smear for schistocytes and measure CBC, LDH, haptoglobin (typically unmeasurable in TMA), renal function, and coagulation studies 1
• Assess blood pressure as severe hypertension with advanced retinopathy (flame hemorrhages, cotton wool spots, papilledema) suggests hypertension-induced TMA rather than TTP or HUS 3

Treatment Algorithm Based on TMA Subtype

For Suspected TTP (ADAMTS13 deficiency)

Begin plasma exchange immediately—within hours of suspicion—along with high-dose glucocorticoids and rituximab 1:

• TTP presents with more severe thrombocytopenia and numerous schistocytes compared to hypertension-induced TMA 3
• Very low ADAMTS13 activity (<10%) confirms TTP, while normal or slightly reduced levels suggest hypertension-induced TMA 3
• Caplacizumab provides significantly better remission rates and decreases TMA-related death 4

For Atypical HUS (aHUS)

Eculizumab (complement inhibitor) is FDA-approved and indicated for aHUS to inhibit complement-mediated thrombotic microangiopathy 2:

• This represents a major therapeutic advance, as eculizumab treats aHUS successfully by blocking the dysregulated complement system 4
• Critical caveat: Eculizumab is NOT indicated for Shiga toxin E. coli-related HUS (STEC-HUS) 2
• Pregnant patients with TMA history should receive hydroxychloroquine continuation and low-dose aspirin before 16 weeks gestation 1

For Malignant Hypertension-Associated TMA

Aggressive blood pressure lowering is the primary and often sole intervention needed 3, 1:

• This form typically shows only moderate thrombocytopenia and few schistocytes, distinguishing it from TTP and HUS 3
• BP-lowering treatment improves TMA within 24-48 hours, whereas TTP and HUS require different therapies 3
• High systolic blood pressure (>140 mmHg) on admission carries a sevenfold increased risk of severe kidney disease 5
• Mean arterial pressure >100 mmHg indicates fourfold increased risk for acute renal failure 5

Key Clinical Pitfalls

The coexistence of severe BP elevation with advanced retinopathy (bilateral flame hemorrhages, cotton wool spots, papilledema) is usually sufficient to discriminate malignant hypertension-induced TMA from TTP or HUS 3:

• Do not delay plasma exchange for suspected TTP while awaiting ADAMTS13 results—mortality increases significantly with treatment delays 1
• High C-reactive protein levels on admission correlate with renal failure during disease course 5
• Older age is an independent risk factor for death in TMA 5
• TMA more commonly occurs secondary to coexisting conditions (infection, pregnancy, autoimmune disease, malignancy) than as primary TTP or HUS 6

Special Therapeutic Considerations

• Defibrotide has been established in phase III studies for therapy-associated TMA (veno-occlusive disease/sinusoidal obstruction syndrome) to significantly improve outcomes 4
• Daily plasma exchange and fresh frozen plasma infusion remain the mainstay for TTP when newer agents are unavailable 4, 7
• Immunosuppressants may be added as adjunctive therapy for refractory cases 7