Is Thrombotic Microangiopathy (TMA) the same as Thrombotic Thrombocytopenic Purpura (TTP)?

TMA and TTP: Not the Same Entity

No, Thrombotic Microangiopathy (TMA) is not the same as Thrombotic Thrombocytopenic Purpura (TTP); rather, TTP is one specific subtype of TMA characterized by severe ADAMTS13 deficiency (<10% activity). 1

Understanding the Relationship

TMA is the umbrella term that encompasses multiple distinct disease entities, while TTP represents just one specific form within this broader category. 2, 3

TMA as the Broader Category

TMA is a clinicopathological syndrome characterized by:

• Endothelial injury leading to platelet activation and formation of platelet-rich thrombi in the microcirculation 2
• Microangiopathic hemolytic anemia with schistocytes 2
• Thrombocytopenia due to platelet consumption 4
• Organ damage from microcirculation obstruction 2

Multiple TMA Subtypes

The most clinically relevant forms of TMA include:

1. Thrombotic Thrombocytopenic Purpura (TTP)

• Defined specifically by ADAMTS13 activity <10% 1
• Caused by autoantibodies against ADAMTS13 (acquired) or genetic mutations (congenital) 4, 5
• Results in ultra-large von Willebrand factor multimers that promote platelet aggregation 2, 4

2. Complement-Mediated TMA (including atypical HUS)

• Results from complement dysregulation damaging endothelial cells 2
• Associated with genetic abnormalities in complement regulatory proteins 3

3. Antiphospholipid Syndrome-Associated TMA

• Antiphospholipid antibodies promote microvascular thrombosis 2
• Found in approximately 30% of SLE patients 1

4. Secondary TMA Forms

• Shiga-toxin hemolytic uremic syndrome 1
• Drug-induced TMA 1, 6
• Malignancy-associated TMA 6
• Malignant hypertension-associated TMA 2

Critical Diagnostic Distinction

The key diagnostic test is ADAMTS13 activity measurement. 1

• ADAMTS13 <10% = TTP diagnosis confirmed 1
• ADAMTS13 >10% = Rules out TTP; consider other TMA etiologies 6

While awaiting ADAMTS13 results in adults with suspected TTP, the PLASMIC score can risk-stratify patients, and those with intermediate-to-high risk should receive plasma exchange and glucocorticoids empirically. 1

Treatment Implications of the Distinction

This distinction is not merely academic—it determines life-saving treatment decisions:

For confirmed TTP (ADAMTS13 <10%):

• Plasma exchange, high-dose glucocorticoids, rituximab, and/or caplacizumab 1

For complement-mediated TMA:

• Eculizumab may be effective 1, 2

For antiphospholipid syndrome-associated TMA:

• Long-term anticoagulation with warfarin (not direct oral anticoagulants) 1
• Plasma exchange for catastrophic cases 1

For malignant hypertension-associated TMA:

• Aggressive blood pressure control 2

Common Pitfall

The most dangerous error is assuming all TMA presentations are TTP and initiating plasma exchange without considering alternative diagnoses. 6 While plasma exchange is appropriate for suspected TTP pending ADAMTS13 results, other TMA forms require entirely different therapeutic approaches. 1, 2 Co-management with an experienced hematologist is preferable when expertise is available. 1