The thrombotic microangiopathies (TMAs) — thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS) — are life-threatening syndromes of microangiopathic hemolysis, thrombocytopenia, and organ injury from small-vessel microthrombi. Rapid diagnosis and treatment are essential, and the therapeutic toolkit has expanded substantially, including a first-ever recombinant enzyme.
Recombinant ADAMTS13
The clearest advance is recombinant ADAMTS13 (apadamtase alfa, Adzynma), which replaces the deficient von Willebrand factor-cleaving protease. For congenital TTP, it is now an approved therapy — the pivotal Phase 3 crossover trial showed that prophylaxis reduced acute events to nearly zero while maintaining normal ADAMTS13 activity, and it gained approval in the US (2023) and the EU and Japan (2024) for prophylactic and on-demand use. It thus shifts congenital TTP from reactive plasma infusion toward reliable enzyme replacement. For immune (acquired) TTP, recombinant ADAMTS13 remains investigational, with encouraging results as an adjunct in refractory, critically ill patients.
Caplacizumab for acquired TTP
Caplacizumab, an anti-von Willebrand factor nanobody, added to plasma exchange and immunosuppression, shortened the time to platelet normalization and reduced the composite of TTP-related death, recurrence, and thromboembolic events in the HERCULES trial. Mild-to-moderate mucocutaneous bleeding is the main adverse effect. It is now standard in the initial management of acquired TTP, particularly in high-risk or relapsing disease.
Complement inhibition for aHUS
For complement-mediated aHUS, terminal complement inhibition with eculizumab transformed outcomes — improving platelet counts and renal function and achieving event-free status in most patients — and the longer-acting ravulizumab now offers equivalent efficacy with less frequent dosing. Meningococcal vaccination is mandatory before starting either.
| Therapy | Indication | Key result | Notes |
|---|---|---|---|
| Recombinant ADAMTS13 | Congenital TTP | Near-zero acute events with prophylaxis | Approved (2023–2024); investigational in immune TTP |
| Caplacizumab | Acquired (immune) TTP | Faster platelet recovery; fewer TTP events | Mucocutaneous bleeding |
| Eculizumab / ravulizumab | aHUS | Platelet and renal recovery | Meningococcal vaccination required |
Further reading: recombinant ADAMTS13 in congenital TTP (Scully et al., NEJM 2024) and refractory immune TTP (Bendapudi et al., NEJM 2024); HERCULES caplacizumab (Scully et al., NEJM 2019); eculizumab in aHUS (Legendre et al., NEJM 2013).