ISTH Updates TTP Treatment Guidelines Backing Recombinant ADAMTS-13
The 2025 ISTH guideline update elevates recombinant ADAMTS-13 as the preferred therapy for congenital TTP while maintaining prior immune TTP recommendations.
Summary
The International Society on Thrombosis and Haemostasis released a 2025 focused update to its 2020 guidelines on thrombotic thrombocytopenic purpura (TTP). For congenital TTP (cTTP) in remission, a new strong recommendation supports recombinant ADAMTS-13 over fresh frozen plasma, backed by moderate-certainty evidence. Where recombinant ADAMTS-13 is unavailable, fresh frozen plasma remains preferable to a watch-and-wait approach, though evidence is very low certainty. For immune TTP (iTTP), the panel reviewed new data on caplacizumab combined with plasma exchange, corticosteroids, and rituximab but found no basis to change existing recommendations. A multidisciplinary GRADE-based panel developed these updates, emphasizing shared decision-making that weighs benefits, harms, and care burden for individual patients.
Detailed Summary
Thrombotic thrombocytopenic purpura is a rare, life-threatening blood disorder caused by severely deficient ADAMTS-13 activity — either from autoimmune destruction (iTTP) or inherited mutations (cTTP). Timely, evidence-based treatment is critical to preventing organ damage and death, making updated clinical guidelines essential as new therapies emerge.
In March 2024, the ISTH convened a multidisciplinary panel — including hematologists, intensivists, nephrologists, pathologists, and patient representatives — to evaluate new evidence and update its 2020 TTP management guidelines. The panel applied the GRADE methodology to systematically appraise studies and formulate recommendations across both TTP subtypes.
The most significant change concerns cTTP: a new strong recommendation now supports recombinant ADAMTS-13 replacement over fresh frozen plasma for patients in remission, based on moderate-certainty evidence. Recombinant ADAMTS-13 offers a more favorable benefit-risk profile, avoiding plasma-associated risks such as transfusion reactions and infection. For settings where recombinant ADAMTS-13 is inaccessible, fresh frozen plasma is still conditionally recommended over watchful waiting, though this rests on very low certainty evidence.
For iTTP, the panel reviewed emerging publications supporting the therapeutic efficacy, potential survival benefit, and cost profile of caplacizumab added to standard triple therapy (plasma exchange, corticosteroids, rituximab). Despite this new data, the panel concluded the existing 2020 recommendations remain appropriate without revision. Minor modifications were made to good practice statements regarding concomitant antithrombotic agent use.
These updates reinforce the shift toward targeted enzyme-replacement strategies in hereditary TTP while maintaining a cautious, evidence-anchored stance on iTTP management. Clinicians should incorporate patient preferences, access constraints, and shared decision-making into treatment planning.
Key Findings
- Strong new recommendation: recombinant ADAMTS-13 preferred over fresh frozen plasma for cTTP in remission.
- Fresh frozen plasma still conditionally recommended over watch-and-wait for cTTP when recombinant ADAMTS-13 is unavailable.
- No changes made to 2020 iTTP recommendations despite new caplacizumab efficacy and survival data.
- GRADE methodology applied; cTTP recombinant ADAMTS-13 recommendation supported by moderate-certainty evidence.
- Shared decision-making emphasized, factoring in benefits, harms, and burden of care for each patient.
Methodology
A multidisciplinary ISTH panel formed in March 2024 systematically reviewed emerging TTP literature using the GRADE framework to assess evidence certainty and formulate updated recommendations. The panel included clinicians across specialties and patient representatives to ensure broad perspective. Recommendations were graded as strong or conditional based on evidence quality, benefits, and patient values.
Study Limitations
The cTTP fresh frozen plasma recommendation rests on very low certainty evidence, limiting confidence in that specific guidance. The panel's decision not to update iTTP recommendations may lag real-world adoption of caplacizumab as new efficacy data accumulates. Several panel members disclosed financial relationships with manufacturers of relevant therapies, introducing potential conflict-of-interest considerations.
Enjoyed this summary?
Get the latest longevity research delivered to your inbox every week.