Syndrome
Transplant-associated TMA (TA-TMA)
Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial-injury syndrome after (usually allogeneic) hematopoietic cell transplant, in which complement — including the lectin pathway — is activated, driving microvascular thrombosis. The kidney is a frequent target: hypertension, proteinuria, and AKI. It overlaps mechanistically with drug-induced TMA but arises in the transplant context and is graded by its own harmonized criteria.
Diagnostic hallmarks
- Anemia / thrombocytopenia — Often transfusion-refractory; a falling platelet count is an early clue.
- Microangiopathic hemolysis — Schistocytes on smear, elevated LDH, low haptoglobin.
- Elevated soluble C5b-9 (sC5b-9) — Marker of terminal complement activation; supports the diagnosis and tracks activity.
- Proteinuria — Random urine protein-to-creatinine elevation — a key renal and prognostic feature.
- Organ dysfunction — Kidney (AKI, hypertension), GI (bleeding), CNS, or pulmonary (hypertension) involvement.
High-risk feature check
- Organ dysfunction — Renal, GI, CNS, or pulmonary injury attributable to TMA.
- Concurrent acute GVHD — Strongly associated with inferior survival in adult cohorts.
- Concurrent infection — A major driver of non-relapse mortality.
- Elevated sC5b-9 — Terminal-complement activation above the lab reference range.
- Proteinuria (>30 mg/dL) — Proteinuria on urinalysis; combined with elevated sC5b-9 at TMA diagnosis this marks the highest-risk group (<20% 1-year survival in the pediatric/young-adult cohort of Jodele et al., Blood 2014; PMID 24876561).
Select the features present (each is described above) to see where the evidence places the risk.
No high-risk features selected
Without high-risk features, many TA-TMA cases are monitored with trigger control and supportive care. Continue close surveillance of platelets, LDH, sC5b-9, proteinuria, and organ function — risk can evolve.
The complement-directed toolkit
- Address the triggers first
Treat GVHD and infection; consider dose-reducing (rather than abruptly stopping) calcineurin/mTOR inhibitors, since abrupt withdrawal can flare GVHD.
- Supportive care
Blood-pressure control, transfusion support, and renal support as needed.
- C5 inhibition (eculizumab, ravulizumab)
Complement blockade; effective in pediatric high-risk TA-TMA. In adults the data are mixed — recent series show no clear survival benefit and higher infection-related mortality — so use is individualized, biomarker-guided, and ideally within trials.
- Narsoplimab (anti-MASP-2, lectin pathway) — FDA-approved
Yartemlea (narsoplimab-wuug) was FDA-approved in late 2025 as the first and only therapy indicated for HSCT-associated TA-TMA, in adults and children ≥2 years — the first lectin-pathway (MASP-2) inhibitor. Its pivotal HSCT-TMA trial reported a 61% response; real-world access/cost considerations still apply.
TA-TMA vs drug-induced TMA
Drug-induced TMA is triggered by a specific nephrotoxin (e.g. gemcitabine, mitomycin C, VEGF inhibitors, carfilzomib) and is managed by stopping that drug ± complement blockade. TA-TMA is a transplant endothelial syndrome driven by conditioning, GVHD, infection, and calcineurin/mTOR inhibitors, with prominent complement/lectin-pathway activation — the complement-directed toolkit overlaps, but the context, triggers, and prognosis differ.
For the drug-induced side of the microangiopathy story, see the gemcitabine & mitomycin TMA and carfilzomib TMA deep dives.
Evidence
Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a study in children and young adults.
Jodele S et al. · Blood 2014 · PMID 24876561 (opens PubMed in a new tab)
The pediatric/young-adult risk-stratification cohort behind the high-risk features: proteinuria plus elevated sC5b-9 at TMA diagnosis marked the highest-risk group (<20% 1-year survival).
An ASTCT, CIBMTR, EBMT, and APBMT Consensus Statement Defining Response Criteria for Hematopoietic Cell Transplantation Associated Thrombotic Microangiopathy (TA-TMA) Directed Therapy.
Schoettler ML et al. · Transplant Cell Ther 2025 · PMID 40514012 (opens PubMed in a new tab)
International consensus on TA-TMA diagnostic/response criteria, including sC5b-9 and organ manifestations.
Clinical Outcomes and Treatment Strategies of Adult Transplant-Associated Thrombotic Microangiopathy: External Validation of Harmonizing Definitions and High-Risk Criteria.
Acosta-Medina AA et al. · Am J Hematol 2025 · PMID 40047384 (opens PubMed in a new tab)
Adult validation: infection, acute GVHD, and organ dysfunction predicted poor survival; eculizumab ORR 70%; suggests dose-reducing (not stopping) CNI/mTOR.
Outcomes of Terminal Complement Blockade in Adults with High-Risk Transplant-Associated Thrombotic Microangiopathy: A Comparative Analysis.
Alhomoud M et al. · Transplant Cell Ther 2025 · PMID 41319917 (opens PubMed in a new tab)
Cautionary adult data: terminal complement blockade did not improve survival and was associated with higher non-relapse (infection-related) mortality.
Narsoplimab, a Mannan-Binding Lectin-Associated Serine Protease-2 Inhibitor, for the Treatment of Adult Hematopoietic Stem-Cell Transplantation-Associated Thrombotic Microangiopathy.
Khaled SK et al. · J Clin Oncol 2022 · PMID 35439028 (opens PubMed in a new tab)
Pivotal single-arm trial of lectin-pathway (anti-MASP-2) blockade in HSCT-TMA — 61% response.
Translating biomarker insights into practice: a path forward in TA-TMA management.
Jodele S, Gavriilaki E · Front Med 2025 · PMID 40406401 (opens PubMed in a new tab)
Biomarker-guided approach (sC5b-9 for terminal complement activation) to diagnosis and complement-inhibitor selection.
Complement System as a New Target for Hematopoietic Stem Cell Transplantation-Related Thrombotic Microangiopathy.
Ardissino G et al. · Pharmaceuticals (Basel) 2022 · PMID 35890144 (opens PubMed in a new tab)
Review of complement activation in TA-TMA and the agents (eculizumab, narsoplimab, ravulizumab, others) targeting it.
See onconephrology for the wider field and methods for how the atlas is sourced.