TMA

Thrombotic Microangiopathy

Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.

13signature agents

Deep diveVEGF-inhibitor TMA Deep diveCytotoxic TMA Deep diveProteasome-inhibitor TMA

Landmark evidence4 seminal studies

Where it strikes

Vasculature / Endothelium

Glomerular & peritubular capillaries

Glomerulus

Filtration barrier (podocytes + endothelium)

See it on the nephron

Agents’ overall severity

Each agent’s whole-drug severity grade, not the severity of this lesion specifically — an agent whose signature injury is elsewhere can still be graded severe here.

Severe· 5Moderate· 6Mild· 2

Agents’ overall reversibility

Often irreversible· 1Partially reversible· 2Variable· 8Reversible· 2

Does the kidney recover? Cross-drug outcomes

Agents’ onset window

How soon each agent’s kidney toxicity typically appears — a whole-drug tempo, not specific to this lesion.

Acute (days)· 1Subacute (weeks)· 1Delayed (weeks–months)· 5Variable· 6

Real-world reporting for this lesion

FAERS across all lesions →

Agents with a disproportionate FAERS reporting signal for thrombotic microangiopathy (reporting odds ratio with a 95% CI lower bound above 1) — a spontaneous-reporting signal, not incidence or proven causation. FAERS carries reporting and indication biases and has no denominator.

27Corroborated

Documented in the atlas profile and carrying a FAERS signal — the strongest claim the atlas makes.

9Documented, FAERS-silent

Documented in a profile with no reporting signal. Mostly expected: naming this lesion on a report can require a biopsy, and silence is not evidence against the literature.

4Not attributable

A real reporting signal that is not evidence for this drug-lesion pair: no MedDRA term names it, the naming subset asked alone came back flat, or the 2026-08 review attributed the reporting to the population, co-therapy, or class-level literature.

47Reported by name

The terms that name this lesion are disproportionate, but no profile documents it for that agent. Most are echoed by a sibling agent in the same class. Leads for review, never lesions the atlas claims.

5-Fluorouracil Atezolizumab Azacitidine Bendamustine Bevacizumab Bleomycin Blinatumomab Bortezomib Brentuximab vedotin Busulfan Capecitabine Carboplatin Carfilzomib Carmustine (BCNU)Cetuximab Cisplatin Clofarabine Cyclophosphamide Cytarabine Dacarbazine Dactinomycin (actinomycin D)Dasatinib Decitabine Dinutuximab Docetaxel Dostarlimab Doxorubicin Durvalumab Elotuzumab Erlotinib Etoposide Everolimus Fludarabine Gemcitabine Gemtuzumab ozogamicin Ibritumomab tiuxetan Idarubicin Ifosfamide Imatinib Inotuzumab ozogamicin Interleukin-2 (high-dose)Isatuximab Ixazomib Lenalidomide Lenvatinib Lifileucel Lorlatinib Melphalan Methotrexate (high-dose)Mitomycin C Mitoxantrone Mogamulizumab Naxitamab Nivolumab Oxaliplatin Paclitaxel Panitumumab Pazopanib Pegaspargase Pembrolizumab Pemetrexed Pentostatin Polatuzumab vedotin Ponatinib Ramucirumab Rituximab Ruxolitinib Sirolimus Sorafenib Sunitinib Tafasitamab Temsirolimus Thalidomide Thiotepa Topotecan Trabectedin Vincristine Vinorelbine

78 agents with a significant TMA reporting signal.

§Mechanism, step by step

How anti-cancer drugs cause thrombotic microangiopathy

One lesion, two mechanistic routes — direct endothelial toxicity and VEGF withdrawal — converging on the glomerular capillary. Scroll to follow the injury from the endothelial surface to the sheared red cells on the smear.

Schematic · not to scale

At the bedside

VEGF-TMA deep dive →

TMA is a final common pathway — the workup turns on the cause. Narrow the differential, then estimate the pretest probability of TTP before reaching for plasma exchange. After hematopoietic cell transplant, see the dedicated TA-TMA page.

What's driving this TMA?

Thrombotic microangiopathy is a final common pathway — the treatment turns entirely on the cause. Select a driver.

ADAMTS13

Normal / near-normal

How to tell

A temporal link to a culprit nephrotoxin. VEGF inhibitors give a renal-limited, proteinuric picture; gemcitabine, mitomycin C, carfilzomib, and calcineurin inhibitors give more systemic disease.

The trigger

The offending drug — dose-dependent/cumulative (VEGF, mitomycin, gemcitabine) or immune (quinine). Gemcitabine's mechanism is unsettled; its best-documented risk is cumulative-dose, so it is grouped with the dose-dependent agents here.

Directed treatment

Stop the offending agent — the single most important step. Blood-pressure control; complement blockade only for severe, systemic, or refractory disease. Not plasma exchange as reflex.

VEGF-inhibitor TMA — the deep dive

PLASMIC score

Bendapudi 2017 · PMID 28259520

Pretest probability of severe ADAMTS13 deficiency (TTP) in an adult with thrombotic microangiopathy. Answer each feature — a Yes scores one point. The score appears once all seven are answered.

Platelet count < 30 × 10⁹/LThe profound thrombocytopenia typical of TTP.

Hemolysis presentReticulocytes > 2.5%, undetectable haptoglobin, or indirect bilirubin > 2.0 mg/dL.

No active cancerNo cancer treated within the past year (active malignancy points away from TTP).

No solid-organ or stem-cell transplantNo history of transplant (transplant points toward TA-TMA instead).

MCV < 90 fLMean corpuscular volume below 90 femtoliters.

INR < 1.5A normal INR argues against DIC as the cause.

Creatinine < 2.0 mg/dLPreserved renal function (marked renal failure points toward aHUS/other TMA).

Answer all seven criteria to see the score and risk band (0/7 answered).

Educational aid only — not medical advice. The PLASMIC score supplements, and does not replace, ADAMTS13 activity testing and clinical judgment.

Management approach

Full framework →

Stop the culprit drug — the single most important step — with supportive care; complement-pathway-directed therapy for severe, refractory, or complement-mediated cases.

Drug-level levers

Discontinue the offending agent promptly; re-exposure risk is high.
Distinguish dose-dependent/toxic TMA (e.g. mitomycin C, gemcitabine, VEGF inhibitors, carfilzomib) from complement-mediated TMA — the latter is the one most likely to respond to complement blockade.
Switch out of class for ongoing therapy — drug-induced TMA tends to recur on rechallenge.
Control hypertension aggressively.

Pharmacologic toolkit

C5 inhibition (eculizumab, ravulizumab) — First-line complement blockade for severe or drug-discontinuation-refractory TMA; eculizumab achieved renal recovery in ~80% of reported drug-induced cases (gemcitabine, carfilzomib, bevacizumab). Ravulizumab is the longer-acting C5 alternative. Cover/vaccinate against encapsulated organisms before dosing.
Narsoplimab (anti-MASP-2, lectin pathway) — Targets the lectin pathway driving transplant-associated (HSCT) TMA; its pivotal single-arm trial reported a 61% response. FDA-approved in late 2025 as Yartemlea (narsoplimab-wuug) — the first therapy indicated for HSCT-associated TA-TMA, in adults and children ≥2 years — though access/cost considerations apply and responses vary.
Emerging complement inhibitors — Iptacopan (factor B), pegcetacoplan (C3), crovalimab and danicopan are under investigation; second-line selection after a suboptimal C5-inhibitor response is increasingly guided by complement biomarkers (e.g. sC5b-9).
Supportive care — Transfusion, blood-pressure control, and dialysis as needed.
Plasma exchange — Generally ineffective for drug-induced TMA (unlike TTP) and not routinely recommended.

When to biopsy

Consider when the diagnosis is unclear; but the peripheral smear (schistocytes), LDH, haptoglobin, and platelet count usually establish TMA noninvasively.

Monitoring

· CBC, schistocytes, LDH, haptoglobin
· Creatinine and blood pressure
· Urine protein
· Complement activation markers (e.g. sC5b-9) where complement-mediated TMA is suspected

Grounding

Educational use only. Educational synthesis of the published literature — not a treatment protocol, dosing guide, or medical advice. Regimens and agents shown are illustrative of what the literature describes; verify against current guidelines (ASON / KDIGO / ASCO / NCCN) and individualize to the patient. Using this site creates no clinician–patient relationship.

What the guidelines say

All guidelines →

Society and consensus recommendations that speak to thrombotic microangiopathy.

Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.

ADQIConventional cytotoxic chemotherapy-associated nephrotoxicity: consensus report of the 34th Acute Disease Quality Initiative (ADQI) WorkgroupKidney Int 2026 · PMID 41881107Cisplatin is identified as a leading cytotoxic nephrotoxin; the workgroup details preventive measures (adequate isotonic hydration, correction of volume depletion, avoidance of concurrent nephrotoxins, attention to electrolyte/magnesium wasting) and management of cisplatin-associated AKI, with a research agenda for knowledge gaps.

Cited incidence across agents

Where the literature gives a representative thrombotic microangiopathy figure, the agents ranked highest first. Hover a dot for its cited note.

Representative per-agent thrombotic microangiopathy incidence where a published figure is citable — open an agent's name for its profile and cited source, or hover its dot for the source inline. Agents without a citable figure are omitted; a tier without a number is not the same as a low number.

Offending agents

Any agent44 Primary (#1) only13

Signature offenders

Agents for which thrombotic microangiopathy is the defining renal lesion.

GemcitabineDelayed — months of cumulative exposure.Estimates span three orders of magnitude by ascertainment. The only figure with a real denominator is the manufacturer safety-database review: 12 cases against 78,800 patient exposures, a crude 0.015% (range 0.008–0.078%). The product characteristics give 0.01%. Against that, a single center reported 2.7% — four of its five cases on nab-paclitaxel/gemcitabine, where a pharmacokinetic interaction is suspected. Historically high mortality: of 23 cases with reported outcome in the literature tally, 11 died within a few weeks, death directly attributed to HUS in two.Severe Mitomycin CDelayed — after cumulative dosing, sometimes after therapy ends.Dose-dependent, generally 4–15%; nearly every case in the landmark 85-patient registry had received a cumulative total dose above 60 mg. >50% historical mortality.Severe CarfilzomibVariable — frequently early (first cycles), but TMA can also appear later, sometimes after a treatment break and re-escalation.Renal complications are common and a recognized class concern: in a 114-patient real-world cohort, ~17% had carfilzomib-attributable renal events (TMA ~5%, albuminuria >1 g/day ~6%, otherwise-unexplained grade >=3 AKI ~5%), occurring mostly early and unpredictably. On the prospective CARDAMON trial 8 patients experienced TMA (6 of 8 hypertensive at presentation, 7 of 8 with AKI); after a protocol amendment adding aggressive hypertension management, carfilzomib step-up dosing at the start of maintenance and dexamethasone premedication, the rate fell from 4.2 to 1.6 events per 1,000 patient-cycles with no further maintenance events. Pharmacovigilance (FAERS) shows carfilzomib carries by far the strongest TMA signal among proteasome inhibitors.Severe Moxetumomab pasudotoxCycle-related: CLS within the first days of a cycle; HUS often during/after cycles 2-3.Boxed warning for capillary-leak syndrome (CLS) and hemolytic-uremic syndrome (HUS)/TMA. In the pivotal phase 3 trial HUS occurred in ~7.5% and CLS in ~5%; reviews cite roughly 9% each. Fatal CLS has been reported (in a pediatric ALL case).Severe Tegafur-uracil (UFT)Variable; TMA/HUS typically emerges after weeks to months of cumulative exposure.Direct renal injury from UFT is rare and largely class-level. Fluoropyrimidine-associated thrombotic microangiopathy / hemolytic-uremic syndrome is a rare, mostly case-report-level event, frequently in combination regimens (e.g., with mitomycin C). No reliable drug-specific incidence rate is established.Severe BusulfanWeeks after conditioning/transplant.Transplant-associated thrombotic microangiopathy (TA-TMA) with renal involvement complicates a subset of conditioning regimens; high-dose busulfan (e.g., 16 mg/kg) has been identified as an independent risk factor for post-transplant TMA, and high busulfan exposure also drives sinusoidal obstruction syndrome/VOD.Moderate Trastuzumab emtansine (T-DM1)Variable; reported after initiation, over weeks to months of therapy.Renal toxicity is rare and case-level. FDA adverse-event analyses flagged renal events with trastuzumab-based therapy, and biopsy-proven cases (collapsing focal segmental glomerulosclerosis; TMA-like microvascular injury) have been reported. Incidence is not quantified.Moderate BortezomibRare adverse renal events can occur at any point during therapy, from weeks to several months after initiation; the beneficial light-chain reduction is often rapid.Bortezomib is generally renal-friendly and often improves renal function in myeloma by rapidly reducing light-chain-driven cast nephropathy; it requires no renal dose adjustment. Thrombotic microangiopathy and glomerular microangiopathy are rare, case-level events, and pharmacovigilance shows a far weaker TMA signal than carfilzomib.Moderate IxazomibVariable; reported after weeks to months of therapy, including with cumulative exposure. Class median time to TMA onset ~8 days from a triggering cycle.Drug-induced thrombotic microangiopathy (TMA) is a rare, case-level event for ixazomib and is not reliably quantified. In a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS, 2004-2023), proteasome inhibitors as a class were significantly associated with TMA (225 cases in 213 exposed individuals; ROR 1.71), but carfilzomib dominated the signal (58.7% of exposed individuals, 125 of 213; ROR 17.97), with bortezomib and ixazomib contributing far fewer reports. The ixazomib signal is therefore extrapolated largely from the class.Moderate DoxifluridineVariable; class-level TMA typically after prolonged cumulative exposure.No drug-specific nephrotoxicity incidence is established. Renal risk is inferred at the fluoropyrimidine-class level (rare TMA/HUS); direct doxifluridine renal injury reports are sparse.Moderate Carmofur (HCFU)Variable; class-level TMA after cumulative exposure.No established drug-specific renal incidence. Renal risk is class-level (rare fluoropyrimidine TMA/HUS). Carmofur's characteristic serious toxicity is leukoencephalopathy, not nephrotoxicity.Moderate OxaliplatinAcute if immune-mediated (often on re-challenge).Lowest nephrotoxic potential of the platinums; AKI is rare and case-level, in some cases immune-mediated.Mild 5-FluorouracilTMA often delayed (weeks to months); prerenal effects acute with GI toxicity.Intrinsic nephrotoxicity is low; the recognized vascular renal complication is thrombotic microangiopathy/hemolytic-uremic syndrome, classically with mitomycin C, with 5-FU as a frequent co-agent. In TTP/HUS series the most common antecedent chemotherapy is mitomycin C plus 5-FU.Mild

See these on the Toxic-Ties graph All 14 lesions