---
title: "Acquired immune-mediated TTP after ivonescimab chemoimmunotherapy with cholestatic liver injury an"
id: "frontiers-in-immunology-18-acquired-immune-mediated-thrombotic-thrombocytopenic-purpura-with-severe"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-18-acquired-immune-mediated-thrombotic-thrombocytopenic-purpura-with-severe"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1908239"
published_at: "2026-08-04T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Acquired immune-mediated TTP after ivonescimab chemoimmunotherapy with cholestatic liver injury an
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-18-acquired-immune-mediated-thrombotic-thrombocytopenic-purpura-with-severe
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1908239)
- **Published At:** 2026-08-04T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The source provided is a Frontiers in Immunology article page, with the title reporting a case of **acquired immune-mediated thrombotic thrombocytopenic purpura** occurring after **ivonescimab-containing chemoimmunotherapy**, complicated by severe **cholestatic liver injury** and reversible **acute kidney injury**. - The provided page content contains site navigation, journal sections, and metadata but does not include the article text, case details, clinical data, diagnostic studies, treatment, or outcomes. - No patient demographics, timeline of events, laboratory values, imaging findings, ADAMTS13 testing results, biopsy data, specific therapies (beyond the mention of ivonescimab in the title), or follow-up details were present in the supplied source text. - The source did not report the authorship, institutional affiliations, or exact novel points from the literature review component referenced in the title. - Critical elements typically required to interpret a case report—such as onset relative to chemoimmunotherapy, exclusion of alternative causes, interventions employed, response to therapy, and long-term outcome—were not available in the supplied content. - Because the article body was not present in the supplied source, no additional clinical facts, study results, or recommendations can be extracted; statements about pathophysiology, management, or prognosis were therefore not reported and must not be inferred.
## Clinical Analysis & Structured Key Points
Frontiers | Acquired immune-mediated thrombotic thrombocytopenic purpura with severe cholestatic liver injury and reversible acute kidney injury after ivonescimab-containing chemoimmunotherapy: a case report and literature review 90 fL lowered the score; definitive diagnosis therefore depended on ADAMTS13 testing. Treatment included corticosteroids, 10 sessions of DPMAS/TPE support with transition to FFP-based plasma exchange once iTTP was recognized, and rituximab 500 mg weekly from April 17 to May 8, 2026. Caplacizumab was not used because it was unavailable locally. No platelet transfusions were administered; red blood cells and plasma were transfused as clinically indicated. ADAMTS13 activity increased to 23.82% and inhibitor titer decreased to 0.85 BU/mL on the available follow-up test, but serial ADAMTS13 and complement measurements were not available. The patient had biochemical improvement and normalization of renal function.ConclusionThis case highlights ADAMTS13 inhibitor-positive iTTP as a rare, actionable toxicity after ivonescimab-containing chemoimmunotherapy rather than proof of ivonescimab as the sole causal agent. The renal phenotype should be framed as severe but reversible AKI rather than dialysis-dependent renal failure. In patients receiving PD-1/VEGF-directed combination therapy, thrombocytopenia with microangiopathic hemolysis and organ injury should trigger smear review, PLASMIC scoring, urgent ADAMTS13 testing, and early mechanism-directed therapy."> CASE REPORT article Front. Immunol. , 04 August 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1908239 Published in Frontiers in Immunology Cancer Immunity and Immunotherapy 7 impact factor 11.3 citescore Part of a Research Topic Personalized strategies for managing emergent toxicities in advanced solid tumor therapies Submission open 839 views 2 articles Editor & Reviewers Edited by M S Matteo Simonelli Reviewed by T T Taichiro Tokura C Z Caihong Zeng Outline Figures and Tables Figure 1 View in article Table 1 Diagnostic evidence supporting iTTP and PLASMIC score breakdown. View in article Table 2 Treatment and laboratory timeline. View in article Table 3 Focused literature review of ICI-associated TTP/iTTP and comparison with the present case. View in article CASE REPORT article Front. Immunol. , 04 August 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1908239 Acquired immune-mediated thrombotic thrombocytopenic purpura with severe cholestatic liver injury and reversible acute kidney injury after ivonescimab-containing chemoimmunotherapy: a case report and literature review Q C Qiqi Chen 1 † X S Xiaojing Song 2 † M Z Ming Zhang 3 † H N Hongxia Niu 1 * W G Wei Guo 2 * 1. Department of Emergency, Beijing Electric Power Hospital of State Grid Corporation of China, Beijing, China 2. Department of Emergency, Peking University People’s Hospital, Beijing, China 3. Department of Cardiology, Beijing Electric Power Hospital of State Grid Corporation of China, Beijing, China See more Article metrics View details Abstract Background: Ivonescimab is a PD-1/VEGF bispecific antibody that combines immune checkpoint blockade with anti-angiogenic activity. As PD-1/VEGF-directed regimens enter routine solid-tumor care, rare toxicities at the interface of immune activation, endothelial injury, and thrombotic microangiopathy require careful case-level characterization. Case presentation: A 63-year-old man with stage IVB lung adenocarcinoma (cT1bN2M1c, with multiple extrathoracic rib metastases) received an ivonescimab-containing combination regimen consisting of three cycles of ivonescimab plus nab-paclitaxel and cisplatin, followed by chemotherapy alone after partial response. He developed fever, severe cholestatic liver injury, and KDIGO stage 3 acute kidney injury requiring temporary continuous renal replacement therapy. Serum creatinine peaked at 767 µmol/L and subsequently normalized. Evolving anemia, thrombocytopenia, schistocytes, Coombs-negative hemolysis, and organ injury prompted evaluation for thrombotic microangiopathy. ADAMTS13 activity was 8.87% with a functional inhibitor of 1.8 BU/mL, confirming acquired immune-mediated thrombotic thrombocytopenic purpura. The PLASMIC score was 5, reflecting intermediate clinical probability because active malignancy and MCV >90 fL lowered the score; definitive diagnosis therefore depended on ADAMTS13 testing. Treatment included corticosteroids, 10 sessions of DPMAS/TPE support with transition to FFP-based plasma exchange once iTTP was recognized, and rituximab 500 mg weekly from April 17 to May 8, 2026. Caplacizumab was not used because it was unavailable locally. No platelet transfusions were administered; red blood cells and plasma were transfused as clinically indicated. ADAMTS13 activity increased to 23.82% and inhibitor titer decreased to 0.85 BU/mL on the available follow-up test, but serial ADAMTS13 and complement measurements were not available. The patient had biochemical improvement and normalization of renal function. Conclusion: This case highlights ADAMTS13 inhibitor-positive iTTP as a rare, actionable toxicity after ivonescimab-containing chemoimmunotherapy rather than proof of ivonescimab as the sole causal agent. The renal phenotype should be framed as severe but reversible AKI rather than dialysis-dependent renal failure. In patients receiving PD-1/VEGF-directed combination therapy, thrombocytopenia with microangiopathic hemolysis and organ injury should trigger smear review, PLASMIC scoring, urgent ADAMTS13 testing, and early mechanism-directed therapy. 1 Introduction Immune checkpoint inhibitors have reshaped the management of advanced solid tumors, but their clinical benefit is accompanied by immune-related adverse events that may involve virtually any organ system ( 1 , 2 ). Ivonescimab is a tetravalent PD-1/VEGF bispecific antibody designed to integrate checkpoint blockade and anti-angiogenic activity in a single molecule. Randomized phase 3 studies in non-small cell lung cancer have shown clinically meaningful activity of ivonescimab-containing regimens ( 3 , 4 ). Acquired immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare but life-threatening thrombotic microangiopathy caused by severe ADAMTS13 deficiency, usually mediated by inhibitory autoantibodies ( 5 ). Clinical prediction tools such as the PLASMIC score can help triage suspected thrombotic microangiopathy before ADAMTS13 results return, but ADAMTS13 activity and inhibitor testing remain decisive when the presentation is confounded by malignancy, infection, chemotherapy, renal injury, or liver dysfunction ( 5 , 6 ). International consensus definitions distinguish laboratory improvement from formal clinical response, clinical remission, exacerbation, relapse, and ADAMTS13 remission ( 7 ). Current iTTP management guidance supports urgent therapeutic plasma exchange and immunosuppression ( 8 , 9 ). Caplacizumab and rituximab may be considered according to drug availability, bleeding risk, relapse risk, and clinical context ( 10 , 11 ). Pharmacovigilance analyses and early case reports support a rare ICI-associated TTP signal ( 12 – 14 ). Cases after nivolumab, checkpoint inhibitor immunotherapy, and metastatic non-small-cell lung cancer treatment illustrate the diagnostic heterogeneity and variable severity of this toxicity ( 15 – 17 ). Pembrolizumab-associated reports and dual-checkpoint cases further show that outcomes range from fatal disease to durable remission with extended plasma exchange, rituximab, and ADAMTS13 monitoring ( 18 – 20 ). More recent nivolumab-, pembrolizumab-, and PD-L1/taxane-associated cases extend the phenotype across checkpoint classes and combination regimens ( 21 – 23 ). Anti-VEGF therapy can independently promote glomerular endothelial injury and renal thrombotic microangiopathy ( 24 , 25 ). Rather than proposing a new toxicity entity, the present case documents confirmed ADAMTS13 inhibitor-positive iTTP in a PD-1/VEGF bispecific antibody-containing chemoimmunotherapy setting, where immune activation, endothelial injury, cholestatic liver injury, and reversible AKI overlapped. 2 Case presentation 2.1 Oncologic background and treatment exposure A 63-year-old man had coronary artery disease and benign prostatic hyperplasia, with no known autoimmune disease, chronic liver disease, chronic kidney disease, hematologic disorder, alcohol use, or chronic medication exposure. In September 2025, chest CT incidentally revealed a right lower-lobe lung mass during evaluation for urinary retention. PET/CT on November 20, 2025 showed a hypermetabolic right lower-lobe lesion, mediastinal and bilateral hilar lymphadenopathy, and suspected right fourth and fifth rib metastases. CT-guided biopsy confirmed lung adenocarcinoma. PD-L1 tumor proportion score was approximately 1% by Ventana SP263 testing, and next-generation sequencing identified complex KRAS exon 2 mutations. Because the fourth and fifth rib lesions represented multiple extrathoracic metastases, the clinical stage was revised to cT1bN2M1c, stage IVB. First-line therapy consisted of ivonescimab 1000 mg with nab-paclitaxel and cisplatin. Cycle 1 began on December 24, 2025, with ivonescimab on day 4. Cycles 2 and 3 included ivonescimab on day 2; the final ivonescimab dose was administered on February 11, 2026. Restaging before cycle 4 showed partial response, and the multidisciplinary team omitted ivonescimab from cycle 4 on March 4, 2026, giving chemotherapy alone. 2.2 Initial presentation and physical examination On March 14, 2026, 10 days after the final chemotherapy and 31 days after the final ivonescimab dose, the patient developed fever to 39.3 °C with headache, sore throat, and rhinorrhea. On March 18, creatinine was 94 µmol/L and liver tests were normal. By March 20, creatinine had increased to 175 µmol/L. On March 22, jaundice and dark urine appeared; ALT was 179 U/L, AST 237 U/L, ALP 419 U/L, total bilirubin 19.5 µmol/L, albumin 27.9 g/L, and creatinine 375 µmol/L. Abdominal CT showed enlarged kidneys with perirenal exudation, mild biliary and pancreatic ductal dilatation, and gallbladder wall thickening. Urinalysis showed protein (++) and occult blood (+/-). On March 23, creatinine rose to 552-767 µmol/L, total bilirubin was 43.1 µmol/L, C-reactive protein was 20.7 mg/L, leukocytes were 2.17 ×10^9/L, hemoglobin was 106 g/L, and D-dimer was 874 ng/mL. On admission, vital signs were temperature 36.3 °C, pulse 94 beats/min, respiratory rate 19 breaths/min, and blood pressure 122/75 mmHg. He was conscious and fluent but fatigued, with Glasgow Coma Scale score 14 and mild scleral icterus. No petechiae, ecchymoses, focal neurologic deficit, abdominal tenderness, rebound tenderness, or guarding was documented. Breath sounds were coarse bilaterally without obvious rales; cardiac auscultation did not reveal a significant murmur. Bilateral pitting edema was present in the lower extremities. 2.3 Diagnostic assessment The initial differential diagnosis included severe infection, acute tubular injury, drug-induced liver injury, immune-related hepatitis/nephritis, biliary disease, chemotherapy-associated toxicity, and thrombotic microangiopathy (TMA). Meropenem, continuous renal replacement therapy (CRRT), and methylprednisolone 40 mg/day were started. MRCP showed cholecystitis, Glisson sheath edema, and ascites without obstructive jaundice. Autoimmune serology, hepatitis E IgM, hepatitis E RNA, and HBV DNA were negative or undetectable, and direct antiglobulin testing was negative. Despite improvement in inflammatory markers, cholestatic liver injury progressed, with total bilirubin reaching 293.2 µmol/L by March 31 and 440.4 µmol/L by April 13. Because liver and kidney biopsies were not performed, we describe the hepatic phenotype as severe cholestatic liver injury rather than biopsy-proven cholestatic hepatitis. The hematologic evolution redirected the diagnosis. Peripheral smear on March 31 showed approximately 1% schistocytes. Plasma free hemoglobin was 50 mg/L on April 2. Progressive anemia, thrombocytopenia, schistocytes, Coombs-negative hemolysis, acute kidney injury, and elevated D-dimer raised concern for TMA. On April 14, rheumatology recommended ADAMTS13 activity, inhibitor testing, and complement assessment. On April 15, ADAMTS13 activity was 8.87% and functional inhibitor was 1.8 BU/mL, establishing acquired iTTP according to accepted diagnostic thresholds ( 5 ). Complement factor Ba was 1891 ng/mL, whereas soluble C5b-9 was 195 ng/mL, suggesting alternative pathway activation as a possible amplifier rather than proving primary complement-mediated atypical hemolytic uremic syndrome. Complement genetic testing was not performed; after severe ADAMTS13 deficiency with a functional inhibitor was confirmed, aHUS was considered less likely, although incomplete complement evaluation remains a limitation. The PLASMIC score was calculated as 5 points: platelet count 2 mg/dL equivalent and MAHA features +1 PLASMIC No active cancer No; active stage IVB lung adenocarcinoma +0 PLASMIC No transplant No solid-organ or stem-cell transplant +1 PLASMIC MCV <90 fL No; MCV 93.6 fL before TTP diagnosis and 92.2 fL after diagnosis +0 PLASMIC INR <1.5 Yes; INR 0.94 +1 PLASMIC Creatinine <2.0 mg/dL at iTTP work-up Yes; creatinine 130 µmol/L on Apr 13 and 74 µmol/L on Apr 18 +1 PLASMIC Total score 5 Intermediate clinical probability; ADAMTS13 testing was essential and diagnostic. Diagnostic evidence supporting iTTP and PLASMIC score breakdown. The renal course is important for accurate case framing. The patient had KDIGO stage 3 AKI requiring temporary CRRT, followed by recovery rather than dialysis dependence. Creatinine decreased to 276 µmol/L on March 31, 186 µmol/L on April 7, 130 µmol/L on April 13, and 74 µmol/L on April 18, with eGFR 92.7 mL/min/1.73 m². Thus, the kidney injury should be described as severe but reversible AKI requiring short-term CRRT support. The integrated diagnostic and treatment timeline is shown in Figure 1 . Figure 1 Integrated diagnostic and treatment timeline. (A) Dynamic trends in platelet count, serum creatinine, and total bilirubin from March 18 to May 8, 2026. The figure shows severe AKI with subsequent renal recovery, peak cholestatic liver injury, delayed platelet nadir, and later hematologic improvement. (B) Treatment course and mechanistic checkpoints, including CRRT support, DPMAS/TPE sessions, corticosteroid dosing, rituximab administration, first schistocyte detection, confirmatory ADAMTS13 activity/inhibitor testing, elevated factor Ba, and the available follow-up ADAMTS13 result. Abbreviations: CRRT, continuous renal replacement therapy; DPMAS, double plasma molecular adsorption system; FFP, fresh frozen plasma; TPE, therapeutic plasma exchange. 2.4 Therapeutic intervention and follow-up Management evolved with the diagnostic formulation. Initial treatment emphasized infection control, renal support, hepatoprotection, and corticosteroids. On March 30-31, ivonescimab-associated immune-related liver and kidney injury was considered, immune therapy was permanently discontinued, methylprednisolone was escalated, and double plasma molecular adsorption system (DPMAS) artificial liver support was started. DPMAS reduced bilirubin burden but did not directly target the ADAMTS13 inhibitor. Corticosteroid treatment was administered as follows: methylprednisolone 40 mg/day from March 25 to March 31, 120 mg/day from March 31 to April 13, 60 mg/day from April 14 to April 16, and 40 mg/day from April 17 to April 21. After iTTP was confirmed, treatment shifted toward mechanism-directed therapy. DPMAS/TPE support was performed for a total of 10 sessions between March 31 and April 19, 2026; after the ADAMTS13 result, the exchange strategy was redirected toward fresh frozen plasma (FFP)-based therapeutic plasma exchange to remove inhibitor and replenish ADAMTS13. The course therefore was not a fully standardized daily TPE protocol from the first TMA clue; rather, it reflects diagnostic evolution from cholestatic liver failure support to iTTP-directed plasma exchange. DPMAS/TPE was discontinued on April 19 after renal recovery, falling bilirubin, absence of new ischemic organ injury, and improving ADAMTS13/inhibitor results; formal clinical-response criteria could not be fully assessed because platelet normalization and serial LDH were unavailable. Rituximab was administered as a fixed 500 mg intravenous dose on April 17, April 24, May 1, and May 8, 2026. The fixed-dose regimen reflected local clinical practice and concern for infection risk in a patient with advanced malignancy and recent severe systemic illness; it should not be interpreted as replacing the conventional body-surface-area-based rituximab regimen in guideline algorithms. Caplacizumab was not used because it was unavailable at the treating institution. No platelet transfusions were administered during the course because there was no life-threatening bleeding; red blood cell and plasma transfusions were given as clinically indicated. The treatment course and key laboratory milestones are summarized in Table 2 . Table 2 Date Clinical/laboratory status Treatment Interpretation Mar 14-23 Fever, respiratory symptoms, jaundice, dark urine, creatinine peak 767 µmol/L Initial outpatient and emergency evaluation; broad differential including infection, drug injury, irAE, biliary disease, AKI No TTP diagnosis yet Mar 24-30 Admission with AKI, cholestatic liver injury, anemia, thrombocytopenia Meropenem, CRRT, methylprednisolone 40 mg/day, hepatoprotective therapy Renal support started Mar 31-Apr 13 TBiL rose to 293.2 then 440.4 µmol/L; schistocytes ~1%; free
## Related Clinical Research

- [Avoiding Cardiac Toxicity with Immune Checkpoint Inhibitors: Safety Review (Title Only Available)](https://medichelpline.com/clinical-feed/frontiers-in-immunology-15-avoidance-of-cardiac-toxicity-during-the-application-of-immune-checkpoint.md)
- [PD-L1 expression and survival in unresectable or recurrent gastric cancer treated with first-line](https://medichelpline.com/clinical-feed/british-journal-of-cancer-0-pd-l1-expression-and-survival-in-unresectable-recurrent-gastric-cancer-treated.md)
- [IL-33 and kidney disease: article metadata and reporting gaps in Frontiers in Immunology](https://medichelpline.com/clinical-feed/frontiers-in-immunology-13-beyond-the-alarm-unveiling-the-multifaceted-role-of-il-33-in-kidney-disease.md)
- [Response-Adapted Bladder Preservation in MIBC: RETAIN-2 Phase II Results and ctDNA Dynamics](https://medichelpline.com/clinical-feed/medrxiv-2-response-adapted-bladder-preservation-in-muscle-invasive-bladder-cancer-results.md)
- [Perioperative enfortumab vedotin plus pembrolizumab improves outcomes in cisplatin-eligible MIBC](https://medichelpline.com/clinical-feed/nature-reviews-clinical-oncology-0-benefit-from-perioperative-enfortumab-vedotin-pembrolizumab-in-cisplatin.md)

## Navigation
- [← Back to Infectious Disease Feed](https://medichelpline.com/clinical-feed/infectious-disease.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.