A Rare Case of Thrombotic Thrombocytopenic Purpura Developed During Nivolumab Treatment in a Patient with Hodgkin Lymphoma

A Rare Case of Thrombotic Thrombocytopenic Purpura Developed During Nivolumab Treatment in a Patient with Hodgkin Lymphoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Rare Case of Thrombotic Thrombocytopenic Purpura Developed During Nivolumab Treatment in a Patient with Hodgkin Lymphoma derya deniz kürekci This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7140002/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Nivolumab is an anti-PD-1 monoclonal antibody used in the treatment of relapsed/refractory Hodgkin lymphoma. Case: Herein, we present a rare case of TTP developed following nivolumab treatment in a patient with Hodgkin lymphoma. Conclusion: This case draws attention to hematological toxicities associated with immune checkpoint inhibitors. Hematology Hodgkin lymphoma Nivolumab thrombotic thrombocytopenic purpura immunotherapy case report Introduction Hodgkin lymphoma is a lymphoproliferative disorder with high treatment success. However, in relapsed/refractory cases, immunotherapies—particularly PD-1 inhibitors such as nivolumab and pembrolizumab—have become prominent. Nivolumab, as a checkpoint inhibitor, may lead to immune-mediated adverse effects. Hematologic adverse events like TTP are extremely rare and underreported. Here, we present a rare case of TTP developed after nivolumab treatment in a patient with Hodgkin lymphoma. Case Presentation A 30-year-old male presented in 2012 with a swelling on the left side of the neck. A 34×20 mm lymphadenopathy was detected in the left cervical region, and excisional biopsy revealed nodular sclerosing Hodgkin lymphoma. Imaging studies revealed stage IIA disease. The patient received 6 cycles of ABVD following a partial response after 2 cycles. Due to disease progression on post-treatment PET-CT, he received 2 cycles of DHAP as salvage therapy and underwent autologous stem cell transplantation in 2013. In 2016, the patient relapsed again with B symptoms. Nivolumab 300 mg every 2 weeks was initiated. The disease remained stable on follow-up PET-CTs. While receiving nivolumab, the patient developed petechiae, purpura, and fatigue. Initial tests revealed creatinine 1.8 mg/dL, Hb 9 g/dL, and platelet count 12,000/mm³. He was referred to our hospital. Peripheral blood smear showed numerous schistocytes. Reticulocyte count was 8%, LDH 2800 U/L, total/direct bilirubin 4/1 mg/dL. Platelet count ranged between 10,000–20,000/mm³. PLASMIC score was 5. Given these findings, plasma exchange was initiated. Before treatment, blood samples were sent for ADAMTS13 antigen, activity, and inhibitor levels. Methylprednisolone (1 mg/kg/day) was started. With daily plasma exchange, platelet counts increased and LDH levels decreased. External laboratory results showed ADAMTS13 antigen 0.05 (ref: 0.19–0.81), ADAMTS13 activity 0.57 (ref: 40–130), and inhibitor >80,000 (ref: <12,000). Rituximab was administered off-label weekly for 4 weeks at 375 mg/m². Hemolysis resolved and platelet counts normalized. Nivolumab was paused, and a PET-CT was performed, which showed disease progression. Two months later, nivolumab was restarted. The patient currently maintains stable disease under nivolumab and is regularly monitored for TTP recurrence. Discussion TTP development secondary to nivolumab is extremely rare. Clinical findings, laboratory parameters, and suppressed ADAMTS13 activity in our patient support the diagnosis. PD-1 inhibitors are known to cause hematologic adverse effects such as autoimmune hemolytic anemia, immune thrombocytopenia, and rarely TTP. Although rechallenge with nivolumab is generally not recommended after severe immune-related adverse events ( 1 ), our patient had responded exclusively to nivolumab. Upon discontinuation, rapid disease progression occurred. This necessitated a carefully monitored reinitiation of nivolumab. Similar cases may guide future clinical decisions on managing such severe adverse events ( 2 – 4 ). Conclusion TTP is a rare but serious hematologic complication of immune checkpoint inhibitors. Early recognition and timely treatment are critical to prevent fatal outcomes. This case emphasizes the need for vigilance among hematologists and oncologists in recognizing TTP in patients receiving immunotherapy. Declarations Patient Consent Statement Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. The patient was informed about the nature of the publication and agreed to the disclosure of anonymized clinical data for scientific and educational purposes. References Cortazar FB et al. Rechallenge With Immune Checkpoint Inhibitors in Kidney Immune-Related Adverse Events. N Engl J Med. 2020;383(15):1436–1446. Wang DY, Salem JE, Cohen JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 2018;4(12):1721–1728. Al-Nawakil C, et al. Immune checkpoint inhibitor-associated thrombotic thrombocytopenic purpura. Eur J Cancer. 2021;150:267–270. Deleuze J et al. Immune checkpoint inhibitors–related TTP: Lessons from pharmacovigilance data. ESMO Open. 2023;8(2):100682. Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7140002","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":486331345,"identity":"7819e672-6ee1-46e2-b67c-db539ad8a328","order_by":0,"name":"derya deniz kürekci","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYDCCAwwGDAxsDAz8IE5CASlaJBtAWgxI0WJwAMQjRgvf7cPbPvOU3bE3Pr868cMDAwZ5frED+LVInksrns1z7hmz2Y23myWADjOcOTsBvxaDMzzGzLxth9nMbpzdANKSYHCbSC08xjPObv5BkhYJA/7ebcTZInmGrZhxzrnDBhI3eLdZJBhIEPYL3xnmzQxvyg7b8/ef3XzzR4WNPL80AS0gwMQDIiXAKiUIKwcBxh8gkv8AcapHwSgYBaNg5AEAi7pDeUZ0ytMAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-0537-9289","institution":"Samsun Training and Research Hospital, Hematology Department","correspondingAuthor":true,"prefix":"","firstName":"derya","middleName":"deniz","lastName":"kürekci","suffix":""}],"badges":[],"createdAt":"2025-07-16 12:24:02","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7140002/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7140002/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87021213,"identity":"90f188c6-4e3f-4bb9-9190-47f808e4579d","added_by":"auto","created_at":"2025-07-18 11:14:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":195379,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7140002/v1/a0a71517-ba23-4f09-a375-c107971c782f.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eA Rare Case of Thrombotic Thrombocytopenic Purpura Developed During Nivolumab Treatment in a Patient with Hodgkin Lymphoma\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHodgkin lymphoma is a lymphoproliferative disorder with high treatment success. However, in relapsed/refractory cases, immunotherapies\u0026mdash;particularly PD-1 inhibitors such as nivolumab and pembrolizumab\u0026mdash;have become prominent. Nivolumab, as a checkpoint inhibitor, may lead to immune-mediated adverse effects. Hematologic adverse events like TTP are extremely rare and underreported. Here, we present a rare case of TTP developed after nivolumab treatment in a patient with Hodgkin lymphoma.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 30-year-old male presented in 2012 with a swelling on the left side of the neck. A 34\u0026times;20 mm lymphadenopathy was detected in the left cervical region, and excisional biopsy revealed nodular sclerosing Hodgkin lymphoma. Imaging studies revealed stage IIA disease. The patient received 6 cycles of ABVD following a partial response after 2 cycles. Due to disease progression on post-treatment PET-CT, he received 2 cycles of DHAP as salvage therapy and underwent autologous stem cell transplantation in 2013. In 2016, the patient relapsed again with B symptoms. Nivolumab 300 mg every 2 weeks was initiated. The disease remained stable on follow-up PET-CTs.\u003c/p\u003e\n\u003cp\u003eWhile receiving nivolumab, the patient developed petechiae, purpura, and fatigue. Initial tests revealed creatinine 1.8 mg/dL, Hb 9 g/dL, and platelet count 12,000/mm\u0026sup3;. He was referred to our hospital. Peripheral blood smear showed numerous schistocytes. Reticulocyte count was 8%, LDH 2800 U/L, total/direct bilirubin 4/1 mg/dL. Platelet count ranged between 10,000\u0026ndash;20,000/mm\u0026sup3;. PLASMIC score was 5. Given these findings, plasma exchange was initiated. Before treatment, blood samples were sent for ADAMTS13 antigen, activity, and inhibitor levels. Methylprednisolone (1 mg/kg/day) was started.\u003c/p\u003e\n\u003cp\u003eWith daily plasma exchange, platelet counts increased and LDH levels decreased. External laboratory results showed ADAMTS13 antigen 0.05 (ref: 0.19\u0026ndash;0.81), ADAMTS13 activity 0.57 (ref: 40\u0026ndash;130), and inhibitor \u0026gt;80,000 (ref: \u0026lt;12,000). Rituximab was administered off-label weekly for 4 weeks at 375 mg/m\u0026sup2;. Hemolysis resolved and platelet counts normalized. Nivolumab was paused, and a PET-CT was performed, which showed disease progression. Two months later, nivolumab was restarted. The patient currently maintains stable disease under nivolumab and is regularly monitored for TTP recurrence.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTTP development secondary to nivolumab is extremely rare. Clinical findings, laboratory parameters, and suppressed ADAMTS13 activity in our patient support the diagnosis. PD-1 inhibitors are known to cause hematologic adverse effects such as autoimmune hemolytic anemia, immune thrombocytopenia, and rarely TTP. Although rechallenge with nivolumab is generally not recommended after severe immune-related adverse events (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e), our patient had responded exclusively to nivolumab. Upon discontinuation, rapid disease progression occurred. This necessitated a carefully monitored reinitiation of nivolumab. Similar cases may guide future clinical decisions on managing such severe adverse events (\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTTP is a rare but serious hematologic complication of immune checkpoint inhibitors. Early recognition and timely treatment are critical to prevent fatal outcomes. This case emphasizes the need for vigilance among hematologists and oncologists in recognizing TTP in patients receiving immunotherapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u0026nbsp;Patient Consent Statement Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. The patient was informed about the nature of the publication and agreed to the disclosure of anonymized clinical data for scientific and educational purposes.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCortazar FB et al. Rechallenge With Immune Checkpoint Inhibitors in Kidney Immune-Related Adverse Events. N Engl J Med. 2020;383(15):1436\u0026ndash;1446.\u003c/li\u003e\n\u003cli\u003eWang DY, Salem JE, Cohen JV, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 2018;4(12):1721\u0026ndash;1728.\u003c/li\u003e\n\u003cli\u003eAl-Nawakil C, et al. Immune checkpoint inhibitor-associated thrombotic thrombocytopenic purpura. Eur J Cancer. 2021;150:267\u0026ndash;270.\u003c/li\u003e\n\u003cli\u003eDeleuze J et al. Immune checkpoint inhibitors\u0026ndash;related TTP: Lessons from pharmacovigilance data. ESMO Open. 2023;8(2):100682.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hodgkin lymphoma, Nivolumab, thrombotic thrombocytopenic purpura, immunotherapy, case report","lastPublishedDoi":"10.21203/rs.3.rs-7140002/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7140002/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction: Nivolumab is an anti-PD-1 monoclonal antibody used in the treatment of relapsed/refractory Hodgkin lymphoma.\u003c/p\u003e\u003cp\u003eCase: Herein, we present a rare case of TTP developed following nivolumab treatment in a patient with Hodgkin lymphoma.\u003c/p\u003e\u003cp\u003eConclusion: This case draws attention to hematological toxicities associated with immune checkpoint inhibitors.\u003c/p\u003e","manuscriptTitle":"A Rare Case of Thrombotic Thrombocytopenic Purpura Developed During Nivolumab Treatment in a Patient with Hodgkin Lymphoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-18 11:06:12","doi":"10.21203/rs.3.rs-7140002/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cccbf76d-a893-488a-b988-0fd80ceff934","owner":[],"postedDate":"July 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":51628753,"name":"Hematology"}],"tags":[],"updatedAt":"2025-07-18T11:06:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-18 11:06:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7140002","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7140002","identity":"rs-7140002","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}