Thrombotic thrombocytopenic purpura as a complication of pembrolizumab: a case report and literature review

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However, this progress has been accompanied by a rise in immune-related adverse events (irAEs). One such irAE is thrombotic thrombocytopenic purpura (TTP), a rare and potentially life-threatening complication. This report presents a unique case of TTP following a single dose of pembrolizumab. A 76-year-old man with suspected advanced renal cell carcinoma received pembrolizumab as initial treatment. Eleven days later, the patient developed severe thrombocytopenia, bleeding problems, and hemolytic anemia. The following day, the ADAMTS13 activity levels was 3.8% (ref. 40-130%), confirming the diagnosis of TTP. Given the patient's poor overall condition and limited life expectancy, plasma exchange was not initiated. The patient passed away 15 days after receiving pembrolizumab. In conclusion, physicians should be aware that even a single dose of the ICI pembrolizumab can trigger TTP. A review of current case reports on pembrolizumab-induced TTP is also provided. Thrombotic thrombocytopenic purpura TTP Immune checkpoint inhibitors ICI Pembrolizumab Case report Figures Figure 1 Introduction The Nobel Prize in 2018 was awarded to James P. Allison and Tasuku Honjo for their discovery of a new type of cancer therapy achieved by inhibition of an innate immunosuppressive process [1]. Immune checkpoint inhibitors (ICIs) are humanized monoclonal antibodies that block programmed cell death protein-1 (PD-1) on lymphocytes or its ligand, PD-L1, on tumors. This blockade results in enhanced antitumor activity by unbridling the immune system [31]. Pembrolizumab, a humanized monoclonal IgG4 antibody that specifically targets PD-1, is one of the most widely used ICIs in clinical practice [2]. The success of this immunotherapy has revolutionized oncology, with new therapies and indications expanding every year. Pembrolizumab is currently used to treat a variety of cancers, including non-small cell lung cancer, advanced renal cell carcinoma, melanoma [2]. However, alongside the growing success of ICIs, there has been an increase in reports of immune-related adverse events (irAEs). These adverse effects commonly involve the skin, gastrointestinal tract, and endocrine organs. More rarely, adverse effects involve the nervous, hematopoietic, or urinary systems [3]. One such rare and life-threatening complication is acquired thrombotic thrombocytopenic purpura (aTTP). aTTP is a thrombotic microangiopathy characterized by the formation of microthrombi in the microcirculation, which leads to thrombocytopenia, hemolytic anemia, and organ damage [4,7]. The pathogenesis stems from an acquired deficiency in ADAMTS13, a metalloprotease enzyme responsible for cleaving ultralarge von Willebrand factor (vWF) multimers [4,7]. When ADAMTS13 activity decreases, these large vWF multimers accumulate and promote excessive platelet aggregation and thrombus formation. This leads to platelet consumption simultaneous with thrombotic, ischemic organ damage [4,7]. aTTP often results from infections, autoimmune diseases, or medications. The clinical presentation is varied but can include thrombocytopenia, hemolytic anemia with schistocytes on blood smears, neurological symptoms (e.g., confusion, seizures), renal dysfunction, and fever [4,7]. Early recognition and treatment are critical to reduce organ damage, and are typically initiated with plasma exchange, glucocorticoids and caplacizumab [5,8,26]. The current report presents a unique case of aTTP occurring after a single dose of pembrolizumab. While a few case reports have documented aTTP following the use of pembrolizumab, to our knowledge, this is one of few instances of aTTP developing after just one dose. A review of current case reports on pembrolizumab-induced aTTP will also be provided to contextualize this case within the limited existing literature. Narrative A 76-year-old man presented to his primary care physician with dyspnea, significant weight loss, and hemoptysis over the last few weeks. His past medical history was significant for hypertension and a 35-year smoking history. He also reported a family history of stomach cancer, although the specific type was unknown. CT-imaging revealed a suspected advanced cystic renal tumor and possible metastases in the liver, abdomen, lungs, and submandibular glands. A biopsy was taken, but due to the high degree of necrosis, a tissue diagnosis could not be established with this sample. Nevertheless, a review of all the data at a multidisciplinary conference supported a high clinical suspicion of advanced renal cell carcinoma, which led to a decision to initiate treatment with pembrolizumab given the rapid clinical progression. A subsequent biopsy several days later revealed that the tumor was vascular in nature, reducing the suspicion of advanced renal cell carcinoma. However, at that time, the patient had already received his first dose of pembrolizumab. Approximately six days after receiving pembrolizumab, the patient presented to the emergency department (ED), of a cancer specialty university hospital, with worsening dyspnea, hypoxia (oxygen saturation of 67%), a fever of 38.8°C, hematuria, and petechiae that had lasted 10 days. His hemoglobin upon presentation was 72 g/L, despite having received two units of blood three days earlier as part of his advanced home care treatment. He was subsequently given an additional 2 units of blood transfusion. At the time, platelet counts, and coagulation test were within normal limits, but microscopic hematuria was confirmed. Bleeding was suspected to be due to the tumor. The CRP and procalcitonin levels were 141 and 1.1 respectively. Computer tomography (CT) of the chest revealed ground-glass infiltrates in all the lung lobes. These factors along with the rapid worsening of the patient’s clinical condition prompted the initiation of an empirical treatment of intravenous piperacillin-tazobactam (Pip/Taz). A preliminary diagnosis of pneumonitis was made; subsequently, 40 mg of prednisolone was administered daily as part of the management. Given his deteriorating condition, the patient was transferred to a higher care facility on the same day. Blood cultures and beta-glucan tests returned negative. Radiographic findings revealed tumor progression with metastasis in the lungs, kidney, liver and mediastinal lymph nodes. A repeat biopsy on hospital day 2 revealed high-grade angiosarcoma in both the kidneys and liver. Considering the patient's poor prognosis and the aggressive nature of the disease, a decision was made, on day 3, to initiate weekly paclitaxel treatment, at a dosage of 80 mg/m². Before paclitaxel administration, on day 2, the patient's platelet count had already dropped to 119 x10^9/L, a significant decline from baseline. On hospital days 4-5, the patient's lab results indicated hemolysis, with elevated bilirubin and lactate dehydrogenase (LDH), falling hemoglobin, and dropping haptoglobin levels (Table 1). On day 5, his platelet count had dropped to 19 x10^9/L and the patient showed signs of bleeding at multiple sites, including melena. Because of ongoing clinical bleeding and thrombocytopenia, the patient received a transfusion of platelets on day 5. Given his critical condition, gastroscopy was not performed. On day 6, to manage the bleeding, tranexamic acid and an additional 2 units of platelets were administered. A hematology consultant was consulted and determined that acquired thrombotic thrombocytopenic purpura (aTTP) could be a possibility. An ADAMTS13 activity test was performed. On day 7, the ADAMTS13 test results returned and indicated abnormally low activity at 3.8% (ref. 40-130%), confirming the diagnosis of aTTP. At this point, the test for ADAMTS13 antibodies was negative. Owing to the patient's overall poor condition, it was decided in consultation with the oncologist not to initiate plasma exchange. Instead, 120 mg of methylprednisolone was administered with the goal of improving the patient's well-being. Unfortunately, after three days of steroid treatment with limited benefit, the decision was made to discontinue corticosteroids in favor of pure palliative care. He passed away the same day, on hospital day 9. Table 1 Blood parameters of the patient during hospital stay. For days with multiple measurements, the lowest value is reported Blood Parameters Day 0 (ED Admission) Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 9 Platelets (145–348) × 10^9/L 188 160 119 109 72 19 27 54 47 32 Nr of PLT Transfusion 1 1 PK (INR) (<1,3) sec 1,2 1,2 1,2 1,2 1,2 1,2 APTT (20-30) sec 26 26 25 26 26 Hemoglobin (134-170) g/L 72 80 87 73 72 72 75 76 82 78 Units of Blood transfusion given 2 1 2 2 Creatinine (<100) µmol/L 93 83 84 75 77 95 144 185 236 266 CRP (<3) mg/L 146 185 163 103 95 110 133 129 127 91 WBC (3,5-8,8) x10^9/L 17,1 15,1 16,6 18,5 16,9 14,5 12 10,4 8,1 8,6 Lactate Dehydrogenase (<4,3) mikrokat/L 9,5 9 10,9 11,1 15 Bilirubin (<26) mikromol/L 28 17 21 18 23 48 52 42 30 Haptoglobin (0,24-1,9) g/L 0,96 0,29 <0,1 <0,1 <0,1 ADAMTS13 Activity (40-130) % 3,8 ADAMTS13 Antibodies (<0,4) kBE/L <0,4 Fecal Occult Blood (F-Hb) Positive Patient Perspective The patient was diagnosed with highly malignant angiosarcoma two days after presenting to the emergency department. Despite the severity of the diagnosis, the patient expressed a strong desire to pursue treatment and was fully aware of the precarious nature of the situation. However, after seven additional days, the patient was actively involved in the decision to discontinue further therapy, a decision made in alignment with his wishes. Discussion This patient was diagnosed with thrombotic thrombocytopenic purpura (TTP) 13 days after a single dose of pembrolizumab. The diagnosis of aTTP was confirmed by low ADAMTS13 activity. Given the rapid onset of TTP symptoms eleven days after pembrolizumab administration, it is most likely that the immune checkpoint inhibitor played a central role in triggering aTTP, which is consistent with known hematologic toxicities associated with ICIs [ 3 , 9 , 12 , 13 , 14 , 15 ]. Although this patient tested negative for anti-ADAMTS13 antibodies it is not uncommon for aTTP patient to present with negative antibodies, at least initially. In contrast, paclitaxel, which was first administered after the onset of clinical bleeding and thrombocytopenia, is less likely to be a culprit in this case due to the timing and because paclitaxel is rarely associated with thrombocytopenia-related complications such as TTP [ 30 ]. Although congenital TTP (cTTP) can present later in life [ 10 ], this patient's advanced age, the timing of recent pembrolizumab use, and the known immune-related adverse effects of ICIs [ 9 , 11 , 12 , 15 ], make cTTP less likely. The standard treatment for aTTP includes plasma exchange, rituximab, corticosteroids, and caplacizumab [ 4 , 5 ]. In this case, despite plasma exchange being recommended by the hematologist, the attending oncologist decided not to initiate plasma exchange due to the patient’s instability. There was no mention of consideration of treatment with caplacizumab and rituximab in this patient’s record. Instead, high-dose methylprednisolone was attempted, but provided limited benefit. Platelet transfusions, while typically used in cases of severe thrombocytopenia, can worsen TTP by accelerating platelet aggregation [ 32 ]. In this case, platelet transfusion was given due to ongoing bleeding before the ADAMTS13 test had returned and after the patient already experienced severe thrombocytopenia with bleeding. In this case, it is unlikely that there was a clinical deterioration because of the transfusion. Autoantibody negativity In our case, the patient tested negative for anti-ADAMTS13 antibodies. These antibodies would be expected to be present as part of the pathophysiology of aTTP. However, a literature review shows that aTTP can initially present without detectable ADAMTS13 antibodies [ 30 ]. A possible explanation for the negative anti-ADAMTS13 antibody result could be a technical issue with the assay used to detect the antibodies. Another explanation could be due to low antibody levels early in the course of the disease. In fact, studies have documented that false negatives can occur, particularly in the early stages of immune-related TTP (iTTP) [ 16 , 17 ]. A retrospective study of all ADAMTS13 activity tests performed in a single center [ 16 ] revealed that, among patients with low ADAMTS13 activity and no detectable antibodies, the majority later tested positive for anti-ADAMTS13 antibodies in subsequent assays. However, not all patients demonstrated this progression. The authors suggested that most initial negative antibody tests resulted from low or transient autoantibody production at the time of initial testing. Simon et al. [ 17 ] conducted a similar retrospective study of patients with aTTP who had ADAMTS13 deficiency at presentation. They reported that 21% of those who initially tested negative for anti-ADAMTS13 antibodies later tested positive during follow-up. With either of these studies, it could not be ascertained whether initial negative antibody tests in those who later tested positive resulted from a test sensitivity problem or de facto negative (or extremely low) serum antibody levels. Future case reports examining ICI-induced aTTP would benefit greatly from routine testing for anti-ADAMTS13 antibodies to explore the relationship between autoimmunity and the development of thrombocytopenia in this context. Such testing could enhance our understanding of the disease mechanism and provide important prognostic insights, especially as the role of autoimmune activation in ICI-induced aTTP continues to be investigated. Literature Review Table 2 Overview of reported cases of thrombotic thrombocytopenic purpura associated with pembrolizumab. Author & Year Age & Sex Type of Cancer Cancer Treatment Timing of TTP from last regimen Clinical Presentation of TTP ADAMTS13 Activity ADAMTS13 antibodies Treatment of TTP Outcome Dickey et al. 2020 (19) 60-year F NSCLC Pembrolizumab × 5 cycles - every 3 weeks; Total dose 1000 mg 14 days Chest pain, pyrexia & Dyspnea 3% Not reported PE x 5, methylprednisolone, prednisolone Initially, complete remission. 4 days later probable relapse. Abstained from further treatment. Death. De Filippis et al. 2021 (20) 61-year M NSCLC Pembrolizumab, carboplatin, paclitaxel × 5 cycles then pembrolizumab × 2 cycles – every 3 weeks; Total dose 1400 mg 46 days Jaundice, scleral icterus, costovertebral tenderness (probably due to underlying tumor) 10–12% Positive PE x 5, methylprednisolone, prednisolone After stabilization, patient declined further treatment and died out-of-hospital. Nelson et al. 2022 (21) 68-year M Metastatic urothelial carcinoma Pembrolizumab x 3 cycles Not Reported Confusion, SOB, Mild Tachycardia 8% Positive Not initiated Death Sharma et al. 2023 (22) 69-year F Stage IV lung cancer Pembrolizumab 2 doses Not Reported SOB, 3 days later hypoxia, hypotension, limb paresis & facial drop 0.56 IU/mL (0.68–1.63 IU/mL) Not reported Not initiated Death Kozak et al. 2023 (23) 56-year M Metastatic Lung Adenocarcinoma pemetrexed, carboplatin, pembrolizumab x 4 cycles. 1 month later 5th maintenance dose of pemetrexed and pembrolizumab. 2 months from last Pembrolizumab Episode 1: Altered Mental Status & Thrombocytopenia. Episode 2: Fatigue, Chills & Severe Diarrhea (positive C. difficile toxin B). Episode 1: not measured. Episode 2:<5% Positive Episode 1: PE x 6, corticosteroids Episode 2: PE x 7, high dose dexamethasone, Rituximab (375 mg/m 2 ) x 4 Complete remission. No reported relapse of TTP. Luong et al. 2024 (24) 73-year F Metastatic pancreatic Adenocarcinoma Pembrolizumab x 1 1 month after Pembrolizumab DKA & Diarrhea. Thrombocytopenia & hemolytic anemia. No lab done before PE. After PE: 48% Not reported PE x 1, corticosteroids Moved to home hospice. Unclear outcome This case 76-year M Angiosarcoma (suspected advanced renal cell carcinoma) Pembrolizumab x 1 11 days after Pembrolizumab Dyspnea, Fever, hematuria, Petechia 3% Negative Methylprednisolone, prednisolone Death As of Mars 2025, we performed a literature review on pembrolizumab-induced acquired thrombocytopenic purpura (aTTP) by searching data from PubMed and Web of Science, which identified six case reports on the subject, excluding ours. These reports, summarized in Table 2 , provide key insights into the clinical manifestations, diagnosis, treatment, and outcomes of TTP in patients receiving pembrolizumab. In a previous review of case reports of pembrolizumab-induced aTTP by Gilbar et al. [ 18 ], only three case reports had been published, indicating that the body of evidence on this adverse event is still expanding. The median age of patients across the reviewed cases was 68 years, with a range of 20 years. The median time from the last dose of pembrolizumab to the onset of TTP symptoms was 30 days, although the earliest occurred 11 days and the latest occurred 2 months later. Among the seven patients reported, four were male, and three were female. In terms of treatment cycles, the number of pembrolizumab cycles administered ranged from 1 to 7 cycles, with De Filippis et al. [ 20 ] noting the highest number of cycles. However, details on the dosage of pembrolizumab were often not included in the case reports, making it difficult to draw firm conclusions on the role of dose in triggering hematologic complications. Gilbar et al. [ 18 ] speculated that the shift from bodyweight-based dosing to flat dosing could explain an increase in adverse effects, as the flat dose might be disproportionately high for many patients, potentially contributing to an increased risk of hematologic toxicity. The clinical presentations of aTTP varied across the reported cases. This is in line with the conclusions drawn from a review of case reports on ICI-induced TTP by Yikilmaz et al [ 25 ]. One interesting case by Luong et al. (24) involved the development of DKA due to a new onset of type 1 diabetes mellitus (DM1) alongside aTTP after pembrolizumab treatment, indicating an autoimmune mechanism. Pembrolizumab-induced autoimmune diabetes has been described in the literature and has been suggested to be caused by a dysregulation of cytotoxic T-lymphocytes [ 27 , 28 ]. However, whether autoantibodies were responsible for the observed diabetes and aTTP in the case by Luong et al. [ 24 ] remains undetermined [ 29 ], highlighting the need for further research into the immune mechanisms at play in pembrolizumab-induced adverse effects. ADAMTS13 activity, as measured through enzyme assays, was low in almost all cases, confirming the diagnosis of aTTP. However, many authors did not measure or report anti-ADAMTS13 antibodies. In three case reports, the authors tested for anti-ADAMTS13 antibodies and found them positive, while the others did not report antibody testing. Similar findings were observed in other case reports on ICI-induced aTTP [ 25 ]. Treatment strategies varied, with plasma exchange (PE) and corticosteroids being the most commonly administered therapies, as per the International Society on Thrombosis and Haemostasis (ISTH) clinical guidelines for aTTP [ 5 , 26 ]. Recently, caplacizumab has emerged as a promising new therapy for aTTP and is recommended to be used alongside PE in acute cases. However, ISTH has emphasized that, although caplacizumab may offer significant therapeutic benefits, its availability remains limited, and many clinicians are unfamiliar with its use and the necessary monitoring protocols [ 26 ]. As evident by our review and the review by Yikilmaz et al. [ 25 ], no case in the literature initiated caplacizumab therapy, highlighting that its integration into routine practice is still developing. Four cases initiated PE, whereas three cases did not, with the decision to forgo PE being made in consultation with the patient, particularly in cases where the patients were in poor clinical condition. For example, Nelson et al. [ 21 ] reported a patient who declined all treatments, including PE and corticosteroids, due to prior comorbidities and a decision to focus on comfort care. Similarly, Sharma et al. [ 22 ] described a patient who chose not to pursue further treatment after the diagnosis of TTP. In our case, the decision was made not to initiate PE, but rather to try high-dose methylprednisolone. However, these were discontinued, with the patient’s consent, after three days due to the patient’s poor prognosis and declining condition. The ISTH strongly recommends plasma exchange (PE) in combination with corticosteroids for patients experiencing a first acute episode of aTTP, as well as those experiencing a relapse [ 26 ]. Evidence shows a 90% survival rate following PE after the first episode, with treatment to be administered daily until signs of organ damage resolve and platelet counts stabilize, underscoring the importance of early diagnosis and timely initiation of PE [ 4 ]. In our review, Kozak et al. [ 23 ] performed 11 sessions of PE (for two episodes) and used rituximab, resulting in complete remission. This case, being the only one case to show complete remission, highlights the crucial role of multiple sessions of PE in achieving favorable outcomes. Among the seven patients reviewed, five patients died, which reflects the high mortality associated with pembrolizumab-induced aTTP. One patient achieved complete remission, while the outcome for another patient remains unclear. It is important to note that all patients had multiple comorbidities, making it difficult to isolate the contribution of aTTP alone in the patients' poor outcomes. In several cases, the presence of cancer, severe infections, and other preexisting health conditions likely contributed to a poor outcome. This review suggests that early recognition and treatment of aTTP may be important for improving patient prognosis, although the limited data available do not allow for definitive conclusions. Conclusion In conclusion, this case highlights the importance of recognizing pembrolizumab-induced TTP as a cause of thrombocytopenia, even after a single dose. This review of the current case reports highlights the need to be vigilant for ICI-induced TTP and to consider the potential autoimmune pathophysiology as soon as the diagnosis is established. Early testing for anti-ADAMTS13 antibodies can benefit both researchers’ and clinicians’ knowledge base as well as inform individual patient treatment decisions. Since treatment for aTTP is distinct from other causes of thrombocytopenia, physicians must recognize aTTP early to optimize the chances for treatment success. Declarations Funding No funding was received for this study. Ethics declaration Ethics approval was not required for this type of study in accordance with institutional policies. Competing Interests The authors declare no competing interests. Consent to Publish Informed consent was obtained from the patient’s relative for publication of this case report and accompanying data. 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Journal of immunotherapy and precision oncology , 8 (1), 15–22. https://doi.org/10.36401/JIPO-24-2 Zheng, X. L., Vesely, S. K., Cataland, S. R., Coppo, P., Geldziler, B., Iorio, A., Matsumoto, M., Mustafa, R. A., Pai, M., Rock, G., Russell, L., Tarawneh, R., Valdes, J., & Peyvandi, F. (2020). ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. Journal of thrombosis and haemostasis : JTH , 18 (10), 2496–2502. https://doi.org/10.1111/jth.15010 Bhanderi, H., Khalid, F., Bodla, Z. H., Muhammad, T., Du, D., & Meghal, T. (2023). Autoimmune diabetes from pembrolizumab: A case report and review of literature. World journal of clinical oncology , 14 (11), 535–543. https://doi.org/10.5306/wjco.v14.i11.535 Clotman, K., Janssens, K., Specenier, P., Weets, I., & De Block, C. E. M. (2018). Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. The Journal of clinical endocrinology and metabolism , 103 (9), 3144–3154. https://doi.org/10.1210/jc.2018-00728 Quandt, Z., Young, A., & Anderson, M. (2020). Immune checkpoint inhibitor diabetes mellitus: a novel form of autoimmune diabetes. Clinical and experimental immunology , 200 (2), 131–140. https://doi.org/10.1111/cei.13424 Smock KJ. ADAMTS13 testing update: Focus on laboratory aspects of difficult thrombotic thrombocytopenic purpura diagnoses and effects of new therapies. Int J Lab Hematol. 2021 Jul;43 Suppl 1(S1):103–8. https://doi.org/10.3892/ol.2015.3338 Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Mar 22;12(4):252–64. https://doi.org/10.3892/ol.2015.3338 Benhamou Y, Baudel J-L, Wynckel A, Galicier L, Azoulay E, Provôt F, et al. Are platelet transfusions harmful in acquired thrombotic thrombocytopenic purpura at the acute phase? Experience of the French thrombotic microangiopathies reference center. Am J Hematol. 2015 Jun;90(6):E127-9. https://doi.org/10.3892/ol.2015.3338 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 27 Feb, 2026 Read the published version in Annals of Hematology → Version 1 posted Editorial decision: Revision requested 02 Oct, 2025 Reviews received at journal 23 Sep, 2025 Reviewers agreed at journal 19 Aug, 2025 Reviewers invited by journal 14 Aug, 2025 Editor assigned by journal 30 Jun, 2025 Submission checks completed at journal 30 Jun, 2025 First submitted to journal 23 Jun, 2025 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. 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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-6959398","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":502677545,"identity":"ef86f4aa-624a-41d5-bc41-8169459cd579","order_by":0,"name":"Gregory Palega","email":"","orcid":"","institution":"Karolinska University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Gregory","middleName":"","lastName":"Palega","suffix":""},{"id":502677546,"identity":"011a45f5-7c91-4550-8736-7a72ac3939ee","order_by":1,"name":"Ihab Ahmad Al-Rikabi","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Ihab","middleName":"Ahmad","lastName":"Al-Rikabi","suffix":""},{"id":502677547,"identity":"532c2b1c-53ad-460c-a0c5-10c1f055cca5","order_by":2,"name":"Cecilia Karlström","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+0lEQVRIie2PMUvDQBiG3yDU5SDrlcL5C4RAIFPpb/lC4bo4CI4OBoTkL+gf6fyVg2RpcVUK0iJkcugYoaB3FRGHS1aHe4aD73gfvu8FAoF/Cu8SQAIRn8bzEjyo0Ldik2RfUQ8rp+CvInV/Oq7u90zXM4yrzW710b2qy8c2ZxynXkWu68QeNsdELBIj6CbNtpo5Kv2rEnnlupxBQcOAKF9uFwVHhfErF+9OuYOKW6w6p7w0hT3ss2eLcIrBxLZm4ZTnETNG3NNFuy6NGD+0MEJTmq01cV7OvUpcmbfD4Xir5JOO9t2UVNbUqf2ZeZUfxN+RBoVAIBAI9PEFE65aCZBLUUwAAAAASUVORK5CYII=","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":true,"prefix":"","firstName":"Cecilia","middleName":"","lastName":"Karlström","suffix":""}],"badges":[],"createdAt":"2025-06-23 19:08:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6959398/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6959398/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00277-026-06907-3","type":"published","date":"2026-02-27T15:57:41+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":89641730,"identity":"b1333475-7de9-4c10-a579-ea4c7cf41277","added_by":"auto","created_at":"2025-08-22 08:11:22","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":44990,"visible":true,"origin":"","legend":"\u003cp\u003eTimeline\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6959398/v1/102e3c7377e9844eccbceac9.jpeg"},{"id":103765545,"identity":"609f62a0-a81b-464f-8df1-8b12c9c4eafa","added_by":"auto","created_at":"2026-03-02 16:03:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":636182,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6959398/v1/ecae557d-2593-4a7b-8c80-e0ef40a68d5b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Thrombotic thrombocytopenic purpura as a complication of pembrolizumab: a case report and literature review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe Nobel Prize in 2018 was awarded to James P. Allison and Tasuku Honjo for their discovery of a new type of cancer therapy achieved by inhibition of an innate immunosuppressive process [1]. Immune checkpoint inhibitors (ICIs) are humanized monoclonal antibodies that block programmed cell death protein-1 (PD-1) on lymphocytes or its ligand, PD-L1, on tumors. This blockade results in enhanced antitumor activity by unbridling the immune system [31]. Pembrolizumab, a humanized monoclonal IgG4 antibody that specifically targets PD-1, is one of the most widely used ICIs in clinical practice [2].\u003c/p\u003e\n\u003cp\u003eThe success of this immunotherapy has revolutionized oncology, with new therapies and indications expanding every year. Pembrolizumab is currently used to treat a variety of cancers, including non-small cell lung cancer, advanced renal cell carcinoma, melanoma [2]. However, alongside the growing success of ICIs, there has been an increase in reports of immune-related adverse events (irAEs). These adverse effects commonly involve the skin, gastrointestinal tract, and endocrine organs. More rarely, adverse effects involve the nervous, hematopoietic, or urinary systems [3].\u003c/p\u003e\n\u003cp\u003eOne such rare and life-threatening complication is acquired thrombotic thrombocytopenic purpura (aTTP). aTTP is a thrombotic microangiopathy characterized by the formation of microthrombi in the microcirculation, which leads to thrombocytopenia, hemolytic anemia, and organ damage [4,7]. The pathogenesis stems from an acquired deficiency in ADAMTS13, a metalloprotease enzyme responsible for cleaving ultralarge von Willebrand factor (vWF) multimers [4,7]. When ADAMTS13 activity decreases, these large vWF multimers accumulate and promote excessive platelet aggregation and thrombus formation. This leads to platelet consumption simultaneous with thrombotic, ischemic organ damage [4,7]. aTTP often results from infections, autoimmune diseases, or medications. The clinical presentation is varied but can include thrombocytopenia, hemolytic anemia with schistocytes on blood smears, neurological symptoms (e.g., confusion, seizures), renal dysfunction, and fever [4,7]. Early recognition and treatment are critical to reduce organ damage, and are typically initiated with plasma exchange, glucocorticoids and caplacizumab [5,8,26].\u003c/p\u003e\n\u003cp\u003eThe current report presents a unique case of aTTP occurring after a single dose of pembrolizumab. While a few case reports have documented aTTP following the use of pembrolizumab, to our knowledge, this is one of few instances of aTTP developing after just one dose. A review of current case reports on pembrolizumab-induced aTTP will also be provided to contextualize this case within the limited existing literature.\u003c/p\u003e\n\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Narrative","content":"\u003cp\u003eA 76-year-old man presented to his primary care physician with dyspnea, significant weight loss, and hemoptysis over the last few weeks. His past medical history was significant for hypertension and a 35-year smoking history. He also reported a family history of stomach cancer, although the specific type was unknown. CT-imaging revealed a suspected advanced cystic renal tumor and possible metastases in the liver, abdomen, lungs, and submandibular glands. A biopsy was taken, but due to the high degree of necrosis, a tissue diagnosis could not be established with this sample. Nevertheless, a review of all the data at a multidisciplinary conference supported a high clinical suspicion of advanced renal cell carcinoma, which led to a decision to initiate treatment with pembrolizumab given the rapid clinical progression. A subsequent biopsy several days later revealed that the tumor was vascular in nature, reducing the suspicion of advanced renal cell carcinoma. However, at that time, the patient had already received his first dose of pembrolizumab.\u003c/p\u003e\u003cp\u003eApproximately six days after receiving pembrolizumab, the patient presented to the emergency department (ED), of a cancer specialty university hospital, with worsening dyspnea, hypoxia (oxygen saturation of 67%), a fever of 38.8°C, hematuria, and petechiae that had lasted 10 days. His hemoglobin upon presentation was 72 g/L, despite having received two units of blood three days earlier as part of his advanced home care treatment. He was subsequently given an additional 2 units of blood transfusion. At the time, platelet counts, and coagulation test were within normal limits, but microscopic hematuria was confirmed. Bleeding was suspected to be due to the tumor.\u0026nbsp;\u003c/p\u003e\u003cp\u003eThe CRP and procalcitonin levels were 141 and 1.1 respectively. Computer tomography (CT) of the chest revealed ground-glass infiltrates in all the lung lobes. These factors along with the rapid worsening of the patient’s clinical condition prompted the initiation of an empirical treatment of intravenous piperacillin-tazobactam (Pip/Taz). A preliminary diagnosis of pneumonitis was made; subsequently, 40 mg of prednisolone was administered daily as part of the management.\u0026nbsp;\u003c/p\u003e\u003cp\u003eGiven his deteriorating condition, the patient was transferred to a higher care facility on the same day. Blood cultures and beta-glucan tests returned negative. Radiographic findings revealed tumor progression with metastasis in the lungs, kidney, liver and mediastinal lymph nodes. A repeat biopsy on hospital day 2 revealed high-grade angiosarcoma in both the kidneys and liver. Considering the patient's poor prognosis and the aggressive nature of the disease, a decision was made, on day 3, to initiate weekly paclitaxel treatment, at a dosage of 80 mg/m².\u0026nbsp;\u003c/p\u003e\u003cp\u003eBefore paclitaxel administration, on day 2, the patient's platelet count had already dropped to 119 x10^9/L, a significant decline from baseline. On hospital days 4-5, the patient's lab results indicated hemolysis, with elevated bilirubin and lactate dehydrogenase (LDH), falling hemoglobin, and dropping haptoglobin levels (Table 1). On day 5, his platelet count had dropped to 19 x10^9/L and the patient showed signs of bleeding at multiple sites, including melena. Because of ongoing clinical bleeding and thrombocytopenia, the patient received a transfusion of platelets on day 5. Given his critical condition, gastroscopy was not performed. On day 6, to manage the bleeding, tranexamic acid and an additional 2 units of platelets were administered. A hematology consultant was consulted and determined that acquired thrombotic thrombocytopenic purpura (aTTP) could be a possibility. An ADAMTS13 activity test was performed.\u003c/p\u003e\u003cp\u003eOn day 7, the ADAMTS13 test results returned and indicated abnormally low activity at 3.8% (ref. 40-130%), confirming the diagnosis of aTTP. At this point, the test for ADAMTS13 antibodies was negative. Owing to the patient's overall poor condition, it was decided in consultation with the oncologist not to initiate plasma exchange. Instead, 120 mg of methylprednisolone was administered with the goal of improving the patient's well-being. Unfortunately, after three days of steroid treatment with limited benefit, the decision was made to discontinue corticosteroids in favor of pure palliative care. He passed away the same day, on hospital day 9.\u003c/p\u003e\u003cp\u003eTable 1 Blood parameters of the patient during hospital stay. For days with multiple measurements, the lowest value is reported\u003c/p\u003e\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eBlood Parameters\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003eDay 0 (ED Admission)\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003eDay 1\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eDay 2\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eDay 3\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003eDay 4\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eDay 5\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003eDay 6\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eDay 7\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eDay 8\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eDay 9\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003ePlatelets (145–348) × 10^9/L\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e188\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e160\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e119\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e109\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eNr of PLT Transfusion\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003ePK (INR) (\u0026lt;1,3) sec\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;1,2\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;1,2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp; 1,2\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp; 1,2\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026nbsp;1,2\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp; 1,2\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eAPTT (20-30) sec\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;26\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp; 26\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp; 25\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026nbsp; 26\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp; 26\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eHemoglobin (134-170) g/L\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eUnits of Blood transfusion given\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eCreatinine (\u0026lt;100) µmol/L\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e83\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e95\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e144\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e185\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e236\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e266\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eCRP (\u0026lt;3) mg/L\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e146\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e185\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e163\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e103\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e95\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e110\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e133\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e129\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e127\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eWBC (3,5-8,8) x10^9/L\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e17,1\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e15,1\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e16,6\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e18,5\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e16,9\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e14,5\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e10,4\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e8,1\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e8,6\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eLactate Dehydrogenase (\u0026lt;4,3) mikrokat/L\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e9,5\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e10,9\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e11,1\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eBilirubin (\u0026lt;26) mikromol/L\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eHaptoglobin (0,24-1,9) g/L\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e0,96\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e0,29\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt;0,1\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026lt;0,1\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt;0,1\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eADAMTS13 Activity (40-130) %\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e3,8\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eADAMTS13 Antibodies (\u0026lt;0,4) kBE/L\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026lt;0,4\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd style=\"width: 115px;\"\u003e\n \u003cp\u003eFecal Occult Blood (F-Hb)\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 79px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 49px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 44px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/table\u003e"},{"header":"Patient Perspective","content":"\u003cp\u003eThe patient was diagnosed with highly malignant angiosarcoma two days after presenting to the emergency department. Despite the severity of the diagnosis, the patient expressed a strong desire to pursue treatment and was fully aware of the precarious nature of the situation. However, after seven additional days, the patient was actively involved in the decision to discontinue further therapy, a decision made in alignment with his wishes.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis patient was diagnosed with thrombotic thrombocytopenic purpura (TTP) 13 days after a single dose of pembrolizumab. The diagnosis of aTTP was confirmed by low ADAMTS13 activity. Given the rapid onset of TTP symptoms eleven days after pembrolizumab administration, it is most likely that the immune checkpoint inhibitor played a central role in triggering aTTP, which is consistent with known hematologic toxicities associated with ICIs [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Although this patient tested negative for anti-ADAMTS13 antibodies it is not uncommon for aTTP patient to present with negative antibodies, at least initially. In contrast, paclitaxel, which was first administered after the onset of clinical bleeding and thrombocytopenia, is less likely to be a culprit in this case due to the timing and because paclitaxel is rarely associated with thrombocytopenia-related complications such as TTP [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Although congenital TTP (cTTP) can present later in life [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], this patient's advanced age, the timing of recent pembrolizumab use, and the known immune-related adverse effects of ICIs [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], make cTTP less likely.\u003c/p\u003e\u003cp\u003eThe standard treatment for aTTP includes plasma exchange, rituximab, corticosteroids, and caplacizumab [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In this case, despite plasma exchange being recommended by the hematologist, the attending oncologist decided not to initiate plasma exchange due to the patient\u0026rsquo;s instability. There was no mention of consideration of treatment with caplacizumab and rituximab in this patient\u0026rsquo;s record. Instead, high-dose methylprednisolone was attempted, but provided limited benefit.\u003c/p\u003e\u003cp\u003ePlatelet transfusions, while typically used in cases of severe thrombocytopenia, can worsen TTP by accelerating platelet aggregation [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In this case, platelet transfusion was given due to ongoing bleeding before the ADAMTS13 test had returned and after the patient already experienced severe thrombocytopenia with bleeding. In this case, it is unlikely that there was a clinical deterioration because of the transfusion.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eAutoantibody negativity\u003c/h2\u003e\u003cp\u003eIn our case, the patient tested negative for anti-ADAMTS13 antibodies. These antibodies would be expected to be present as part of the pathophysiology of aTTP. However, a literature review shows that aTTP can initially present without detectable ADAMTS13 antibodies [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eA possible explanation for the negative anti-ADAMTS13 antibody result could be a technical issue with the assay used to detect the antibodies. Another explanation could be due to low antibody levels early in the course of the disease. In fact, studies have documented that false negatives can occur, particularly in the early stages of immune-related TTP (iTTP) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. A retrospective study of all ADAMTS13 activity tests performed in a single center [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] revealed that, among patients with low ADAMTS13 activity and no detectable antibodies, the majority later tested positive for anti-ADAMTS13 antibodies in subsequent assays. However, not all patients demonstrated this progression. The authors suggested that most initial negative antibody tests resulted from low or transient autoantibody production at the time of initial testing.\u003c/p\u003e\u003cp\u003eSimon et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] conducted a similar retrospective study of patients with aTTP who had ADAMTS13 deficiency at presentation. They reported that 21% of those who initially tested negative for anti-ADAMTS13 antibodies later tested positive during follow-up. With either of these studies, it could not be ascertained whether initial negative antibody tests in those who later tested positive resulted from a test sensitivity problem or de facto negative (or extremely low) serum antibody levels.\u003c/p\u003e\u003cp\u003eFuture case reports examining ICI-induced aTTP would benefit greatly from routine testing for anti-ADAMTS13 antibodies to explore the relationship between autoimmunity and the development of thrombocytopenia in this context. Such testing could enhance our understanding of the disease mechanism and provide important prognostic insights, especially as the role of autoimmune activation in ICI-induced aTTP continues to be investigated.\u003c/p\u003e\u003c/div\u003e"},{"header":"Literature Review","content":"\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOverview of reported cases of thrombotic thrombocytopenic purpura associated with pembrolizumab.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"11\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAuthor \u0026amp; Year\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAge \u0026amp; Sex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eType of Cancer\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCancer Treatment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTiming of TTP from last regimen\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eClinical Presentation of TTP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eADAMTS13 Activity\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eADAMTS13 antibodies\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eTreatment of TTP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eOutcome\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDickey et al. 2020 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e60-year F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNSCLC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePembrolizumab\u0026thinsp;\u0026times;\u0026thinsp;5 cycles - every 3 weeks;\u003c/p\u003e\u003cp\u003eTotal dose 1000 mg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14 days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eChest pain, pyrexia \u0026amp; Dyspnea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNot reported\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003ePE x 5, methylprednisolone, prednisolone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eInitially, complete remission. 4 days later probable relapse. Abstained from further treatment. Death.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDe Filippis et al. 2021 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e61-year M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNSCLC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePembrolizumab, carboplatin, paclitaxel\u0026thinsp;\u0026times;\u0026thinsp;5 cycles then pembrolizumab\u0026thinsp;\u0026times;\u0026thinsp;2 cycles \u0026ndash; every 3 weeks; Total dose 1400 mg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e46 days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eJaundice, scleral icterus, costovertebral tenderness (probably due to underlying tumor)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e10\u0026ndash;12%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003ePE x 5, methylprednisolone, prednisolone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eAfter stabilization, patient declined further treatment and died out-of-hospital.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNelson et al. 2022 (21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e68-year M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMetastatic urothelial carcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePembrolizumab x 3 cycles\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNot Reported\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eConfusion, SOB, Mild Tachycardia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNot initiated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eDeath\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSharma et al. 2023 (22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e69-year F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eStage IV lung cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePembrolizumab 2 doses\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNot Reported\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSOB, 3 days later hypoxia, hypotension, limb paresis \u0026amp; facial drop\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.56 IU/mL (0.68\u0026ndash;1.63 IU/mL)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNot reported\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNot initiated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eDeath\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKozak et al. 2023 (23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e56-year M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMetastatic Lung Adenocarcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003epemetrexed, carboplatin, pembrolizumab x 4 cycles. 1 month later 5th maintenance dose of pemetrexed and pembrolizumab.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 months from last Pembrolizumab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eEpisode 1: Altered Mental Status \u0026amp; Thrombocytopenia. Episode 2: Fatigue, Chills \u0026amp; Severe Diarrhea (positive C.\u0026thinsp;difficile toxin B).\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eEpisode 1: not measured. Episode 2:\u0026lt;5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eEpisode 1: PE x 6, corticosteroids\u003c/p\u003e\u003cp\u003eEpisode 2: PE x 7, high dose dexamethasone, Rituximab (375\u0026thinsp;mg/m\u003csup\u003e2\u003c/sup\u003e) x 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eComplete remission. No reported relapse of TTP.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLuong et al. 2024 (24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e73-year F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMetastatic pancreatic Adenocarcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePembrolizumab x 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 month after Pembrolizumab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eDKA \u0026amp; Diarrhea. Thrombocytopenia \u0026amp; hemolytic anemia.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo lab done before PE. After PE: 48%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNot reported\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003ePE x 1, corticosteroids\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eMoved to home hospice. Unclear outcome\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThis case\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e76-year M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAngiosarcoma (suspected advanced renal cell carcinoma)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePembrolizumab x 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e11 days after Pembrolizumab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eDyspnea, Fever, hematuria, Petechia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eMethylprednisolone, prednisolone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eDeath\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAs of Mars 2025, we performed a literature review on pembrolizumab-induced acquired thrombocytopenic purpura (aTTP) by searching data from PubMed and Web of Science, which identified six case reports on the subject, excluding ours. These reports, summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, provide key insights into the clinical manifestations, diagnosis, treatment, and outcomes of TTP in patients receiving pembrolizumab. In a previous review of case reports of pembrolizumab-induced aTTP by Gilbar et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], only three case reports had been published, indicating that the body of evidence on this adverse event is still expanding.\u003c/p\u003e\u003cp\u003eThe median age of patients across the reviewed cases was 68 years, with a range of 20 years. The median time from the last dose of pembrolizumab to the onset of TTP symptoms was 30 days, although the earliest occurred 11 days and the latest occurred 2 months later. Among the seven patients reported, four were male, and three were female. In terms of treatment cycles, the number of pembrolizumab cycles administered ranged from 1 to 7 cycles, with De Filippis et al. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] noting the highest number of cycles. However, details on the dosage of pembrolizumab were often not included in the case reports, making it difficult to draw firm conclusions on the role of dose in triggering hematologic complications. Gilbar et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] speculated that the shift from bodyweight-based dosing to flat dosing could explain an increase in adverse effects, as the flat dose might be disproportionately high for many patients, potentially contributing to an increased risk of hematologic toxicity.\u003c/p\u003e\u003cp\u003eThe clinical presentations of aTTP varied across the reported cases. This is in line with the conclusions drawn from a review of case reports on ICI-induced TTP by Yikilmaz et al [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. One interesting case by Luong et al. (24) involved the development of DKA due to a new onset of type 1 diabetes mellitus (DM1) alongside aTTP after pembrolizumab treatment, indicating an autoimmune mechanism. Pembrolizumab-induced autoimmune diabetes has been described in the literature and has been suggested to be caused by a dysregulation of cytotoxic T-lymphocytes [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. However, whether autoantibodies were responsible for the observed diabetes and aTTP in the case by Luong et al. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] remains undetermined [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], highlighting the need for further research into the immune mechanisms at play in pembrolizumab-induced adverse effects.\u003c/p\u003e\u003cp\u003eADAMTS13 activity, as measured through enzyme assays, was low in almost all cases, confirming the diagnosis of aTTP. However, many authors did not measure or report anti-ADAMTS13 antibodies. In three case reports, the authors tested for anti-ADAMTS13 antibodies and found them positive, while the others did not report antibody testing. Similar findings were observed in other case reports on ICI-induced aTTP [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTreatment strategies varied, with plasma exchange (PE) and corticosteroids being the most commonly administered therapies, as per the International Society on Thrombosis and Haemostasis (ISTH) clinical guidelines for aTTP [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Recently, caplacizumab has emerged as a promising new therapy for aTTP and is recommended to be used alongside PE in acute cases. However, ISTH has emphasized that, although caplacizumab may offer significant therapeutic benefits, its availability remains limited, and many clinicians are unfamiliar with its use and the necessary monitoring protocols [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. As evident by our review and the review by Yikilmaz et al. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], no case in the literature initiated caplacizumab therapy, highlighting that its integration into routine practice is still developing.\u003c/p\u003e\u003cp\u003eFour cases initiated PE, whereas three cases did not, with the decision to forgo PE being made in consultation with the patient, particularly in cases where the patients were in poor clinical condition. For example, Nelson et al. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] reported a patient who declined all treatments, including PE and corticosteroids, due to prior comorbidities and a decision to focus on comfort care. Similarly, Sharma et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] described a patient who chose not to pursue further treatment after the diagnosis of TTP. In our case, the decision was made not to initiate PE, but rather to try high-dose methylprednisolone. However, these were discontinued, with the patient\u0026rsquo;s consent, after three days due to the patient\u0026rsquo;s poor prognosis and declining condition.\u003c/p\u003e\u003cp\u003eThe ISTH strongly recommends plasma exchange (PE) in combination with corticosteroids for patients experiencing a first acute episode of aTTP, as well as those experiencing a relapse [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Evidence shows a 90% survival rate following PE after the first episode, with treatment to be administered daily until signs of organ damage resolve and platelet counts stabilize, underscoring the importance of early diagnosis and timely initiation of PE [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In our review, Kozak et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] performed 11 sessions of PE (for two episodes) and used rituximab, resulting in complete remission. This case, being the only one case to show complete remission, highlights the crucial role of multiple sessions of PE in achieving favorable outcomes. Among the seven patients reviewed, five patients died, which reflects the high mortality associated with pembrolizumab-induced aTTP. One patient achieved complete remission, while the outcome for another patient remains unclear. It is important to note that all patients had multiple comorbidities, making it difficult to isolate the contribution of aTTP alone in the patients' poor outcomes. In several cases, the presence of cancer, severe infections, and other preexisting health conditions likely contributed to a poor outcome. This review suggests that early recognition and treatment of aTTP may be important for improving patient prognosis, although the limited data available do not allow for definitive conclusions.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, this case highlights the importance of recognizing pembrolizumab-induced TTP as a cause of thrombocytopenia, even after a single dose. This review of the current case reports highlights the need to be vigilant for ICI-induced TTP and to consider the potential autoimmune pathophysiology as soon as the diagnosis is established. Early testing for anti-ADAMTS13 antibodies can benefit both researchers\u0026rsquo; and clinicians\u0026rsquo; knowledge base as well as inform individual patient treatment decisions. Since treatment for aTTP is distinct from other causes of thrombocytopenia, physicians must recognize aTTP early to optimize the chances for treatment success.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval was not required for this type of study in accordance with institutional policies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from the patient\u0026rsquo;s relative for publication of this case report and accompanying data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGregory Palega: Drafted the manuscript, clinical oversight, revised manuscript, final revision.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIhab Ahmad Al-Rikabi: Drafted the manuscript, performed literature review, revised manuscript. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCecilia Karlstr\u0026ouml;m: Supervision, approved final version.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNobel Prize Outreach. 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A Case of Immune Thrombocytopenia as a Rare Side Effect of an Immunotherapy with PD1-Blocking Agents for Metastatic Melanoma. \u003cem\u003eTransfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie\u003c/em\u003e, \u003cem\u003e44\u003c/em\u003e(6), 426\u0026ndash;428. https://doi.org/10.1159/000479237\u003c/li\u003e\n\u003cli\u003eChaudhry H, Sholzberg M, Pavenski K. Adamts-13 inhibitor testing is often negative on initial testing. Blood. 2018;132(Suppl 1):5051. doi: https://doi.org/10.1182/blood-2018-99-119399\u003c/li\u003e\n\u003cli\u003eSimon, D., Leclercq, M., Joly, B., Veyradier, A., Coppo, P., \u0026amp; Benhamou, Y. (2020). Acquired thrombotic thrombocytopenic purpura without detectable anti-ADAMTS13 antibodies: A possible underlying autoimmune mechanism. \u003cem\u003eHaematologica\u003c/em\u003e. https://haematologica.org/article/view/haematol.2024.285391\u003c/li\u003e\n\u003cli\u003eGilbar, P. 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Nat Rev Cancer. 2012 Mar 22;12(4):252\u0026ndash;64. https://doi.org/10.3892/ol.2015.3338\u003c/li\u003e\n\u003cli\u003eBenhamou Y, Baudel J-L, Wynckel A, Galicier L, Azoulay E, Prov\u0026ocirc;t F, et al. Are platelet transfusions harmful in acquired thrombotic thrombocytopenic purpura at the acute phase? Experience of the French thrombotic microangiopathies reference center. Am J Hematol. 2015 Jun;90(6):E127-9. https://doi.org/10.3892/ol.2015.3338\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Thrombotic thrombocytopenic purpura, TTP, Immune checkpoint inhibitors, ICI, Pembrolizumab, Case report","lastPublishedDoi":"10.21203/rs.3.rs-6959398/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6959398/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe success of immune checkpoint inhibitors (ICIs) has revolutionized oncology, with an increasing number of patients receiving treatment every year. However, this progress has been accompanied by a rise in immune-related adverse events (irAEs). One such irAE is thrombotic thrombocytopenic purpura (TTP), a rare and potentially life-threatening complication. This report presents a unique case of TTP following a single dose of pembrolizumab. A 76-year-old man with suspected advanced renal cell carcinoma received pembrolizumab as initial treatment. Eleven days later, the patient developed severe thrombocytopenia, bleeding problems, and hemolytic anemia. The following day, the ADAMTS13 activity levels was 3.8% (ref. 40-130%), confirming the diagnosis of TTP. Given the patient's poor overall condition and limited life expectancy, plasma exchange was not initiated. The patient passed away 15 days after receiving pembrolizumab. In conclusion, physicians should be aware that even a single dose of the ICI pembrolizumab can trigger TTP. A review of current case reports on pembrolizumab-induced TTP is also provided.\u003c/p\u003e","manuscriptTitle":"Thrombotic thrombocytopenic purpura as a complication of pembrolizumab: a case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-22 08:11:17","doi":"10.21203/rs.3.rs-6959398/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-02T07:39:22+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-23T15:02:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"303580272349727644474108758452445325682","date":"2025-08-19T15:58:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-14T08:51:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-30T12:21:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-30T12:19:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"Annals of Hematology","date":"2025-06-23T18:53:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"annals-of-hematology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"aohe","sideBox":"Learn more about [Annals of Hematology](http://link.springer.com/journal/277)","snPcode":"277","submissionUrl":"https://submission.nature.com/new-submission/277/3","title":"Annals of Hematology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"2a1a1cd3-ab1f-429e-a90c-c7cf9758c024","owner":[],"postedDate":"August 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-02T16:01:26+00:00","versionOfRecord":{"articleIdentity":"rs-6959398","link":"https://doi.org/10.1007/s00277-026-06907-3","journal":{"identity":"annals-of-hematology","isVorOnly":false,"title":"Annals of Hematology"},"publishedOn":"2026-02-27 15:57:41","publishedOnDateReadable":"February 27th, 2026"},"versionCreatedAt":"2025-08-22 08:11:17","video":"","vorDoi":"10.1007/s00277-026-06907-3","vorDoiUrl":"https://doi.org/10.1007/s00277-026-06907-3","workflowStages":[]},"version":"v1","identity":"rs-6959398","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6959398","identity":"rs-6959398","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}