Nivolumab-Induced Hemophilia A Presenting as Gastric Ulcer Bleeding in a Patient With NSCLC

Kato, Ryuichi; Hayashi, Hidetoshi; Sano, Keigo; Handa, Kohei; Kumode, Takahiro; Ueda, Hayato; Okuno, Tatsuya; Kawakami, Hisato; Matsumura, Itaru; Kudo, Masatoshi; Nakagawa, Kazuhiko

doi:10.1016/j.jtho.2018.06.024

Cited by 20 publications

(23 citation statements)

References 9 publications

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“…In their report of a case of acquired hemophilia A, which appeared after nivolumab administration, Gokozan et al stated that a similar mechanism might play a role in the production of factor VIII inhibitors after immunotherapy in addition to T-cell-related mechanisms [ 11 ]. Acquired hemophilia A reportedly appeared after nivolumab administration [ 11 , 12 ], and in the present case, AFVI developed after nivolumab administration. These findings suggested that, in the present patient, factor V deficiency may have resulted from an autoimmune response to factor V caused by nivolumab administration.…”

Section: Discussionmentioning

confidence: 52%

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A Case of Acquired Factor V Inhibitor Following Nivolumab Administration

Kida¹,

Nakaya²,

Ito³

et al. 2022

Cureus

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Acquired factor V inhibitor (AFVI) is a very rare disease. We presented herein a case of hypopharyngeal cancer in which AFVI developed after nivolumab administration. Blood test findings two weeks after the first dose of nivolumab showed a significant prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT), indicating a marked abnormality in the coagulation function.Factor V activity had decreased significantly and was below the detection limit (<3%), and the factor V inhibitor level was as high as 16 Bethesda units (BU)/mL. His underlying illness was a malignant tumor, but we considered that nivolumab administration was the cause of AFVI, considering the time when coagulation abnormality developed. No significant bleeding tendency was observed in the subsequent course, and the AFVI was followed up without treatment. To the best of our knowledge, the present study is the first to report AFVI occurrence after immune checkpoint inhibitor administration.

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Section: Discussionmentioning

confidence: 52%

“…To the best of our knowledge, the present report is the first to describe AFVI occurring after immune checkpoint inhibitor administration. The present study was approved by the Tokyo Metropolitan Tama Medical Center Research Ethics Committee (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

A Case of Acquired Factor V Inhibitor Following Nivolumab Administration

Kida¹,

Nakaya²,

Ito³

et al. 2022

Cureus

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“…Table 2 presents the baseline demographics, diagnostic findings, and chief features of IMG from the individual cases ( n =24) 10,11,19–33. The median age of the included cases was 53.5 years old, and there was no difference in distribution with regard to sex.…”

Section: Resultsmentioning

confidence: 99%

Clinical Characteristics and Outcomes of Gastritis Associated With Immune Checkpoint Inhibitors: Scoping Review

Obeidat

Silangcruz

Kozai

et al. 2022

Journal of Immunotherapy

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Among immune-related adverse events associated with immune checkpoint inhibitors, immune-mediated gastritis (IMG) has been rarely described in the literature and has not yet been well characterized. This scoping review aimed to characterize IMG in terms of precipitating agents, clinical presentations, and prognosis. After the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including "gastritis," "immune checkpoint inhibitor," and "immune-related adverse event" from their inception to December 28, 2021. Twenty-two articles, including 5 observational studies and 17 case reports and case series, were included. Nivolumab, pembrolizumab, and combination therapy with those and cytotoxic T-lymphocyte-associated antigen-4 inhibitor (ipilimumab) were commonly used in those with IMG. 59.8% had epigastric pain, and 50% had erosive gastritis. 87.5% had Common Terminology Criteria for Adverse Events (CTCAE) grade 3 gastritis, and 91.2% received corticosteroids. Recurrence was noted in 16.7%, and only 1 expiration was noted. 4.3% had positive helicobacter pylori and cytomegalovirus from the gastric specimen. Similar to immunerelated colitis, patients with IMG may have a favorable prognosis with a better response to immune checkpoint inhibitors if treated appropriately. The diagnosis of IMG is made by exclusion, and a thorough workup is necessary to rule out concurrent helicobacter pylori and cytomegalovirus involvement. Further studies are critical for a better understanding of this complication.

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“…Acquired hemophilia A has been reported in a melanoma patient after three cycles of ipilimumab completely recovered after treatment with corticosteroids and recombinant VIII factor [ 102 ], and in two patients with non-small cell lung carcinoma on nivolumab successfully treated with cyclophosphamide [ 103 ] and rituximab [ 104 ]. To our knowledge, no cases of ICI-related acquired Von Willebrand’s syndrome or other bleeding disorders have been reported.…”

Section: Methodsmentioning

confidence: 99%

Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy

et al. 2022

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Immunotherapy has dramatically changed the therapeutic landscape of oncology, and has become standard of care in multiple cancer types in front or late lines of therapy, with some longstanding responses and outstanding results. Notwithstanding, its use has brought a totally unique spectrum of adverse events, characterized by a myriad of diverse manifestations affecting nearly every organ and system of the body, including the endocrine, nervous, cardiac, respiratory and gastrointestinal systems. Uncommon adverse events, defined as those occurring in less than 1% of patients, comprise an even more heterogeneous group of diseases that are being seen more recurrently as the use of immune check-point inhibitors increases and indications spread in different tumor types and stages. Here, we comprehensively review some uncommon, but exceedingly important, immune-related adverse events, with special emphasis in the clinical approach and diagnostic workup, aiming to reunite the evidence published previously, allowing an increase in awareness and knowledge from all specialists implicated in the diagnosis, treatment, and care of cancer patients treated with immunotherapy.

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Nivolumab-Induced Hemophilia A Presenting as Gastric Ulcer Bleeding in a Patient With NSCLC

Cited by 20 publications

References 9 publications

A Case of Acquired Factor V Inhibitor Following Nivolumab Administration

A Case of Acquired Factor V Inhibitor Following Nivolumab Administration

Clinical Characteristics and Outcomes of Gastritis Associated With Immune Checkpoint Inhibitors: Scoping Review

Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy

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