Current Knowledge of Immune Checkpoint Inhibitor-Induced Thrombocytopenia: Epidemiology, Mechanisms, and Management.

Introduction

Cancer is the second leading cause of mortality worldwide, posing substantial social, economic, and public health challenges [ 1 , 2 ]. Over the past decade, immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic modality. These agents enhance antitumor immunity by targeting critical immune checkpoints such as cytotoxic T lymphocyte antigen‐4 (CTLA‐4), programmed cell death protein 1 (PD‐1), programmed death‐ligand 1 (PD‐L1), lymphocyte activation gene‐3 (LAG‐3), and T cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif (ITIM) domain (TIGIT) [ 3 , 4 ]. To date, the U.S. Food and Drug Administration (FDA) has approved various ICIs for cancer treatment [ 5 ], including pembrolizumab (PD‐1 inhibitor), atezolizumab (PD‐L1 inhibitor), and ipilimumab (CTLA‐4 inhibitor). Although immunotherapy generally exhibits a more favorable safety profile than conventional treatments, it may still lead to a variety of immune‐related adverse events (irAEs) [ 6 ]. Hematologic toxicities, while relatively rare, can be severe and potentially life‐threatening [ 7 ].

In 2023, the Chinese Society of Clinical Oncology (CSCO) formally introduced the concept of immune checkpoint inhibitor‐induced thrombocytopenia (ICIIT) [ 8 ]. As a distinct subtype of cancer therapy‐induced thrombocytopenia (CTIT), ICIIT is defined as a clinical condition characterized by peripheral platelet counts below 100 × 10 9 /L, directly attributed to ICI therapy [ 9 ]. Although a standardized nomenclature has been established, ICIIT continues to be referred to as immune thrombocytopenia (ITP) [ 10 ], immunotherapy‐associated ITP (IO‐ITP) [ 11 ], or drug‐induced ITP [ 12 ] in clinical settings. As an exclusionary diagnosis [ 13 ], ICIIT is frequently misdiagnosed, leading to inappropriate or delayed treatment. Given the expanding clinical application of ICIs in oncology, a thorough understanding of the pathogenesis and management of ICIIT is essential to optimize therapeutic decision‐making and improve patient outcomes.

This review aims to synthesize the current evidence on ICIIT, with a focus on its epidemiology, pathogenesis, mechanisms, diagnosis, and management strategies. By offering a comprehensive overview of this complex condition, we aim to enhance clinical recognition and management of ICIIT and to delineate key directions for future research.

Material and Methods

Search Strategy

A systematic literature search was performed in PubMed, Embase, Cochrane Library, Web of Science, and proceedings from major international conferences, including the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO). The search included English‐language records published up to March 6, 2026. Key search terms such as “immune checkpoint inhibitors induced thrombocytopenia”, “immune checkpoint inhibitors”, and “thrombocytopenia” were combined in the search strategy. To ensure comprehensive coverage, reference lists of all relevant articles, reviews, and meta‐analyses were manually screened. In cases of multiple publications, the most recent or most comprehensive dataset was selected.

Eligibility Criteria

Studies were included based on the following predefined criteria: (1) original articles, reviews, case reports, or clinical studies reporting ICIIT; (2) articles published in English. Exclusion criteria included: (1) conference abstracts without sufficient interested data or outcomes; (2) duplicate publications; (3) studies focusing on non‐ICI related thrombocytopenia.

Epidemiology of ICIIT

Among various hematologic irAEs, ICIIT is recognized as one of the most clinically significant toxicities [ 14 , 15 , 16 ] (Table 1 ). Retrospective studies have reported the incidence of ICIIT to be below 1% [ 17 , 18 ]. However, observational studies have documented a relatively higher frequency of ICIIT, accounting for 25%–29% of hematological irAEs [ 19 , 20 ]. In contrast, an analysis of the VigiBase pharmacovigilance database identified only 3 cases of ICIIT among 333 ICI‐related hematological adverse reactions [ 21 ]. Meta‐analyses have reported the incidence of all‐grade ICIIT to be approximately 2% to 2.8%, with severe (grade 3–5) ICIIT ranging from 1.6% to 1.8% [ 22 , 23 , 24 ]. The substantial variability in these estimates across different study designs likely reflects the inherent limitations of each methodology. Moreover, ICIIT is often difficult to distinguish from chemotherapy‐induced thrombocytopenia, precluding precise calculation of the absolute incidence of ICI‐induced thrombocytopenia.

The incidence of ICIIT varies significantly depending on patient characteristics and tumor types [ 13 , 26 ]. ICIIT has been reported across a spectrum of malignancies, such as lung cancer, melanoma, and renal cell carcinoma [ 27 , 28 , 29 ]. A review summarizing 34 case reports of ICIIT identified melanoma in 16 cases (43.2%) and lung cancer in 19 cases (51.4%) [ 25 ]. Pharmacovigilance studies provide supporting evidence for these clinical observations. Analyses based on the VigiBase and FDA adverse event reporting system (FAERS) databases consistently demonstrate that lung cancer and melanoma are the tumor types most frequently associated with ICIIT reports [ 13 , 16 ]. However, interpretation of these pharmacovigilance data requires careful consideration of inherent reporting biases and heterogeneity across different databases. Consequently, these findings should be regarded as clinical signals primarily useful for hypothesis generation and guiding future prospective study designs. Furthermore, a retrospective analysis involving 94 patients with metastatic bone cancer demonstrated a higher incidence of ICIIT in this population compared to previous studies focusing on patients without bone metastases, with 7 patients (7.45%) diagnosed with severe ICIIT [ 18 ]. Given the tumor type‐specific variations in ICIIT incidence, future clinical research should establish more tailored management and monitoring strategies.

Furthermore, the incidence rate is also affected by the selection of ICI. An analysis based on the FAERS reporting system revealed that the probability of ICIIT was significantly higher with combination therapy than with monotherapy (OR, 2.75; 95% CI, 1.64–4.60) in lung cancer [ 30 ]. A network meta‐analysis further indicated that combination regimens incorporating PD‐1/PD‐L1 inhibitors and chemotherapy exhibit the highest risk profile [ 31 ] in digestive tumors. FAERS data analysis revealed that among patients receiving nivolumab in combination with ipilimumab, ITP cases accounted for 29%, suggesting that combination immunotherapy regimens may significantly increase the risk of developing ICIIT [ 13 ]. However, a retrospective study has suggested the absence of specific risk factors for ICIIT [ 32 ]. Thus, these conclusions should be interpreted with caution due to the inherent limitations of retrospective study designs and the overall low incidence of ICIIT.

While most cases of ICIIT occur within the first 12 weeks of treatment, there are also reports indicating that ICIIT has shown delayed performance; the temporal onset is variable and can emerge at any time during or after immunotherapy [ 14 , 16 , 33 ]. Compared with ICI monotherapy, combination ICI therapy demonstrates an accelerated onset of hematological irAE [ 24 ], and CTLA‐4 inhibitors are associated with earlier toxicity manifestation than PD‐1/PD‐L1 agents [ 34 ].

Prognosis of ICIIT

The Duality of Prognosis

ICIIT is generally non‐fatal; however, its prognostic implications are complex. A clinical study has reported that mild ICIIT may be positively correlated with overall survival (OS), suggesting that the development of thrombocytopenia as an immune‐related adverse event could serve as an indicator of prolonged survival in patients receiving ICI therapy [ 35 ]. We therefore hypothesize that ICIIT may not merely represent drug toxicity, but may also reflect, to some extent, systemic immune activation. Platelets have long been recognized as key drivers of hemostasis and thrombosis. In recent years, accumulating evidence has revealed additional roles of platelets in cancer [ 36 ]. Platelets not only promote tumor progression through the release of growth factors such as TGF‐β [ 37 ], but also contribute to immune evasion. Studies have demonstrated that platelets express PD‐L1 (pPD‐L1) on their surface, which may induce T‐cell exhaustion by binding to PD‐1 on T cells [ 38 ]. Additionally, platelets can shield circulating tumor cells from immune recognition [ 39 ]. Thus, while ICI therapy relieves T‐cell inhibition, it may also deplete these platelets. In this context, mild thrombocytopenia may serve as a hallmark of this immune activation process.

However, severe forms are often associated with increased mortality and reduced OS [ 15 , 19 , 26 , 40 , 41 , 42 ]. Data from the FAERS database revealed that 9.3% of ICIIT cases were fatal, with an additional 10.8% developing life‐threatening complications [ 13 ]. Davis et al. also reported a fatality rate of 11% among patients with ICIIT [ 16 ]. The association between ICIIT and poorer OS stems from multiple pathophysiological factors. ICIIT may increase the risk of severe bleeding episodes that directly raise mortality rates. Furthermore, managing ICIIT often requires stopping or reducing treatment, which restricts further therapeutic choices [ 43 ]. Additionally, interventions used to address ICIIT might themselves lead to negative outcomes. These factors underscore the importance of comparative research to assess whether the likelihood of significant bleeding differs between ICIIT patients and those with thrombocytopenia due to other causes.

Impact of ICI Regimen and Confounding Factors

The choice of ICI may also affect the prognosis of patients. Donald et al. reported a 19% mortality rate in patients receiving PD‐1/PD‐L1 therapy [ 19 ]. Additional studies by Geliang Liu [ 44 ] and Ohashi [ 24 ] also support the notion that anti‐PD‐1 therapy significantly increases the risk of death of ICIIT patients. Nevertheless, it remains uncertain whether the observed tumor progression was attributable to ICIIT itself or to the use of anti‐ICIIT medications. These findings underscore the clinical necessity for vigilant monitoring of patients receiving ICI therapy, especially those at elevated risk, to facilitate early detection and effective management of immune‐related adverse events. The implementation of such proactive monitoring strategies is essential for optimizing therapeutic outcomes and improving patient prognosis.

However, interpretation of the association between ICIIT and survival requires consideration of confounders. Tumor burden is a key factor, as thrombocytopenia in cancer patients may result from bone marrow involvement or anticancer treatment [ 45 ]. Corticosteroid exposure is also relevant, while it is commonly used to manage immune‐related adverse events [ 46 ], corticosteroids may impair ICI antitumor efficacy [ 47 , 48 ]. Thus, whether reduced survival is driven by thrombocytopenia, treatment interruption, or corticosteroid use remains unclear. Future prospective studies should adjust for tumor burden and corticosteroid exposure to clarify the causal relationship between ICIIT and survival.

Pathogenesis of ICIIT

Although the general mechanisms underlying thrombocytopenia are relatively well understood, the specific pathogenesis of ICIIT remains to be fully elucidated. Figure 1 presents an overview of the proposed mechanisms of ICIIT.

Immune‐Mediated Platelet Destruction

ICIIT may primarily result from disruption of peripheral immune tolerance by ICIs. Through inhibiting PD‐1/PD‐L1 or CTLA‐4, ICIs disrupt peripheral immune tolerance, enabling autoreactive CD8 + T cells to recognize platelet surface antigens and subsequently mediate platelet destruction [ 49 , 50 , 51 ]. Activated T cells secrete interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α), which upregulate Fas expression on platelets, thereby enhancing their susceptibility to phagocytosis by macrophages [ 52 ]. By releasing the brakes on T cells, ICIs reshape the network of interactions among immune cells, including T cells and macrophages, which can ultimately lead to tissue injury or autoimmunity [ 53 ]. ICIs can also enhance humoral immunity by driving B‐cell differentiation into plasma cells, resulting in the production of platelet‐associated immunoglobulin G (PA‐IgG), which facilitates platelet clearance by splenic macrophages. This is supported by elevated anti‐platelet antibody levels observed in patients with ICIIT [ 26 , 54 , 55 ]. Clinical‐based evidence also suggests that the repeated administration of PD‐1 inhibitors may override the body's “immune brakes,” resulting in T cell‐mediated autoimmune responses [ 7 , 27 , 33 ]. Moreover, CD38 appears to play a contributory role in ICIIT pathogenesis [ 56 ]. In the context of ICI‐mediated immune responses, CD38 overexpression may exacerbate immune dysregulation [ 57 , 58 ].

Impaired Megakaryopoiesis

Impaired bone marrow megakaryocytopoiesis may also represent an underlying mechanism. A case report of thrombocytopenia following duvvalumab treatment noted that CD8 + T cells may induce Fas‐mediated apoptosis of megakaryocytes, which in turn impairs platelet production [ 59 ]. Additionally, it has been proposed that ICIs may also directly influence the platelet life cycle, further complicating the hematologic profile of affected individuals [ 60 ].

Tumor Microenvironment‐Platelet Crosstalk

In the tumor microenvironment, platelets act as dynamic participants in cancer progression and immune modulation [ 61 ]. Preclinical studies suggest that tumor cells might transfer PD‐L1 to platelets through fibronectin and glioblastoma protein (α5β1 and GPIbα), generating tumor‐educated platelets (TEPs) that express PD‐L1, which may in turn promote T cell exhaustion [ 62 ]. Exhausted CD4 + helper T cells and CD8 + cytotoxic T cells may reactivate inflammatory signaling pathways, which impair hematopoietic stem cell function and megakaryocyte maturation, ultimately exacerbating thrombocytopenia [ 63 , 64 ]. Furthermore, studies have demonstrated significantly increased PD‐L1 expression on platelets in patients with lung cancer [ 15 , 65 , 66 ]. Given the close interplay between the pulmonary microenvironment and platelet biology [ 67 , 68 ], and evidence suggesting that the lungs serve as the main organ for platelet production [ 69 ], this may partially explain the increased susceptibility to ICIIT among patients with lung cancer.

Diagnosis of ICIIT

ICIIT is a diagnosis of exclusion and remains particularly challenging in cancer patients undergoing multidrug regimens [ 11 ]. It must be differentiated from other causes of thrombocytopenia, including drug‐induced thrombocytopenia (e.g., heparin, chemotherapy), infections, bone marrow infiltration by malignancy, chemotherapy‐induced bone marrow suppression, tumor‐related platelet consumption, secondary hematologic malignancies (e.g., myelodysplastic syndrome), hypersplenism, and thrombotic thrombocytopenic purpura [ 15 , 43 , 70 ].

According to current guidelines and literature, recommended diagnostic evaluations include peripheral blood smear examination, testing for antinuclear antibodies and antiplatelet IgG, bone marrow biopsy, assessments for infections, drug toxicity, and connective tissue disorders [ 8 , 59 ]. Laboratory findings commonly reveal the absence of platelet clumping, schistocytes, or platelet fragments on peripheral blood smears. Hemoglobin and white blood cell counts are typically within normal ranges, and antinuclear antibody tests are negative. However, elevated anti‐platelet IgG levels are frequently observed. There is usually no evidence of myelosuppression, dysplasia, or malignant bone marrow infiltration [ 8 , 71 ]. Physical examination findings generally include no hepatosplenomegaly or lymphadenopathy.

Although most patients do not exhibit significant bleeding tendencies, severe cases may present with cutaneous ecchymoses, petechiae, or other hemorrhagic symptoms [ 26 , 72 ]. Based on current literature, bone marrow biopsies may not be clinically necessary. Diagnosis is often based on a recent history of ICI exposure, the onset of thrombocytopenia, and peripheral smear findings. It should be noted that elevated PA‐IgG levels can occur in both immune and non‐immune thrombocytopenia [ 73 ]. Due to the lack of definitive diagnostic tests and the broad differential, ICIIT should be considered in any patient developing thrombocytopenia following ICI therapy. Future research should prioritize the identification of simpler and more specific diagnostic markers. Figure 2 outlines the proposed diagnostic process for ICIIT.

Management of ICIIT

Graded Management Principles

Effective management of ICIIT is essential in the context of cancer immunotherapy. According to the American Society of Clinical Oncology (ASCO) guidelines, a graded approach based on the severity of thrombocytopenia is currently recommended (Table 2 ) [ 74 , 75 ]. In mild cases (Grade 1: platelet count 75–100 × 10 9 /L), close monitoring is sufficient, and discontinuation of ICIs is generally not required. For moderate thrombocytopenia (Grade 2: platelet count 50–75 × 10 9 /L), temporary interruption of ICI is recommended. According to the ASCO 2021 guideline [ 75 ], first‐line treatment consists of oral prednisone at a starting dose of 1 mg/kg/day (range: 0.5–2 mg/kg/day) for 4 weeks, followed by a gradual taper over 4–6 weeks to the lowest effective dose. Intravenous immunoglobulin (IVIG) may be considered in combination with corticosteroids when a more rapid increase in platelet count is required.

In severe cases (Grade 3/4: platelet count < 50 × 10 9 /L), immediate discontinuation of ICI therapy and initiation of high‐dose corticosteroids (prednisone or dexamethasone 40 mg daily for 4 days) or pulse IVIG therapy (1 g/kg as a single dose) are warranted [ 75 , 76 , 77 ]. If platelet counts recover topromptly, steroid tapering may commence after 2–4 weeks of treatment [ 77 ]. Platelet transfusions should be reserved for critically low counts (< 10 × 10 9 /L) or active bleeding episodes [ 78 , 79 ]. Management strategies for patients refractory to corticosteroids and/or IVIG vary across guidelines. ASCO recommends rituximab, thrombopoietin receptor agonists (TPO‐RAs), or other immunosuppressive agents [ 75 ]. CSCO includes TPO‐RAs, rituximab, splenectomy, or second‐line immunosuppressants such as cyclosporine and azathioprine [ 80 , 81 , 82 ]. ESMO specifically suggests oral TPO‐RAs (e.g., eltrombopag) [ 83 ]. Overall, TPO‐RAs and rituximab represent the most consistently endorsed options across current guidelines. Figure 3 demonstrated the treatment flow chart according to the grading strategy.

The management of ICI rechallenge following ICIIT remains clinically uncertain. According to ASCO guidelines, ICI resumption may be considered only after toxicity has resolved to grade 1. However, this approach is challenged by evidence from Grinsztejn E et al. [ 11 ], who strongly advise against rechallenge due to substantial risks of ICIIT recurrence and bleeding‐related mortality, particularly in patients who experienced life‐threatening ICIIT during perioperative treatment. For milder cases, cautious rechallenge under strict platelet monitoring, potentially with concurrent low‐dose corticosteroids, may be considered, though supporting data remain limited [ 16 , 77 , 84 ]. Given the potential for ICIIT recurrence and the lack of robust evidence, clinical vigilance is warranted. Future research should prioritize optimizing rechallenge protocols and identifying predictive biomarkers to better inform patient selection.

Specific Drug Selection

Corticosteroids

Corticosteroids are the first‐line treatment for ICIIT and remain the most commonly employed therapeutic agents in clinical practice. This can be attributed to their relative availability, low cost, and the experience of doctors compared with other options [ 14 ]. Corticosteroids mitigate platelet destruction by suppressing immune responses, restoring immune homeostasis, and reducing antibody‐mediated platelet clearance [ 15 ] (Figure 1 ). Pulse corticosteroid therapy is often applied to rapidly elevate platelet counts. However, many studies have shown that corticosteroid treatment is often ineffective [ 14 , 19 , 34 ]. Some reports also suggest that high‐dose corticosteroid therapy may adversely affect survival outcomes and increase the risk of infections and other complications associated with long‐term immunosuppression [ 85 , 86 ]. Moreover, corticosteroids may impair T‐cell activity, potentially diminishing the antitumor efficacy of ICIs [ 48 ]. Therefore, although the use of corticosteroids has usually been proven effective [ 43 , 83 , 87 ], these strategies must be balanced against the need to maintain effective tumor treatment, especially in patients with advanced malignant tumors [ 88 ]. In cases of refractory or severe thrombocytopenia, alternative strategies may be required, with close monitoring to evaluate efficacy and potential side effects.

IVIG

According to current guidelines, IVIG is recommended for patients with ICIIT who require a rapid increase in platelet count [ 74 , 76 ]. IVIG primarily functions by inhibiting antibody‐dependent cytotoxicity and reducing platelet destruction through the blockade of Fc receptors on monocytes and macrophages [ 89 ] (Figure 1 ). In clinical practice, IVIG is typically not administered as monotherapy; instead, it is often combined with corticosteroids or other agents to enhance therapeutic efficacy.

TPO Agents

When corticosteroid therapy is inadequate, TPO agents represent a critical therapeutic alternative [ 9 ]. Currently, two classes of TPO agents have been developed: recombinant human thrombopoietin (rhTPO) and thrombopoietin receptor agonists (TPO‐RAs) [ 90 ]. In recent years, TPO agents have shown promise in the treatment of thrombocytopenia. In China, rhTPO is recommended as a first‐line treatment for CTIT [ 80 , 91 ]. CSCO guidelines for immune checkpoint inhibitor‐related toxicity management also recommend the use of TPO to stimulate platelet production [ 82 ]. Kroll MH et al. further support the rapid introduction of a TPO agent when corticosteroids and/or IVIG do not work [ 92 ].

However, as TPO agents are currently utilized only in select countries in Asia and the Americas [ 9 ], the global clinical data and experience are still limited. Thus, in current clinical practice, eltrombopag is more frequently employed. Eltrombopag, a first‐generation oral TPO‐RA, induces dose‐dependent phosphorylation of STAT3/5, AKT, and ERK, thereby enhancing platelet counts by promoting megakaryocyte maturation and proplatelet formation [ 9 , 93 , 94 ] (Figure 1 ). It is commonly used in patients who are refractory to or intolerant of corticosteroids and those requiring long‐term management. Cancer patients inherently have an elevated thrombosis risk due to tumor‐driven procoagulant factors and fibrinolytic dysfunction [ 95 , 96 , 97 ]. Additionally, ICI therapy may promote thrombogenesis through T‐cell activation, endothelial inflammation, and neutrophil extracellular trap release [ 98 ]. Although evidence suggests that TPO agents do not increase thromboembolic risk [ 99 , 100 ], caution is warranted given the baseline thrombotic risk in cancer patients and the prothrombotic potential of ICI therapy. Furthermore, megakaryocytes have been implicated in tumor progression, particularly in multiple myeloma and lymphoma [ 101 ]. While direct evidence linking TPO‐RAs to stimulation of malignant megakaryocytic clones remains lacking, this theoretical risk warrants further investigation. However, current evidence for TPO agents in ICIIT is largely extrapolated from ITP and CTIT studies, as dedicated randomized controlled trials in this setting are lacking. Prospective studies with rigorous safety monitoring are urgently needed to validate their efficacy and safety specifically in patients receiving ICIs.

rhIL ‐11

rhIL‐11 was one of the earliest therapeutic agents approved by the FDA for treating post‐chemotherapy thrombocytopenia [ 102 ]. As a non‐specific hematopoietic growth factor, it enhances platelet production by stimulating the proliferation and differentiation of hematopoietic stem cells and megakaryocytes [ 103 , 104 , 105 ] (Figure 1 ). However, due to its modest efficacy and adverse effects, the clinical use of rhIL‐11 in ICIIT is limited [ 106 ].

Rituximab

Rituximab is a monoclonal antibody targeting CD20 that induces B‐cell apoptosis and facilitates their clearance [ 107 ] (Figure 1 ). It serves as a therapeutic option for patients with ICIIT who do not respond to first‐line therapies [ 80 , 81 ]. However, the use of rituximab remains relatively rare, and its efficacy is generally moderate. G. Qiu et al. reported that a combination of rituximab, steroids, and TPO agents was ineffective [ 71 ]; M. Ito et al. documented a relapse following rituximab discontinuation [ 108 ]; and M. Wei et al. reported intolerance to rituximab in one case [ 109 ]. Results from TriNetX demonstrated that as for second‐line treatment, experts tend to prefer TPO agents for ICIIT, while rituximab is more commonly used for ITP [ 11 ]. Thus, although rituximab may be considered a salvage therapy for refractory ICIIT, further clinical trials are necessary to substantiate its efficacy and safety.

Other Drugs and Treatment Strategies

Y. Hayashi et al. [ 56 ] reported a successful case of ICIIT treatment in a patient with multiple myeloma using the anti‐CD38 monoclonal antibody daratumumab [ 110 ]. Research has shown that anti‐CD38 therapies can suppress platelet phagocytosis [ 111 ] (Figure 1 ). Although daratumumab is well‐established in the treatment of multiple myeloma, its use in ICIIT remains limited, and its potential therapeutic value warrants further investigation. Additionally, therapeutic plasma exchange has been reported as an effective intervention in grade 3–4 irAEs [ 112 ]. Matsumoto S et al. proposed that in cases where the bone marrow is unable to produce platelets, preserving ICI and initiating supportive blood transfusion is crucial [ 113 ]. Meanwhile, supportive care strategies and long‐term follow‐up monitoring are also necessary [ 18 ].

Current treatment strategies for ICIIT are diverse. The clinical efficacy and safety of these interventions still require further validation through large‐scale randomized controlled trials (RCTs) to optimize individualized treatment approaches.

Conclusion

Although ICIIT is rare, it can be life‐threatening and thus warrants greater clinical attention. For cancer patients, severe thrombocytopenia may affect subsequent decisions on anti‐tumor treatment and anticoagulant therapy. Thus, accurate identification and timely diagnosis are critical. Therefore, during the treatment with ICI, any alterations in platelet count should be carefully evaluated due to potential clinical significance. Increased susceptibility to ICIIT may be related to tumor type and ICI drug selection, but larger‐scale prospective studies are still needed for further verification. The underlying mechanisms of ICIIT remain inadequately understood, which merits further investigation. While ICIIT typically responds favorably to corticosteroids, treatment outcomes in severe cases are often suboptimal. TPO agents have shown promising therapeutic potential in clinical settings, but their exact effect still requires more clinical research support. Future research should prioritize the conduct of RCTs to explore novel therapeutic strategies for ICIIT.

Author Contributions

Youran Dai: writing – original draft. Wenhui Yang: writing – original draft. Zexing Sun: writing – original draft. Linfeng Wu: writing – review and editing. Keding Shao: writing – review and editing. Dijiong Wu: supervision, writing – review and editing, funding acquisition.

Funding

The present study was supported by National Key R&D Program of China (Young Scientists Project) (NO. 2025YFC3511400), Joint TCM Science & Technology Projects of National Demonstration Zones for Comprehensive TCM Reform (NO. GZY‐KJS‐ZJ‐2026‐006), Zhejiang Provincial Natural Science Foundation of China (LMS26H290004), Clinical Medical Research Project of Zhejiang Medical Association (NO. 2022ZYC‐Z25), Young Clinical Talents Training Program of Chinese Society of Traditional Chinese Medicine (NO. CYJH2024043), and Project of Academic Inheritance Studio of Famous and Aged Chinese Medicine Experts in Zhejiang Province (NO. GZS2021022).

Conflicts of Interest

The authors declare no conflicts of interest.

Acknowledgements

We are deeply appreciative of all the authors for providing their feedback on the manuscript and for fruitful discussions. We also thank BioGDP for providing powerful tools for figure preparation.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

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