Platelet Transfusion for Patients with Cancer: An Update

Abstract

Background

Platelet transfusion is essential for preventing and treating hemorrhage in oncology patients and can markedly improve quality of life and survival. However, access to platelet concentrates is often limited by global shortages and logistical constraints, especially in low-resource settings.

Summary

Maintaining product quality requires stringent donor screening, pathogen-reduction technologies, and optimized storage conditions to preserve hemostatic function and reduce adverse reactions. Common transfusion-related complications (e.g., alloimmunization, non-hemolytic reactions, and circulatory overload) underscore the importance of real-time monitoring and individualized transfusion protocols. Emerging thrombopoietin receptor agonists, such as romiplostim and eltrombopag, exhibited benefit in reducing transfusion dependency and merit further study in cancer-associated thrombocytopenia. This review aims to summarize the research advances and clinical guidelines on platelet transfusion, including platelet production methods, transfusion dosage, pathogen inactivation, leucocyte depletion, types of cancer-related thrombocytopenias, and platelet transfusion strategies and to discuss future research directions and perspectives.

Key Messages

While platelet transfusions remain indispensable for mitigating bleeding risk in immunotherapy and CAR-T recipients, the heterogeneity of patient responses underscores the need for prospective trials to evaluate the impact of transfusion practices on both hemostatic and immunologic outcomes.

Introduction

Radiotherapy and chemotherapy remain fundamental to cancer therapy but frequently induce thrombocytopenia, predisposing patients to life-threatening hemorrhages such as intracranial bleeding. Previous studies reported that about 20% of solid tumor patients developed thrombocytopenia within 1 year of diagnosis, whereas rates exceed 60% in those with hematologic malignancies [1–3]. The incidence and severity of thrombocytopenia are influenced by chemotherapy regimen, dose intensity, and cancer type, manifesting clinically as fatigue, mucocutaneous bleeding, and petechiae, all of which markedly impair physical, emotional, and psychological well-being [4, 5]. Symptoms often include neurocognitive discomfort and profound weakness, correlating with declines in overall quality of life.

Prophylactic and therapeutic platelet transfusions are considered the cornerstone intervention to prevent and treat bleeding, with randomized trials demonstrating significant reductions in hemorrhagic mortality when protocol-driven transfusions are employed [6]. However, global platelet inventories are constrained, and shortages – especially in developing regions – affect patient care [7, 8]. Beyond hemostasis, platelets regulate innate and adaptive immunity and interact with tumor cells to promote immune evasion, angiogenesis, and metastatic seeding [9, 10]. Moreover, transfusion of activated platelets may inadvertently exacerbate tumor progression by supplying growth factors and shielding circulating tumor cells [11]. Despite the widespread adoption of transfusion protocols, there remain many contentious and unknown issues.

To comprehensively synthesize current advancements in platelet transfusion for cancer patients and discuss future research directions, a systematic literature search was conducted. The search was performed across major databases, including PubMed, Embase, and the Cochrane Library, from inception to May 1, 2025. The following search terms were used in various combinations: “platelet transfusion”, “cancer patients”, “thrombocytopenia”, “chemotherapy”, “radiotherapy”, “transfusion risks”, “platelet products”, and “transfusion guidelines”. Only original research articles, systematic reviews, and meta-analyses written in English were included. Conference abstracts, case reports, and editorials were excluded. Titles and abstracts were initially screened by two independent authors to identify potentially relevant studies, with full-text articles retrieved for further evaluation. Disagreements were resolved through discussion or by consulting a third reviewer. This rigorous selection process aimed to ensure that the review incorporated the most relevant and high-quality evidence, enabling a thorough and accurate discussion of the current state and future prospects of platelet transfusion in cancer patients.

Preparation and Quality Aspects of Platelets for Transfusion

Platelet concentrates (PCs) for transfusion can be produced using three methods: platelet-rich plasma, buffy coat, and apheresis-PC. Platelet-rich plasma platelet concentrate involves initial low-speed centrifugation to separate platelet-rich plasma, followed by a second centrifugation to concentrate platelets. Buffy coat platelet concentrate is derived from the buffy coat layer obtained from at least four donors after high-speed centrifugation, subsequently pooled and processed. This pooling step might influence various aspects related to transfusion risks, such as the potential for transmitting infectious agents or the likelihood of immune reactions due to exposure to multiple donors’ antigens. Apheresis-PC or single-donor platelets are collected directly from donors using apheresis machines, offering higher platelet yields and reduced leukocyte contamination compared to whole-blood-derived methods [12].

Storage and transportation conditions greatly affect platelet viability and function. Normally, PCs are stored at 20–24°C with continuous gentle agitation; their shelf life is limited to 5–7 days because of bacterial growth [13, 14]. Platelet storage temperature has been explored at 1–6°C, and the shelf life was extended with reduced bacterial growth; however, it may induce platelet function disturbance by lowering glycoprotein VI (GPVI) levels [15, 16]. Since GPVI is essential for platelet adhesion and aggregation, cold storage may not be an ideal option. Furthermore, platelet and their transportation may undergo mechanical stress, which leads to platelet fragmentation. This results in impaired platelet activation, increased GPVI receptor shedding, and mitochondria dysfunction and therefore compromises platelet function and transfusion safety [17].

To enhance transfusion safety, pathogen reduction treatments (PRTs) have been developed [18]. The INTERCEPT system inactivates a broad range of pathogens by using amotosalen and UVA light. Similarly, the MIRASOL system inactivates pathogens by riboflavin and UVB light without additional removal steps, preserving platelet functionality [19, 20]. PRTs reduce the risk for transfusion-transmitted infectious diseases effectively. Notably, in the context of global health challenges, their importance has become even more pronounced. For instance, the emergence of pathogens such as the West Nile virus in Europe and the growing relevance of hepatitis E in transfusion medicine, especially for immunocompromised cancer patients, underscore the critical role of PRTs [21]. The recent COVID-19 pandemic has further highlighted the potential impact of infectious threats on platelet transfusion practices. Concerns regarding the potential transmission of the virus through transfusion, as well as the need to maintain a safe and reliable blood supply amidst disruptions in the healthcare system, brought the importance of PRTs into sharp focus. Although there is currently limited evidence of COVID-19 transmission via blood products, the pandemic experience has emphasized the necessity of robust pathogen reduction strategies to prepare for future infectious disease outbreaks. Pathogen inactivation strategies such as THERAFLEX MB-Plasma and THERAFLEX UV-Platelets systems could reduce the risk of transmission of SARS-CoV-2 with an average ≥5.03 log₁₀ [22]. However, it is important to note that PRTs are not without drawbacks. These treatments may slightly reduce platelet counts and post-transfusion recovery rates. Clinicians must carefully evaluate the benefits of enhanced infection prevention against the potential impact on platelet functionality to optimize transfusion outcomes for patients, especially for those immunocompromised patients. Future research should aim to further refine PRT technologies to minimize these drawbacks while maximizing their effectiveness in protecting patients from transfusion-transmitted infections.

Leukoreduction, removal of white blood cells from PCs, is an important quality assurance step. It reduces the risk of alloimmunization and transmission of leukocyte-associated pathogens [23, 24]. Leukoreduction can be achieved by filtration during or after preparation of components [25]. Additionally, virus inactivation is carried out by chemical drugs or ultraviolet light, and pathogen reduction is perfumed by filtration [26, 27]. Collectively, ensuring the platelet safety and efficacy necessitates the meticulous attention to collection methods, storage conditions, leukoreduction, and pathogen reduction protocols. These measures are critical to maintain platelet functionality and minimize transfusion-related risks.

Cancer-Related Thrombocytopenia

Cancer patients frequently develop thrombocytopenia, either from the malignancy itself or cancer treatment. In clinical practice, thrombocytopenia in cancer is categorized by etiology: direct effects of the tumor on hematopoiesis, cytotoxic chemotherapy, and immune-related mechanisms (notably checkpoint inhibitors). Each category has a distinct pathophysiology and implication. Thrombocytopenia poses various challenges to the cancer care. The normal level of platelet counts in adults ranges from 150 to 450 ×10⁹/L. Thrombocytopenia is described as a platelet count that falls below the normal level. The 2020 revised version 5.0 of the US National Institute of Health Common Terminology Criteria for Adverse Events (CTCAE) classified thrombocytopenia associated with cancer treatment as follows: grade 1, 75–150 ×10⁹/L; grade 2, 50–75 × 10⁹/L; grade 3, 25–50 × 10⁹/L; grade 4, <25 × 10⁹/L [5].

Direct Cancer-Induced Thrombocytopenia

Tumor infiltration of bone marrow is a major direct cause of thrombocytopenia in cancer [28]. When malignant cells (e.g., solid tumor metastases) invade the marrow, they disrupt normal hematopoiesis. In advanced malignancies, disseminated tumor cells infiltrate the bone marrow via heterogeneous dissemination or direct invasion and destroy its architecture [29]. Clinically, this often presents with pancytopenia. Previous studies reported that bone marrow metastases typically cause moderate anemia and thrombocytopenia [29]. The cancers most likely to spread to bone marrow include gastric, breast, lung, and prostate cancers [30]. Metastatic disease can also induce extramedullary hematopoiesis, particularly in the spleen. Premature splenic release of hematopoietic cells can result in leukoerythroblastosis in peripheral blood [31]. A normal-sized spleen contains one-third of the total platelet. However, with splenomegaly, up to 50–90% of the platelet mass may be trapped in the spleen, causing peripheral thrombocytopenia [32]. The thrombocytopenia has significant implications for platelet transfusion. Due to the impaired platelet production caused by tumor infiltration, the efficacy of platelet transfusion may be compromised. Even with transfusions, the body’s ability to maintain an adequate platelet count is limited as the underlying bone marrow defect persists. Moreover, the presence of splenomegaly can lead to platelet sequestration in the enlarged spleen, which means that transfused platelets may be rapidly removed from the circulation, reducing their lifespan and effectiveness in preventing bleeding. As a result, higher transfusion thresholds or more frequent platelet transfusions may be required to achieve hemostasis, increasing the risk of transfusion-related complications. Clinicians must carefully balance the need for platelet transfusions against these potential risks, considering alternative strategies such as growth factor support to stimulate endogenous platelet production when possible. In addition, for patients with thrombocytopenia caused by splenomegaly, when considering platelet transfusion, it is also necessary to comprehensively evaluate the degree of splenomegaly and its impact on platelet sequestration to develop a more reasonable transfusion strategy.

Splenomegaly can occur as a reversible consequence of hepatic metastasis resection or due to hematologic malignancies, each with distinct bleeding risks. After hepatic metastasis resection, splenomegaly is frequently observed, primarily driven by growth factors and cytokines that induce liver regeneration and incidentally also promote spleen expansion. In one study, 78% of patients undergoing partial hepatectomy for colorectal metastases experienced an increase in spleen volume [33]. Six months after surgery, spleen volume had increased by 40–45% on average, before returning to baseline size at 9 months. An inverse correlation between spleen size and platelet count was observed following hepatectomy [34]. In this patient population, the bleeding risk may be relatively lower during the period of transient splenomegaly as the condition is self-limiting. However, close monitoring of platelet counts and bleeding signs is essential. Platelet transfusion was performed for patients with significant thrombocytopenia or those with active bleeding. Splenomegaly is also an important cause of thrombocytopenia in hematologic malignancies [35]. These patients typically face a higher bleeding risk due to the combination of reduced platelet production in the bone marrow and increased platelet sequestration in the enlarged spleen. Therefore, more aggressive transfusion thresholds may be considered, especially for these presenting additional risk factors for bleeding. Although splenectomy and partial splenic embolization are rarely performed in patients with solid or hematologic malignancies, they have been associated with sustained platelet count improvement and reduced transfusion requirements [36–38]. However, their use must be carefully evaluated, weighing the potential benefits against the surgical or procedural risks, particularly in patients with compromised health status due to their underlying malignancies.

Beyond physical marrow involvement, cancers can induce consumptive coagulopathies. Tumor-associated disseminated intravascular coagulation (DIC) consumes platelets and clotting factors. Systemic activation of coagulation in DIC leads to microvascular thrombosis and potentially life-threatening hemorrhage attributed to the consumption of platelets and coagulation factors [39]. In this context, an underlying malignancy (such as pancreatic or mucinous adenocarcinoma) often drives the DIC process. Similarly, cancer-associated thrombotic microangiopathy (TMA) can cause profound thrombocytopenia. TMA is characterized by widespread endothelial injury and microthrombus formation. In cancer patients, it is mediated by endothelial dysfunction and results in microangiopathic hemolytic anemia and platelet consumption. Cancer-related TMA tends to occur in advanced disease and carries a poor prognosis [40].

Chemotherapy-Induced Thrombocytopenia

Chemotherapy-induced thrombocytopenia (CIT) prevalence varies significantly by regimen and cancer type. In a US outpatient oncology study, gemcitabine-based regimens had the highest thrombocytopenia incidence at 64.2%, followed by platinum-based (55.2%), anthracycline-based (37.8%), and taxane-based regimens (21.9%) [41]. Another US claims study reported the highest association of thrombocytopenia with gemcitabine (14%), carboplatin (13%), and oxaliplatin (11%) [2]. Besides, the study by Hitron et al. [42] found the highest incidence of thrombocytopenia with the gemcitabine/cisplatin (57% for bladder cancer), gemcitabine/carboplatin (29% for lung cancer), and cisplatin/etoposide (18% for lung cancer) regimens. Regarding tumor types, a large US observational cohort found that 13% of solid tumor patients and 28% of hematologic malignancies had platelet counts <100 × 10⁹/L within 3 months of starting chemotherapy [1]. Among common solid tumors, thrombocytopenia incidence was highest in lung cancer (14.3%), followed by colorectal (13.5%), pancreatic (12.9%), and breast (9.6%) cancer. Severe (grade ≥3) CIT occurred in about 6.1% of solid tumor patients versus 28.7% of those with hematologic cancers (Table 1) [1]. A recent guideline notes that CIT affects approximately one-third of patients with solid tumors and half of those with hematologic malignancies, underscoring its clinical significance [43].

Table 1.

Incidence of CIT (CTCAE: any grade) in typical chemotherapy regimens and cancer types [1]

​	Overall, %	Severe CIT (grade ≥ 3), %
Chemotherapy regimen
Gemcitabine-based	15.8	8.0
Platinum-based	13.6	6.3
Anthracycline	16.4	10.7
Taxane	6.6	2.8
Cancer type after chemotherapy
All solid tumors	12.8	6.1
Melanoma	21.4	18.3
Ovarian	14.7	6.4
Lung	14.3	7.7
Bladder	14.2	9.5
Colorectal	13.5	6.0
Uterine	13.3	8.3
Pancreatic	12.9	5.4
Breast	9.6	3.6
All hematologic malignancies	28.2	28.7
Multiple myeloma	37.3	42.3
Non-Hodgkin lymphoma	24.4	22.3
Hodgkin lymphoma	4.7	6.4

CIT arises from myelosuppression; chemotherapeutic agents affect hematopoietic stem cells and bone marrow microenvironment, reducing megakaryocyte and platelet production [44]. Most CIT is transient (“nadir” counts mid-cycle and recover before the next cycle), but it may become persistent or recurrent with intensive regimens [5]. Clinically, CIT can compromise cancer treatment. It may lead to chemotherapy delays or dose reductions to prevent bleeding, which in turn can worsen oncologic outcomes. Bleeding risk rises as counts drop: in severe thrombocytopenia (e.g., <5 × 10⁹/L), spontaneous hemorrhage is a leading fatal complication [45]. In practice, clinicians often reduce dose intensity when CIT occurs, as reflected by observed inferior survival with decreased dose intensity in various cancers.

Management of CIT is primarily supportive, aiming to reduce disease progression or achieve remission. There are currently no standardized guidelines for CIT, and published guidelines stress that only platelet transfusion reliably prevents bleeding in acute severe CIT. For example, transfusion is indicated for major invasive procedures at platelet counts of ≤50 × 10⁹/L and prophylactic transfusions for <10 × 10⁹/L [46]. Beyond transfusions, a few interventions are used: recombinant human IL-11 oprelvekin was historically approved to raise platelets, but its cardiac toxicity limits use [47]. Thrombopoietin receptor agonists (TPO-RAs, e.g., romiplostim/eltrombopag) have shown promise in stimulating platelet production. In a phase II trial, romiplostim prevented chemotherapy dose reductions in 70% of long-term users and maintained platelet counts with an acceptable safety profile [48]. While TPO-RAs can elevate platelet counts in CIT, their impact on reducing bleeding, transfusion needs, or chemotherapy delays remains uncertain [43]. Thus, current practice for CIT relies on dose modification, transfusion support, and in refractory cases consideration of off-label TPO-RA use.

Immune Thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts due to both increased peripheral destruction and impaired production [49]. Autoantibodies target platelet glycoproteins, leading to their clearance and inducing megakaryocyte apoptosis. Additionally, cytotoxic T cells contribute to platelet destruction and suppress megakaryocyte maturation [50]. ITP may occur primarily or secondary to other conditions such as infection, malignancy, drug usage, and autoimmune disease concomitant. ITP associated with solid tumors has been described through case reports and patient series. Studies that link ITP to hematological neoplasms are mainly focused on non-Hodgkin and Hodgkin lymphoma [51–53]. For solid tumors, ITP is most common in lung cancer, Kaposi’s sarcoma, and breast cancer, followed by renal cell carcinoma and ovarian cancer, but is rare in prostate cancer [54, 55]. Additionally, thrombocytopenia affects 20% of patients with large granular lymphocyte lymphoma due to splenomegaly, ITP, and large granular lymphocyte-induced megakaryopoiesis [56].

Most ITP cases may be asymptomatic and require no emergent treatment, but rarely in patients with suspected ITP and critical hemorrhage, physicians should initiate urgent intervention to rapidly raise platelet counts and restore hemostasis. Current management of ITP is mainly following the 2019 clinical practice guidelines from the American Society of Hematology [57]. Acute therapies include platelet transfusion, high-dose corticosteroids, and intravenous immunoglobulin (IVIG), used alone or in combination with TPO-RAs [57, 58]. For the patients with upcoming procedures, platelet transfusions are previously used in a small fraction of the hospitalized ITP patients despite controversial benefits [59]. A machine learning model analyzing 34 variables found that procedural risk and patient factors (e.g., anticoagulant use, anemia, and age) are primary predictors of post-procedure bleeding in ITP [60]. Platelet transfusion volume correlated with bleeding risk but did not independently reduce it, underscoring the importance of individualized risk assessment over routine transfusion. Large randomized trials in ITP management are scarce, leading to practice variability. A systematic review identified 29 treatment combinations for critical bleeds in ITP [61]. The five most common regimens were corticosteroids plus platelet transfusion and splenectomy, corticosteroids with IVIG, and splenectomy alone. Reported mortality rates were 30.6% in adults and 19.7% in pediatric patients. The lower evidence quality limits the assessment of individual therapies’ impact on outcomes. These findings highlight the urgent need for consensus-based, standardized algorithms to optimize the treatment of ITP.

Clinical Guidelines and Practice for Platelet Transfusion in Cancer Patients

Prophylactic and Therapeutic Platelet Transfusions Use

At present, the main indication for platelet transfusion is bleeding and prevention of bleeding in thrombocytopenic patients with bone marrow failure, intensive chemotherapy, or hematopoietic stem cell transplantation [62, 63]. The Association for the Advancement of Blood & Biotherapies (AABB – formerly known as the American Association of Blood Banks) recommends prophylactic platelet transfusion when the platelet count falls below 10 × 10⁹/L. Therapeutic platelet transfusions are indicated if the platelet count is lower or higher than 10 × 10⁹/L and bleeding occurs [46, 64]. In patients with platelet counts >10 × 10⁹/L, prophylactic platelet transfusion may be considered if additional bleeding risk factors are present or invasive interventions are planned.

Patients with hematologic malignancies who receive chemotherapy or hematopoietic stem cell transplantation often have long-term thrombocytopenia and need frequent platelet transfusions. Evidences from randomized clinical trials and meta-analyses support the use of prophylactic platelet transfusion strategy for patients with hematologic malignancies [62, 65, 66]. Wandt et al. [65] showed that prophylactic platelet transfusion could significantly decrease the incidence of grade 2–4 bleeding events compared with therapeutic transfusion only. In patients with hematological disorder, a transfusion threshold of 10 × 10⁹/L does not increase bleeding risk compared to higher threshold (20 × 10⁹/L or 30 × 10⁹/L), though evidence quality remains low [67]. A systematic review identified seven randomized clinical trials with 1,642 hospitalized thrombocytopenic patients, and prophylactic platelet transfusion may reduce clinically important bleeding relative to no prophylaxis [68]. Notably, the impact on all-cause mortality remained uncertain, highlighting the need for further high-quality research.

In specific clinical scenarios, the optimal use of platelet transfusion remains undefined, such as critical illness, surgical and pediatric patients with thrombocytopenia [69]. Baron et al. [70] reported that, in critically ill cancer patients with thrombocytopenia, over 50% of transfusion episodes results in poor increments, defined as a corrected count increment <7 or a platelet transfusion recovery <0.2. Consistently, a multicenter observational study found 73.9% of prophylactic platelet transfusions in critically ill patients lead to suboptimal response, with 93.5% of hematologic patients exhibiting a corrected count increment ≤7 at 18–24 h after transfusion [71]. These results suggest that standard prophylactic strategies may be less efficient in this population.

Several papers also explored restrictive transfusion in intensive care. Retrospective study by Berenger et al. [72] have shown that a restrictive prophylactic strategy did not result in higher rate of grade ≥2 bleeding or increased 28-day mortality. However, an association between low platelet nadirs (<5 × 10⁹/L) and mortality was found, suggesting that while restrictive strategies seem achievable in ICU, close monitoring is mandatory. Moreover, in procedural settings, omitting prophylaxis transfusion may be associated with increased bleeding risk. Van Baarle et al. [6] reported that thrombocytopenic cancer patients who did not receive prophylactic transfusions before central venous catheter placement experienced significantly more catheter-related bleeding.

Optimal Platelet Transfusion Dose

The optimal dose and threshold of prophylactic platelet transfusion is a major challenge in transfusion medicine. Several studies have compared the clinical outcomes of different doses of prophylactic platelet transfusion for patients with hematologic malignancies. Randomized controlled trials, including the PLADO study, have demonstrated that varying prophylactic platelet transfusion (low dose, 1.1 × 10¹¹/m²; medium dose, 2.2 × 10¹¹/m²; high dose, 4.4 × 10¹¹/m²) in patients with hypoproliferative thrombocytopenia does not significantly influence bleeding incidence, duration of bleeding days, severe hemorrhage, and overall mortality rates [73]. Although higher doses increase the total platelet yield per transfusion, they also heighten the risk of transfusion-related adverse events, while lower doses simply require more frequent transfusions without compromising safety or efficacy. A comprehensive meta-analysis corroborated that low-dose prophylaxis (2.01–4.6 × 10¹¹/L) does not raise bleeding risk compared to higher doses (3.35–7.7 × 10¹¹/L) [74]. Based on these findings, the 2015 International Collaboration for Transfusion Medicine guidelines (ICTMG) recommended low-dose prophylactic platelet transfusion (e.g., 1.1 × 10¹¹/m² or 2.2 × 10¹¹/m²) for hospitalized patients with chemotherapy- or transplant-induced thrombocytopenia, rather than high-dose strategies (4.4 × 10¹¹/m²) [75]. The conclusions have been supported by subsequent systematic reviews and guideline updates [46, 76, 77]. These findings reported no increase in bleeding outcomes or transfusion frequency between low-dose (1.1 ×10¹¹/m² ± 25%), standard-dose (2.2 ×10¹¹/m² ± 25%), and high-dose (4.4 ×10¹¹/m² ± 25%) and recommended against routine use of high-dose prophylaxis.

Platelet Transfusion in Antibodies Treatment/CAR-T Therapy-Related Thrombocytopenia

Immunotherapy strategies like immune checkpoint inhibitors (ICIs, e.g., PD-1/PD-L1 and CTLA-4 antagonists) and CAR-T transfusion can rarely provoke an ITP-like syndrome in oncology patients. The incidence rate of any grade ≥3 thrombocytopenia is 8.6% in over 1,000 patients receiving ICIs, but only 1.73% was attributed to the ICI [78]. Those developing ICI-related severity thrombocytopenia experienced markedly worse overall survival compared to non-thrombocytopenia (4.17 vs. 13.31 months). Pharmacovigilance analyses reveal significant reporting signals for ICI‐induced ITP across most agents, with pembrolizumab and nivolumab demonstrating the highest odds ratios [79]; combination of PD-1/CTLA-4 appears to carry notable great risk, though no validated patient‐specific predictors have been established to date. Management of ICI‐associated thrombocytopenia follows established ITP protocols. Guidelines recommend continuation of ICIs for grade 1–2 thrombocytopenia, with close monitoring [57]; for grade 3–4 (platelets <50 × 10⁹/L), ICIs should be withheld and high‐dose corticosteroids (±IVIG) initiated promptly. If platelet counts remain <50 × 10⁹/L after 24–72 h of steroids, adjunctive therapies (such as infliximab or rituximab) and TPO-RAs like eltrombopag may be considered [80]; persistent, steroid‐refractory cases often necessitate permanent discontinuation of immunotherapy.

CAR-T therapy also induces significant hematotoxicity (immune effector cell-associated hematotoxicity), with grade ≥3 thrombocytopenia reported in 28–62% of recipients after CD19-directed products (axi-cel, tisa-cel, liso-cel) and contributing to profound and prolonged cytopenias [81, 82]. An international EHA/EBMT survey highlighted substantial heterogeneity in grading and managing immune effector cell-associated hematotoxicity post-CAR-T therapy [83]. These efforts promote best practice consensus recommendations that classify early (day 0–30) versus late (>day 30) cytopenias and outline diagnostic workups, risk stratification (e.g., CAR-HEMATOTOX score), and interventions including growth factors, antimicrobial prophylaxis, transfusions, and stem cell boosts.

Transfusion support is a key surrogate for severe cytopenias, with more than half of patients requiring red blood cells (RBCs) or platelet transfusion in the 6-month time surrounding infusion [81]. Multivariate analyses identify a high CAR-HEMATOTOX score (≥2) and prior transfusion history as consistent predictors of both early and late transfusion need for RBC and platelet, whereas factors like ICANS and tocilizumab use further influence late‐phase platelet requirements. Transfusions may also modulate immune responses that are linked to reduced CAR-T efficacy, with early and late platelet transfusions correlating with inferior PFS and overall survival [84]. Given the critical balance between preventing hemorrhage and avoiding immunosuppressive effects, current guidelines emphasize individualized risk assessment and judicious use of transfusion support. For the prolonged thrombocytopenic patients after CAR-T therapy, TPO-RAs show a possible benefit though data are limited to small case series [82, 85]. Overall, while platelet transfusions remain indispensable for mitigating bleeding risk in immunotherapy and CAR-T recipients, the heterogeneity of patient responses underscores the need for prospective trials to evaluate the impact of transfusion practices on both hemostatic and immunologic outcomes.

Future Development and Prospects of Platelet Transfusion in Cancer Patients

Current significant challenges of platelet transfusion include limited supply due to short shelf life, storage constraints, and transfusion refractoriness. Novel approaches are being investigated to improve platelet available, function, and transfusion efficacy. The ex vivo platelet generation from stem cells may be one promising approach, particularly induced pluripotent stem cells (iPSCs) [86]. This strategy provides a platelet source that is both immunologically compatible and sustainable. The creation of immortalized megakaryocyte progenitor cell lines and the VerMES bioreactor can increase platelet yield by using controlled turbulence [87]. These technologies have enabled to produce more than 100 billion iPSC-derived platelets. These platelets were verified in first-in-human clinical trial (iPLAT1) in a patient with alloimmune transfusion refractoriness [88]. Autologous platelet transfusion was shown to be safety in the trail, with doses increasing from 1 × 10¹⁰ to 1 × 10¹¹ platelets [89]. However, platelet count exhibited no significant increase post-transfusion, potentially due to rapid clearance and abnormal platelet activation. Further researches are needed to improve function and circulation of iPSC-derived platelets.

New technologies (e.g., machine learning and artificial intelligence) are also applied to improve transfusion practice. Machine learning models can be used to predict the platelet transfusion need and optimize inventory management [90–92]. Using data from all patients admitted to a medical-multipurpose hospital, Engelke et al. [93] established a deep learning-based risk assessment system to predict platelet transfusion demand in the next 24 h. This model exhibited a high predictive accuracy in hematology-oncology departments (AUC-PR: 0.84; ROC-AUC: 0.98). Another study [94] developed five machine learning models to predict RBC and PLT transfusion requirement in acute myeloid leukemia. These models could also be employed to predict transfusion-related survival. In summary, the future of platelet transfusion in cancer care can be seen in new production methods, platelet biology understanding, and novel technological advancements.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Na Ma and Yufeng Wang wrote the manuscript. Yan Wang and Lvling Zhang reviewed the draft manuscript and made suggestions and modifications. All authors approved the final version for submission.

Funding Statement

This study was not supported by any sponsor or funder.