Human platelet transfusion: a narrative review

Introduction

More than sixty years ago, platelet transfusion was introduced to manage patients with bleeding tendencies or active bleeding caused by thrombocytopenia or platelet dysfunction. This practice became an integral part of supportive care during high-dose chemotherapy or bone marrow transplantation. As our understanding of platelets has deepened, it has become clear that their roles extend far beyond hemostasis. Platelets play a pivotal role in promoting coagulation and inflammation, contributing to overall procoagulant and inflammatory states, promoting tumor growth and metastasis, facilitating angiogenesis and wound healing, and driving the development of atherosclerosis.

In parallel with this expanded knowledge, novel platelet component therapies have emerged in clinical trials, some of which show promising results. However, recent evidence reveals uncertainties regarding the risk-benefit profile of platelet transfusions (1). Platelets are frequently implicated in transfusion-related adverse events, as reported by various hemovigilance systems. Moreover, bleeding events continue to occur despite varying guidelines suggesting different thresholds for prophylactic platelet transfusions. In clinical practice, clinicians often overemphasize the bleeding risks associated with thrombocytopenia, leading to a preference for liberal platelet transfusion strategies. Meanwhile, their access to the latest information on platelets and recommendations for platelet transfusions varies by region and the availability of institutional resources.

In this review, we synthesize recent research findings in platelet biology to highlight the multifaceted roles of platelets beyond hemostasis. We aim to provide practical and evident-based recommendations for clinicians to adjust their transfusion strategies, thereby enhancing the safety and effectiveness of platelet transfusion and ultimately improving patient outcomes. We present this article in accordance with the Narrative Review reporting checklist (available at https://aob.amegroups.com/article/view/10.21037/aob-24-26/rc).

Methods

Our search methodology is summarized in Table 1.

Platelet biology: exploring new roles in various diseases

Platelets are cytoplasmic fragments shed from megakaryocytes in the bone marrow. Approximately 100 billion platelets are produced daily in adults, but not all platelets are involved in circulation immediately. In fact, approximately one-third of all platelets are stored in the spleen, which can be released into the circulation during rapid platelet consumption (2). Platelets have a short half-life (7–9 days) and are primarily cleared by mononuclear phagocytes within the spleen. Beyond their role in coagulation and hemostasis, platelets also play crucial roles in inflammation regulation, maintenance of vascular integrity, metabolic regulation, facilitation of tumor metastasis, angiogenesis and wound healing.

Participation in various immune processes

In recent years, platelets have garnered increasing attention for their important role in regulating the body’s immune system. These tiny anucleate cell fragments can detect invading pathogens and the inflammatory environment, thereby participating in the human innate and adaptive immune responses. The surface of platelets expresses a variety of receptors related to immune regulation. Through degranulation, platelets exhibit high levels of membrane surface molecules and adhesion factors, which enabling them to bind to various immune cells such as neutrophils, monocytes, and dendritic cells. Simultaneously, they release a wide array of effector molecules such as cytokines and chemokines. This process activates and regulates the proliferation and migration of immune cells while balancing pro-inflammatory and anti-inflammatory responses, thereby achieving effective immune regulation (3).

Contribution to angiogenesis and wound healing

Platelets also play a crucial role in tissue repair, especially angiogenesis and wound healing. Upon activation, they release a variety of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), which can stimulate the proliferation and migration of vascular endothelial cells to the injured area, thereby promoting formation of new vessels. Simultaneously, these factors will also accelerate the movement of normal cells from the surrounding cutaneous tissue to the center of the wound, enhancing their division and proliferation, and thereby speed up the wound-healing process (4). Moreover, platelets can promote the proliferation of fibroblasts and collagen synthesis, regulate extracellular matrix (ECM) remodeling, and provide essential structural support for new blood vessels (5).

Based on the pivotal role of platelets in tissue repair, human platelet lysate (HPL), as a lysate rich in platelet-derived bioactive components, has begun to be gradually introduced into regenerative medicine and clinical applications. As early as 2019, the International Society of Blood Transfusion (ISBT) Cell Therapy Working Group published a position statement on the production and quality requirements of HPL (6). Compared with direct use of platelets, the standardized preparation process of HPL ensures a more stable and controllable supply of signaling molecules essential for angiogenesis and wound healing. The multifaceted advantages of HPL make it vital for advancing regenerative therapies. Recent studies have demonstrated its potential in treating intracerebral hemorrhage (ICH) by mitigating neuroinflammation and promoting neurovascular repair, although clinical trials are still underway (7). In cardiovascular applications, HPL synergizes with mesenchymal stem cells (MSCs) to enhance cardiac repair after myocardial infarction, improve cardiac function, and reduce fibrosis (8). For wound healing purposes, HPL-cultured stem cell sheets can accelerate both tissue regeneration and angiogenesis (9).

Role in tumor growth and metastasis

The role of platelets in tumor metastasis is gradually being recognized, with evidence showing their involvement in assisting cancer cells to survive and helping them evade immune surveillance. The interaction between platelets and tumor cells facilitates this process. During the hematogenous metastasis of tumor cells, platelets adhere to the surface of tumor cells via various adhesion molecules on their surfaces, such as glycoprotein Ib-IX-V and glycoprotein IIb-IIIa, forming a “protective layer” for tumor cells that blocks recognition and killing by natural killer (NK) cells. This phenomenon is known as tumor cell-induced platelet aggregation (TCIPA), facilitates immune evasion and enhances tumor cell survival (10).

Tumor growth and metastasis depend on angiogenesis, which is significantly influenced by VEGF, a key factor primarily derived from activated platelets that promotes tumor proliferation (11). Cancer cells can also accelerate their own proliferation and migration by secreting specific cytokines, such as transforming growth factor (TGF)-β, and activating multiple signaling pathways with platelets, such as the phosphorylation signaling pathway of signal transducer and activator of transcription 6 (STAT6). Whether inappropriate platelet transfusions in cancer patients might increase the risk of tumor metastasis remains to be further clarified by additional evidence.

Immunogenicity of platelets

The interaction between platelet antigens and their antibodies plays a key role in immune-related thrombocytopenia, such as immune-mediated platelet transfusion refractory (IPTR) and fetal and neonatal alloimmune thrombocytopenia (FNAIT). Platelet surface antigens can be categorized into two types: platelet-related antigens and human platelet-specific antigens. The former are antigens shared with other cell surfaces or tissues, mainly including: human leukocyte antigen (HLA)-class I molecules found on leukocytes; Carbohydrate antigens, such as A and B, present on the surface of red blood cells; and the CD36 antigens, which are also expressed on monocytes/macrophages. Human platelet-specific antigens, including the human platelet antigens (HPA), are expressed uniquely on platelets and megakaryocytes (12). Since platelets express HLA class I antigens, HLA mismatches can lead to more complex immune responses from an immunogenicity perspective. These responses, including cell-mediated immunity, are typically stronger and more complex than those caused by antibodies against red blood cell antigens (13). In the past, HLA typing primarily relied on serological and cellular methods. However, with the rapid advancement of polymerase chain reaction (PCR) technology, these traditional methods have been gradually replaced by HLA genotyping. Currently, the HLA antigen specificity is predicted based on the results of HLA genotyping, offering higher specificity and accuracy. There are two different levels of resolution for HLA genotyping. Low resolution typing refers to 2-digit typing (e.g., A*01), which is equivalent to serological typing (e.g., A1). High-resolution typing refers to alleles reported at least at the 4-digit level, allowing for the discrimination of individual alleles within each serotype (e.g., A01:01 or A01:03).

Recent advances in platelet transfusion therapy

Cold stored platelets (CSPs)

CSPs have recently regained attention in transfusion medicine and are considered to have the potential to improve logistics of clinical supply of platelets. Due to the short shelf life of platelets, the outbreak of coronavirus disease 2019 (COVID-19) in the United States led to an increased risk of platelet inventory shortages, thereby accelerating the promotion and application of CSPs (14). However, CSPs were previously associated with decreased recovery and survival upon transfusion compared to room temperature-storaged (RTS) platelet. The possible reason is that cold storage induces clustering of von Willebrand factor (vWF) receptors on the platelet surface and morphological changes in the platelets, leading to enhanced clearance by hepatic macrophages and reduced platelet survival in the recipient. Therefore, currently, room temperature storage (22±2 ℃) remains the sole widely used method for preserving platelets globally. However, this also increases the risk of bacterial contamination and platelet storage lesion (PSL), which significantly shortens the shelf life of platelet components. PSL refers to the functional and morphological changes that occur during the preparation and storage of platelet concentrates, which can lead to a shortened in vivo lifespan and decreased therapeutic efficacy of transfused platelets. During RTS, oxidative stress damages cellular structures of platelet, while metabolic exhaustion from glucose depletion and pH changes further impair their function and viability (15). In contrast, cold storage can significantly lower metabolic activity of platelets and reduce the glucose consumption and lactate production through glycolysis, leading to a better-quality product with a prolonged shelf life (16). Additionally, cold storage can significantly inhibit or stop microbial growth within platelet units, and reduce the risk of transfusion-transmitted bacterial infections (TTBI) (17). The Food and Drug Administration (FDA) has updated guidance for CSPs in June 2023 and approved the alternative procedures for the manufacture of CSPs intended for the treatment of active bleeding when conventional platelets are not available or their use is not practical, and the storage duration was extended to 14 days from 5 days (17). More and more clinical trials have been initiated to compare the efficacy and safety of RTS-Platelets and CSPs. In fact, only limited retrospective studies concluded that CSPs can increase the platelet inventory availability for patient use during a period of platelet shortages. Larger clinical trials are awaited to substantiate these findings and to facilitate broader clinical application and guideline development.

Cryopreserved platelets

Cryopreservation is another attempt by humans to extend the shelf life of platelets. Recent studies show that platelets cryopreserved in hypertonic saline show high recovery rates and maintain hemostatic function in vitro (18). Dimethyl sulfoxide (DMSO) is regularly used as a cryoprotectant agent for the cryopreservation of platelets at −80 ℃ and extends the platelets shelf-life from 7 days to 2 years. Therefore, cryopreservation is expected to improve the inventory and availability of platelet components. Despite the advantage of cryopreserved platelets, DMSO is considered toxic for human and only limited comparative trial data supports the safety and effectiveness of cryopreserved platelets. Moreover, a delay in obtaining the platelet unit due to thawing and reconstitution with plasma is another potential concern with cryopreserved platelets. This process typically requires an additional 30 to 40 minutes (19). Cryopreserved platelets are not yet available in clinical practice, but they have been used in military settings. Furthermore, cryopreserved platelets are potentially suitable for preserving HLA/HPA matched platelet units (autologous or allogeneic units) for highly alloimmunized patients as its longer shelf life or the management of bleeding in remote hospitals (20).

Related transfusion adverse reactions

According to the data from numerous hemovigilance system reports worldwide, platelets are the most frequently implicated blood component in transfusion reactions. Serious adverse reactions caused by platelet transfusions can include bacterial sepsis, transfusion-associated circulatory overload (TACO), and transfusion-related acute lung injury (TRALI). Less severe adverse reactions include allergic reaction and febrile non-hemolytic transfusion reactions (FNHTR). Due to the general policy of transfusing platelets without considering the ABO type compatibility between the donor and recipient, extremely rare cases of transfusion-associated hemolytic reactions can occur (21). The incidence of these adverse transfusion reactions is relatively high following platelet transfusion.

Allergic reactions

Allergic reactions are common after platelet concentrates transfusion, and the risk ranging from 0.09% to 21% (22). The pathogenesis of allergic reactions is highly heterogeneous. Possible causes include: (I) IgE and IgG antibodies in the recipient directed against plasma proteins in the transfused platelet components, (II) transfusion of cytokines, chemokines, and histamine generated within the platelet product during preparation and storage (23). The severity of allergic reactions is highly variable. In some cases, manifestations of an allergic reaction may present as isolated pruritus and urticaria. Systemic reactions are also defined as anaphylaxis and may present with bronchoconstriction, hypotensive reactions, or even shock. Symptoms usually subside if the transfusion is halted and parenteral antihistamines are given. For patients with a history of allergic transfusion reactions, platelet additive solution (PAS)-suspended apheresis platelets might be considered, as these components contain less plasma than conventional platelets, which may help reduce the occurrence of allergic reactions (24).

Transfusion transmitted bacterial infection/sepsis

Because the conventional platelets are stored at room temperature, they are more susceptible to bacterial contamination, leading to a higher risk of TTBI or sepsis than in red blood cells or plasma transfusions. The reported incidence of TTBI following platelet transfusions is significantly higher than that after red blood cell transfusion (25). To reduce infection risks, in addition to optimizing aseptic techniques during the blood collection process and monitoring the culture of platelet components, the application of pathogen inactivation technology in PAS has gained increasing attention in recent years. For instance, the FDA-approved INTERCEPT^® System uses chemical additives that intercalate into the DNA and RNA of pathogens and white blood cells within platelet components, leading to pathogen inactivation upon exposure to ultraviolet A (UVA) light; furthermore, by partially replacing plasma with PAS, the potential sources of contamination from donor plasma are reduced, thereby indirectly reducing the risk of TTBI (26). Additionally, storing platelets at 4 ℃ can effectively reduce the occurrence of transfusion-associated sepsis when used in indicated patients (17).

Platelet transfusion refractoriness (PTR)

PTR is common among transfusion-dependent patients, particularly those in hematology and oncology. However, the occurrence of PTR can result in poor prognosis and increased mortality (27). PTR is defined as a repeated suboptimal response to platelet transfusions with lower-than-expected post-transfusion count increments. The Corrected Count Increment (CCI) is the most widely used metric for diagnosing PTR and is calculated using the following formula: [post-transfusion platelet count (PLTC) – pre-transfusion PLTC] × body surface area (BSA) (m²)/transfused platelet (×10⁹). Usually, if the 24-hour CCI is ≤5,000/mL after two sequential transfusions of ABO-compatible platelets, PTR is suspected; In such cases, further calculations of the 10-minute to 1-hour CCI should be performed. If the 10-minute to 1-hour CCI is also ≤5,000 /mL, IPTR should be considered (28).

Factors associated with PTR

The causes of PTR mainly include two categories: immune factors and non-immune factors, of which non-immune factors account for more than 80% of PTR episodes (29). Therefore, the non-immune factors should be differentiated or treated promptly before the work up of IPTR (see Table 2). The non-immune mediated PTR is associated with rapid platelet consumption from the circulation. Conversely, immune factors account for approximately 10–20% of PTR, of these; about 80% of immune-mediated PTR (IPTR) is mainly caused by HLA antibodies, followed by HPA antibodies, and a small number of patients have both antibodies; less commonly, CD36 antibodies and drug-dependent antiplatelet antibodies (30). In initiating the workup for IPTR, the enzyme-linked immunosorbent assay (ELISA) is commonly chosen as a screening tool due to its simplicity, time-saving, and relatively low cost (31). It is used to detect the presence of HLA class I, HPA, or CD36 antibodies. An example of such a qualitative solid-phase ELISA kit is PakPlus; if the result is positive, a comprehensive refractory workup should be conducted. Solid phase testing, also known as single-antigen bead or Luminex assay, has been widely used to identify multiple HLA/HPA antibody specificities that could not be distinguished by the traditional cytotoxic assays.

How to manage immune-mediated PTR

Selecting compatible platelets is the important therapeutic option to manage IPTR, and the choice of matching method is crucial for selecting the compatible platelets. ABO-matched apheresis platelet units should be selected first for patients newly diagnosed with PTR. For patients newly diagnosed with PTR, ABO-matched apheresis platelet units should be selected first. If this approach is ineffective, the next step involves attempting a transfusion of cross-match-compatible platelets while closely monitoring the 1-hour CCI. Should this trial also fail, HLA-matched or HLA-selected platelets should be provided based on the identified platelet antibodies and the development status of the local HLA donor pool (31). However, in cases where there is a shortage of both ABO and HLA antigen-matched blood donors, priority should be given to HLA antigen matching. In such situations, major or minor ABO-incompatible apheresis platelets without high-titer anti-A or anti-B antibodies can be considered (25).

Serological platelet cross-matching process

Cross-matched platelets represent the simplest and quickest option for providing compatible platelets. Compatibility between the patient’s serum and donor platelets is evaluated using solid-phase red-cell adherence (SPRCA) techniques to detect cross-reactivity. By selecting a certain number of apheresis donor platelets for the process (usually 5–10), donor platelets with negative reactions are prioritized based on the cross-reactivity results for transfusion therapy. If there are no donor platelets with negative reactions available, and the patient requires urgent platelet transfusion for resuscitation, platelets with weak positive reactions can be chosen appropriately. Due to its time-efficiency and simplicity, the serological cross-matching process has been widely used worldwide for IPTR patients. However, its disadvantage is that it is difficult to obtain a compatible donor platelet unit for patients who are highly sensitized to HLA/HPA antigens. Additionally, random cross-matching can easily lead to further alloimmunization by transfusing new mismatched HLA/HPA antigens, resulting in the production of additional alloantibodies (31).

Provision of HLA matched/selected platelets

To further minimize the risk of alloimmunization in patients with IPTR after transfusion of serologically cross-matched platelets, it is recommended to provide HLA-matched platelet transfusions. HLA matching includes both antigen-level and epitope-level matching. The former involves selecting donors with identical or acceptable mismatched antigens based on the principle of HLA cross-reactive groups (CREGs), using low-resolution HLA genotype results. The degree of HLA matching can be divided into A, BU, BX, C, and D. Among them, A and BU grade-matched platelet transfusions have the best efficacy and are superior to cross-matched platelets, and there is no significant difference between B2X, C and D grade-matched platelets with random platelets (32). As most of the HLA genotyping data accumulated globally in the past are of low resolution and the consideration of cost-effectiveness, CREG matching is still widely used by blood services and bone marrow registries around the world. However, in recent years, it has been gradually replaced by epitope-level matching based on high-resolution HLA genotyping results (31). An epitope is the specific region on an antigen that is recognized and binds to an antibody or immune cell receptor, initiating an immune response. Due to the polymorphism of HLA antigen molecules, antigen level matching is difficult to completely resolve the mismatches of public epitope, which can be shared by multiple HLA antigens molecules. HLAMatchmaker (http://www.epitopes.net/) is a useful and freely available tool for determining epitope-based HLA compatibility, aiding in the selection of HLA-identical donors or acceptable HLA mismatches with low eplet loads. Blood transfusion services should establish their local HLA donor pool and expand the HLA donor pool to be large enough based on the local population, thereby increasing the likelihood of finding HLA-matched donors.

For patients who have developed HLA class I or HPA antibodies, selecting the antibody-specific antigen negative platelets for transfusion can also be adopted as another strategy for PTR. This approach involves identifying the specific antibodies from the patient and then selecting corresponding antigen-negative donor in donor gene database. There is evidence showing that the transfusion of antigen-negative platelets is no worse than that of HLA matched platelets (33). Especially when the donor pool is limited, antibody-specific antigen-negative platelets provide a more beneficial option compared to HLA-matched platelets or those selected through cross-matching. In clinical practice, it is often necessary to use a combination of different matching strategies to provide compatible platelets to the patient, so that the pool of available donor platelets can be expanded accordingly.

HLA/HPA matched platelets

As mentioned above, there are different types of antigens expression on the surface of platelets, especially HLA antigens, which are highly polymorphic. Patients with repeated transfusions of blood components or multiple pregnancies may be alloimmunized to HLA class I antigens or HPA antigens expressed on platelets, resulting in IPTR. IPTR is associated with an increased risk of bleeding, prolonged hospital stays, and higher hospital costs (34).

The prediction of HLA or HPA antigen specificity is based on the genotype results of both donor and recipient. Timely provision of HLA-matched platelets by blood transfusion service may improve PLTC increments and save lives. To avoid the occurrence of IPTR, strategy of prophylactically providing HLA matched platelets to the patients at high risk of developing IPTR has been implemented in a few developed countries or regions. HLA matched platelets also have been proved to be superior to cross-matched platelets in situations with non-immune mediated PTR (35). However, smooth supply of HLA-matched platelets is not easy. It requires rapid identification of suitable and available donors for platelet-apheresis, and the donor pool should be large enough to meet the demand.

Optimizing platelet transfusion strategy

PLTC remain stable during life (150–300 ×10⁹/L). There is a relatively broad international consensus that defines PLTC less than 150×10⁹/L as absolute thrombocytopenia. However, the normal range of PLTC varies by age, gender, and ethnicity. Since healthy individuals with a PLTC in the range of 100–150 ×10⁹/L do not exhibit obvious bleeding tendencies, some countries or regions have recommended adopting a PLTC threshold of less than 100×10⁹/L as a new criterion for defining thrombocytopenia in their local populations (33). The severity of thrombocytopenia can be further subdivided based on PLTC into moderate thrombocytopenia, <50×10⁹/L; and severe thrombocytopenia, <20×10⁹/L (36). Platelets play a vital role in stopping bleeding and maintaining vascular integrity. Therefore, platelet transfusion holds significance in reducing bleeding risk in patients with active bleeding, platelet dysfunction, or severe thrombocytopenia. However, the strength of this relationship remains unclear.

Thrombocytopenia and risk of spontaneous bleeding

With the deepening of research, the rationality of relying solely on low PLTC as indication to guide decisions for a prophylactic platelet transfusion has been challenged. In the PLADO randomized controlled trial, when evaluating the impact of platelet dose on bleeding in patients, the authors found that the trial data indicated that the risk of bleeding was not reduced by platelet transfusion when the PLTC ranged from 6 to 80 ×10⁹/L. In fact, in addition to low PLTC, various clinical factors also play a crucial role in the occurrence of spontaneous bleeding, such as undergoing bone marrow transplantation or chemotherapy, fever, female gender and history of recent bleeding events (2,37). Therefore, the decision to administer platelet transfusions should be based on a comprehensive assessment of the patient’s overall condition rather than solely focusing on a low PLTC. It is also essential to consider the potential adverse reactions associated with platelet transfusions and to balance the benefits against the risks of therapy.

Restrictive platelet transfusion strategy

The restrictive transfusion strategy of red blood cell blood components has been promoted for many years, and numerous evidences have confirmed that the restrictive red blood cell transfusion strategy significantly improves patient prognosis and mortality (38). To improve patient outcomes and in facing the challenges of low inventory of platelet products, restrictive platelet transfusion strategies have begun to be valued by clinicians. A restrictive platelet transfusion strategy in intensive care unit (ICU) reduces the use of platelet concentrates in hematology patients. This strategy is not correlated with a greater occurrence of grade ≥2 bleeding, nor is associated with short-term mortality (1). The threshold of 10×10⁹/L is now commonly recommended by various clinical guidelines; as early as 2015, the practice of transfusing hospitalized patients with a PLTC <10×10⁹/L was recommended by Association for the Advancement of Blood & Biotherapies (AABB) to reduce the risk of spontaneous bleeding (39). A risk-adapted approach to platelet transfusions may be more prudent in thrombocytopenic patients without bleeding, rather than applying a transfusion threshold PLTC of 10×10⁹/L (2). Single therapeutic dose platelets policy should also be implemented in prophylactic platelet transfusion, existing evidence confirms that administering double doses or more of platelets does not reduce the risk of bleeding, as a PLTC ≥5×10⁹/L is sufficient to maintain endothelial integrity and hemostasis; moreover, liberal platelet transfusion strategy was also associated with an increased risk of transfusion-related adverse events (37,39).

Contraindication

Platelet transfusions are contraindicated in patients with thrombotic thrombocytopenic purpura (TTP), immune thrombocytopenic purpura (ITP), or heparin induced thrombocytopenia (HIT). However, it is common for clinicians to use platelet transfusions as prophylaxis therapy in hospitalized patients with the platelet consumptive or destructive disorders. Unfortunately, this practice can worsen microangiopathic thrombosis and increase mortality in patients with thrombotic microangiopathy (TMA) and HIT (40). In the case of TMA, platelet transfusions are only used to treat life-threatening bleeding.

Conclusions

Platelet transfusion is an essential part of transfusion therapy and platelets are increasingly recognized for their extensive roles in physiological processes and pathophysiological conditions that extend beyond hemostasis and thrombosis. However, unreasonable transfusions have been shown to increase mortality in patients. According to hemovigilance systems, platelets are the blood component most frequently associated with transfusion reactions (2). Clinicians should update their knowledge of platelet transfusion therapy based on the latest evidence to better evaluate the risks and benefits before making a transfusion decision. When managing patients with severe thrombocytopenia, a restrictive platelet transfusion strategy should be adopted whenever possible to minimize unnecessary transfusions, thereby improving patient outcomes and assisting in regulating platelet inventory pressure. Clinicians can also correct thrombocytopenia status by treating the underlying disease or by non-transfusion therapies, such as using thrombopoietin receptor agonists (TPO-RAs) when appropriate (41). Minimizing allogenic antigen exposure is a key preventive measure for IPTR, on the other hand, clinicians should also optimize their management approach for IPTR. Given the high polymorphism of HLA antigens, blood services should investigate the distribution of platelet antibodies and antigen-antibody characteristics among local IPTR patients to build a targeted HLA gene database to optimize platelet matching services and enhance the efficacy of platelet transfusions.

Despite substantial advancements in our understanding of platelet biology compared to the past, evidence regarding the clinical implications of platelet transfusions on patient outcomes remains limited. For instance, there is insufficient evidence concerning the increased risk of tumor metastasis following platelet transfusion in patients with various types of cancer, as well as the specific impact of platelet transfusions on patient outcomes in the context of infection or systemic inflammation. Although the concept of a restrictive platelet transfusion strategy has gained increasing attention in recent years, current international guidelines for platelet transfusion thresholds, particularly for surgeries or invasive procedures, often lack robust supporting evidence. Therefore, more large-scale clinical trials are still needed to provide clinicians with more evidence to optimize their platelet transfusion strategies.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://aob.amegroups.com/article/view/10.21037/aob-24-26/rc

Peer Review File: Available at https://aob.amegroups.com/article/view/10.21037/aob-24-26/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aob.amegroups.com/article/view/10.21037/aob-24-26/coif). P.H. serves as an unpaid editorial board member of Annals of Blood from June 2024 to May 2026. P.H. also serves as President of Macao Laboratory Medicine Association and Member of AIDS Prevention and Treatment Committee of Macau. K.W.C. is a council member in Macao Laboratory Medicine Association (unpaid). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Berenger JB, Saillard C, Sannini A, et al. Prophylactic versus restrictive platelet transfusion strategy in patients with haematological malignancies in the ICU setting, a propensity-score analysis. J Crit Care 2024;83:154817. [Crossref] [PubMed]
2. Stanworth SJ, Shah A. How I use platelet transfusions. Blood 2022;140:1925-36. [Crossref] [PubMed]
3. Tyagi T, Jain K, Gu SX, et al. A guide to molecular and functional investigations of platelets to bridge basic and clinical sciences. Nat Cardiovasc Res 2022;1:223-37. [Crossref] [PubMed]
4. Liao K, Zhang X, Liu J, et al. The role of platelets in the regulation of tumor growth and metastasis: the mechanisms and targeted therapy. MedComm (2020) 2023;4:e350.
5. Diller RB, Tabor AJ. The Role of the Extracellular Matrix (ECM) in Wound Healing: A Review. Biomimetics (Basel) 2022;7:87. [Crossref] [PubMed]
6. Schallmoser K, Henschler R, Gabriel C, et al. Production and Quality Requirements of Human Platelet Lysate: A Position Statement from the Working Party on Cellular Therapies of the International Society of Blood Transfusion. Trends Biotechnol 2020;38:13-23. [PubMed]
7. Qiu D, Wang L, Wang L, et al. Human platelet lysate: a potential therapeutic for intracerebral hemorrhage. Front Neurosci 2025;18:1517601. [PubMed]
8. Najafipour H, Rostamzadeh F, Jafarinejad-Farsangi S, et al. Human platelet lysate combined with mesenchymal stem cells pretreated with platelet lysate improved cardiac function in rats with myocardial infarction. Sci Rep 2024;14:27701. [PubMed]
9. Chen YC, Chuang EY, Tu YK, et al. Human platelet lysate-cultured adipose-derived stem cell sheets promote angiogenesis and accelerate wound healing via CCL5 modulation. Stem Cell Res Ther 2024;15:163. [PubMed]
10. Jain S, Zuka M, Liu J, et al. Platelet glycoprotein Ib alpha supports experimental lung metastasis. Proc Natl Acad Sci U S A 2007;104:9024-8. [PubMed]
11. Holmes CE, Huang JC, Pace TR, et al. Tamoxifen and aromatase inhibitors differentially affect vascular endothelial growth factor and endostatin levels in women with breast cancer. Clin Cancer Res 2008;14:3070-6. [PubMed]
12. Curtis BR, McFarland JG. Human platelet antigens - 2013. Vox Sang 2014;106:93-102. [PubMed]
13. Couvidou A, Rojas-Jiménez G, Dupuis A, et al. Anti-HLA Class I alloantibodies in platelet transfusion refractoriness: From mechanisms and determinants to therapeutic prospects. Front Immunol 2023;14:1125367. [Crossref] [PubMed]
14. Braathen H, Hagen KG, Kristoffersen EK, et al. Implementation of a dual platelet inventory in a tertiary hospital during the COVID-19 pandemic enabling cold-stored apheresis platelets for treatment of actively bleeding patients. Transfusion 2022;62:S193-S202. [Crossref] [PubMed]
15. Mittal K, Kaur R. Platelet storage lesion: An update. Asian J Transfus Sci 2015;9:1-3. [Crossref] [PubMed]
16. George CE, Saunders CV, Morrison A, et al. Cold stored platelets in the management of bleeding: is it about bioenergetics? Platelets 2023;34:2188969. [Crossref] [PubMed]
17. Alternative Procedures for the Manufacture of Cold-Stored Platelets Intended for the Treatment of Active Bleeding when Conventional Platelets Are Not Available or Their Use Is Not Practical. FDA-2023-D-2034. Available online: https://www.regulations.gov/docket/FDA-2023-D-2034
18. Ehn K, Wikman A, Uhlin M, et al. Cryopreserved Platelets in a Non-Toxic DMSO-Free Solution Maintain Hemostatic Function In Vitro. Int J Mol Sci 2023;24:13097. [Crossref] [PubMed]
19. Cohn CS, Williams S. Cryopreserved platelets: the thaw begins … (Article, p. 2794). Transfusion 2019;59:2759-62. [Crossref] [PubMed]
20. Bohoněk, M. Cryopreservation of Platelets: Advances and Current Practice. IntechOpen 2018. doi: 10.5772/intechopen.81906.10.5772/intechopen.81906
21. Stolla M, Refaai MA, Heal JM, et al. Platelet transfusion - the new immunology of an old therapy. Front Immunol 2015;6:28. [Crossref] [PubMed]
22. Geiger TL, Howard SC. Acetaminophen and diphenhydramine premedication for allergic and febrile nonhemolytic transfusion reactions: good prophylaxis or bad practice? Transfus Med Rev 2007;21:1-12. [Crossref] [PubMed]
23. Kiefel V. Reactions Induced by Platelet Transfusions. Transfus Med Hemother 2008;35:354-8. [Crossref] [PubMed]
24. Mathur A, Swamy N, Thapa S, et al. Adding to platelet safety and life: Platelet additive solutions. Asian J Transfus Sci 2018;12:136-40. [Crossref] [PubMed]
25. Jones SA, Jones JM, Leung V, et al. Sepsis Attributed to Bacterial Contamination of Platelets Associated with a Potential Common Source - Multiple States, 2018. MMWR Morb Mortal Wkly Rep 2019;68:519-23. [Crossref] [PubMed]
26. Irsch J, Lin L. Pathogen Inactivation of Platelet and Plasma Blood Components for Transfusion Using the INTERCEPT Blood System™. Transfus Med Hemother 2011;38:19-31. [Crossref] [PubMed]
27. Fu Q, Xu L, Zhang X, et al. Platelet transfusion refractoriness after T-cell-replete haploidentical transplantation is associated with inferior clinical outcomes. Sci China Life Sci 2018;61:569-77. [Crossref] [PubMed]
28. Forest SK, Hod EA. Management of the Platelet Refractory Patient. Hematol Oncol Clin North Am 2016;30:665-77. [Crossref] [PubMed]
29. Juskewitch JE, Norgan AP, De Goey SR, et al. How do I … manage the platelet transfusion-refractory patient?. Transfusion 2017;57:2828-35. [PubMed]
30. Ren J, Li J, Liu Y, Zhou Z. Research progress on the immunological platelet transfusion refractoriness in patients with acute leukemia: a narrative review. Ann Blood 2021;6:27. [Crossref]
31. Cohn CS. Platelet transfusion refractoriness: how do I diagnose and manage? Hematology Am Soc Hematol Educ Program 2020;2020:527-32. [Crossref] [PubMed]
32. Schmidt AE, Refaai MA, Coppage M. HLA-Mediated Platelet Refractoriness. Am J Clin Pathol 2019;151:353-63. [Crossref] [PubMed]
33. Chinese Society of Internal Medicine. Expert consensus for diagnosis and treatment of thrombocytopenia in China. Zhonghua Nei Ke Za Zhi 2020;59:498-510. [PubMed]
34. Stanworth SJ, Navarrete C, Estcourt L, et al. Platelet refractoriness--practical approaches and ongoing dilemmas in patient management. Br J Haematol 2015;171:297-305. [Crossref] [PubMed]
35. Seike K, Fujii N, Asano N, et al. Efficacy of HLA virtual cross-matched platelet transfusions for platelet transfusion refractoriness in hematopoietic stem cell transplantation. Transfusion 2020;60:473-8. [Crossref] [PubMed]
36. Williamson DR, Albert M, Heels-Ansdell D, et al. Thrombocytopenia in critically ill patients receiving thromboprophylaxis: frequency, risk factors, and outcomes. Chest 2013;144:1207-15. [Crossref] [PubMed]
37. Slichter SJ, Kaufman RM, Assmann SF, et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. N Engl J Med 2010;362:600-13. [PubMed]
38. Carson JL, Stanworth SJ, Guyatt G, et al. Red Blood Cell Transfusion: 2023 AABB International Guidelines. JAMA 2023;330:1892-902. [PubMed]
39. Kaufman RM, Djulbegovic B, Gernsheimer T, et al. Platelet transfusion: a clinical practice guideline from the AABB. Ann Intern Med 2015;162:205-13. [PubMed]
40. Goel R, Ness PM, Takemoto CM, et al. Platelet transfusions in platelet consumptive disorders are associated with arterial thrombosis and in-hospital mortality. Blood 2015;125:1470-6. [PubMed]
41. Capecchi M, Serpenti F, Giannotta J, et al. Off-Label Use of Thrombopoietin Receptor Agonists: Case Series and Review of the Literature. Front Oncol 2021;11:680411. [PubMed]