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Transfusion and Apheresis Science :... Jun 2024While there are various aspects of platelet biology that can be studied in the lab (i.e. adhesion, degranulation, integrin activation), the master test for platelet... (Review)
Review
While there are various aspects of platelet biology that can be studied in the lab (i.e. adhesion, degranulation, integrin activation), the master test for platelet function is that which gives a measure of the platelet aggregation capacity upon stimulation with an agonist. Platelet function testing is necessary for the diagnosis of platelet disorders and the monitoring of patients receiving anti-platelet treatments. Furthermore, it becomes relevant in the quality control of platelet concentrates for transfusion purposes, especially considering the global concern about long term storage, other forms of storage (i.e. cryopreservation, lyophilization), and the impact of Pathogen Reduction Treatments (PRTs) on platelet performance upon transfusion. However, it has been acknowledged as technically difficult and demanding, since a fine platelet function test must be carried out under specific conditions. Still, there might be occasions that preclude the platelet function testing abiding to the gold standard requirements, thus, leaving us with the necessity to redefine which variables may condition or limit the analysis of platelet function testing. In the present manuscript, we test different variables (such as the anticoagulant used or the time elapsed since extraction) and the possibility to reconstitute blood prior to platelet function analysis. This study aims to provide windows of action at the diagnostics lab, especially when not all of the recommended procedures and conditions can be followed: for example, when a sample is sent from a long distance, when there is a limitation on blood extraction volume or when certain parameters (platelet count) preclude reliable test results.
Topics: Humans; Platelet Function Tests; Platelet Count; Blood Platelets
PubMed: 38644062
DOI: 10.1016/j.transci.2024.103930 -
Blood Research Jun 2024Surgical patients are at risk of postoperative complications and mortality, necessitating preoperative patient optimization through the identification and correction of... (Review)
Review
Surgical patients are at risk of postoperative complications and mortality, necessitating preoperative patient optimization through the identification and correction of modifiable risk factors. Although preoperative platelet transfusions aim to reduce the risk of bleeding, their efficacy remains uncertain. Similarly, red blood cell transfusion in patients with anemia does not reduce the risk of postoperative mortality and may exacerbate complications. Therefore, developing individualized strategies that focus on correcting preoperative complete blood count abnormalities and minimizing transfusion requirements are essential. This review aimed to examine complete blood count abnormalities and appropriate transfusion strategies to minimize postoperative complications.
PubMed: 38847904
DOI: 10.1007/s44313-024-00021-x -
Emerging Infectious Diseases Oct 2023During May 2018‒December 2022, we reviewed transfusion-transmitted sepsis cases in the United States attributable to polymicrobial contaminated apheresis platelet... (Review)
Review
During May 2018‒December 2022, we reviewed transfusion-transmitted sepsis cases in the United States attributable to polymicrobial contaminated apheresis platelet components, including Acinetobacter calcoaceticus‒baumannii complex or Staphylococcus saprophyticus isolated from patients and components. Transfused platelet components underwent bacterial risk control strategies (primary culture, pathogen reduction or primary culture, and secondary rapid test) before transfusion. Environmental samples were collected from a platelet collection set manufacturing facility. Seven sepsis cases from 6 platelet donations from 6 different donors were identified in patients from 6 states; 3 patients died. Cultures identified Acinetobacter calcoaceticus‒baumannii complex in 6 patients and 6 transfused platelets, S. saprophyticus in 4 patients and 4 transfused platelets. Whole-genome sequencing showed environmental isolates from the manufacturer were closely related genetically to patient and platelet isolates, indicating the manufacturer was the most probable source of recurrent polymicrobial contamination. Clinicians should maintain awareness of possible transfusion-transmitted sepsis even when using bacterial risk control strategies.
Topics: Humans; United States; Blood Platelets; Platelet Transfusion; Sepsis; Blood Transfusion; Bacteria
PubMed: 37561399
DOI: 10.3201/eid2910.230869 -
Platelets Dec 2023Alantolactone (ALT), a sesquiterpene lactone compound isolated from ., has recently attracted much attention for its anti-tumor properties. ALT reportedly functions by...
Alantolactone (ALT), a sesquiterpene lactone compound isolated from ., has recently attracted much attention for its anti-tumor properties. ALT reportedly functions by regulating the Akt pathway, which has been shown to be involved in programmed platelet death (apoptosis) and platelet activation. However, the precise effect of ALT on platelets remains unclear. In this study, washed platelets were treated with ALT , and apoptotic events and platelet activation were detected. , platelet transfusion experiments were employed to detect the effect of ALT on platelet clearance. Platelet counts were examined after intravenous injection of ALT. We found that ALT treatment induced Akt activation and Akt-mediated apoptosis in platelets. ALT-activated Akt elicited platelet apoptosis by activating phosphodiesterase (PDE3A) and PDE3A-mediated protein kinase A (PKA) inhibition. Pharmacological inhibition of the PI3K/Akt/PDE3A signaling pathway or PKA activation was found to protect platelets from apoptosis induced by ALT. Moreover, ALT-induced apoptotic platelets were removed faster , and ALT injection resulted in the platelet count decline. Either PI3K/Akt/PDE3A inhibitors or a PKA activator could protect platelets from clearance, ultimately ameliorating the ALT-induced decline in platelet count in the animal model. These results reveal the effects of ALT on platelets and their related mechanisms, suggesting potential therapeutic targets for the prevention and alleviation of possible side effects resulting from ALT treatments.
Topics: Animals; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Apoptosis; Lactones
PubMed: 36813739
DOI: 10.1080/09537104.2023.2173505 -
Vox Sanguinis Jun 2024Respiratory transfusion reactions associate strongly with morbidity and mortality, and transfusion-associated circulatory overload (TACO) is the leading cause of...
BACKGROUND AND OBJECTIVES
Respiratory transfusion reactions associate strongly with morbidity and mortality, and transfusion-associated circulatory overload (TACO) is the leading cause of reaction-related deaths. Risk factors for TACO include transfusion speed and volume and cardiorenal comorbidities.
MATERIALS AND METHODS
An academic health network haemovigilance database was interrogated to assess variables associating with 371 cases of TACO and involved-visit outcomes, using univariate and multivariate regression analysis.
RESULTS
TACO reactions over 11 years were reported in 179 males and 192 females, median age (interquartile range) 65 (53-75) years. In-hospital and 28-day mortality were 17.5% and 12.9%, respectively. In univariate regression modelling, male sex, injury severity grade, product volume administered, the use of platelets and intensive care admissions were each associated with in-hospital and 28-day mortality (p < 0.05). However, after multivariate regression analysis, only male sex in transfusion recipients independently associated with mortality (p < 0.05).
CONCLUSION
In this cohort, male recipient sex and platelet administration were associated with TACO-involving admissions not ending in survival.
PubMed: 38872390
DOI: 10.1111/vox.13690 -
Vox Sanguinis Mar 2024This study describes the use of the Epvix platform for virtual cross-matching (VC) of human leucocyte antigen (HLA)-compatible platelets for patients with immune...
BACKGROUND AND OBJECTIVES
This study describes the use of the Epvix platform for virtual cross-matching (VC) of human leucocyte antigen (HLA)-compatible platelets for patients with immune platelet refractoriness, and demonstrates effectiveness of the selected platelets.
MATERIALS AND METHODS
A prospective cohort of haematological patients was evaluated from 2018 to 2022. HLA-typed donor bank profile was previously uploaded to the Epvix platform. Each patient's antibody reactivity panel (PRA) was included in the platform. Then, search, selection and VC were performed, and 24-h-corrected count increment (CCI) platelet transfusion was calculated (reference ≥2500).
RESULTS
Six patients were included (four female, two male), with mean age of 61 years. HLA antibodies were detected as the cause of immunity for all patients, whereas four patients also had non-immune causes. High percentage of alloimmunization was detected in all studied patients (mean PRA: 85.7%). Thirty different donors were able to schedule and perform platelet donations. The mean 24-h CCI count was 9882. All platelet transfusions achieved a satisfactory CCI count except for two transfusion events. Presence of non-immune causes identified in these two cases could account for the unsatisfactory CCI.
CONCLUSION
Epvix is a free application hosted on the Web and uses the HLAMatchmaker algorithm to generate histocompatibility reports. This study demonstrates the efficiency of VC performed by Epvix. However, physical cross-matching will still be necessary in some instances, as the platform does not support human platelet antigen polymorphism.
Topics: Humans; Male; Female; Middle Aged; Prospective Studies; Blood Platelets; Thrombocytopenia; Blood Transfusion; Platelet Transfusion; HLA Antigens; Histocompatibility Antigens Class I
PubMed: 38050782
DOI: 10.1111/vox.13565 -
Journal of Intensive Care Oct 2023Previous studies have reported conflicting results regarding fresh frozen plasma (FFP)-to-red blood cell (RBC) ratio and platelet-to-RBC ratio on outcomes for massive...
BACKGROUND
Previous studies have reported conflicting results regarding fresh frozen plasma (FFP)-to-red blood cell (RBC) ratio and platelet-to-RBC ratio on outcomes for massive transfusion for trauma. Moreover, nationwide data on massive transfusion practices for trauma in the real-world clinical setting are scarce. This study aimed to examine the nationwide practice patterns and trends in massive transfusion for trauma in Japan using a national administrative, inpatient database.
METHOD
We identified patients who underwent emergency hospitalization for trauma and received massive transfusion, defined as administration of at least 20 units of RBC within the first 2 days of admission, using the nationwide inpatient database, which covers approximately 90% of all tertiary emergency hospitals in Japan, between 2011 and 2020. Trends in the incidence and practice patterns of massive transfusion were described by calendar year. The association of practice patterns with mortality or adverse events was tested.
RESULTS
A total of 3,530,846 trauma hospitalizations were identified, of which 5247 (0.15%) received massive transfusion. A significant declining trend was observed in the incidence of massive transfusion in trauma hospitalizations from 0.24% in 2011 to 0.10% in 2020 (P for trend < 0.001). The FFP-to-RBC ratio rose significantly from 0.77 in 2011 to 1.08 in 2020 (P for trend < 0.001), while the platelet-to-RBC ratio remained virtually unchanged from 0.71 in 2011 to 0.78 in 2020 (P for trend 0.060). Massive transfusion with lower FFP-to-RBC (< 0.75) and platelets-to-RBC ratio (< 1.00) were associated with increased in-hospital mortality compared with those ≥ 1.00, while there were linear increases in adverse events with increasing FFP and platelets ratios.
CONCLUSIONS
This study demonstrated a declining trend in the incidence and a rise in higher FFP-to-RBC ratios in massive transfusion in association with patient outcomes for trauma from 2011 to 2020 in Japan.
PubMed: 37853484
DOI: 10.1186/s40560-023-00685-0 -
Pediatric Research Dec 2023Studies have demonstrated increased morbidity and mortality with platelet transfusions in the neonatal period. Platelets are as important for host immunity and... (Observational Study)
Observational Study
BACKGROUND
Studies have demonstrated increased morbidity and mortality with platelet transfusions in the neonatal period. Platelets are as important for host immunity and inflammation as for hemostasis. Increased inflammation may explain the dose-associated increase in mortality, bleeding, and lung disease.
OBJECTIVE
This study aims to assess if there are any changes in inflammatory cytokines post-platelet transfusion in babies in NICU.
METHODS
This prospective observational study recruited babies due to receive a non-emergency platelet transfusion. Dried whole blood samples were collected prior to and 2 h post-transfusion. Samples were processed using multiplex immunoassay to enable analysis of tiny blood volumes. Statistical analysis was performed using R.
RESULTS
Seventeen babies underwent 26 platelet transfusions across two centers. Median birthweight was 1545 g (535-3960 g) and median birth gestation was 31 weeks and 1 day (23 + 1 to 40 + 5). Median pre-transfusion platelet count was 19.5 × 10/l. There was a significant increase in levels of CXCL5 (p < 0.001), CD40 (p = 0.001), and TGF-β (p = 0.001) in neonatal blood samples post-platelet transfusion in the study group.
CONCLUSION
The increase in the cytokines CXCL5, CD40 and TGF-β after platelet transfusion in babies in NICU could potentiate existing inflammation, NEC, lung, or white matter injury. This could potentially explain long-term harm from platelet transfusion in babies.
IMPACT
There is a change in levels of immunomodulatory proteins CXCL5, CD40, and TGF-β after platelet transfusion in babies in NICU. Murine neonatal models have demonstrated an increase in cytokine levels after platelet transfusions. This is the first time that this has been demonstrated in human neonates. The increase in proinflammatory cytokines could potentially explain the long-term harm from platelet transfusion in babies, as they could potentiate existing inflammation, NEC, lung injury, or white matter injury.
Topics: Infant, Newborn; Humans; Animals; Mice; Platelet Transfusion; Blood Platelets; Cytokines; Inflammation; Transforming Growth Factor beta
PubMed: 37443343
DOI: 10.1038/s41390-023-02731-x -
Journal of Thrombosis and Haemostasis :... Jan 2024Thrombocytopenia is a common adverse effect of chemotherapy. The development of chemotherapy-induced thrombocytopenia (CIT) is influenced by cancer type and therapy,...
Thrombocytopenia is a common adverse effect of chemotherapy. The development of chemotherapy-induced thrombocytopenia (CIT) is influenced by cancer type and therapy, occurring in approximately one-third of patients with a solid tumor diagnosis and half of all patients with a hematologic malignancy. CIT may complicate the administration of chemotherapy, leading to therapeutic delays or dose reductions. This guidance document, presented by the International Society on Thrombosis and Haemostasis (ISTH) Subcommittee on Hemostasis and Malignancy, provides a comprehensive summary of the evidence and offers direction on the use of thrombopoietin receptor agonists (TPO-RAs) in various settings of CIT, including solid tumors, acute myeloid leukemia, stem cell transplant, and lymphoma. Studies have shown that TPO-RAs can improve platelet counts in CIT, but the clinical benefits of TPO-RA in terms of reducing bleeding, limiting platelet transfusion, avoiding chemotherapy delay, or dose reduction are uncertain. Further research is needed to optimize the selection of appropriate indications and study design to manage thrombocytopenia following chemotherapy.
Topics: Humans; Thrombocytopenia; Leukemia, Myeloid, Acute; Thrombosis; Antineoplastic Agents; Hemostasis; Thrombopoietin; Recombinant Fusion Proteins
PubMed: 37827380
DOI: 10.1016/j.jtha.2023.09.031 -
Journal of Translational Medicine Apr 2024Platelets not only participate in thrombosis and hemostasis but also interact with tumor cells and protect them from mechanical damage caused by hemodynamic shear stress... (Review)
Review
Platelets not only participate in thrombosis and hemostasis but also interact with tumor cells and protect them from mechanical damage caused by hemodynamic shear stress and natural killer cell lysis, thereby promoting their colonization and metastasis to distant organs. Platelets can affect the tumor microenvironment via interactions between platelet-related factors and tumor cells. Metastasis is a key event in cancer-related death and is associated with platelet-related factors in lung, breast, and colorectal cancers. Although the factors that promote platelet expression vary slightly in terms of their type and mode of action, they all contribute to the overall process. Recognizing the correlation and mechanisms between these factors is crucial for studying the colonization of distant target organs and developing targeted therapies for these three types of tumors. This paper reviews studies on major platelet-related factors closely associated with metastasis in lung, breast, and colorectal cancers.
Topics: Humans; Blood Platelets; Hemostasis; Thrombosis; Colorectal Neoplasms; Neoplasm Metastasis; Tumor Microenvironment
PubMed: 38637802
DOI: 10.1186/s12967-024-05126-6