Immature Platelet Fraction and Acute Coronary Syndrome; a Systematic Review and Meta-Analysis.

Introduction: Immature Platelet Fraction (IPF) is a measure of the proportion of reticulated platelets (RPs) to all platelets in circulation. IPF may have both prognostic and diagnostic values in patients with Acute Coronary Syndrome (ACS). This study aims to comprehensively summarize the diagnostic utility of IPF levels in patients with ACS, specifically focusing on its ability to differentiate between different subtypes of ACS. Methods: We conducted a systematic search in online databases including MEDLINE, Scopus, and Google Scholar up to March 4th 2024, to identify relevant studies. The random-effect model, employing inverse variance for mean differences (MD) and Mantel-Haenszel methods for odds ratios (OR) were utilized to combine the data. Joanna Briggs Institute (JBI) appraisal tool was employed to assess the quality of included studies. Results: Our systematic review contains 15 articles with a total sample size of 2,030 ACS patients. Pooled analysis revealed significant differences in IPF levels of ACS patients compared to healthy controls (MD (95%CI): 2.85 (0.86, 4.85), P-value = 0.004) and stable angina patients (MD (95%CI): 0.58 (0.23, 0.92), P-value < 0.001). Subgroup comparisons within ACS patients demonstrated higher IPF levels in myocardial infarction (MI) vs. unstable angina (UA) (MD (95%CI): 1.81 (0.41, 3.22), P-value = 0.01), ST elevation MI (STEMI) vs. non-ST elevation (NSTEMI) ACS (MD (95%CI): 0.74 (0.31, 1.17), P-value < 0.001), and NSTEMI vs. UA (MD (95% CI): 1.07 (0.24, 1.90), P-value = 0.01). Conclusion: IPF levels could increase in patients with ACS, particularly during the acute phase of STEMI. This suggests that IPF may be a useful biomarker for early diagnosis of ACS. Additionally, IPF levels may help differentiate between ACS subtypes.

Immature platelet counts in transfused platelet units given to neonates.

BACKGROUND: Immature platelets, young and large platelets recently released from the bone marrow, have gained interest over the last decade as a clinically informative variable during thrombocytopenic presentations. These immature platelets are found in all donated platelet units, however, the role, if any, that these younger platelets play post transfusion is not known. It has also been reported that the immune response can affect responses to platelet transfusions. Thus, we looked at PLT increments in a cohort of neonates receiving platelet transfusions in our neonatal intensive care unit. METHODS: During a twelve-month period, platelet transfusions received by neonates born and not discharged from our institution at time of transfusion were retrospectively analyzed. In the study period a total of 33 patients received either a single or multiple transfusions during their hospitalization, for a total of 100 transfusion events. RESULTS: The cohort was mostly premature neonates with a mean gestational age of 29.6 weeks. The units transfused appeared to have a broad range of absolute immature platelet counts (A-IPC) but overall, it was similar between those receiving single or multiple transfusions. Considering that platelet count was similar among aliquots transfused, it appeared that count increments were influenced by higher A-IPC content of the aliquot especially among 2nd trimester and 3rd trimester premature neonates. Patients with higher baseline platelet count (PLT) tended to receive a single transfusion aliquot while those receiving multiple transfusions had lower baseline PLT (p = 0.0022). Looking at aliquot dose, regardless if receiving a single or multiple transfusions, younger patients received incrementally higher dose (ml/kg) with each transfusion. CONCLUSIONS: A-IPC in platelet aliquots transfused to neonates may influence post-transfusion PLT. Full effect of A-IPC in platelet aliquots may not be seen since irradiation of units may hamper immature platelets viability and function. Further research is needed to determine if A-IPC plays an active role to limit the need for further transfusions of patients receiving transfusions.

Pretreatment Absolute Immature Platelet Count is a Promising Predictor of Response to Short-Term Dexamethasone Monotherapy or Combination Therapy in Newly Diagnosed Adult Primary Immune Thrombocytopenia.

Reliable indicators that can predict drug responsiveness in primary immune thrombocytopenia (ITP) patients are urgent. We aimed to establish a reference interval of percentage of immature platelet fraction (IPF%) and absolute immature platelet count (A-IPC), and assess their efficacy in discriminating ITP patients from controls, especially their predictive value for responsiveness to drug treatment. We retrospectively studied 72 treatment-naive adult patients with ITP who received Dexamethasone monotherapy or combination therapy. Baseline (pretreatment) information was collected from medical records. Reference intervals for A-IPC and IPF% were established based on controls and their effectiveness in discriminating ITP patients from controls was assessed. Predictive value of pretreatment IPF% and A-IPC at four co-primary endpoints of treatment response in patients were investigated. The 95% reference intervals for A-IPC and IPF% were (2.7-15.6) × 109/L and 1.2%-7.3%, respectively. Both A-IPC and IPF% had excellent discrimination ability for ITP patients from controls. It showed highly statistically significant differences in pretreatment A-IPC for predicting treatment response at day 7 between responders and non-responders, but not at days 14, 21 and 28. Pretreatment A-IPC had the higher area under the ROC curve with a cut-off of 0.86 than that of IPF% with a cut-off of 14.5% in predicting the treatment response in ITP patients at day 7. Pretreatment A-IPC exhibited acceptable predictive power and could be a promising predictor of response to short-term Dexamethasone monotherapy or combination therapy at day 7 in ITP patients.

Immature platelet fraction as a systemic inflammation marker in patients with chronic obstructive pulmonary disease.

INTRODUCTION: Recently, there has been an increasing interest to find a simple, low cost, widely available biomarker for outcome predictors in chronic obstructive pulmonary disease (COPD). METHODS: Absolute immature platelet count (AIPC), the percentage of AIPC to the total platelet count (immature platelet fraction [IPF%]), symptoms, spirometry results, age-dyspne-airflow obstruction index, and C-reactive protein tests of COPD patients and control group were recorded. Neutrophil/lymphocyte, monocyte/lymphocyte, and platelet/lymphocyte ratios and Charlson comorbidity index scores were calculated. RESULTS: One hundred and thirty-four COPD patients and 30 healthy control subjects were included in the study. Eighty-nine patients were in exacerbation (AECOPD) and 45 of them were in stable COPD period. There was a difference between IPF% values and AIPC of COPD group and control group (3.45 ± 2.41 vs. 2.04 ± 1.12, p = 0.01; 5.87 ± 2.45 vs. 5.20 ± 3.02, p = 0.01). A positive correlation was observed between IPF% with white blood cell count and neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio in all patients (r = 0.352, p < 0.001; r = 0.399, p < 0.001; r = 0.186, p = 0.032; r = 0.200, p = 0.021) and AECOPD (r = 0.356, p < 0.001; r = 0.414, p < 0.001; r = 0.239, p = 0.025; r = 0.273, p = 0.010). At a cut-off of 3.4, IPF% showed the highest accuracy in identifying COPD (sensitivity: 80.3%, specificity: 82.5%) using receiver-operating characteristic analysis. CONCLUSION: This is the first study to examine the relationship between AIPC, IPF%, and COPD. The higher IPF% values in COPD and the positive correlation between IPF% and other inflammatory markers are suggested that IPF may be an indicator of systemic inflammation in COPD.

A Case of Thrombocytopenia, Anasarca (Edema, Pleural Effusion, and Ascites), Fever, Reticulin Fibrosis/Renal Dysfunction, and Organomegaly (TAFRO) Syndrome Initially Not Presenting With Thrombocytopenia: A Role of Immature Platelet Fraction.

Thrombocytopenia, anasarca (edema, pleural effusion, and ascites), fever, reticulin fibrosis/renal dysfunction, and organomegaly (TAFRO) syndrome is a rare and severe systemic disease. The emergence of thrombocytopenia, however, may be preceded by other signs or symptoms, which could delay the diagnosis of the disease. We reported a case in which an increased immature platelet fraction (IPF), a surrogate marker for megakaryocytic activity, preceded the development of thrombocytopenia, and finally, we diagnosed the patient with TAFRO syndrome. A 79-year-old male with a previous history of uninephrectomy due to bladder and ureteral cancer was admitted to our hospital because of massive edema and progressive impairment in renal function. On admission, inguinal lymphadenopathy, elevated C-reactive protein (CRP), bilateral pleural effusion, and ascites were observed, and the lymph node biopsy showed that atrophic lymphoid follicles and germinal centers were observed along with prominent glomeruloid vascular proliferation and the expansion of the interfollicular spaces consistent with the feature of Castleman's disease. The peripheral platelet count did not reach the level of the criteria for TAFRO syndrome (13.9×104/µL), but the immature platelet fraction was increased (11.6%), and bone marrow biopsy revealed hyperplasia of megakaryocytes. During the course of the preemptive treatment with prednisolone and tocilizumab, thrombocytopenia was uncovered, and the patient was finally diagnosed as having TAFRO syndrome. Thus, the present case may offer valuable information on the role of the immature platelet fraction in the establishment of the early diagnosis of TAFRO syndrome.

Prognostic Implications of Immature Platelet Fraction at 5-Year Follow-up Among ACS Patients Treated With Dual Antiplatelet Therapy.

Objective: Platelets are strongly associated with cardiovascular events due to their role in thrombotic processes. Reticulated platelets have higher prothrombotic potential. The aim of the study was to evaluate the effectiveness of immature platelet fraction (IPF) in predicting long-term clinical outcomes in patients with acute coronary syndrome (ACS). Methods: This prospective, observational study enrolled patients with ACS treated with dual antiplatelet therapy comprising acetylsalicylic acid and clopidogrel or ticagrelor. The primary outcome was a composite endpoint defined as major adverse cardiovascular events (MACE): all-cause death, myocardial infarction (MI), ischemic stroke, or unplanned revascularization. IPF was determined using flow cytometry in the first 24 h of hospitalization. MACE were evaluated by 2 physicians based on electronic databases and source documentation including discharge letters received from patients upon telephone contact. Results: Overall, there were 140 ACS patients (mean age 65.1 ± 11.7, 37 females [26.4%]) included in this study. Of them, 22.9% had diabetes mellitus, 69.3% hyperlipidemia, 25% had a history of MI. The median IPF values were 2.85 [1.8-4.2] %. Clinical follow-up (median time: 57 months [interquartile range 55-59 months]) was available for 130 patients (92.9%). MACE occurred in 27 patients (20.8%). There were higher rates of MACE at higher IPF tertiles (3rd vs 1st tertile: HR = 5.341 95% CI: 1.546-18.454, P = .008). Cox regression analyses showed that IPF level was independently associated with MACE. Time-dependent receiver-operating characteristic curve analysis revealed area under the curve of 0.656 for 5-year outcome with an IPF cutoff point of 3.45% being 63.0% sensitive and 65.0% specific for MACE. Conclusions: The study showed IPF may be an independent predictor of long-term mortality and MACE (ClinicalTrials.gov number, NCT06177587).

Reference guide for the diagnosis of adult primary immune thrombocytopenia, 2023 edition.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia due to accelerated platelet destruction and impaired platelet production. Diagnosis of ITP is still challenging because ITP has been diagnosed by exclusion. Exclusion of thrombocytopenia due to bone marrow failure is especially important in Japan because of high prevalence of aplastic anemia compared to Western countries. Hence, we propose a new diagnostic criteria involving the measurement of plasma thrombopoietin (TPO) levels and percentage of immature platelet fraction (RP% or IPF%); 1) isolated thrombocytopenia with no morphological evidence of dysplasia in any blood cell type in a blood smear, 2) normal or slightly increased plasma TPO level (< cutoff), 3) elevated RP% or IPF% (> upper limit of normal), and 4) absence of other conditions that potentially cause thrombocytopenia including secondary ITP. A diagnosis of ITP is made if conditions 1-4 are all met. Cases in which criterion 2 or 3 is not met or unavailable are defined as "possible ITP," and diagnosis of ITP can be made mainly by typical clinical course. These new criteria enable us to clearly differentiate ITP from aplastic anemia and other forms of hypoplastic thrombocytopenia and can be highly useful in clinical practice for avoiding unnecessary bone marrow examination as well as for appropriate selection of treatments.

Towards a greater understanding of reduced response to aspirin in children with congenital heart disease post-cardiac surgery using immature platelet fraction.

OBJECTIVE: A high platelet turnover rate may produce a population of platelets that confers an inadequate response to aspirin. We aimed to investigate the relationship between residual platelet aggregation and platelet turnover in paediatric cardiology patients on aspirin monotherapy by evaluating the fraction of immature platelets as a marker for turnover and secondly to test the predictive value of the immature platelet fraction (IPF) to classify patients as responsive or non-responsive to aspirin. METHODS: Sixty patients divided into two age categories (≤90 days, >90 days of age) were included in this prospective observational study. Patients were then stratified into tertiles using their IPF level. Platelet studies included thromboelastography with platelet mapping (TEGPM). RESULTS: The overall incidence of 'inadequate response to aspirin' was 38 % in our patient cohort recently post-cardiac surgery a consequence that warrants further study. The frequency of inadequate response to aspirin was higher in the upper tertile of IPF when compared to the lower tertile, (88 %) versus (4 %) respectively (p < 0.05). The 'cut off' for IPF was determined to be 3.9 % with a sensitivity of 95.7 %, and a specificity of 92.9 % (area under the curve of 0.955 [CI 0.896-1.014, p < 0.05]). CONCLUSION: This study demonstrates that inadequate response to aspirin occurs in approximately 38 % of patients undergoing specific high-risk congenital cardiac procedures using the dosing practice of a national centre. This study supports the hypothesis that an elevated platelet turnover may result in aspirin being less effective in patients who are recently post cardiac surgery. These data are of direct translational relevance.

Immature platelet fraction and immature platelet count as novel biomarkers of elevated platelet reactivity in NSTE-ACS patients receiving dual antiplatelet therapy.

BACKGROUND: Antiplatelet therapy is the cornerstone of treatment for patients presenting with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Some patients may not respond to such therapy adequately, which is associated with a greater risk of ischemic events. Reticulated platelets are the youngest, largest, and most active platelet subtype. They have been initially shown to be associated with an increased risk of cardiovascular (CV) events and increased platelet activity. OBJECTIVES: The aim of the presented study was to evaluate whether the immature platelet fraction (IPF) reflects the response to antiplatelet treatment in invasively managed ACS patients. MATERIAL AND METHODS: This prospective study enrolled ACS patients treated with PCI and dual antiplatelet therapy (DAPT) comprising acetylsalicylic acid (ASA) and clopidogrel or ticagrelor. In all patients, venous blood was collected within 24 h after the procedure. Platelet parameters were measured, including IPF using the Sysmex hematological analyzer and adenosine diphosphate (ADP)-induced platelet reactivity using the Multiplate® Analyzer. RESULTS: A total of 108 patients were enrolled, including 62 with ST-segment elevation ACS (STE-ACS) and 46 with non-ST-segment elevation ACS (NSTE-ACS). Of them, 20.4% had diabetes mellitus, 26.9% had a history of MI and 59.2% of smoking. Spearman's correlation analysis demonstrated that higher IPF and immature platelet count (IPC) values are associated with increased ADP-induced platelet reactivity (respectively: rho = 0.387, 95% confidence interval (95% CI): 0.101-0.615, p = 0.008; and rho = 0.458, 95% CI: 0.185-0.666, p = 0.001) in NSTE-ACS but not in STE-ACS patients. CONCLUSION: Immature platelet count and IPF may be valuable markers of platelet activity in patients with NSTE-ACS treated invasively and receiving DAPT (ClinicalTrials.gov No. NCT06177587).

Reticulated Platelet Count as a Diagnostic Tool in Immune Thrombocytopenia (ITP).

OBJECTIVE: This study aimed to compare the reticulated platelet count between patients having thrombocytopenia secondary to autoimmune destruction (immune thrombocytopenia {ITP}), bone marrow failure, and healthy controls who presented to a tertiary care hospital in Karachi, Pakistan. METHODOLOGY: A cross-sectional study was conducted from February 2021 to October 2022 in the Department of Hematology, National Institute of Blood Disease (NIBD) Hospital in Karachi, Pakistan, that involved examining three groups: 30 patients with immune thrombocytopenia, 30 patients with thrombocytopenia secondary to reduced production from bone marrow, and 30 healthy controls. The study utilized the Sysmex XN-1000 (Hyogo, Japan: Sysmex Corporation) automated hematology analyzer to perform a complete blood count (CBC) test. Additionally, peripheral blood was stained with Leishman stain and examined under a microscope to eliminate pseudo thrombocytopenia and identify any abnormal cells or dysplasia. The immature platelet fraction (IPF) was then performed on Sysmex XN 1000 after ensuring adequate quality control. Finally, the data were analyzed using DATAtab (Graz, Austria: DATAtab) and SPSS version 25 (Armonk, NY: IBM Corp.). RESULTS: Of the ninety participants, the median age was 33 years with a range of 18-71 years. Patients with ITP had a significantly higher median IPF% (median=26.65, IQR=15-39.4) than thrombocytopenia due to bone marrow failure (median=9.25, IQR=4.55-14.30) and healthy controls (median=7, IQR=4.40-9.90), with a p-value of 0.001. The immune thrombocytopenia group demonstrated an increase in IPF% as platelet counts increased, indicating a significant moderate correlation between IPF% and platelets in these patients (r=0.438, p=0.016) and confirming that IPF% was an independent predictor for the detection of ITP. CONCLUSION: Reticulated platelet count may be a useful diagnostic tool to differentiate between ITP and thrombocytopenia caused by bone marrow failure. Because of its non-invasive nature, IPF is a valuable tool for expediting the management of thrombocytopenia associated with increased IPF.

Stability over time of immature platelet fraction and comparison between EDTA and citrated whole blood samples.

BACKGROUND: Immature platelets (IP) are the youngest circulating platelets, released from megakaryocytes, and demonstrating increased dimensions, significant RNA content, and enhanced activity. Immature platelet research focuses on a differential diagnostic help in patients with thrombocytopenia. The objectives of this study were to compare the variability of IP in citrate and EDTA samples, and to determine stability over time. METHODS: Fifty-six patients were included for comparison between EDTA and citrate whole blood sample collection. Among the patients, 28 had thrombocytopenia (platelet count < 150G/L). Platelet measurement impedancemetry and fluorimetry were performed with Sysmex XN-9000. The immature platelet fraction (IPF) and absolute immature platelet count (A-IPC) were determined with a fluorescent method. RESULTS: The mean value of platelet count with fluorescence was, in EDTA sample, 215 ± 171 and, in citrate sample, 153 ± 118 G/L. No significant difference was observed between IPF between EDTA and citrate (7.74 ± 6.68% vs. 8.45 ± 7.37%, p = 0.69), respectively. With the Bland-Altman analysis, the mean difference in the EDTA sample, between 1 and 24 h, was 8.06 ± 6.96% and 8.73 ± 7.12% for IPF, whereas in the citrate sample, between 1 and 6 h, it was 8.60 ± 7.29% and 7.54 ± 6.97%, for IPF. Comparing 1 h EDTA sample with 6 h citrate sample, the variance ratio was 0.974 (95% CI: 0.864-1.084) in IPF. CONCLUSIONS: We confirmed the potential to conduct IP measurements up to 24 h in the EDTA sample and IPF measurements in the citrate sample for up to 6 h. These results may be useful for the use of IPF, which is a promising parameter whose interest in clinical practice and standardization is not yet well defined.

Measurement of immature platelet fraction is useful in the differential diagnosis of MYH9 disorders.

INTRODUCTION: Although the presence of large and giant platelets is important in screening for MYH9 disorders, platelet morphology evaluation is dependent on operator subjectivity. Immature platelet fraction (IPF%) is widely used in clinical practice because of its rapidity and reproducibility; however, IPF% has been rarely analyzed in MYH9 disorders. Therefore, our study aimed to clarify the usefulness of IPF% in the differential diagnosis of MYH9 disorders. METHODS: We assessed 24 patients with MYH9 disorders, 10 with chronic immune thrombocytopenia (cITP), 14 with myelodysplastic syndromes (MDS) with thrombocytopenia (<100 × 109 /L), and 20 healthy volunteers. Platelet-related data, including IPF% and platelet morphology (diameter, surface area, and staining), were retrospectively analyzed. RESULTS: Median IPF% in MYH9 disorders, 48.7%, was significantly higher than in all other groups (cITP: 13.4%, MDS: 9.4%, controls: 2.6%). IPF% in MYH9 disorders was significantly negatively correlated with platelet count and significantly positively correlated with the diameter and surface area of platelets, but a correlation was not found between IPF% and platelet staining. The area under the curve of IPF% for the differential diagnosis of MYH9 disorders was 0.987 (95% CI: 0.969-1.000), with a sensitivity of 95.8% and specificity of 93.2% when the cutoff value of IPF% was 24.3%. CONCLUSION: Our study strongly suggests that IPF% is useful in the differential diagnosis between MYH9 disorders and other types of thrombocytopenia.

Comparison of platelet indices in dengue fever patients based on platelet transfusion: A prospective observational study in a tertiary care center.

CONTEXT: Dengue fever is the most prevalent mosquito-borne viral disease in humans. Platelet indices (PIs) are given by the cell counters but are often not reported which is possibly due to under-recognition of the utility of these parameters. AIMS: This study aimed to compare PIs in patients with dengue fever to assess their role in the outcome such as hospital stay and platelet transfusion requirements. SETTINGS AND DESIGN: Prospective observational study in a tertiary care center, Thrissur, Kerala. SUBJECTS AND METHODS: A group of 250 dengue patients was studied over a period of 18 months. The platelet parameters (platelet count, mean platelet volume [MPV], platelet distribution width [PDW], platelet large cell ratio [PLCR], plateletcrit [PCT] and immature platelet fraction [IPF]) were measured with Sysmex XN-1000 and followed up every 24 h. The clinical features, duration of hospital stay and platelet transfusion requirements details were collected. STATISTICAL ANALYSIS USED: Independent t-test, Chi-square test, Karl Pearson correlation coefficient. RESULTS: A total of sample size was 250. The study showed normal PDW and MPV, low platelet count and PCT, and high PLCR and IPF in dengue patients. There were significant differences in PIs (lower platelet count and PCT, higher MPV, PDW, PLCR, and IPF) in comparison between dengue patients based on platelet transfusion. CONCLUSIONS: PIs may act as a predictive tool in the diagnosis and predicting outcomes in dengue fever. Low platelet count and PCT, high PDW, MPV, PLCR, and IPF in transfused dengue patients were found to be statistically significant. Clinicians need to be sensitized about the utility and limitations of these indices and rationalize the need for red cell and platelet transfusions in dengue.

Immature platelets in COVID-19.

Platelets play a critical role in immune response. Coronavirus disease 2019 (COVID-19) patients with a severe course often show pathological coagulation parameters including thrombocytopenia, and at the same time the proportion of immature platelets increases. In this study, the platelet count and the immature platelet fraction (IPF) of hospitalized patients with different oxygenation requirements was investigated daily over a course of 40 days. In addition, the platelet function of COVID-19 patients was analyzed. It was found that the number of platelets in patients with the most severe course (intubation and extracorporeal membrane oxygenation (ECMO)) was significantly lower (111.5 ∙ 106 /mL) than in the other groups (mild (no intubation, no ECMO): 203.5 ∙ 106 /mL, p < .0001, moderate (intubation, no ECMO): 208.0 ∙ 106 /mL, p < .0001). IPF tended to be elevated (10.9%). Platelet function was reduced. Differentiation by outcome revealed that the deceased patients had a highly significant lower platelet count and higher IPF (97.3 ∙ 106 /mL, p < .0001, 12.2%, p = .0003).

What is the context? Pathological coagulation is a feature of severe cases of COVID-19, with both bleeding complications and thrombosis. Patients with severe COVID-19 are frequently treated with extracorporeal membrane oxygenation (ECMO), which is often associated with bleeding complications. Platelets play an important role in blood clotting. The proportion of immature platelets has been characterized as hyperreactive and associated with high prothrombotic activity. In addition, they are discussed as predictors of COVID-19 disease severity.What is new? In grading the severity of disease in our patient cohort, we consider the required oxygenation measures. Thus, the focus is on severe cases requiring intubation and ECMO compared to moderate (intubation, no ECMO) and mild (no intubation, no ECMO) cases.What is the impact? This study focuses on severely ill patients who require ECMO treatment. Therefore, this study provides further evidence to use immature platelet fraction to predict the outcome of severe COVID-19 courses.

Immature platelet fraction in cardiovascular diagnostics and antiplatelet therapy monitoring.

Immature platelet fraction (IPF), circulating platelets still containing RNA, can be easily calculated by automated flow cytometry, this makes them an accessible biomarker. Higher IPF concentrations were reported in patients with thrombocytopenia, patients who were smokers, and also those who were diabetics. Several studies have reported their diagnostic and prognostic importance in patients presenting with acute coronary syndromes, especially ST-segment elevation myocardial infarction, where increased IPF level is an independent predictor of cardiovascular death. In addition, higher IPF were reported in patients with inadequate response to either clopidogrel or prasugrel, suggesting their potential role in antiplatelet therapy monitoring. Their prognostic significance was also observed in both coronary artery disease and postcardiac surgery status, where their higher levels correlated with the risk of major adverse cardiac events. The current review aims to present the current evidence on diagnostic, prognostic and potentially therapeutic roles of IPF in cardiovascular medicine.

Platelet ageing: A review.

Platelet ageing is an area of research which has gained much interest in recent years. Newly formed platelets, often referred to as reticulated platelets, young platelets or immature platelets, are defined as RNA-enriched and have long been thought to be hyper-reactive. This latter view is largely rooted in associations and observations in patient groups with shortened platelet half-lives who often present with increased proportions of newly formed platelets. Evidence from such groups suggests that an increased proportion of newly formed platelets is associated with an increased risk of thrombotic events and a reduced effectiveness of standard anti-platelet therapies. Whilst research has highlighted the existence of platelet subpopulations based on function, size and age within patient groups, the common intrinsic changes which occur as platelets age within the circulation are only just being explored. By understanding the changes that occur during the natural ageing processes of platelets, we may be able to identify the triggers for alterations in platelet life span and platelet reactivity. Here we review research on platelet ageing in the context of health and disease, paying particular attention to the experimental approaches taken and the robustness of conclusions that can be drawn.

Machine learning-based improvement of MDS-CBC score brings platelets into the limelight to optimize smear review in the hematology laboratory.

BACKGROUND: Myelodysplastic syndromes (MDS) are clonal hematopoietic diseases of the elderly characterized by chronic cytopenias, ineffective and dysplastic haematopoiesis, recurrent genetic abnormalities and increased risk of progression to acute myeloid leukemia. A challenge of routine laboratory Complete Blood Counts (CBC) is to correctly identify MDS patients while simultaneously avoiding excess smear reviews. To optimize smear review, the latest generations of hematology analyzers provide new cell population data (CPD) parameters with an increased ability to screen MDS, among which the previously described MDS-CBC Score, based on Absolute Neutrophil Count (ANC), structural neutrophil dispersion (Ne-WX) and mean corpuscular volume (MCV). Ne-WX is increased in the presence of hypogranulated/degranulated neutrophils, a hallmark of dysplasia in the context of MDS or chronic myelomonocytic leukemia. Ne-WX and MCV are CPD derived from leukocytes and red blood cells, therefore the MDS-CBC score does not include any platelet-derived CPD. We asked whether this score could be improved by adding the immature platelet fraction (IPF), a CPD used as a surrogate marker of dysplastic thrombopoiesis. METHODS: Here, we studied a cohort of more than 500 individuals with cytopenias, including 168 MDS patients. In a first step, we used Breiman's random forests algorithm, a machine-learning approach, to identify the most relevant parameters for MDS prediction. We then designed Classification And Regression Trees (CART) to evaluate, using resampling, the effect of model tuning parameters on performance and choose the "optimal" model across these parameters. RESULTS: Using random forests algorithm, we identified Ne-WX and IPF as the strongest discriminatory predictors, explaining 37 and 33% of diagnoses respectively. To obtain "simplified" trees, which could be easily implemented into laboratory middlewares, we designed CART combining MDS-CBC score and IPF. Optimal results were obtained using a MDS-CBC score threshold equal to 0.23, and an IPF threshold equal to 3%. CONCLUSIONS: We propose an extended MDS-CBC score, including CPD from the three myeloid lineages, to improve MDS diagnosis on routine laboratory CBCs and optimize smear reviews.

Immature platelet fraction in rheumatoid arthritis with interstitial lung disease.

BACKGROUND: Platelets have an effect on the hemostatic defense of the lung. Immature platelet fractions (iPF) reflects the number of young platelets containing ribonucleic acid in the circulation and real-time production. Information about their roles in rheumatic diseases is limited and there are no studies on iPF in RA with interstitial lung disease (ILD). Our aim is to investigate the association between the iPF level and occurrence of ILD in RA and the correlation of iPF with disease activity in general or only in RA with ILD. METHODS: The study included 50 RA patients without ILD, 33 RA patients with ILD, and 30 healthy controls. Demographic data, Disease Activity Score 28 (DAS28), autoantibodies, and iPF were evaluated. ILD was diagnosed by using high-resolution computed tomography with clinical findings and chest X-ray. The samples were analyzed for complete blood count with platelet indices included, on Mindray BC-6800 hematology analyzer, Hamburg, Germany. RESULTS: iPF levels were higher in RA patients with ILD compared to healthy controls and RA patients without ILD. A weakly positive correlation between DAS28 with iPF was found in all RA patients. iPF levels were found as 2.85 to detect ILD with 66.7% sensitivity and 65% specificity. CONCLUSIONS: Our results showed that the iPF was detected higher in RA with ILD compared to RA without ILD. iPF, a routine cheap and easy test during hemogram, can provide important information in terms of disease activity and lung involvement in RA.

Immature platelet fraction in rheumatoid arthritis with interstitial lung disease / Fracción plaqueta inmadura en artritis reumatoide con enfermedad pulmonar intersticial

Background: Platelets have an effect on the hemostatic defense of the lung. Immature platelet fractions (iPF) reflects the number of young platelets containing ribonucleic acid in the circulation and real-time production. Information about their roles in rheumatic diseases is limited and there are no studies on iPF in RA with interstitial lung disease (ILD). Our aim is to investigate the association between the iPF level and occurrence of ILD in RA and the correlation of iPF with disease activity in general or only in RA with ILD. Methods: the study included 50 RA patients without ILD, 33 RA patients with ILD, and 30 healthy controls. Demographic data, Disease Activity Score 28 (DAS28), autoantibodies, and iPF were evaluated. ILD was diagnosed by using high-resolution computed tomography with clinical findings and chest X-ray. The samples were analyzed for complete blood count with platelet indices included, on Mindray BC-6800 hematology analyzer, Hamburg, Germany. Results: iPF levels were higher in RA patients with ILD compared to healthy controls and RA patients without ILD. A weakly positive correlation between DAS28 with iPF was found in all RA patients. iPF levels were found as 2.85 to detect ILD with 66.7% sensitivity and 65% specificity. Conclusions: Our results showed that the iPF was detected higher in RA with ILD compared to RA without ILD. iPF, a routine cheap and easy test during hemogram, can provide important information in terms of disease activity and lung involvement in RA.(AU)

Antecedentes: Las plaquetas tienen un efecto sobre la defensa hemostática del pulmón. Las fracciones de plaquetas inmaduras (FPi) reflejan el número de plaquetas jóvenes que contienen ácido ribonucleico en la circulación y la producción en tiempo real. La información sobre su papel en las enfermedades reumáticas es limitada y no existen estudios sobre la FPi en la AR con enfermedad pulmonar intersticial (EPI). Nuestro objetivo es investigar la asociación entre el nivel de FPi y la aparición de EPI en la AR y la correlación de la FPi con la actividad de la enfermedad en general o solo en la AR con EPI. Métodos: El estudio incluyó a 50 pacientes con AR sin EPI, 33 pacientes con AR con EPI y 30 controles sanos. Se evaluaron los datos demográficos, la puntuación de actividad de la enfermedad 28 (DAS28), los autoanticuerpos y la FPi. La EPI se diagnosticó mediante tomografía computarizada de alta resolución, con hallazgos clínicos y radiografía de tórax. Las muestras fueron analizadas para un recuento sanguíneo completo con índices de plaquetas incluidos, en el analizador de hematología Mindray BC-6800, Hamburgo, Alemania. Resultados: Los niveles de FPi fueron más altos en los pacientes con AR con EPI en comparación con los controles sanos y los pacientes con AR sin EPI. Se encontró una correlación débilmente positiva entre DAS28 y FPi en todos los pacientes con AR. Se encontró que los niveles de FPi eran de 2,85 para detectar ILD con una sensibilidad del 66,7% y una especificidad del 65%. Conclusiones: Nuestros resultados mostraron que la FPi se detectó más en AR con EPI en comparación con AR sin EPI. La FPi, una prueba de rutina barata y fácil durante el hemograma, puede proporcionar información importante en términos de la actividad de la enfermedad y la afectación pulmonar en la AR.(AU)

Comparison of thrombocytopenia between patients with non-alcoholic fatty liver disease and those with hepatitis C virus-related chronic liver disease.

AIM: Thrombocytopenia is widely recognized as a simple surrogate marker of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Thrombocytopenia of NAFLD has not been compared with that of hepatitis C virus-related chronic liver disease (CLD-C). Here, we examined whether there is any difference in the platelet counts between patients with NAFLD and CLD-C and investigated the underlying mechanisms. METHODS: A total of 760 biopsy-confirmed NAFLD and 1171 CLD-C patients were enrolled. After stratification according to the liver fibrosis stage, platelet counts between NAFLD and CLD-C patients were compared. The platelet count, spleen size, serum albumin level, serum thrombopoietin level, and immature platelet fraction (IPF) value were also compared after covariate adjustment using propensity score (PS) matching. RESULTS: The median platelet counts (×104 /µL) of NAFLD and CLD-C patients were 20.2 and 18.7 (p = 2.4 × 10-5 ) in F1; 20.0 and 14.5 (p = 2.1 × 10-12 ) in F2; 16.9 and 12.3 (p = 8.1 × 10-10 ) in F3; and 11.1 and 8.1 (p = 0.02) in F4, respectively. In the F3 group, NAFLD patients had a significantly higher platelet count and significantly smaller spleen volume than CLD-C patients. Although the serum thrombopoietin levels were comparable between NAFLD and CLD-C patients, the IPF value of NAFLD patients was significantly higher than that of CLD-C patients. CONCLUSIONS: NAFLD patients had a significantly higher platelet count than CLD-C patients following stratification according to the liver fibrosis stage. The milder hypersplenism and higher platelet production in NAFLD than CLD-C may have contributed to this difference.