Higher Immature Platelet Fraction Research Articles

High Immature Platelet Fraction is Associated with Early Neurological Deterioration in Acute Ischemic Stroke (P3-5.007)

<h3>Objective:</h3> To investigate the association between the level of immature platelet fraction (IPF) and the prevalence of early neurological deterioration (END) in acute ischemic stroke patients. <h3>Background:</h3> Early neurological deterioration (END) in acute ischemic stroke is a common event. However, the underlying pathophysiological bases are heterogenous and hard to explain. Immature platelet fraction (IPF) is the useful marker of increased platelet production and turnover which could occur in patients with increased platelet activation. High value of IPF was reported in acute coronary syndrome. <h3>Design/Methods:</h3> A total 1655 of acute ischemic stroke patients in single tertiary academic center was enrolled from January 2013 to October 2018 via stroke registry. IPF levels were quantified by whole blood flow cytometry with automated assays (Sysmex XE-2100™). High IPF was defined as the IPF level was more than 5%. Early neurological deterioration was defined as an increment change of at least one point in motor power or total National Institute of Health Stroke Scale (NIHSS) score deterioration ≥2 points within the first week after admission. <h3>Results:</h3> A total of 72 patients (4.4%) experienced END. END was more prevalent in the patients with high IPF [13 (11.7%) vs 59 (3.8%), p&lt;0.0001]. Multivariate logistic regression analysis showed high IPF was an independent predictor of the prevalence of END (adjust odds ratio = 1.32; 95% confidence interval = 1.03–1.70). <h3>Conclusions:</h3> A high IPF levels was associated with the prevalence of END in acute ischemic stroke patients. Future investigation might be needed to evaluate the effective treatment of the high IPF in acute phase of ischemic stroke. <b>Disclosure:</b> Bang-Hoon Cho has nothing to disclose. The institution of Sung-Wook Yu has received research support from Yuhan.

Role of Platelet Indices and Thrombopoietin (TPO) Serum Levels in the Differential Diagnosis of Thrombocytopenia

Background: The differential diagnosis of an isolated thrombocytopenia may be challenging, especially when it comes to differentiate immune thrombocytopenia (ITP) and an isolated thrombocytopenia in the context of bone marrow (BM) failure, in particular myelodysplastic syndromes (MDS); in such cases a BM examination is usually performed. It is known that thrombopoietin (TPO) serum levels are low in patients with ITP, while they are increased in case of amegakaryocytic thrombocytopenia. Furthermore, some platelet indices such as immature platelet fraction (IPF) may help to discriminate between hyporigenerative and consumption thrombocytopenia. Aim: The aim of this study was to compare TPO serum levels and platelet indices in patients with thrombocytopenia of different etiologies. Based on pathogenesis, we chose 3 groups of patients: ITP, amegakaryocytic thrombocytopenia (aplastic anemia (AA) or post-chemotherapy (CHT)) and thrombocytopenia in MDS and acute myeloid leukemia (AML). Although the diagnosis of amegakaryocytic thrombocytopenia and AML is straightforward with BM examination, we included patients with these diseases as a proof of concept and training set for our findings. Methods: This was a monocentric, retrospective, explorative study. Blood samples of patients with a platelet count < 100x109/L were collected. IPF, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), platelet large cell ratio (P-LCR) were obtained using Sysmex XN-1000 hemocytometer (Sysmex Corporation). TPO serum levels were measured with a quantitative sandwich ELISA (R&D Systems). Microsoft Excel software was used for descriptive statistical analysis. Anova and Student's t-test were used for comparisons between groups. A p-value <0.05 was considered statistically significant. Results: We enrolled 84 patients: 50 ITP, 22 AML/MDS (13 AML, 9 MDS), 12 AA/post-CHT (4 AA, 8 post-CHT). Results are reported in Table 1. Neither mean platelet count (p=0.20) nor PCT (p=0.44) were significantly different between the three groups. Mean TPO serum levels were higher in patients with AA/post-CHT compared to ITP and AML/MDS groups (p<0.001). All patients in AA/post-CHT group had a TPO serum level >500 pg/mL, this value was never reached in patients with ITP and AML/MDS. TPO serum levels were higher in AML/MDS patients compared to ITP patients (p<0.001). While TPO serum levels were available for all patients, platelet indices were not, due to technical issues. IPF was available in 46/50 ITP patients, 20/22 AML/MDS and 8/12 AA/post-CHT, and it was higher in ITP patients if compared to AA/post-cht (p=0.021) and AML/MDS (p=0.0045). MPV, PDW and P-LCR were available in 27/50 ITP patients, 12/22 AML/MDS and 9/12 AA/post-CHT: they were higher in ITP patients than in the other groups (AML/MDS p=0.0185, AA/post-CHT p=0.017). In our cohort, patients with TPO ≥250 pg/mL and IPF <12% had a higher probability to belong to AML/MDS group (TPO: OR 0.08, 95% CI 0.02-0.32; IPF: OR 0.19, 95% CI 0.06-0.59). These findings were confirmed by multivariate analysis (IPF: p-value = 0.0185, CI 0.8647-0.9868; TPO: p-value = 0.004, CI 1.002-1.011). The other platelet indices were not included in this analysis due to the paucity of data. No correlation was found between platelet count, TPO and IPF in ITP patients. Of note, no differences were observed in terms of platelet count, TPO serum levels ad IPF between patients with AML and MDS. Conclusions: Our findings confirm that, in patients with the same platelet count, those with consumptive thrombocytopenia have higher IPF and lower TPO levels, while patients with amegakaryocytic thrombocytopenia have higher TPO levels and lower IPF. While TPO levels alone can distinguish amegakaryocytic thrombocytopenia from other etiologies, these preliminary data suggest that by combining IPF and TPO, patients with consumptive thrombocytopenia can be distinguished from MDS patients. This could be useful to spare BM examination in selected cases, or as an additional tool when the diagnosis remains uncertain also with BM examination. These data need to be confirmed in larger cohorts. The role of the other platelet indices, and the technical issues in their determination, needs further studies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Correlation between Immature Platetet Fraction Value and SOFA Score in Sepsis Patient

Sepsis is a medical emergency that describes systemic inflammation reaction to infectious process that can lead to organ dysfunction and death. Sequential Organ Failure Assesment (SOFA) score is used to assess severity of organ dysfunction in septic patients. Immature platelet fraction (IPF) value can be used to evaluate thrombopoiesis. Research shows IPF can provide information regarding inflammatory activity and disease prognosis. A high IPF value in septic patient indicates the formation and recruitment of immature platelets that are triggered by infection. The aim of this study was to determine correlation between IPF value and SOFA score in sepsis patients. This was an analytical study with a cross-sectional design in 28 patients with sepsis who met the inclusion and exclusion criteria and conducted IPF tests at Central Laboratory of Dr M. Djamil Padang Hospital. The study was conducted from February 2020 to March 2021. Value of IPF was performed using automated hematology analyzer with flow cytometry method and SOFA scores are assessed by clinicians and obtained from medical records. Data were analyzed by Pearson correlation test, significant if p &lt;0.05. Median value of IPF in patients with sepsis was 4.8 (1.4-15.7) %. Median of SOFA score in patients with sepsis was 5,5 (2-12). Correlation test showed a strong positive correlation between IPF values and SOFA score with r= 0.684 and p &lt;0.05. There was a strong positive correlation between IPF values and SOFA score in sepsis.

Plasma Fibrinogen Independently Predicts Hypofibrinolysis in Severe COVID-19

High rates of thrombosis are present in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Deeper insight into the prothrombotic state is essential to provide the best thromboprophylaxis care. Here, we aimed to explore associations among platelet indices, conventional hemostasis parameters, and viscoelastometry data. This pilot study included patients with severe COVID-19 (n = 21) and age-matched controls (n = 21). Each patient received 100 mg aspirin therapy at the time of blood sampling. Total platelet count, high immature platelet fraction (H-IPF), fibrinogen, D-dimer, Activated Partial Thromboplastin Time, von Willebrand factor antigen and von Willebrand factor ristocetin cofactor activity, plasminogen, and alpha2-antiplasmin were measured. To monitor the aspirin therapy, a platelet function test from hirudin anticoagulated whole blood was performed using the ASPI test by Multiplate analyser. High on-aspirin platelet reactivity (n = 8) was defined with an AUC > 40 cut-off value by ASPI tests. In addition, in vitro viscoelastometric tests were carried out using a ClotPro analyser in COVID-associated thromboembolic events (n = 8) (p = 0.071) nor the survival rate (p = 0.854) showed associations with high on-aspirin platelet reactivity status. The platelet count (p = 0.03), all subjects. COVID-19 patients presented with higher levels of inflammatory markers, compared with the controls, along with evidence of hypercoagulability by ClotPro. H-IPF (%) was significantly higher among non-survivors (n = 18) compared to survivors (p = 0.011), and a negative correlation (p = 0.002) was found between H-IPF and plasminogen level in the total population. The platelet count was significantly higher among patients with high on-aspirin platelet reactivity (p = 0.03). Neither the ECA-A10 (p = 0.008), and ECA-MCF (p = 0.016) were significantly higher, while the tPA-CFT (p < 0.001) was significantly lower among patients with high on-aspirin platelet reactivity. However, only fibrinogen proved to be an independent predictor of hypofibrinolysis in severe COVID-19 patients. In conclusion, a faster developing, more solid clot formation was observed in aspirin ‘non-responder’ COVID-19 patients. Therefore, an individually tailored thromboprophylaxis is needed to prevent thrombotic complications, particularly in the hypofibrinolytic cluster.

Immature Platelet Fraction in Thrombocytopenic Patients

Bone marrow puncture (BMP), is usually performed to identify thrombopoiesis activity and is still the gold standard to determine the etiology of thrombocytopenia. This diagnostic test is invasive hence it may cause discomfort to the patient. One of noninvasive test to determine the etiology of thrombocytopenia is by measuring immature platelet fraction (IPF). IPF is highly correlated to the activity of thrombopoiesis and by understanding the value, clinicians are able to use it in determining whether or not invasive examination is needed and more importantly avoiding unnecessary platelet transfusion. This research was a cross-sectional descriptive observational study aimed to evaluate IPF value in thrombocytopenic inpatients in the Department of Internal Medicine, Haji Adam Malik Hospital Medan. 83 people were recruited, 48 were female (57.83%) and 35 were male (42.16%). IPF values ranged 0,5-59,6% using Sysmex XN-1000 (reference range 1-4,8%). There were 5 (6.02%) low IPF values, 29 (34.93%) normal IPF values and 49 (59.03%) high IPF values. Evaluation of IPF in thrombocytopenic patients is a promising tool to discriminate central from peripheral thrombocytopenia.

An Analysis of Immature Platelet Fraction Values

IntroductionImmune thrombocytopenia (ITP) in children typically manifests with acute, severe thrombocytopenia leading to variable mucocutaneous and tissue bleeding. Despite gaining insight into disease biology, there is no confirmatory diagnostic test, leaving the clinician to exclude other causes of thrombocytopenia through clinical and laboratory findings. The immature platelet fraction (IPF) is determined by hematologic analyzers via platelet size and RNA content and serves as a measure of bone marrow thrombocyte production. A higher value indicates increased thrombopoiesis. While data exists regarding the validity of IPF as a diagnostic tool for differentiating hypo-productive and consumptive etiologies of thrombocytopenia in the adult population, there is a paucity of data regarding its use in the pediatric population.ObjectivesThis study set out to determine how the IPF value may be utilized to support the diagnosis of ITP among pediatric patients.MethodsThis is a retrospective cohort study at a single tertiary care children's hospital. The electronic medical record (EMR) system was reviewed to include all patients who had an IPF resulted from January 1, 2016 through December 31, 2021. The investigators utilized REDCap ® (Research Electronic Data Capture) to create a database of pediatric patients with thrombocytopenia including their laboratory findings and final diagnoses.Patients were classified as either ITP or non-ITP. Characteristics of ITP and non-ITP cohorts were compared using Wilcoxon rank sum test and Pearson Chi-square test. An ROC-AUC analysis was conducted to identify the IPF value which best predicted if the patient had ITP or not with a 95% confidence interval (CI). The optimal cutoff value was estimated using Youden's index. Sensitivity and specificity were estimated for the cutoff value. Univariable logistic regression was then used to estimate associations between patient characteristics and diagnosis of ITP. Multivariable logistic regression was used to estimate the association between binary IPF and ITP adjusting for other predictors. Statistical significance was assessed at the 0.05 level.ResultsDemographics shown in Table 1 are stratified by patients who had their IPF within 30 days of diagnosis of thrombocytopenia and those who did not. The IPF was significantly higher at presentation in all patients with ITP than patients without ITP (median IPF 12.8% vs 10.5%, P=0.018). An optimal IPF cutoff point for ITP vs. not ITP among all patients was determined to be 5.4% with a sensitivity of 0.85, specificity of 0.39, and AUC of 0.623 (95% CI: 0.527, 0.718). The platelet count for patients with ITP was significantly lower at presentation than in patients without ITP (median 16 x 10 9/L vs 86 x 10 9/L, P<0.001). Logistic regression modeling using IPF as a binary variable, either >5.4% or not, showed that IPF >5.4% is significantly associated with ITP (P<0.001). Platelet count at presentation was also significantly associated with a diagnosis of ITP (P<0.001) and a single unit increase in platelet count decreased odds of ITP by a factor 0.98 (95% CI: 0.97, 0.99). After adjusting for platelet count, IPF >5.4% was still significantly associated with ITP (P=0.003). Those with an IPF >5.4% were 3.34 times more likely to have ITP than non-ITP (95% CI: 1.49, 7.31).When the population was adjusted to include only patients with a platelet count of <100 x 10 9/L at presentation and those that had an IPF obtained within 30 days, the optimal cutoff point for IPF was 15% with a sensitivity of 0.46, specificity of 0.80 and AUC of 0.58 (95% CI: 0.458, 0.719).ConclusionThe data demonstrates that in thrombocytopenic patients, a high IPF (>5.4%) is associated with ITP, but the sensitivity for predicting ITP is low. [Display omitted] DisclosuresDespotovic: Apellis: Consultancy; Agios: Consultancy; Novartis: Consultancy, Research Funding; UpToDate: Patents & Royalties: Royalties. Kirk: Biomarin: Honoraria.

The immature platelet fraction affects the efficacy of platelet rich plasma therapy for knee osteoarthritis.

IntroductionPlatelet-rich plasma (PRP) therapy is used to treat pathological conditions such as degenerative inflammatory diseases including osteoarthritis (OA) by enhancing tissue repair and promoting anti-inflammatory effects. Although PRP therapy for patients with knee OA improved pain and functional scores, the association of clinical outcomes and quality of PRP including cell composition and concentration is unclear.MethodsTherefore, this study analyzed blood cell counts, including the immature platelet fraction (IPF), in peripheral blood and PRP of 144 patients with knee OA who underwent PRP therapy. The mean leukocyte and platelet concentrations in whole blood and PRP were analyzed using an XN-1000 automated hematology analyzer. Visual analogue scale (VAS) scores and knee injury and osteoarthritis outcome scores (KOOS) before and 1 month after a single PRP injection were also determined.ResultsHigher platelet and lower leukocyte concentration rates were observed in PRP compared with whole blood. The platelet concentration in whole blood was negatively correlated with VAS improvement. The percentage of IPF (IPF%) in whole blood was positively correlated with VAS improvement and KOOS (pain) improvement, whereas the IPF% in PRP tended to correlate with VAS improvement. Furthermore, multivariate logistic regression demonstrated the high IPF% in whole blood was significantly associated with VAS improvement. The low percentage of neutrophil (neutrophil%) in PRP was significantly associated with the VAS improvement and KOOS (ADL) improvement.ConclusionsTherefore, PRP efficacy for OA might depend on the patient's biological status.

A Case Report, Suspected Megakaryoblastic Transformation In A Chronic Myeloid Leukemia Patient

Preliminary: Chronic myeloid leukaemia (CML) is a clonal hematopoiesis stem cell disorder, characterised by reciprocal translocation between chromosomes 9 and chromosomes 22, originally named the ‘Philadelphia chromosome’(Ph). The megakaryoblastic transformation of a CML is extremely rare, consisting <3% of transformed cases. Case description: A 68-year-old male presented with a CML history since 2000 and received Imatinib therapy. The patient currently showed anemia and splenomegaly. Laboratory results showed hemoglobin 8.1 g/dL, leukocyte count 31,740/?L, platelet count 7,000/?L, Immature Platelet Fraction (IPF) 29.2%, BCR-ABL gene fusion is positive. Bone marrow examination showed CML blastic crisis phase with 45% blasts which had megakaryoblast morphology so it was concluded as a CML that underwent a transformation into megakaryoblastic. The results of bone marrow aspirate using Sysmex-XN1000 showed a very high IPF value which indicated an increased megakaryopoietic proliferative activity. Immunophenotyping examination showed blast population with CD45 dim, low side scatter, with the expression of CD34+, CD33+, CD13+ corresponding to the megakaryoblast area. Examination of the CD41 and CD61 specific megakaryoblast markers was not performed due to reagent limitations. Discussion: Clinical features, morphology, immunophenotyping and molecular findings help the identification of CML with suspected megakaryoblastic transformation. Conclusion: A CML patient has been reported with suspected megakaryoblastic transformation based on the bone marrow morphology, immunophenotyping, molecular and elevated IPF examination.

Role of immature platelet fraction (IPF) in sepsis patients: A systematic review.

Sepsis is extremely common amongst critically ill patients and requires early diagnosis. Hence, identifying a biomarker that could acknowledge sepsis at its prior stage is of vital significance. Immature platelets are a percentage of circulating platelets that contain RNA and is a newer parameter that is measured using automated hematology analyzers in diagnosing sepsis. This review article discusses 10 articles that reveal the role of immature platelet fraction in predicting the onset of sepsis and its relationship with mortality in sepsis. Literature search was done using PubMed, Scopus and Google Scholar and words like platelet indices and immature platelet fraction were typed in the search bar. The aim of this review article is to present a precise form of data that talk about immature platelet fraction (IPF) and its association with the severity and mortality of sepsis. Five out of 10 articles suggest that immature platelet fraction can predict the onset of sepsis and eight out of 10 articles suggest that increased IPF values are associated with high mortality.

CLINICAL RELEVANCE OF EXTENDED PLATELET INDICES IN THE DIAGNOSIS OF IMMUNE THROMBOCYTOPENIA.

SUMMARYImmune thrombocytopenia (ITP) is an autoimmune disorder. Besides platelet count, immature platelet fraction (IPF) can be used as a tool to predict megakaryocytic activity in ITP patients. The aim of the study was to evaluate the utility of extended platelet indices in ITP diagnosis and their association with disease persistence and severity. This case-control study (1:1), conducted from January 2015 to December 2017, included 111 ITP patients and 111 healthy controls. ITP patients were grouped as newly diagnosed ITP, persistent ITP, chronic ITP, and refractory ITP patients. Peripheral blood was collected and complete blood profile parameters were recorded using Sysmex XN 1000. Significant (p≤0.05) difference between the groups of ITP patients and healthy control subjects was determined by Fisher exact test, while Pearson correlation was used to evaluate platelet count correlation with IPF using SPSS ver. 23. Low hemoglobin and platelet counts with high total leukocyte count and IPF were detected in ITP patients as compared to healthy subjects (p≤0.001). Among all groups of ITP patients, very low platelet count (6.9±6.02.x109/L) with highest mean IPF (27.1±19.2%) was observed in newly diagnosed ITP group. Other platelet parameters including mean platelet volume (MPV), plateletcrit, platelet large cell ratio (P-LCR) and platelet distribution width values were also altered in patient groups. Pearson correlation revealed negative relationship between platelet count and IPF in all patient groups. With the advent of new, sophisticated hematologic analyzers, the IPF and other platelet parameters provide simple, reliable and easier tools for predicting platelet disorders such as ITP, and to some extent the disease severity. Besides IPF, the MPV and P-LCR seemed to predict disease severity, treatment responsiveness, and duration of the disease to some extent.

Immature platelet fraction based diagnostic predictive scoring model for immune thrombocytopenia.

Background/AimsThe diagnosis of immune thrombocytopenia (ITP) is based on clinical manifestations and there is no gold standard. Thus, even hematologic malignancy is sometimes misdiagnosed as ITP and adequate treatment is delayed. Therefore, novel diagnostic parameters are needed to distinguish ITP from other causes of thrombocytopenia. Immature platelet fraction (IPF) has been proposed as one of new parameters. In this study, we assessed the usefulness of IPF and developed a diagnostic predictive scoring model for ITP.MethodsWe retrospectively studied 568 patients with thrombocytopenia. Blood samples were collected and IPF quantified using a fully-automated hematology analyzer. We also estimated other variables that could affect thrombocytopenia by logistic regression analysis.ResultsThe median IPF was significantly higher in the ITP group than in the non-ITP group (8.7% vs. 5.1%). The optimal cut-off value of IPF for differentiating ITP was 7.0%. We evaluated other laboratory variables via logistic regression analysis. IPF, hemoglobin, lactate dehydrogenase (LDH), and ferritin were statistically significant and comprised a diagnostic predictive scoring model. Our model gave points to each of variables: 1 to high hemoglobin (> 12 g/dL), low ferritin (≤ 177 ng/mL), normal LDH (≤ upper limit of normal) and IPF ≥ 7 and < 10, 2 to IPF ≥ 10. The final score was obtained by summing the points. We defined that ITP could be predicted in patients with more than 3 points.ConclusionsIPF could be a useful parameter to distinguish ITP from other causes of thrombocytopenia. We developed the predictive scoring model. This model could predict ITP with high probability.

Impact of active smoking on the immature platelet fraction and its relationship with the extent of coronary artery disease.

Smoking represents a major cardiovascular risk factor, due to the induction of oxidative stress and low-grade, continuous, inflammation that contribute to promote atherothrombosis. However, the mechanisms leading to increased platelet aggregability associated with smoking are only partially defined. A potential role has been hypothesized for immature platelets, a younger and potentially more reactive fraction, previously associated with the main determinants of coronary artery disease (CAD). Therefore, the aim of our study was to define the impact of smoking on the immature platelet fraction (IPF) and its relationship with prevalence and extent of coronary artery disease. We enrolled a cohort of consecutive patients undergoing coronary angiography in a single centre. Significant CAD was defined as at least 1 vessel stenosis >50%, while severe CAD was defined as left main and/or three-vessel disease. IPF was measured at admission by routine blood cell count (Sysmex XE-2100). We included in our study 2553 patients who were divided according to smoking status (active smokers: 512; nonactive smokers: 2041). Smokers were younger, more frequent males, with lower rate of diabetes mellitus, previous PCI and previous CABG (P<.001, respectively) and were in treatment less often with ARB, BB, nitrates, statins, ASA, clopidogrel, CCB and diuretics (P<.001, respectively) as compared to nonactive smokers. Higher percentage of smokers was observed in patients with higher IPF values, and at multivariate analysis, active smoking resulted as an independent predictor of higher IPF (adjusted OR [95% CI]=1.59[1.03-2.45], P=.035). Among smokers, higher IPF was associated with lower ejection fraction (P=.034), percentage of acute coronary syndrome (P=.002) and platelet count (P<.001) compared to ones with lower IPF. However, the IPF (according to quartiles values) was not associated with the prevalence and extent of CAD (82.5%, 80.4%, 86.1% and 80.9%, from 1st to 4th quartile, respectively, adjusted OR[95% CI]=0.98[0.79-1.23], P=.89) and severe CAD (31%, 31.1%, 39.1% and 35.2%, from 1st to 4th quartile, respectively, adjusted OR[95% CI]=1.03[0.86-1.23], P=.76). The present study shows an independent association between active smoking and the levels of immature platelet fraction in patients undergoing coronary angiography. However, among active smokers, IPF did not result as an independent predictor of CAD or severe CAD.

Association of the immature platelet fraction with sepsis diagnosis and severity

Objective To explore the relationship between immature platelet fraction(IPF) with severity of sepsis and prognosis in patients with septic shock. Methods A total of 40 patients admitted to intensive care units of Tianjin First Central Hospital from June 2016 to June 2017 were enrolled. Of them,10 patients contracted non-sepsis infected,13 patietns with septic shock, and 17 patients with non-complicated sepsis. Ten healthy subjects were recruited as control groups from Tianjin Medical University.IPF and immature reticulocyte fraction (IRF) were detected, and SOFA and APACHEⅡ scores were calculated, and clinical findings of all groups were recorded. The differences in IPF and IRF between the groups were analyzed. The relationship between the IPF and SOFA score was studied, and the role of IPF in the diagnosis of septic shock was evaluated. Statistical methods include t test, Mann-Whitney test, Spearman correlation analysis, and ROC procedure,and P<0.05 was considered significant. Results Significantly higher IPF level was observed in patients with sepsis than that in patients with non-sepsis infection.(6.25±2.92) vs. (2.49±1.03), P<0.01. Significantly higher IPF level was observed in patients with septic shock than that in patients with non-complicated sepsis(4.71±1.79) vs. (8.25±2.94), P<0.01. IPF correlated with sepsis severity scores (7.41±3.51) vs. (4.5±1.7), P=0.005; r=0.58, P=0.001. This study presented the highest diagnostic accuracy for the presence of sepsis by all studied clinical and laboratory parameters (AUC=0.78, P=0.01). Conclusion IPF levels could be used as a biomarker for diagnosis and severity of sepsis. Key words: Immature platelet fraction; Sepsis; Septic shock; APACHE Ⅱ; SOFA

Novel hematological parameters for the evaluation of patients with myeloproliferative neoplasms: the immature platelet and reticulocyte fractions

New automated hematology analyzers have led to the availability of novel hematological parameters, including the immature platelet fraction (IPF) and the immature reticulocyte fraction (IRF), both of potential interest in patients with myeloproliferative neoplasms (MPNs). We performed a prospective analysis of 217 patients with MPN, including 32 (15%) with essential thrombocythemia (ET), 43 (20%) with polycythemia vera (PV), and 142 (65%) with myelofibrosis (MF); the IPF and IRF were measured by the Sysmex XN analyzer. As compared to patients with ET, both a higher IPF and IRF were observed among patients with PV and MF. Factors associated with high IPF among patients with PV/ET were male sex, thrombocytopenia, and diagnosis of PV; among patients with MF, they were elevated peripheral blasts, low platelet count, JAK2 V617F mutation, and previous therapy. Factors associated with high IRF among patients with PV/ET were low hemoglobin, high reticulocyte count, and PV diagnosis; among patients with MF, they were peripheral blasts and elevated reticulocytes. The IPF and IRF represent novel parameters in patients with MPN with potential relevant clinical implications. Comparison with healthy subjects and those with secondary polycythemia is needed to confirm our preliminary findings.

Immature Platelet Fraction Is Associated with JAK2 V617F Mutation and Features of Advanced Disease in Myelofibrosis

Introduction: The Immature Platelet Fraction (IPF) is a generally available hematological parameter, identifying a portion of "young" and hemostatically more active platelets, typically increasing in presence of thrombocytopenia. A high IPF has been associated with JAK2 mutation and increased risk of thrombosis in patients with polycythemia vera (PV) and essential thrombocytemia (ET). However its significance has never been explored in patient with myelofibrosis (MF).Methods: IPF was measured using the Sysmex XN-Series analyzer; an IPF greater than 6.2% was defined high, in accordance with previous studies. Categorical and continuous variables were compared using the χ2 or Fisher exact tests, and the Mann-Whitney test, as appropriate. Logistic regression was used for multivariable analysis of categorical variable. Survival was calculated using the method of Kaplan and Meier, and univariable comparisons were made using the log-rank test. All p-values < 0.05 were considered significant.Results. One hundred and forty-two sequential unselected patients with MF were included in the study; baseline characteristics at time of IPF measurement are shown in the Table.Seventy (49%) patients had a high IPF. Factors associated with high IPF on univariate analysis were elevated white blood count (p=0.04), elevated peripheral blasts (p=0.04), low platelet count (<0.001), secondary MF (p=0.004), JAK2 mutation (p=0.002), and previous therapy (p=0.007). On multivariable analysis, the factors which remained associated with high IPF were elevated peripheral blasts (odd ratio [OR] 3.3, 95% confidence interval [CI] 1.4-8.1; p=0.009), low platelet count (OR 3.7, 95% CI 1.6-8.8; p=0.003), JAK2 mutation (OR 4.3, 95% CI 1.7-10.8; p=0.002) and previous therapy (OR 2.6, 95% CI 1.2-5.8; p=0.02). After a median follow-up of 22 months (range, 1-26) from the date of IPF measurement, no thrombotic events were reported, 11 patients developed secondary acute myeloid leukemia, and 25 patients died. Median overall survival has not been reached. IPF was not significantly associated with any of these outcomes.Discussion. Similarly to PV and ET, also in patient with MF high IPF associates with JAK-2 mutation, suggesting an interaction between the JAK-STAT pathway and platelet activation in these patients; in addition, high IPF associates with markers of advanced disease, such as elevated peripheral blasts, low platelets and previous exposure to therapy. Longer follow-up is needed to assess the impact of IPF on the risk of thrombosis and transformation, and survival. [Display omitted] DisclosuresVerstovsek:Geron: Research Funding; Pfizer: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Research Funding; Promedior: Research Funding; CTI BioPharma Corp: Research Funding; NS Pharma: Research Funding; Lilly Oncology: Research Funding; AstraZeneca: Research Funding; Roche: Research Funding; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Galena BioPharma: Research Funding; Seattle Genetics: Research Funding; Gilead: Research Funding; Celgene: Research Funding.

A time course study of high on treatment platelet reactivity in acute coronary syndrome male patients on dual antiplatelet therapy

IntroductionLimited data are available on the natural history of high on treatment platelet reactivity (HPR) by arachidonic acid and ADP - markers of unfavorable prognosis in acute coronary syndrome patients -. Material and methodsIn a cohort of acute coronary syndrome male patients (n=101), we evaluated the time-course of HPR by ADP (platelet aggregation by 10μM ADP≥70%) and arachidonic acid (platelet aggregation by 1mmol arachidonic acid≥20%) measuring platelet function in the acute phase (T0), at 6months (T1) and 1year (T2). ResultsWe identified persistent (HPR at T0,T1 and T2), acute non persistent (HPR only at T0), and late (HPR only at T1 or T2). Patients with persistent HPR by ADP were more frequently with higher values of BMI. Patients carrying CYP2C19*2 variant were more prevalent in the group of persistent HPR (33%). Significant higher values of immature platelet fraction and high immature platelet fraction at 6 and 12months and mean platelet volume were present in patients with late HPR. Immature platelet fraction was the only variable significantly associated with late HPR by ADP at multivariate analysis (OR=1.6 (1.08-2.3), p=0.016). Patients with persistent HPR by arachidonic acid were more frequently diabetics. Immature platelet fraction at 6months and high immature platelet fraction at 6 and 12months were the parameters associated with late HPR by AA (OR=1.4 (1.0-1.9), p=0.036; OR=1.5 (1.08-2.4), p=0.05; OR=4.9 (1.3-18.8), p=0.018, respectively). ConclusionsAbout 25% of 101 patients has persistent HPR; they are more frequently diabetics, overweight or carriers of CYP2C19*2. The occurrence of an inflammatory state, indicated by the increase of immature platelet fraction, is associated with the occurrence of late HPR.

Immature platelet fraction measurement is influenced by platelet size and is a useful parameter for discrimination of macrothrombocytopenia

BackgroundReticulated platelets (RPs) as measured using flow cytometry are useful parameters of thrombopoiesis; however, difficulties remain with standardization between laboratories. On the other hand, immature platelet fraction (IPF) measurement, as determined using an automated hematology analyzer, is simple, reproducible, and displays a good correlation with RP, although specific factors may affect its value. We previously noticed that a small proportion of patients exhibit extremely high IPF values that do not correlate with flow cytometrically measured RP.ObjectivesWe investigated the mechanism of the aberrant increase in IPF values of different types of macrothrombocytopenia.Patients/methodsIPF, RP, and other platelet indexes were analyzed using samples from 15 congenital macrothrombocytopenic patients from 12 families, 150 immune thrombocytopenic patients, and 27 normal individuals. We further monitored the change in IPF values and morphology during platelet agglutination.ResultsIPF values were about five times higher in MYH9 disorders (IPF 48.6 ± 1.9%) and about twice as high in other macrothrombocytopenias (IPF 18.4 ± 2.1%) than in immune thrombocytopenic patients with similar platelet counts (IPF 9.2 ± 0.3%). We then examined changes in IPF values during ethylenediaminetetraacetic acid- and macroglobulinemia-induced platelet agglutination. The IPF value significantly increased in a time-dependent manner along with the formation of platelet clumps and was strongly influenced by a few tiny platelet aggregates.ConclusionsThese results suggested that IPF values are influenced by platelet size. Furthermore, IPF could be a useful and convenient parameter for screening of macrothrombocytopenia, which presents with a disproportionately high IPF value.

Immature Platelet Fraction Predicts Outcome and Sepsis Development in Critically Ill Patients Admitted to a General Intensive Care Unit, but Not in Neutropenic Patients

Introduction: Immature platelet fraction (IPF) is a new laboratory parameter, representing a fraction of young platelets in peripheral blood count which is known to correlate with thrombopoiesis. IPF can be reported in absolute numbers or expressed as percentage (IPF%) of total platelet count. IPF% can be used to differentiate individuals at higher risk for bleeding among patients suffering from immune thrombocytopenia and to predict recovery of blood counts after stem cell transplantation (SCT). Moreover, IPF% was also reported to predict the development of sepsis in patients admitted to the general intensive care unit. This study was aimed to prospectively evaluate the value of IPF% as a predictor of clinical outcome and/or mortality in patients susceptible to sepsis.Methods: Two different patient populations at high risk for life-threatening infection, i.e., patients presenting with fever and neutropenia and adults admitted to the general intensive care unit (ICU) of a tertiary health care center for various reasons apart from neutropenic fever were prospectively studied. IPF was measured using the Sysmex XE-2100 analyzer during the first 24 hours of hospitalization. In addition, C-reactive protein (CRP) and Interleukin-6 (IL-6) levels were tested in some of the patients. All patients were monitored and their vital signs, renal function, hemodynamic and respiratory state, as well as final outcome were recorded. For patients with neutropenic fever, the infectious pathogen was listed, whenever identified. Treating physicians were blinded to IPF% results to ensure that clinical decisions were not affected by consideration of this parameter.Results: One hundred and four adults with neutropenic fever and 138 additional adults admitted to the ICU were included in the study.A median age of patients admitted to ICU and those with neutropenic fever was 53 (range 17-88) and 55 (range 18-85) years; males composed 58% and 60% of the cohorts, respectively. A mean IPF% in patients admitted to ICU was significantly higher than that determined in neutropenic patients (8.6 vs 6.8). IPF% levels during the first 24 hours of admission, predicted mortality (p = 0.037) for patients admitted to ICU but not for patients presenting with neutropenic fever. In patients admitted to ICU, high IPF% was also associated with length of stay in the unit, poor hemodynamic status, and death. Neither IL-6 plasma level nor CRP correlated with these clinical outcomes. APACHE-II score (a known disease severity scale in ICU patients) and IPF% were not correlated by Pearson test (p=0.09).Conclusion: IPF% is a valuable biomarker for predicting prognosis in ICU patients independent of APACHE-II score. This study suggests that the validity of IPF% as a predictor of outcome depends on the bone marrow (BM) capacity. In patients with normal bone marrow admitted to ICU, IPF% correlates with the significance of stress and severity of the disease. In patients presenting with neutropenic fever, BM reserve is impaired due to chemotherapy. Larger studies are needed to evaluate the role of IPF% in different patient populations and to determine its application to patients with impaired BM reserves such as immunocompromised patients and those at older age. DisclosuresNo relevant conflicts of interest to declare.

Establishing biological reference intervals for novel platelet parameters (immature platelet fraction, high immature platelet fraction, platelet distribution width, platelet large cell ratio, platelet-X, plateletcrit, and platelet distribution width) and their correlations among each other.

This study aims to establish biological reference interval for novel platelet parameters. A total of 945 healthy individuals, age ranges from 18 to 64 years (881 males and 64 females) coming for voluntary blood donation from June to August 2012 (3 months) were enrolled after exclusion of rejection criteria. The samples were assayed by running in complete blood count + reticulocyte mode on the Sysmex XE-2100 hematology analyzer and the reference interval for the population was calculated using Clinical and Laboratory Standards Institute guidelines. Tests were performed using SPSS (Statistical Product and Service Solutions, developed by IBM corporation), version 13. Student t test and pearsons correlation analysis were also used. The normal range for various parameters was platelet count: 150-520 × 10(3)/cu mm, immature platelet fraction (IPF): 0.3-8.7%, platelet distribution width (PDW): 8.3-25.0 fL, mean platelet volume (MPV): 8.6-15.5 fL, plateletcrit (PCT): 0.15-0.62%, high immature platelet fraction (H-IPF): 0.1-2.7%, platelet large cell ratio (P-LCR): 11.9-66.9% and platelet-X (PLT-X) (ch): 11.0-22.0. Negative correlation was observed between platelet count (r = -0.468 to r = -0.531; P < 0.001) and PCT (r = -0.080 to r = -0.235; P < 0.05 to P < 0.001) with IPF, PDW, MPV, H-IPF, P-LCR, and platelet-X. IPF/H-IPF showed a positive correlation among them and also with PDW, MPV, P-LCR, platelet-X (r = +0.662 to r = +0.925; P < 0.001). These novel platelet parameters offer newer avenues in research and clinical use. Establishing biological reference interval for different platelet parameters would help determine true high and low values and help guide treatment decisions.

Utility Of The Immature Platelet Fraction In Predicting Recovery With Or Without Treatment In Pediatric Immune Thrombocytopenia

BackgroundThe Immature Platelet Fraction (IPF) is a novel parameter available on the Sysmex XE-Series Hematology analyzers. It can be expressed as both IPF percent (IPF %) and absolute IPF count (AIPF#). It has been shown that IPF% is higher in Immune Thrombocytopenia (ITP) than in the normal population, and correlates with bone marrow platelet production or thrombopoiesis. ObjectivesTo evaluates the utility of the IPF parameters to predict treatment response or recovery in pediatric ITP patients. MethodThis is a retrospective, single institution study performed at a 165 bed tertiary care pediatric hospital (Children's Hospital of Eastern Ontario, Ottawa, Canada). We reviewed the medical charts and electronic databases of all patients with ITP who had measured IPF parameters between June 2011 and June 2013. The standard definitions and terminology of the International Working Group were used.Patient age, phase of ITP at the time of the study (acute, persistent, and chronic), initial platelet count, IPF%, AIPF#, and type of therapy given (including observation alone) were recorded. For patients who responded to treatment or had spontaneous recovery without treatment, we analyzed the platelet count, IPF% and AIPF# on subsequent CBCs, then looked at the course of IPF% during platelet count recovery.Comparisons between groups were performed using Kruskal-Wallis tests or Mann-Whitney tests, as appropriate. Association between measured blood parameters was measured using the Spearman correlation coefficient. Within-patient Spearman correlations were also used to study the association between IPF% and platelet counts during recovery. The combined significance of these associations was determined using Stouffer's method. Results•47 patients were included, median age was 9.3 years (Interquartile range (IQR) 4.9-13.3). 16 (34%) patients had newly diagnosed ITP (0-3 Months), 6 (12.8%) had persistent ITP (3-12 Months), and 25 (53.2%) had chronic ITP (>12 Months) at the time of the study.13 patients (27.6%) received treatment and responded (complete response (CR) in 10 patients or response (R) in 3 patients), 11 (23.4%) had recovery without treatment, and 23 (49%) had no recovery.•The initial platelet count was lower in patients who responded to treatment at 8x109/L (IQR 3-8.5) compared to patients who recovered without treatment (21x109/L, IQR 6-30) and those who had no recovery (24x109/L, IQR 9-59) (p=0.008).•AIPF# was lower in patients who responded to treatment at 1.3x109/L (IQR 0.7-1.5) compared to those who had spontaneous recovery of platelet counts without treatment (i.e recovery without treatment) (1.8x109/L, IQR 1.3-3.1)) and those who had no recovery (3.4x109/L, IQR 1.6-4.3) (p= 0.03) (figure 1). IPF% was higher in patients who responded to treatment at 19.4% (IQR 13.8-25) compared to patients who had no recovery (16.4%, IQR9.7 -23)) (p=0.052); there was no significant difference between patients who recovered without treatment and who had no recovery.•IPF% on initial CBC correlated positively to platelet counts on subsequent CBCs (p=0.034 at CBC # 2), indicating that patients with higher IPF% recovered faster.•For patients who responded to treatment and who recovered without treatment the IPF% dropped very significantly with platelet recovery (combined p = 0.04 and 0.001 respectively) (figure 2A&B). [Display omitted] [Display omitted] [Display omitted] ConclusionIPF measurements are easily available parameters that are useful in the management of ITP in pediatric patients. This study suggests the use of AIPF# as a predictive factor for recovery in pediatric ITP patients with and without treatment, and IPF% as a predictive factor for early recovery. Disclosures:No relevant conflicts of interest to declare.