Association of the immature platelet fraction with sepsis diagnosis and severity.
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ABSTRACT:
SUBMITTER: Enz Hubert RM
PROVIDER: S-EPMC4306131 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:Children with Wiskott-Aldrich syndrome (WAS) are often first diagnosed with immune thrombocytopenia (ITP), potentially leading to both inappropriate treatment and the delay of life-saving definitive therapy. WAS is traditionally differentiated from ITP based on the small size of WAS platelets. In practice, microthrombocytopenia is often not present or not appreciated in children with WAS. To develop an alternative method of differentiating WAS from ITP, we retrospectively reviewed all complete blood counts and measurements of immature platelet fraction (IPF) in 18 subjects with WAS and 38 subjects with a diagnosis of ITP treated at our hospital. Examination of peripheral blood smears revealed a wide range of platelet sizes in subjects with WAS. Mean platelet volume (MPV) was not reported in 26% of subjects, and subjects in whom MPV was not reported had lower platelet counts than did subjects in whom MPV was reported. Subjects with WAS had a lower IPF than would be expected for their level of thrombocytopenia, and the IPF in subjects with WAS was significantly lower than in subjects with a diagnosis of ITP. Using logistic regression, we developed and validated a rule based on platelet count and IPF that was more sensitive for the diagnosis of WAS than was the MPV, and was applicable regardless of the level of platelets or the availability of the MPV. Our observations demonstrate that MPV is often not available in severely thrombocytopenic subjects, which may hinder the diagnosis of WAS. In addition, subjects with WAS have a low IPF, which is consistent with the notion that a platelet production defect contributes to the thrombocytopenia of WAS. Knowledge of this detail of WAS pathophysiology allows to differentiate WAS from ITP with increased sensitivity, thereby allowing a physician to spare children with WAS from inappropriate treatment, and make definitive therapy available in a timely manner.
| S-EPMC4450723 | biostudies-literature
Project description:In this retrospective single-institution cohort study of 113 hospitalized pediatric patients with respiratory coronavirus disease 2019, those admitted to the intensive care unit or requiring mechanical ventilation had significantly higher immature platelet fractions than those who did not require intensive care unit-level care or ventilation. Immature platelet fraction may be an accessible biomarker for disease severity in pediatric respiratory coronavirus disease 2019.
| S-EPMC9356758 | biostudies-literature
Project description:The advanced platelet parameters Immature Platelet Fraction and Immature Platelet Fraction Count have been implemented in clinical practice as measures of thrombopoietic activity, mainly in hematologic disorders that cause thrombocytopenia. The purpose of this observational study was to examine thrombopoiesis as reflected by these 2 new CBC parameters in patients infected with dengue. The study was conducted in infectious disease referral hospital in Metro Manila, the Philippines. We enrolled hospitalized patients at admission who were diagnosed with acute dengue or community acquired bacterial infection (CABI). Immature Platelet Fraction (IPF) and Immature Platelet Fraction Count were evaluated at admission and during hospitalization. A total of 606 patients were enrolled from May 1, 2017 to June 1, 2018. The participants consisted of 152 patients with dengue infection, 180 confirmed CABI, and 274 suspected CABI patients. At admission, the percent IPF (IPF%) of the patients with dengue was significantly higher than that of the confirmed CABI patients (median 3.7% versus 1.9%; p <0.001). In a time course evaluation, there was no significant difference of IPF% between the patients with dengue infection and the confirmed CABI patients in the febrile phase (median 1.9% versus 2.4%; p = 0.488), however, the IPF% of the patients with dengue infection increased to be significantly higher than that of the confirmed CABI patients in the critical phase (median 5.2% versus 2.2%; p <0.001). Our study elucidated the unique characteristics and time-course trends of IPF percent and number (IPF#) in the patients with dengue infection. IPF% and IPF# are potentially valuable parameters in dengue and further investigation is required for the optimal use in clinical practice.
| S-EPMC8559939 | biostudies-literature
Project description:IntroductionThe assessment of bone marrow thrombopoietic activity in patients with thrombocytopenia is necessary to achieve an accurate diagnosis and administer effective treatment. We evaluated the discriminatory power of the immature platelet fraction (IPF) in differentiating hyperdestructive/consumptive thrombocytopenia from hypoproductive thrombocytopenia and its potential use as a predictive marker for platelet recovery.MethodsIn this observational study, platelet indices, including IPF, were measured in 105 healthy individuals, 27 patients with hyperdestructive/consumptive thrombocytopenia (all with immune thrombocytopenic purpura [ITP]), and 35 patients with hypoproductive thrombocytopenia (5 with aplastic anemia and 30 with cancer who were undergoing chemotherapy) using a Sysmex XN-3000 hematology analyzer.ResultsThe platelet distribution width, mean platelet volume, platelet large cell ratio, IPF, and absolute immature platelet count (AIPC) were significantly higher in the hyperdestructive/consumptive thrombocytopenia group than in the hypoproductive thrombocytopenia group (P < .001). The IPF showed the highest difference between the two patient groups (200%). Receiver operating characteristics analysis that showed the IPF had the largest area under the curve among all the platelet indices analyzed; its cut-off value was 2.3%. The IPF decreased 3 to 4 days in advance of platelet count elevation in patients with ITP, whereas the delta AIPC increased 3 days in advance. Furthermore, the IPF and delta AIPC increased 5.5 days and 8.5 days, respectively, before platelet counts increased up to 130.0 × 10/L in cancer patients receiving chemotherapy.ConclusionThese data demonstrated that the IPF and delta AIPC are both excellent indicators of the etiology of thrombocytopenia and predictive markers for platelet recovery.
| S-EPMC7035018 | biostudies-literature
Project description:Thrombocytopenia occurs frequently in patients with cirrhosis. The immature platelet fraction (IPF%) is measured to differentiate the causes of thrombocytopenia. To date the relevance of thrombopoietin (TPO) in the context of cirrhosis is unknown. The aim of our study was to investigate the cause of thrombocytopenia in patients with liver cirrhosis by measuring IPF%, TPO and spleen size. In addition we examined the use of IPF% to evaluate the severity of cirrhosis and its complications.Overall, we included 88 in-patients with cirrhosis in our study. The collected data comprises current health status, blood parameters, severity of cirrhosis evaluated by Child-Pugh score and MELD score, spleen diameter, ascites and esophageal varices. The IPF% was measured using an automatic hematology analyzer. TPO was measured with ELISA.IPF% (p = 0.003) and spleen diameter (p = 0.001) were significantly higher in patients with thrombocytopenia. There was no significant difference in TPO between patients with and without thrombocytopenia. The mean values of IPF% varied significantly (p = 0.044) in Child-Pugh stages. IPF% was significantly (p = 0.005) elevated in patients with esophageal varices. Moreover, IPF% higher than 3.85% displayed sensitivity of 76.6% and specificity of 52.4% with an area under receiver operating curve characteristics of 0.669 for the presence of esophageal varices.On closer examination of the three compartments known to have an influence on platelet count splenomegaly seems to be the major cause of thrombocytopenia in patients with cirrhosis according to current knowledge. Higher IPF% in patients with thrombocytopenia indicates peripheral consumption of platelets. The relation between spleen diameter and platelet count indicates the spleen to be the major place of platelets' consumption. TPO did not differ between patients with and without thrombocytopenia. Furthermore, we cannot exclude an influence of impaired thrombopoietin synthesis on platelet counts. The association between IPF% and platelet count suggests that there is physiological regulation of platelets in patients with cirrhosis. In our study IPF% is associated with esophageal varices and the stage of cirrhosis. Further studies are needed to confirm these results.
| S-EPMC5810997 | biostudies-literature
Project description:IntroductionSepsis is a public health problem due to its high prevalence and mortality. Mean platelet volume (MPV), a biomarker reported in routine blood counts, has been investigated and shows promise for determining fatal outcomes in septic patients.ObjectiveEvaluate whether the mean platelet volume (MPV) and mean platelet volume-to-platelet count (MPV/P) ratio are predictors of clinical severity and mortality in patients with sepsis.MethodsA prospective population cohort of 163 patients aged 18-97 years was recruited at the Intensive Care Unit of Pablo Arturo Hospital, Quito, Ecuador from 2017-2019 and followed up for 28 days. Patients were diagnosed with sepsis based on SEPSIS-3 septic shock criteria; in which the MPV and the MPV/P ratio were measured on days 1, 2, and 3. Sequential organ failure assessment (SOFA) score and presence of septic shock assessed clinical severity. Mortality on day 28 was considered the fatal outcome.ResultsThe average age of the patients was 61,15 years (SD 20,94) and female sex was predominant. MPV cutoff points at days 1, 2 and 3 were >9,45fL, >8,95fL and >8, 85fL; and (MPV/P) ratio >8, 18, >4, 12 y >3, 95, respectively. MPV at days 2 (9,85fL) and 3 (8,55fL) and (MPV/P) ratio at days 1 (4,42), 2 (4,21), and 3 (8,55), were predictors of clinical severity assessed by septic shock, which reached significance in the ROC curves. MPV and (MPV/P) ratio were also predictors of clinical severity determined by SOFA at days 1, 2, and 3, where higher values were observed in non-survivors reaching significance in all categories. MPV and MPV/P ratio at days 1, 2 and 3 were independent predictor factors of mortality using Cox proportional hazards model (HR 2,31; 95% CI 1,36-3,94), (HR 2,11; 95% CI 1,17-3,82), (HR 2,13; 95% CI 1,07-4,21) and (HR 2,38; 95% CI 1,38-4,12), (HR 2,15; 95% CI 1,14-4,06), (HR 4,43; 95% CI, 1,72-11,37) respectively.ConclusionsMPV and the MPV/P ratio are predictors of clinical severity and mortality in sepsis. The MPV and its coefficient are indicators of the biological behavior of platelets in sepsis. They should be considered as a cost-effective and rapidly available tool that guides the treatment.
| S-EPMC8735631 | biostudies-literature
Project description:IntroductionThe pathogenesis of thrombocytopenia in patients with sepsis is not fully understood. The aims of this study were to investigate changes in thrombopoietic activity over time by using absolute immature platelet counts (AIPC) and to examine the impact of platelet production on thrombocytopenia and mortality in patients with sepsis.MethodsThis retrospective observational study included adult patients with sepsis admitted to the intensive care unit at a university hospital. Two hundred five consecutive sepsis patients were stratified into four groups according to nadir platelet count: severe (nadir ?40×103/?L), moderate (41-80×103/?L), or mild thrombocytopenia (81-120×103/?L), or normal-increased platelet count (>120×103/?L). The development of thrombocytopenia was assessed during the first week; mortality was assessed at day 28.ResultOf the 205 patients included, 61 (29.8%) developed severe thrombocytopenia. On admission, AIPC did not differ among the four groups. In patients with severe thrombocytopenia, AIPC decreased significantly from days 2 to 7, but remained within or above the normal range in the other three groups (overall group comparison, P<0.0001). Multivariate analysis including coagulation biomarkers revealed that AIPC was independently associated with the development of severe thrombocytopenia (day 3 AIPC, odds ratio 0.49 [95% confidence interval (CI) 0.35-0.66], P<0.0001; day 5 AIPC, 0.59 [95% CI 0.45-0.75], P<0.0001). AIPC was a significant predictor of 28-day mortality in Cox hazard models adjusted for Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores (day 3 AIPC, hazard ratio 0.70 [95% CI 0.52-0.89], P = 0.0029; day 5 AIPC, 0.68 [95% CI 0.49-0.87], P = 0.0012).ConclusionsThrombopoietic activity was generally maintained in the acute phase of sepsis. However, a decrease in AIPC after admission was independently associated with the development of severe thrombocytopenia and mortality, suggesting the importance of suppressed thrombopoiesis in the pathophysiology of sepsis-induced thrombocytopenia.
| S-EPMC5790259 | biostudies-literature
Project description:INTRODUCTION: Sepsis is still a leading cause of morbidity and mortality, even in modern times, and thrombocytopenia has been closely associated with unfavorable disease outcome. Decreases in mitochondrial membrane potential (depolarization) were found in different tissues during sepsis. Previous work suggests that mitochondrial dysfunction of platelets correlates with clinical disease activity in sepsis. However, platelet mitochondrial membrane potential (Mmp) has not been investigated in a clinical follow-up design and not with regard to disease outcome. METHODS: In this study, platelet mitochondrial membrane depolarization was assessed by means of a fluorescent Mmp-Index with flow cytometry in 26 patients with sepsis compared with control patients. Platelet Mmp-Index on admission was correlated with the clinical disease scores Acute Physiology and Chronic Health Evaluation Score II (APACHE II), Sequential Organ Failure Score (SOFA), and Simplified Acute Physiology Score II (SAPS II). Finally, platelet Mmp-Index on admission and follow-up were compared in the group of sepsis survivors and nonsurvivors. Expression of the prosurvival protein Bcl-xL in platelets was quantified by immunoblotting. RESULTS: Platelet mitochondrial membrane depolarization correlated significantly with the simultaneously assessed clinical disease severity by APACHE II (r?=?-0.867; P?<?0.0001), SOFA (r?=?-0.857; P <0.0001), and SAPS II score (r?=?-0.839; P?<?0.0001). Patients with severe sepsis showed a significant reduction in platelet Mmp-Index compared with sepsis without organ failure (0.18 (0.12 to 0.25) versus 0.79 (0.49 to 0.85), P?<?0.0006) or with the control group (0.18 (0.12 to 0.25) versus 0.89 (0.68 to 1.00), P?<?0.0001). Platelet Mmp-Index remained persistently low in sepsis nonsurvivors (0.269 (0.230 to 0.305)), whereas we observed recovery of platelet Mmp-Index in the survivor group (0.9 (0.713 to 1.017)). Furthermore, the level of prosurvival protein Bcl-xL decreased in platelets during severe sepsis. CONCLUSION: In this study, we demonstrated that mitochondrial membrane depolarization in platelets correlates with clinical disease severity in patients with sepsis during the disease course and may be a valuable adjunct parameter to aid in the assessment of disease severity, risk stratification, and clinical outcome.
| S-EPMC4056796 | biostudies-other
Project description:IntroductionIt is widely assumed that sepsis is a life-threatening systemic inflammation caused by a dysregulated host response to infection mediated by an increase in multiple proinflammatory cytokines. The levels of key proinflammatory cytokines tumour necrosis factor, interleukin-1β and interferon γ are poorly characterised during sepsis. We believe this project will produce a 'gold-standard' document to which other reports on cytokine levels will be compared. The objective of this systematic review will be to identify key cytokine circulating levels in patients with sepsis and assess the association between these levels and morbidity and mortality outcomes related to sepsis.Methods and analysisWe would include reports of any design except for case reports. Sepsis patients will comprise those with a diagnosis of sepsis, severe sepsis or septic shock. The primary exposure is levels of three proinflammatory cytokines. The primary outcome is mortality at 28 or 30 days. Study subjects can be of any age, sex or ethnicity. Studies will be restricted to the English language. Medline, Embase, Cochrane Library and Web of Science Core Collection will be searched for eligible studies. A database search will include studies from 1985 to May 2020. Two reviewers will independently screen and select studies, assess methodological quality and extract data. A meta-analysis will be performed, if possible, and the Grading of Recommendations Assessment Development and Evaluation Summary of Findings presented.Ethics and disseminationFormal ethical approval is not required as data will be extracted from existing literature. This systematic review will be disseminated through a peer-reviewed publication and at conference meetings.Prospero registration numberCRD42020179800.
| S-EPMC8354287 | biostudies-literature
Project description:The immature platelet fraction (IPF) is a measure of newly released platelets, which has been used as a marker of platelet production in multiple human studies but is not widely available in multispecies analyzers. We developed gates to measure the IPF in diluted and undiluted murine blood samples on the Sysmex XN-1000V multispecies hematology analyzer. IPF gates were created using undiluted and diluted (1/10) blood samples obtained from adult and newborn (postnatal day 10, P10) C57BL/6J wild-type (WT) mice, and from 3 murine models of thrombocytopenia: c-MPL-/- mice, which lack the thrombopoietin receptor (hyporegenerative); antibody-mediated thrombocytopenia; and acute inflammation-induced thrombocytopenia. P10 mice were chosen because, at their size, we could consistently obtain (by terminal phlebotomy) the blood volume needed to run an undiluted sample. The undiluted blood IPF gate successfully differentiated between mechanisms of thrombocytopenia in both adult and P10 mice. For diluted samples, 2 IPF gates were generated: a thrombocytopenic (T) gate, which performed well in samples with platelet counts (PCs) <800 × 109/L in adult mice and <500 × 109/L in newborn mice, and a non-thrombocytopenic (NT) gate, which performed well in samples with PCs above these thresholds. PCs and IPFs measured in diluted blood using these gates agreed well with those measured in undiluted blood and had good reproducibility. These diluted gates allow for the accurate measurement of PCs and IPFs in small (10 µL) blood volumes, which can be obtained easily from adult and newborn mice as small as P1 to assess platelet production serially.
| S-EPMC8366244 | biostudies-literature