key: cord-0925184-b2w7ojl8 authors: Introcaso, Giovanni; Bonomi, Alice; Salvini, Laura; D’Errico, Tiziana; Cattaneo, Annalisa; Assanelli, Emilio; Barbieri, Silvia Stella; Biondi, Maria Luisa title: High immature platelet fraction with reduced platelet count on hospital admission. Can it be useful for COVID‐19 diagnosis? date: 2021-09-17 journal: Int J Lab Hematol DOI: 10.1111/ijlh.13701 sha: bc109f1d3544b29c77be683a050acd2c1ce26112 doc_id: 925184 cord_uid: b2w7ojl8 INTRODUCTION: Health professions are heavily engaged facing the current threat of SARS‐CoV‐2 (COVID‐19). Although there are many diagnostic tools, an accurate and rapid laboratory procedure for diagnosing COVID‐19 is recommended. We focused on platelet parameters as the additional biomarkers for clinical diagnosis in patients presenting to the emergency department (ED). MATERIALS AND METHODS: Five hundred and sixty‐one patients from February to April 2020 have been recruited. Patients were divided into three groups: (N = 50) COVID‐19 positive and (N = 21) COVID‐19 negative with molecular testing, (N = 490) as reference population without molecular testing. A Multiplex rRT‐PCR from samples collected by nasopharyngeal swabs was performed and the hematological data collected. RESULTS: We detected a mild anemia in COVID‐19 group and lymphopenia against reference population: hemoglobin (g/dL) 13.0 (11.5‐14.8) versus 13.9 (12.8‐15.0) (P = .0135); lymphocytes (10(9)/L) 1.24 (0.94‐1.73) versus 1.99 (1.49‐2.64) (P < .0001). In addition, abnormal platelet parameters as follows (COVID group vs reference population): PLT (×10(9)/L) 209 (160‐258) vs 236 (193‐279) (P = .0239). IPF (%) 4.05 (2.5‐5.9) versus 3.4 (2.2‐4.9) (P = .0576); H‐IPF (%) 1.25 (0.8‐2.2) versus 0.95 (0.6‐1.5) (P = .0171) were identified. In particular, COVID positive group had a high H‐IPF/IPF Ratio compared to reference population [0.32 (0.29‐0.36) versus 0.29 (0.26‐0.32), respectively, (P = .0003)]. Finally, a PLT difference of nearly 50 × 10(9)/L between pre/postCOVID‐19 sampling for each patient was found (N = 42) (P = .0194). CONCLUSIONS: COVID‐19 group results highlighted higher IPF and H‐IPF values, with increased H‐IPF/IPF Ratio, associated to PLT count reduction. These findings shall be adopted for a timely diagnosis of patients upon hospital admission. cases has resulted in an overcrowding of patients. This caused difficulties in triaging patients for rapid and accurate diagnosis and therapy. A large number of studies describing hematological and hemostatic alterations after the onset of COVID-19 symptoms confirm the sequelae of multiorgan lesions of virus infection. Furthermore, most of the patients have mild symptoms such as fever, dry cough, dyspnea, myalgia, and overlapping symptoms with acute myocardial infarction (AMI) as discomfort and chest pain. Thus, it is necessary to quickly identify the infection using a real time reverse transcription polymerase chain reaction (rRT-PCR) and/or rapid test with an integration of clinical and laboratory data. Application of algorithms lowering pressure on isolation rooms and to reduce the number of patients undergo to rRT-PCR testing has been recently proposed. [1] [2] [3] [4] Interestingly, the reduction of blood cells as lymphopenia and thrombocytopenia were well associated with COVID-19 and its severity, [5] [6] [7] [8] [9] and studies on their use for the diagnosis are still ongoing. In particular, a low platelet count at hospital admission has been described as an independent risk factor for COVID-19 disease progression and for in-hospital mortality, 7,10,11 suggesting its potential use in this clinical setting. However, evidence for its diagnostic application as clinical biomarker is so far not established. In this scenario, we investigated the hematological parameters, available in routine testing panel, upon cardiology ED admission, focusing on platelet parameters as potential additional biomarkers for COVID-19 diagnosis. A retrospective and observational pilot study was conducted at the Centro Cardiologico Monzino, Milan, Italy, using the laboratory database and the automated hematology analyzer Sysmex XN (Sysmex corporation) software. Five hundred and sixty-one consecutive patients admitted to our Hospital with complete molecular and hematological data within the period February 1-April 19, 2020 were included in the study. An expert team of cardiologists garnered clinical diagnosis regarding predominantly as first symptom a pulmonary distress along with the suspicion of cardiological diseases. Hematological parameters were evaluated through a comparison between the COVID-19 positive population (N = 50) and a reference population of patients presented to ED in the same period (N = 490). A specific comparison was made against a COVID-19 negative population (N = 21). The study was approved by the Ethical Committee of our center, and conformed to the principles outlined in the Declaration of Helsinki. The analytical platform enabled blood cell counts using fluorescent dyes and specific analytical channels, particularly for fluorescent platelet count. Blood samples were drawn into anticoagulant K3 EDTA tube (Vacutainer BD, PL6 7BP, UK) and within 1 hour pro- Molecular assays were carried out using a Multiplex rRT-PCR from samples collected by nasopharyngeal swabs. Three viral genes: E, RdRP, N, to detect SARS-CoV-2 using GeneFinder COVID-19 Plus RealAmp Kit (OSANG Healthcare, Anyangcheondong-ro, Dongan-gu, Anyang-si, Gyeonggi-do, Korea) on ELITech InGenius platform have been analyzed. Statistical analysis was performed using SAS version 9.4 (SAS Institute). Continuous variables are presented as mean ± standard deviation (SD) and were compared using the t test for independent samples. Variables not normally distributed are presented as median and interquartile ranges and were compared with the Wilcoxon rank-sum test. All performed analyses were adjusted for age and sex by general linear models. A P ≤ .05 was considered to be statistically significant. Main hematological parameters are reported in Table 2 . Hemoglobin concentration, erythrocytes, lymphocytes, eosinophils and basophils were lower in the COVID-19 group compared to reference population of patients presented to ED (Table 2) . When PLT parameters were analyzed in COVID-19 positive ED population and COVID-19 negative groups, we found that COVID-19 positive group displayed a significant lower PLT count than the other two groups (Table 3 and 4 ). In addition, COVID-19 positive patients have increased H-IPF and IPF compared to ED population (Table 3 ) and to COVID-19 negative group (Table 4) , respectively. However, all these differences were lost after adjustment for age and sex. Abbreviations: ACS, acute coronary syndrome; AF, atrial fibrillation; AMI, acute myocardial infarction; HF, heart failure. Interestingly, the H-IPF/IPF Ratio was higher in COVID-19 positive group than in ED population, and after adjustment for confounder factors, this difference was maintained (Table 3) . Derived platelet parameters including platelet distribution width (PDW), mean platelet volume (MPV), platelet-large cell ratio (P-LCR), as well as the absolute IPF count (IPF × 10 9 /L), were similar between the groups (Table 3 and 4 ). In particular, absolute immature platelets did not reach a significant difference between groups likely due to platelet recovery that occurs after COVID-19 infection. Analyzing Abbreviations: H-IPF, high-fluorescent immature platelet fraction; IPF, immature platelet fraction; MPV, mean platelet volume; PCT, plateletcrit; PDW, platelet distribution width; P-LCR, platelet-large cell ratio; PLT, platelets. *P-value obtained from the adjustment through age and sex . However, four cases of increased PLT counts postCOVID-19 disease due to two pneumococcal superinfections and two reactive thrombocytosis were found. (Table 3 and 4) . This leads to interpreting our data specifically for a cardiology population due to the biological characteristics and influence of age and sex. Nonetheless, the H-IPF/IPF Ratio seems increased in the COVID-19 patients also after correction for the two confounder factors ( Abbreviations: H-IPF, high-fluorescent immature platelet fraction; IPF, immature platelet fraction; MPV, mean platelet volume; PCT, plateletcrit; PDW, platelet distribution width; P-LCR, platelet-large cell ratio; PLT, platelets. *P-value obtained from the adjustment through age and sex. We thank all the people who contributed to the work during this difficult time. This study did not receive specific funding but was performed as part of the Italian Research Project n. R1312/-CCM 1380. The authors have no competing interests. AB analyzed data and involved in conceptualization of the work. GI designed, conducted, analyzed data, and wrote the manuscript. TD and AC conducted laboratory work. LS, EA collected clinical data. SSB conducted supervision and writing-review. MLB involved in supervision. Giovanni Introcaso https://orcid.org/0000-0001-5765-8696 Rapid identification of SARS-CoV-2 infected patients at the emergency department using routine testing Validation of the corona score for rapid identification of Sars Cov-2 infections in patients seeking emergency department care in the United States Laboratory markers included in the corona score can identify false negative results on COVID-19 RT-PCR in the emergency room Modified corona score can easily identify covid-19 patients with gastrointestinal symptoms: an Italian proposal Thrombocytopenia is associated with severe coronavirus disease (COVID-19) infections: a metaanalysis The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Platelet-to lymphocyte ratio is associated with prognosis in patients with coronavirus disease-19 What do monitoring platelet counts in COVID-19 teach us? Prediction of severe illness due to COVID-19 based on an analysis of initial fibrinogen to albumin ratio and platelet count Association between platelet parameters and mortality in coronavirus disease 2019: retrospective cohort study Reduced rate of hospital admission for ACS during Covid-19 outbreak in Northern Italy Pulmonary thrombosis in 2019-nCov Pneumonia? Cytokine ''storm'', cytokine ''breeze'', or both in Covid-19? Covid-19: unravelling the clinical progression of nature's virtually perfect biological weapon Hemostatic laboratory derangement in Covid-19 with a focus on platelet count Crucial laboratory parameters in Covid-19 diagnosis and prognosis: an updated meta-analysis Laboratory findings in Covid-19 diagnosis and prognosis Changes of hematological and immunological parameters in COVID-19 patients Covid-19 and hematologywhat do we know so far? SN Endoteliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, crosssectional study Early phases of COVID-19 are characterized by a reduction in lymphocyte populations and the presence of atypical monocytes COVID-19 and the clinical hematology laboratory The emerging threat of (Micro) thrombosis in COVID-19 and its thearapeutic implications Evaluation of COVID-19 coagulopathy; laboratory characterization using thrombin generation and nonconventional haemostasis assays Relationship of Ddimer with severity and mortality in SARS-CoV-2 patients : a metaanalysis Making sense of rapid antigen testing in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) diagnostics