Fibrosis-4 index and mortality in coronavirus disease 2019: a meta-analysis.

BACKGROUND/AIMS: In this meta-analysis, we aimed to evaluate the prognostic value of fibrosis-4 index (FIB-4) in COVID-19. METHODS: We performed a comprehensive literature search of PubMed, Embase, and Scopus databases on 26 November 2020. FIB-4 was calculated by [age (years) × AST (IU/L)]/[platelet count (109/L) × âˆšALT (U/L)]. A value above cutoff point was considered high and a value below cutoff point was considered low. The main outcome was mortality, the association between high FIB-4 and mortality was reported in odds ratio (OR). Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic OR (DOR), area under the curve (AUC) were generated. RESULTS: There were 963 patients from five studies included in this systematic review and meta-analysis. Meta-analysis showed that high FIB-4 was associated with increased mortality [OR 3.96 (2.16-7.27), P < 0.001; I2: 41.3%]. High FIB-4 was associated mortality with a sensitivity of 0.56 (0.40-0.70), specificity of 0.80 (0.72-0.86), PLR 2.8 (1.8-4.2), NLR 0.55 (0.39-0.78), DOR 5 (2-10), and AUC of 0.77 (0.73-0.81). Fagan's nomogram indicated that for a pre-test probability (mortality) of 30%, a high FIB-4 was associated with 54% post-test probability and a low FIB-4 was associated with 19%, respectively. The funnel-plot analysis was asymmetrical, trim-and-fill analysis by imputation of a study on the left side using linear estimator resulted in an OR of 3.48 (1.97-6.14). Egger's test showed no indication of small-study effects (P = 0.881). CONCLUSION: High FIB-4 was associated with mortality in patients with COVID-19.

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.

Daily combined measurement of platelet count and presepsin concentration can predict in-hospital death of patients with severe coronavirus disease 2019 (COVID-19).

The purpose of this study was to classify patients with severe COVID-19 into more detailed risk groups using coagulation/fibrinolysis, inflammation/immune response, and alveolar/myocardial damage biomarkers, as well as to identify prognostic markers for these patients. These biomarkers were measured every day for eight intensive care unit days in 54 adult patients with severe COVID-19. The patients were classified into survivor (n = 40) and non-survivor (n = 14) groups. Univariate and multivariate analyses showed that the combined measurement of platelet count and presepsin concentrations may be the most valuable for predicting in-hospital death, and receiver operating characteristic curve analysis further confirmed this result (area under the curve = 0.832). Patients were consequently classified into three groups (high-, medium-, and low-risk) on the basis of their cutoff values (platelet count 53 × 103/µL, presepsin 714 pg/mL). The Kaplan-Meier curve for 90-day survival by each group showed that the 90-day mortality rate significantly increased as risk level increased (P < 0.01 by the log-rank test). Daily combined measurement of platelet count and presepsin concentration may be useful for predicting in-hospital death and classifying patients with severe COVID-19 into more detailed risk groups.

Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura: a case report and review of the literature.

BACKGROUND: Immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura are both causes of thrombocytopenia. Recognizing thrombotic thrombocytopenic purpura is crucial for subsequent treatment and prognosis. In clinical practice, corticosteroids and rituximab can be used to treat both immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura; plasma exchange therapy is the first-line treatment in thrombotic thrombocytopenic purpura, while corticosteroids are strongly recommended as first-line treatment in immune thrombocytopenic purpura. The differential diagnosis of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is essential in clinical practice. However, case reports have suggested that immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura can occur concurrently. CASE PRESENTATION: We report the case of a 32-year-old Asian female without previous disease who presented with pancytopenia, concurrent with immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura. The morphology of the megakaryocytes in the bone marrow indicated immune-mediated thrombocytopenia. The patient received glucocorticoid treatment, and her platelet count increased; however, schistocytes remained high during the course of the therapy. Further investigations revealed ADAMTS13 activity deficiency and positive ADAMTS13 antibodies. The high titer of antinuclear antibody and positive anti-U1-ribonucleoprotein/Smith antibody indicated a potential autoimmune disease. However, the patient did not fulfill the current criteria for systemic lupus erythematosus or mixed connective tissue disease. The patient responded well to plasma exchange therapy, and her platelet count remained normal on further follow-up. CONCLUSIONS: Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is rare, but clinicians should be aware of this entity to ensure prompt medical intervention. Most of the reported cases involve young women. Human immunodeficiency virus infection, pregnancy, and autoimmune disease are the most common underlying conditions.

Effects of COVID-19 vaccination on platelet counts and bleeding in children, adolescents, and young adults with immune thrombocytopenia.

Coronavirus disease 2019 (COVID-19) vaccines rarely cause de novo immune thrombocytopenia (ITP) but may worsen preexisting ITP in adults. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines impact platelet counts and bleeding in children, adolescents, and young adults (C-AYA) with preexisting ITP is unknown. We report here the very limited effect of COVID-19 vaccination on platelet counts and bleeding in a single-center series of 2 C-AYA with ITP. No patient experienced worsening bleeding and only one child had a significant decrease in platelet count which improved spontaneously to her baseline without intervention. SARS-CoV2 vaccination was safe in C-AYA with ITP in this small cohort.

Inference from longitudinal laboratory tests characterizes temporal evolution of COVID-19-associated coagulopathy (CAC).

Temporal inference from laboratory testing results and triangulation with clinical outcomes extracted from unstructured electronic health record (EHR) provider notes is integral to advancing precision medicine. Here, we studied 246 SARS-CoV-2 PCR-positive (COVIDpos) patients and propensity-matched 2460 SARS-CoV-2 PCR-negative (COVIDneg) patients subjected to around 700,000 lab tests cumulatively across 194 assays. Compared to COVIDneg patients at the time of diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and lower platelet counts. However, as the infection evolves, COVIDpos patients distinctively show declining fibrinogen, increasing platelet counts, and lower white blood cell counts. Augmented curation of EHRs suggests that only a minority of COVIDpos patients develop thromboembolism, and rarely, disseminated intravascular coagulopathy (DIC), with patients generally not displaying platelet reductions typical of consumptive coagulopathies. These temporal trends provide fine-grained resolution into COVID-19 associated coagulopathy (CAC) and set the stage for personalizing thromboprophylaxis.

Frequency of thrombocytopenia in severe COVID-19 pneumonia and its effects on clinical outcomes.

To aim of the study was to determine the frequency of thrombocytopenia and its effect on clinical outcomes in South Asian patients admitted with severe COVID-19. It was a cross-sectional study conducted at the COVID intensive care unit of tertiary care government hospital of Karachi, Pakistan. 190 patients admitted in five months from 1/2/2021 till 30/6/2021 were included in the study. Platelet counts were recorded at presentation and all patients were also followed to observe if they develop thrombocytopenia during the course of hospital stay. The patient outcome and need for mechanical ventilation was assessed 28 days after admission and compared with the frequency of thrombocytopenia. Thrombocytopenia was seen in 26.8% (n=51) admitted patients. Among these, 68.6% patients had thrombocytopenia at presentation and 31.4% patients developed thrombocytopenia during the course of hospital stay. The range of platelet count in thrombocytopenic patients was 11x109 - 150x109. Mean platelets count in thrombocytopenic patients was 110x109 (SD 33). Mortality in patients who developed thrombocytopenia was 73.6% and 56.9.2% in patients without thrombocytopenia (p 0.034). Patients with thrombocytopenia were more likely to require mechanical ventilation (p 0.024). Thrombocytopenia is frequently observed in patients with severe COVID-19 and can be used as a tool for risk stratification.

Evaluation of inflammatory and hematological parameters in patients diagnosed with COVID-19.

INTRODUCTION: This study aims to research the effects of hematological and inflammatory parameters on the prognosis of COVID-19 disease and hospitalization duration. METHODOLOGY: One hundred and eighty-six patients with COVID-19 and a control group consisting of 187 healthy individuals were included in the study. Hematological variables and inflammatory parameters of the patients were recorded on the first and the fifth days of hospitalization. RESULTS: White blood cell count, lymphocyte count, and platelet count were statistically lower, and mean platelet volume (MPV), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) levels were higher in the patient group compared to the control group. It was observed that the neutrophil count and MPV level were lower, and the platelet count and ferritin level were statistically higher on the fifth day of follow-up compared to the admission day. In contrast, there was a significantly positive correlation between the duration of hospitalization and the fifth day D-dimer (r = 0.546, p < 0.001) and ferritin (r = 0.568, p < 0.001); in addition, there was a negative correlation between the duration of hospitalization and admission day lymphocyte count and the fifth-day lymphocyte count. CONCLUSIONS: Increased levels of ferritin and D-dimer, and decreased count of lymphocytes are among the important factors affecting the duration of hospitalization for COVID-19 patients. Furthermore, we think that neutrophil count and MPV levels are low, and platelet count and ferritin levels are high during the disease. Therefore, these parameters can be used as prognostic indicators of the disease.

Right-left digit ratios, a novel form of asymmetry: Patterns of instability in children and relationships to platelet counts and hospitalization in adults with COVID-19.

High right minus left (R-L) asymmetry of digit ratios has been reported to be linked to hospitalization for COVID-19. Here we examined the developmental patterns of this novel form of asymmetry in children and further explored their relationships to platelet counts and hospitalization for COVID-19 in adult patients. We considered ratios calculated from four digits (2D, 3D, 4D, 5D) in: (i) a sample of healthy participants aged 2 years to 18 years (n = 680, 340 males) and (ii) 96 adult patients (42 males) hospitalized for COVID-19 and 100 controls (53 males). The protocol for (ii) included a questionnaire and laboratory test results. In sample (i) of the six unsigned digit ratio asymmetries, those which included 5D had the highest mean asymmetry with the greatest between-individual variation and they were unstable over the age range of 2 years to 18 years. In sample (ii) patients showed higher asymmetries than controls in four ratios (2D:4D, 2D:5D, 3D:5D, 4D:5D) and a sum of asymmetries of the two independent ratios (2D:4D+3D:5D) correlated positively with platelet counts and hospitalization. Conclusion: Means and SDs of digit ratio asymmetry that include the 5th digit are high and age-unstable. Digit ratio asymmetry, particularly 5th digit ratio asymmetry and a composite measure of 2D:4D + 3D:5D asymmetry, may be positively linked to high platelet counts in COVID-19 patients and to an elevated risk of hospitalization.

Association of platelet count with all-cause mortality from acute respiratory distress syndrome: A cohort study.

BACKGROUND: The purpose of this study was to investigate whether platelet count was associated with mortality in acute respiratory distress syndrome (ARDS) patients. METHODS: We analyzed patients with ARDS from Multi-parameter Intelligent Monitoring in Intensive Care Database III (MIMIC-III). Platelet count was measured at the time of intensive care unit (ICU) admission. The cox proportional hazard model and subgroup analysis were used to determine the relationship between the platelet count and mortality of ARDS, as well as the consistency of its association. The primary outcome of this study was 365-day mortality from the date of ICU admission. RESULT: This study enrolled a total of 395 critically ill patients with ARDS. After adjustment for age, gender and ethnicity, the multivariate cox regression model showed that the hazard ratios (HRs) (95% confidence intervals [CIs]) of platelet count <192 × 109 /L and >296 × 109 /L were 2.08 (1.43, 3.04) and 1.35 (0.91, 2.01), respectively, compared with the reference (192-296 ×109 /L). After adjusting for confounding factors, lower platelet count (<192 × 109 /L) was associated with increased mortality (adjusted HR, 1.71; 95% CI 1.06-2.76, p = 0.0284). However, there was no similar trend in the 30-day (adjusted HR,1.02; 95% CI 0.54-1.94) or 90-day (adjusted HR, 1.65; 95% CI 0.94-2.89) mortality. In the subgroup analysis, lower platelet count showed significant interactions with specific populations (p interaction = 0.0413), especially in patients with atrial fibrillation. CONCLUSION: Taken together, our analysis showed that platelet count is an independent predictor of mortality in critically ill patients with ARDS.

A systematic review and meta-analysis of the association between the neutrophil, lymphocyte, and platelet count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio and COVID-19 progression and mortality.

BACKGROUND AND AIMS: Severe manifestations of coronavirus disease 2019 (COVID-19) are associated with alterations in blood cells that regulate immunity, inflammation, and hemostasis. We conducted an updated systematic review and meta-analysis of the association between the neutrophil, lymphocyte, and platelet count, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), and COVID-19 progression and mortality. METHODS: A systematic literature search was conducted in PubMed, Web of Science, and Scopus for studies published between January 2020 and June 2022. RESULTS: In 71 studies reporting the investigated parameters within 48 hours of admission, higher NLR (HR 1.21, 95% CI 1.16 to 1.27, p < 0.0001), relative neutrophilia (HR 1.62, 95% CI 1.46 to 1.80, p < 0.0001), relative lymphopenia (HR 1.62, 95% CI 1.27 to 2.08, p < 0.001), and relative thrombocytopenia (HR 1.74, 95% CI 1.36 to 2.22, p < 0.001), but not PLR (p = 0.11), were significantly associated with disease progression and mortality. Between-study heterogeneity was large-to-extreme. The magnitude and direction of the effect size were not modified in sensitivity analysis. CONCLUSIONS: NLR and neutrophil, lymphocyte, and platelet count significantly discriminate COVID-19 patients with different progression and survival outcomes. (PROSPERO registration number: CRD42021267875).

Human acute inflammatory recovery is defined by co-regulatory dynamics of white blood cell and platelet populations.

Inflammation is the physiologic reaction to cellular and tissue damage caused by trauma, ischemia, infection, and other pathologic conditions. Elevation of white blood cell count (WBC) and altered levels of other acute phase reactants are cardinal signs of inflammation, but the dynamics of these changes and their resolution are not well established. Here we studied inflammatory recovery from trauma, ischemia, and infection by tracking longitudinal dynamics of clinical laboratory measurements in hospitalized patients. We identified a universal recovery trajectory defined by exponential WBC decay and delayed linear growth of platelet count (PLT). Co-regulation of WBC-PLT dynamics is a fundamental mechanism of acute inflammatory recovery and provides a generic approach for identifying high-risk patients: 32x relative risk (RR) of adverse outcomes for cardiac surgery, 9x RR of death from COVID-19, 9x RR of death from sepsis, and 5x RR of death from myocardial infarction.

Structured Early detection of Asymptomatic Liver Cirrhosis: Results of the population-based liver screening program SEAL.

BACKGROUND & AIMS: Detection of patients with early cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. The SEAL program aimed at evaluating the usefulness of a structured screening procedure to detect cirrhosis as early as possible. METHODS: SEAL was a prospective cohort study with a control cohort from routine care data. Individuals participating in the general German health check-up after the age of 35 ("Check-up 35") at their primary care physicians were offered a questionnaire, liver function tests (aspartate and alanine aminotransferase [AST and ALT]), and follow-up. If AST/ALT levels were elevated, the AST-to-platelet ratio index (APRI) score was calculated, and patients with a score >0.5 were referred to a liver expert in secondary and/or tertiary care. RESULTS: A total of 11,859 participants were enrolled and available for final analysis. The control group comprised 349,570 participants of the regular Check-up 35. SEAL detected 488 individuals with elevated APRI scores (4.12%) and 45 incident cases of advanced fibrosis/cirrhosis. The standardized incidence of advanced fibrosis/cirrhosis in the screening program was slightly higher than in controls (3.83‰ vs. 3.36‰). The comparison of the chance of fibrosis/cirrhosis diagnosis in SEAL vs. in standard care was inconclusive (marginal odds ratio 1.141, one-sided 95% CI 0.801, +Inf). Of note, when patients with decompensated cirrhosis at initial diagnosis were excluded from both cohorts in a post hoc analysis, SEAL was associated with a 59% higher chance of early cirrhosis detection on average than routine care (marginal odds ratio 1.590, one-sided 95% CI 1.080, +Inf; SEAL 3.51‰, controls: 2.21‰). CONCLUSIONS: The implementation of a structured screening program may increase the early detection rate of cirrhosis in the general population. In this context, the SEAL pathway represents a feasible and potentially cost-effective screening program. REGISTRATION: DRKS00013460 LAY SUMMARY: Detection of patients with early liver cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. This study demonstrates that the implementation of a structured screening program using easily obtainable measures of liver function may increase the early detection rate of cirrhosis in the general population. In this context, the 'SEAL' pathway represents a feasible and potentially cost-effective screening program.

Platelet-derived immuno-inflammatory indices show best performance in early prediction of COVID-19 progression.

BACKGROUND: Coronavirus disease 2019 (COVID-19) profoundly affects the immune and hematopoietic systems with various degrees of reactive changes in the blood cell counts. Immuno-inflammatory indices are considered a simple and effective tool in the prediction of COVID-19 outcomes. We aimed to evaluate and compare the usefulness of leukocyte and platelet counts-based immuno-inflammatory indices on admission to hospital in predicting COVID-19 progression and mortality. METHODS: A total of 945 patients were enrolled. In addition to blood cell counts, we assessed hemogram-derived immuno-inflammatory indices in relation to COVID-19 progression and death. The indices were tested by analysis of variance, receiver operating characteristic curve analysis, and binomial logistic regressions. RESULTS: Patients with severe COVID-19 had significantly higher counts of neutrophils, eosinophils, and large immature cells (LIC), while decreased counts of platelets and monocytes. Lymphopenia was found in all of the patients, but without significant association with the outcomes. Patients with a LIC count ≥0.265 x 09 /L had 54.7% more odds of having COVID-19 progression. In multivariable analyses, platelets/neutrophil-to-lymphocyte ratio (P/NLR) and platelets-to-neutrophil radio (P/N) were significant independent predictors of COVID-19 progression and mortality. The odds of a poor outcome were two times higher in cases with P/NLR < 43 x 109 /L and P/N < 29 x 109 /L. CONCLUSION: Indices that include platelet count in combination with neutrophil and/or lymphocyte counts displayed the best discriminatory ability and prognostic value of COVID-19 outcomes. Additionally, LIC showed promising results in the early identification of severe COVID-19.

COVID-19 vaccine humoral response in frequent platelet donors with plateletpheresis-associated lymphopenia.

BACKGROUND: Plateletpheresis involves platelet separation and collection from whole blood while other blood cells are returned to the donor. Because platelets are replaced faster than red blood cells, as many as 24 donations can be done annually. However, some frequent apheresis platelet donors (>20 donations annually) display severe plateletpheresis-associated lymphopenia; in particular, CD4+ T but not B cell numbers are decreased. COVID-19 vaccination thereby provides a model to assess whether lymphopenic platelet donors present compromised humoral immune responses. STUDY DESIGN AND METHODS: We assessed vaccine responses following 2 doses of COVID-19 vaccination in a cohort of 43 plateletpheresis donors with a range of pre-vaccination CD4+ T cell counts (76-1537 cells/µl). In addition to baseline T cell measurements, antibody binding assays to full-length Spike and the Receptor Binding Domain (RBD) were performed pre- and post-vaccination. Furthermore, pseudo-particle neutralization and antibody-dependent cellular cytotoxicity assays were conducted to measure antibody functionality. RESULTS: Participants were stratified into two groups: <400 CD4/µl (n = 27) and ≥ 400 CD4/µl (n = 16). Following the first dose, 79% seroconverted within the <400 CD4/µl group compared to 87% in the ≥400 CD4/µl group; all donors were seropositive post-second dose with significant increases in antibody levels. Importantly differences in CD4+ T cell levels minimally impacted neutralization, Spike recognition, and IgG Fc-mediated effector functions. DISCUSSION: Overall, our results indicate that lymphopenic plateletpheresis donors do not exhibit significant immune dysfunction; they have retained the T and B cell functionality necessary for potent antibody responses after vaccination.

Fibrosis-4 (FIB-4) Index and mortality in COVID-19 patients admitted to the emergency department.

Liver damage worsens the prognosis of coronavirus 19 disease (COVID-19). However, the best strategy to stratify mortality risk according to liver damage has not been established. The aim of this study is to test the predictive value of the validated Fibrosis-4 (FIB-4) Index and compared it to liver transaminases and to the AST-to-Platelet ratio index (APRI). Multicenter cohort study including 992 consecutive COVID-19 patients admitted to the Emergency Department. FIB-4 > 3.25 and APRI > 0.7 were used to define liver damage. Multivariable Cox regression and ROC curve analysis for mortality were performed. Secondary endpoints were (1) need for high-flow oxygen and (2) mechanical ventilation. 240 (24.2%) patients had a FIB-4 > 3.25. FIB-4 > 3.25 associated with an increased mortality (n = 119, log-rank test p < 0.001 and adjusted hazard ratio (HR) 1.72 (95% confidence interval [95%CI] 1.14-2.59, p = 0.010). ROC analysis for mortality showed that FIB-4 (AUC 0.734, 95% CI 0.705-0.761) had a higher predictive value than AST (p = 0.0018) and ALT (p < 0.0001). FIB-4 > 3.25 was also superior to APRI > 0.7 (AUC 0.58, 95% CI 0.553-0.615, p = 0.0008). Using an optimized cut-off > 2.76 (AUC 0.689, 95% CI 0.659-0.718, p < 0.0001), FIB-4 was superior to FIB-4 > 3.25 (p = 0.0302), APRI > 0.7 (p < 0.0001), AST > 51 (p = 0.0119) and ALT > 42 (p < 0.0001). FIB-4 was also associated with high-flow oxygen use (n = 255, HR 1.69, 95% CI 1.25-2.28, p = 0.001) and mechanical ventilation (n = 39, HR 2.07, 95% CI 1.03-4.19, p = 0.043). FIB-4 score predicts mortality better than liver transaminases and APRI score. FIB-4 score may be an easy tool to identify COVID-19 patients at worse prognosis in the emergency department.

Alternatives for managing patients with newly diagnosed immune thrombocytopenia: a narrative review.

INTRODUCTION: Primary immune thrombocytopenia (ITP) is an acquired bleeding disorder. Conventionally, first-line ITP therapy aims to obtain a rapid response and stop or decrease the risk of bleeding by increasing the platelet count. At this point, the duration of the response, the tolerability, and the long-term safety of pharmacologic interventions are considered less of a priority. Combination treatments that simultaneously address multiple disease mechanisms are an attractive strategy to increase efficacy in acute ITP therapy. In this review, we discuss the treatment of newly diagnosed ITP patients, emphasizing the use of new combinations to benefit from their synergy. AREAS COVERED: This article summarizes conventional treatment, recent and novel combinations, and COVID-19 management recommendations of newly diagnosed ITP patients. EXPERT OPINION: The key areas for improvement consider the long-term effects of conventional first-line therapy, reducing relapse rates, and extending responses to achieve long-term remission. Although corticosteroids remain a first-line therapy, restricting their use to avoid toxicity and the increasing use of rituximab and TPO-RAs in the first three months after diagnosis open the landscape for future interventions in frontline therapy for ITP. First-line therapy intensification or synergistic drug combination offers a potential and realistic shift in future treatment guidelines.