-
Blood Reviews Sep 2023There are not many publications that provide a holistic view of the management of primary and secondary ITP as a whole, reflecting the similarities and differences... (Review)
Review
There are not many publications that provide a holistic view of the management of primary and secondary ITP as a whole, reflecting the similarities and differences between the two. Given the lack of major clinical trials, we believe that comprehensive reviews are much needed to guide the diagnosis and treatment of ITP today. Therefore, our review addresses the contemporary diagnosis and treatment of ITP in adult patients. With respect to primary ITP we especially focus on establishing the management of ITP based on the different and successive lines of treatment. Life-threatening situations, "bridge therapy" to surgery or invasive procedures and refractory ITP are also comprehensively reviewed here. Secondary ITP is studied according to its pathogenesis by establishing three major differential groups: Immune Thrombocytopenia due to Central Defects, Immune Thrombocytopenia due to Blocked Differentiation and Immune Thrombocytopenia due to Defective Peripheral Immune Response. Here we provide an up-to-date snapshot of the current diagnosis and treatment of ITP, including a special interest in addressing rare causes of this disease in our daily clinical practice. The target population of this review is adult patients only and the target audience is medical professionals.
Topics: Adult; Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Platelet Count; Receptors, Thrombopoietin; Thrombopoietin
PubMed: 37414719
DOI: 10.1016/j.blre.2023.101112 -
Lancet (London, England) Nov 2023Primary immune thrombocytopenia is an autoimmune disorder mediated partly by platelet autoantibodies, resulting in thrombocytopenia, bleeding, and constitutional... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial.
BACKGROUND
Primary immune thrombocytopenia is an autoimmune disorder mediated partly by platelet autoantibodies, resulting in thrombocytopenia, bleeding, and constitutional symptoms. Efgartigimod, a first-in-class novel human IgG1 Fc fragment, binds the neonatal Fc receptor with high affinity and thus reduces serum IgG concentrations, including autoantibodies. The objective of this study was to evaluate the efficacy and safety of efgartigimod in adults with persistent and chronic primary immune thrombocytopenia.
METHODS
This phase 3, multicentre, randomised, double-blinded, placebo-controlled, 24-week study evaluated the efficacy and safety of intravenous efgartigimod in adults aged 18 years or older with chronic or persistent primary immune thrombocytopenia who had an average platelet count of less than 30 000, had responded to at least one previous immune thrombocytopenia therapy, and were on a concurrent therapy at baseline or had received at least a second previous immune thrombocytopenia therapy. The study took place in 71 participating sites from Asia, Europe, and North America. Patients were randomly assigned 2:1 to receive either efgartigimod (10 mg/kg) or placebo intravenously for the first 4 weeks, after which the dosing schedule could be altered to once per week or every other week depending on the patients' platelet count. The primary endpoint, evaluated in the chronic population, was sustained platelet count response (≥50 × 10 for at least 4 of the last 6 weeks). This study is registered with ClinicalTrials.gov (NCT04188379) and is completed.
FINDINGS
A total of 205 patients were screened from Dec 9, 2019, to Feb 3, 2022, and 131 (86 in the efgartigimod group; 45 in the placebo group) were randomly assigned. These patients represented a population with long-term disease who had a mean time since diagnosis of 10·6 years and 67% (88/131) of whom had received at least three previous immune thrombocytopenia treatments. 22% (17/78) of patients with chronic immune thrombocytopenia receiving efgartigimod reached the primary endpoint compared with 5% (2/40) of those receiving placebo (p=0·032; adjusted difference in response, 16% [95% CI 2·6-26·4]). The median number of weeks of disease control in patients with chronic immune thrombocytopenia was 2·0 (IQR 0·0-11·0) for efgartigimod versus 0·0 (0·0-1·0) for placebo (p=0·0009). Efgartigimod was well tolerated; most adverse events were mild to moderate in severity. The most common adverse events of interest in both groups were headache (16% in efgartigimod and 13% in placebo), haematuria (16% in efgartigimod and 16% in placebo), and petechiae (15% in efgartigimod and 27% in placebo).
INTERPRETATION
Efgartigimod significantly increased sustained platelet count responses compared with placebo in patients with chronic immune thrombocytopenia, including those who had received multiple previous immune thrombocytopenia therapies. Upon completion of the ADVANCE IV study, patients could enroll in the ongoing open-label extension. Subcutaneous efgartigimod is currently being evaluated in patients with immune thrombocytopenia in the ADVANCE SC+ trial.
FUNDING
argenx.
Topics: Adult; Humans; Autoantibodies; Double-Blind Method; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Receptors, Fc; Thrombocytopenia; Treatment Outcome
PubMed: 37778358
DOI: 10.1016/S0140-6736(23)01460-5 -
International Journal of Molecular... Feb 2024The management of immune thrombocytopenia (ITP) and the prediction of patient response to therapy still represent a significant and constant challenge in hematology. ITP... (Review)
Review
The management of immune thrombocytopenia (ITP) and the prediction of patient response to therapy still represent a significant and constant challenge in hematology. ITP is a heterogeneous disease with an unpredictable evolution. Although the pathogenesis of ITP is currently better known and its etiology has been extensively studied, up to 75% of adult patients with ITP may develop chronicity, which represents a significant burden on patients' quality of life. A major risk of ITP is bleeding, but knowledge on the exact relationship between the degree of thrombocytopenia and bleeding symptoms, especially at a lower platelet count, is lacking. The actual management of ITP is based on immune suppression (corticosteroids and intravenous immunoglobulins), or the use of thrombopoietin receptor agonists (TPO-RAs), rituximab, or spleen tyrosine kinase (Syk) inhibitors. A better understanding of the underlying pathology has facilitated the development of a number of new targeted therapies (Bruton's tyrosine kinase inhibitors, neonatal Fc receptors, strategies targeting B and plasma cells, strategies targeting T cells, complement inhibitors, and newer TPO-RAs for improving megakaryopoiesis), which seem to be highly effective and well tolerated and result in a significant improvement in patients' quality of life. The disadvantage is that there is a lack of knowledge of the predictive factors of response to treatments, which would help in the development of an optimized treatment algorithm for selected patients.
Topics: Adult; Infant, Newborn; Humans; Purpura, Thrombocytopenic, Idiopathic; Quality of Life; Thrombocytopenia; Platelet Count; Immunoglobulins, Intravenous; Thrombopoietin; Recombinant Fusion Proteins
PubMed: 38396839
DOI: 10.3390/ijms25042163 -
Blood Oct 2023Historically, the majority of patients with complement-mediated atypical hemolytic uremic syndrome (CaHUS) progress to end-stage kidney disease (ESKD). Single-arm trials... (Observational Study)
Observational Study
Historically, the majority of patients with complement-mediated atypical hemolytic uremic syndrome (CaHUS) progress to end-stage kidney disease (ESKD). Single-arm trials of eculizumab with a short follow-up suggested efficacy. We prove, for the first time to our knowledge, in a genotype matched CaHUS cohort that the 5-year cumulative estimate of ESKD-free survival improved from 39.5% in a control cohort to 85.5% in the eculizumab-treated cohort (hazard ratio, 4.95; 95% confidence interval [CI], 2.75-8.90; P = .000; number needed to treat, 2.17 [95% CI, 1.81-2.73]). The outcome of eculizumab treatment is associated with the underlying genotype. Lower serum creatinine, lower platelet count, lower blood pressure, and younger age at presentation as well as shorter time between presentation and the first dose of eculizumab were associated with estimated glomerular filtration rate >60 ml/min at 6 months in multivariate analysis. The rate of meningococcal infection in the treated cohort was 550 times greater than the background rate in the general population. The relapse rate upon eculizumab withdrawal was 1 per 9.5 person years for patients with a pathogenic mutation and 1 per 10.8 person years for those with a variant of uncertain significance. No relapses were recorded in 67.3 person years off eculizumab in those with no rare genetic variants. Eculizumab was restarted in 6 individuals with functioning kidneys in whom it had been stopped, with no individual progressing to ESKD. We demonstrated that biallelic pathogenic mutations in RNA-processing genes, including EXOSC3, encoding an essential part of the RNA exosome, cause eculizumab nonresponsive aHUS. Recessive HSD11B2 mutations causing apparent mineralocorticoid excess may also present with thrombotic microangiopathy.
Topics: Humans; Child, Preschool; Atypical Hemolytic Uremic Syndrome; Platelet Count; Complement System Proteins; Thrombotic Microangiopathies; Cohort Studies; Kidney Failure, Chronic
PubMed: 37369098
DOI: 10.1182/blood.2022018833 -
Periodontology 2000 Feb 2024The use of platelet-rich fibrin (PRF) has gained tremendous popularity in recent years owing to its ability to speed wound healing postsurgery. However, to date, many... (Review)
Review
The use of platelet-rich fibrin (PRF) has gained tremendous popularity in recent years owing to its ability to speed wound healing postsurgery. However, to date, many clinicians are unaware of methods designed to optimize the technology. This overview article will discuss the advancements and improvements made over the years aimed at maximizing cell and growth factor concentrations. First, a general understanding explaining the differences between RPM and RCF (g-force) is introduced. Then, the low-speed centrifugation concept, fixed angle versus horizontal centrifugation, and methods to maximize platelet concentrations using optimized protocols will be discussed in detail. Thereafter, the importance of chemically modified PRF tubes without the addition of chemical additives, as well as regulation of temperature to induce/delay clotting, will be thoroughly described. This article is a first of its kind summarizing all recent literature on PRF designed to optimize PRF production for clinical treatment.
Topics: Humans; Platelet-Rich Fibrin; Centrifugation; Wound Healing; Blood Platelets; Intercellular Signaling Peptides and Proteins; Platelet Count; Blood Coagulation
PubMed: 37681522
DOI: 10.1111/prd.12521 -
American Journal of Obstetrics &... Jul 2023Many studies have reported the association between platelets and preeclampsia. However, sample sizes were small, and their findings were inconsistent. We conducted a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Many studies have reported the association between platelets and preeclampsia. However, sample sizes were small, and their findings were inconsistent. We conducted a systematic review and meta-analysis to evaluate the association in pooled samples and in detail.
DATA SOURCES
A systematic literature search was performed using Medline, Embase, ScienceDirect, Web of Science, Cochrane Library, NICHD-DASH, LILACS, and Scopus from inception to April 22, 2022.
STUDY ELIGIBILITY CRITERIA
Observational studies comparing platelet count between women with preeclampsia and normotensive pregnant women were included.
METHODS
The mean differences with 95% confidence interval in platelet count were calculated. Heterogeneity was assessed using I statistics. Sensitivity and subgroup analyses were conducted. Statistical analysis was performed using RevMan 5.3 and ProMeta 3 software.
RESULTS
A total of 56 studies comprising 4892 preeclamptic and 9947 normotensive pregnant women were included. Meta-analysis showed that platelet count was significantly lower in women with preeclampsia than in normotensive controls (overall: mean difference, -32.83; 95% confidence interval, -40.13 to -25.52; P<.00001; I=92%; mild preeclampsia: mean difference, -18.65; 95% confidence interval, -27.17 to -10.14; P<.00001; I=84%; severe preeclampsia: mean difference, -42.61; 95% confidence interval, -57.53 to -27.68; P<.00001; I=94%). Significantly lower platelet count was also observed in the second trimester (mean difference, -28.84; 95% confidence interval, -44.59 to -13.08; P=.0003; I=93%), third trimester (mean difference, -40.67; 95% confidence interval, -52.14 to -29.20; P<.00001; I=92%), and before the diagnosis of preeclampsia (mean difference, -18.81; 95% confidence interval, -29.98 to -7.64; P=.009; I=87%), but not in the first trimester (mean difference, -15.14; 95% confidence interval, -37.71 to 7.43; P=.19; I=71%). Overall, the pooled sensitivity and specificity of platelet count were 0.71 and 0.77, respectively. The area under the curve was 0.80.
CONCLUSION
This meta-analysis confirmed that platelet count was significantly lower in preeclamptic women, irrespective of severity and presence or absence of associated complications, even before the onset of preeclampsia and in the second trimester of pregnancy. Our findings suggest that platelet count may be a potential marker to identify and predict preeclampsia.
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Platelet Count; Blood Pressure; Pregnancy Trimester, First; Pregnancy Trimester, Third
PubMed: 37098392
DOI: 10.1016/j.ajogmf.2023.100979