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This study aimed to assess the cost-utility of romiplostim (ROMI) compared to eltrombopag (EPAG) as a second-line treatment for chronic primary immune thrombocytopenia (cITP) in Chinese adults. A decision tree-embedded Markov model with a lifetime horizon was used to estimate the quality-adjusted life years (QALYs) and costs for ROMI versus EPAG from the perspective of the Chinese health care system. The model was driven by platelet response with a 4-week cycle. Both QALYs and costs were discounted 5% per year. Clinical data comparing ROMI and EPAG were obtained by matching-adjusted indirect comparison (MAIC), utilizing individual patient data on ROMI and published Chinese Phase III trial data on EPAG. Costs were reported in 2022 US dollars and included drug acquisition costs, monitoring costs, bleeding-related costs, and costs associated with adverse events. Deterministic and probabilistic sensitivity analyses were performed. The CEA model indicated that treatment with ROMI resulted in an average of $4,344.4 higher costs for 0.004 QALYs. One-way sensitivity analysis (OSA) indicated that the model was most sensitive to the high bleeding rate in response (Markov stage) for EPAG and ROMI. Probabilistic sensitivity analysis (PSA) indicated that ROMI was likely to be cost effective in 0.16% cases at a willingness-to-pay threshold of $12039.1 (China per capita GDP in 2022) per QALY. If the price of ROMI is either lower than or equal to that of EPAG, ROMI could likely be considered cost-effective as a second-line treatment for Chinese adults with cITP.
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Patient characteristics and platelet responses at romiplostim initiation according to the duration of immune thrombocytopenia (ITP) are poorly understood. Amongst romiplostim-exposed adults with ITP lasting ≥6 months during 2009-2018 in Denmark, Sweden, and Norway, we examined characteristics at romiplostim initiation, romiplostim dosage, and durable platelet response (≥75% of measurements ≥50 × 109/L at 14-24 weeks) for subcohorts with newly diagnosed (duration <3 months), persistent (3-12 months), or chronic (>12 months) ITP initiating romiplostim. The 285 romiplostim initiators comprised 81 (28%) with newly diagnosed, 47 (16%) with persistent, and 157 (55%) with chronic ITP. More patients with newly diagnosed ITP than longer ITP duration, had low comorbidity levels, two or more prior ITP therapies, and previous bleeding requiring hospitalisation. The median romiplostim doses were similar across subcohorts. During treatment, median platelet counts were similar across subcohorts (75-76 × 109/L), and the durable platelet response was 64.6%, 52.9%, and 52.7% for newly diagnosed, persistent, and chronic ITP, respectively. After treatment cessation, the median platelet count was 138 × 109/L, 68 × 109/L, and 71 × 109/L, respectively. In conclusion, newly diagnosed patients, compared with romiplostim initiators with longer disease duration, had more severe ITP, higher frequency of durable platelet response, and higher median platelet count after cessation.
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INTRODUCTION: Immune thrombocytopenia (ITP) affecting pregnancy is a diagnostic and often a therapeutic challenge. AREAS COVERED: We review the current diagnostic criteria for ITP in pregnancy and the potential utility of laboratory tests. We discuss the impact of ITP on pregnancy outcomes and the effects of pregnancy on patients living with chronic ITP. We describe the criteria for intervention, the evidence supporting first-line treatment approaches and the therapeutic decisions and challenges in cases refractory to steroids and IVIG. We review the evidence supporting the potential use of thrombopoietin receptor agonists for refractory thrombocytopenia. Finally, we describe the diagnostic, prognostic, and treatment approaches to neonatal ITP and considerations regarding breastfeeding. We searched the terms 'immune thrombocytopenia' and 'pregnancy' on PubMed to identify the relevant literature published before 31 December 2023, including within cited references. EXPERT OPINION: Decreased platelet production may play a role in pregnancy-related ITP exacerbation. Putative mechanisms include placental hormones, such as inhibin. Although IVIG and prednisone usually suffice to achieve hemostasis for delivery, second-line agents are sometimes required to allow for neuraxial anesthesia. There is growing evidence supporting the use of romiplostim during pregnancy; however, its risk of venous thromboembolism warrants further evaluation.
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Complicaciones Hematológicas del Embarazo , Púrpura Trombocitopénica Idiopática , Humanos , Embarazo , Femenino , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/terapia , Complicaciones Hematológicas del Embarazo/diagnóstico , Complicaciones Hematológicas del Embarazo/terapia , Complicaciones Hematológicas del Embarazo/tratamiento farmacológico , Inmunoglobulinas Intravenosas/uso terapéutico , Manejo de la Enfermedad , Receptores de Trombopoyetina/agonistas , Trombopoyetina/uso terapéutico , Resultado del Embarazo , Receptores Fc , Proteínas Recombinantes de FusiónRESUMEN
Chemotherapy-induced thrombocytopenia (CIT) is a common challenge of cancer therapy and can lead to chemotherapy dose reduction, delay, and/or discontinuation, affecting relative dose intensity, and possibly adversely impacting cancer care. Besides changing anticancer regimens, standard management of CIT has been limited to platelet transfusions and supportive care. Use of the thrombopoietin receptor agonist romiplostim, already approved for use in immune thrombocytopenia, has shown promising signs of efficacy in CIT. In a phase 2 prospective randomized study of solid tumor patients with platelet counts <100 × 109/L for ≥4 weeks due to CIT, weekly romiplostim corrected the platelet count to >100 × 109/L in 93% (14/15) of patients within 3 weeks versus 12.5% (1/8) of untreated patients (p < 0.001). Including patients treated with romiplostim in an additional single-arm cohort, 85% (44/52) of all romiplostim-treated patients responded with platelet count correction within 3 weeks. Several retrospective studies of CIT have also shown responses to weekly romiplostim, with the largest study finding that poor response to romiplostim was predicted by tumor invasion of the bone marrow (odds ratio, 0.029; 95% CI: 0.0046-0.18; p < 0.001), prior pelvic irradiation (odds ratio, 0.078; 95% CI: 0.0062-0.98; p = 0.048), and prior temozolomide treatment (odds ratio 0.24; 95% CI: 0.061-0.96; p = 0.043). Elsewhere, lower baseline TPO levels were predictive of romiplostim response (p = 0.036). No new safety signals have emerged from romiplostim CIT studies. Recent treatment guidelines, including those from the National Comprehensive Cancer Network, now support consideration of romiplostim use in CIT. Data are expected from two ongoing phase 3 romiplostim CIT trials.
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Antineoplásicos , Receptores Fc , Proteínas Recombinantes de Fusión , Trombocitopenia , Trombopoyetina , Humanos , Receptores Fc/uso terapéutico , Trombopoyetina/uso terapéutico , Trombopoyetina/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/administración & dosificación , Trombocitopenia/tratamiento farmacológico , Trombocitopenia/inducido químicamente , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Recuento de Plaquetas , Receptores de Trombopoyetina/agonistas , Resultado del TratamientoRESUMEN
Peptides are a very critical class of pharmaceutical compounds that can control several signaling pathways and thereby affect many physiological and biochemical processes. Previous research suggests that both peptides and antibodies may serve as potent tools for research, diagnostics, vaccination, and therapeutics across diverse domains. The distinct attributes of peptides, like their profound tissue penetration, efficient cellular internalization, reduced immunogenicity, and adaptability to chemical modification, underscore their significance in biomedical applications. However, they also possess drawbacks such as lower affinity, poor absorption, low stability to proteolytic digestion, and rapid clearance. The advent of peptibodies is a significant advance that improves the limitations of both peptides and antibodies. Peptibodies, or Peptide-Fc fusions, represent a promising therapeutic modality comprising biologically active peptides fused to an Fc domain. The stability and efficacy of the peptide are enhanced by this fusion strategy, which overcomes some of the inherent limitations. Many peptibodies have been developed to treat conditions like cancer, diabetes, and lupus. Romiplostim and Dulaglutide are the only ones approved by the EMA and FDA, respectively. Given the growing significance of peptibodies in the pharmaceutical landscape, this investigation aims to explain key aspects encompassing the intrinsic properties of peptides, the intricacies of peptibody production, and their potential therapeutic applications.
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Idiopathic thrombocytopenic purpura (ITP) is characterized by a persistently low platelet count, which can lead to serious bleeding such as gastritis and hemorrhagic stroke. The formation of auto-antibodies in ITP leads to increased destruction of platelets and then hampers hematopoiesis. Corticosteroids and intravenous immunoglobulin are among the common treatments used for ITP, but they have significant side effects. This is a case report of a 27-year-old woman with ITP who was found to be anemic, thrombocytopenic, and had a ruptured ovarian cyst after the initial romiplostim therapy. The patient benefited from fluid resuscitation, blood transfusion, and corticosteroid therapy; then, the patient's condition improved. This case highlights the complications associated with managing ITP, emphasizing the importance of personalizing therapy regimens through regular monitoring to improve the balance of benefits and risk, resulting in a comprehensive treatment for chronic patients suffering from ITP.
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Thrombopoietin receptor agonists (TPO-Ras; romiplostim/eltrombopag/avatrombopag) have demonstrated high efficacy rates (59-88%) and a good safety profile in clinical trials with adult patients with immune thrombocytopenia (ITP). Similar efficacy and safety results have been observed with romiplostim and eltrombopag in paediatric cohorts. Continuous treatment with TPO-RAs has shown durable responses with long-term use, up to 3 years. The effect of TPO-RAs was generally considered transient, as platelet counts tended to drop to baseline values after a short period of time (about 2 weeks), unless treatment was maintained. Several groups have reported successful discontinuation of TPO-RAs without the need for concomitant treatments. This is referred to as sustained remission off treatment (SROT). Both short- and medium-term treatment with TPO-RAs may reduce costs to our healthcare systems and, more importantly, may reduce the potential side effects that may be associated with continuous TPO-RA treatment. The issue of tapering and discontinuation of TPO-RAs in paediatric patients with ITP has received little attention to date. Given that paediatric ITP has much higher rates of spontaneous remission than ITP in adults, we consider that the possibility of SROT of TPO-RAs in paediatric patients with ITP is a neglected but very relevant issue in this subtype of the disease.
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Immune thrombocytopenia (ITP) is an autoimmune bleeding disease caused by immune-mediated platelet destruction and decreased platelet production. ITP is characterized by an isolated thrombocytopenia (<100 × 109/L) and increased risk of bleeding. The disease has a complex pathophysiology wherein immune tolerance breakdown leads to platelet and megakaryocyte destruction. Therapeutics such as corticosteroids, intravenous immunoglobulins (IVIg), rituximab, and thrombopoietin receptor agonists (TPO-RAs) aim to increase platelet counts to prevent hemorrhage and increase quality of life. TPO-RAs act via stimulation of TPO receptors on megakaryocytes to directly stimulate platelet production. Romiplostim is a TPO-RA that has become a mainstay in the treatment of ITP. Treatment significantly increases megakaryocyte maturation and growth leading to improved platelet production and it has recently been shown to have additional immunomodulatory effects in treated patients. This review will highlight the complex pathophysiology of ITP and discuss the usage of Romiplostim in ITP and its ability to potentially immunomodulate autoimmunity.
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Púrpura Trombocitopénica Idiopática , Receptores Fc , Proteínas Recombinantes de Fusión , Trombopoyetina , Humanos , Receptores Fc/uso terapéutico , Trombopoyetina/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Receptores de Trombopoyetina/agonistasRESUMEN
Objective: Romiplostim is used to treat chemotherapy-induced thrombocytopenia in a variety of tumor types; however, few studies have examined its use in breast and gynecologic cancers. We evaluated platelet response and durability of response to romiplostim in patients with gynecologic or breast cancer complicated by chemotherapy-induced thrombocytopenia. Methods: We retrospectively identified 33 patients with gynecologic or breast cancer who received romiplostim between 07/1/2021-07/31/2022 at an academic cancer center. Results: Thirty-three patients met inclusion criteria; 26 (79 %) had breast cancer, 4 (12 %) had ovarian cancer, and 3 (9 %) had endometrial cancer. Twenty patients (61 %) experienced treatment delays and 12 (36 %) required dose reductions prior to starting romiplostim for chemotherapy-induced thrombocytopenia, with some patients experiencing both. Eleven patients (33 %) did not undergo a dose reduction or delay prior to initiation of romiplostim. Median platelet count prior to romiplostim therapy was 53 k/mcL (range, 40.5-78.8). Median platelet count within 3 weeks following initiation of romiplostim was 147 k/mcL (range, 31-562). Twenty-one patients (64 %) achieved platelet correction within 3 weeks, of whom 10 (48 %) resumed anticancer therapy and maintained platelet levels above 100 k/mcL at 8 weeks. Twelve patients did not achieve platelet correction within 3 weeks of romiplostim initiation; 4 (33 %) required a treatment change secondary to persistent thrombocytopenia, 3 (25 %) required a treatment dose reduction, 3 (25 %) were deemed too ill to continue therapy, and 2 (17 %) required a treatment delay. Conclusions: Romiplostim facilitated the resumption of anticancer therapy in 64 % of patients with gynecologic or breast cancer complicated by chemotherapy-induced thrombocytopenia.
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Plaquetas , Trasplante de Células Madre Hematopoyéticas , Trombopoyetina , Animales , Humanos , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Receptores de Trombopoyetina/agonistas , Trombopoyetina/agonistas , Trombopoyetina/efectos de los fármacos , Trombopoyetina/metabolismoRESUMEN
Few studies have reported the real-world use of both romiplostim and eltrombopag in immune thrombocytopenia (ITP). TRAIT was a retrospective observational study aimed to evaluate the platelet responses and adverse effects associated with the use of these thrombopoietin receptor agonists (TPO-RAs) in adult patients with ITP in the United Kingdom. Of 267 patients (median age at diagnosis, 48 years) with ITP (primary ITP [n = 218], secondary ITP [n = 49]) included in the study, 112 (42%) received eltrombopag and 155 (58%) received romiplostim as the first prescribed TPO-RA. A platelet count ≥30 × 109/L was achieved in 89% of patients with the first TPO-RA treatments, while 68% achieved a platelet count ≥100 × 109/L. Treatment-free response (TFR; platelet count ≥30 × 109/L, 3 months after discontinuing treatment) was achieved by 18% of the total patients. Overall, 61 patients (23%) switched TPO-RAs, most of whom achieved platelet counts ≥30 × 109/L with the second TPO-RA (23/25 who switched from eltrombopag to romiplostim [92%]; 28/36 who switched from romiplostim to eltrombopag [78%]). TFR was associated with secondary ITP, early TPO-RA initiation after diagnosis, the presence of comorbidity and no prior splenectomy or treatment with steroids or mycophenolate mofetil. Both TPO-RAs had similar efficacy and safety profiles to those reported in clinical studies.
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Benzoatos , Hidrazinas , Púrpura Trombocitopénica Idiopática , Pirazoles , Receptores Fc , Receptores de Trombopoyetina , Proteínas Recombinantes de Fusión , Trombopoyetina , Humanos , Receptores de Trombopoyetina/agonistas , Proteínas Recombinantes de Fusión/uso terapéutico , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/administración & dosificación , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Benzoatos/uso terapéutico , Benzoatos/efectos adversos , Masculino , Femenino , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Trombopoyetina/uso terapéutico , Trombopoyetina/efectos adversos , Hidrazinas/uso terapéutico , Hidrazinas/efectos adversos , Receptores Fc/uso terapéutico , Adulto , Reino Unido , Estudios Retrospectivos , Anciano , Recuento de Plaquetas , Resultado del Tratamiento , Anciano de 80 o más Años , Adulto Joven , AdolescenteRESUMEN
Sarcoidosis, a multi-organ system disease, often presents insidiously. Thrombocytopenia in sarcoidosis is frequent because of hypersplenism, granulomas infiltrating the bone marrow, or immune thrombocytopenia (ITP). The diagnosis of ITP relies on exclusionary criteria, given the absence of a definitive laboratory diagnostic feature. In the era prior to modern ITP management, sarcoidosis-associated ITP was known to manifest severely, often showing resistance to treatment and an increased risk of mortality. In this case, we present a young male who was admitted to a district hospital's emergency room, displaying symptoms of hematuria, gingival bleeding, and a petechial rash. Blood tests revealed severe thrombocytopenia with a platelet count of 0, while all other metabolic and serological exams returned normal results. Infectious and autoimmune causes were ruled out, and a bone marrow examination excluded any hematological disorder. Initial management, including platelet transfusion and presumptive treatment for ITP with dexamethasone and Human Immunoglobulin IV (IVIG), failed to improve the patient's platelet count or alleviate the hemorrhagic diathesis. Second-line therapy with Rituximab and Methylprednisolone was initiated with no benefit. Considering the hemorrhagic signs and the delayed response of Rituximab, we shifted to third-line therapy with Romiplostim at the maximal dose and continued Methylprednisolone. The platelet count recovered completely after the second Romiplostim administration (over 350 × 109 platelets/L) and Methylprednisolone was rapidly tapered. To further study the causes of thrombocytopenia a total body CT scan was performed and it identified non-homogeneously hypodense tissue in the bilateral hilar area extending medially to the subcarinal area, suggesting possible lymphatic origin and raising suspicion of sarcoidosis. Further investigations, including Angiotensin Converting Enzyme (ACE) titration, bronchoscopy, bronchoalveolar lavage, and EndoBronchial UltraSound-guided TransBronchial Needle Aspiration (EBUS-TBNA), confirmed the diagnosis of sarcoidosis. Despite a mild restrictive insufficiency noted in spirometry, the patient remained asymptomatic with only a mild respiratory insufficiency, and hence, was enlisted for follow-up. As for the ITP, the platelet count remained normal over a year. Notably, while sarcoidosis onset often predates ITP onset by an average of 48 months, in our case the onset of the two diseases was simultaneously. Our case adds valuable information to the limited body of knowledge regarding the treatment of sarcoidosis-associated ITP.
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Immune thrombocytopenia refractory to multiple thrombopoietin receptor agonists remains a challenging clinical problem. This commentary discusses and contextualizes the recent report on this entity from Moulis and colleagues, and how to move forward with these patients. Commentary on: Moulis et al. Difficult-to-treat primary immune thrombocytopenia in adults: Prevalence and burden. Results from the CARMEN-France Registry. Br J Haematol 2024;204:1476-1482.
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Púrpura Trombocitopénica Idiopática , Pirazoles , Trombocitopenia , Adulto , Humanos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Receptores de Trombopoyetina/agonistas , Trombocitopenia/tratamiento farmacológico , Trombopoyetina/uso terapéutico , Benzoatos/uso terapéutico , Hidrazinas/uso terapéutico , Receptores Fc/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéuticoRESUMEN
GP40141 is a romiplostim biosimilar. A Phase 1 clinical trial was previously conducted in healthy volunteers to evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety of GP40141 compared to the reference romiplostim (NCT05652595). Using noncompartmental analysis, the biosimilarity of PD end points was determined according to the classical criterion (0.8-1.25). PK end points were also in good agreement between GP40141 and the reference romiplostim; however, the confidence interval for the area under concentration-time curve from time 0 to the time of last measurement was slightly out of the bioequivalence range (0.91-1.29). Population PK/PD was used in the present study to characterize the individual PK and PD data of 56 healthy subjects in 2 cross-over periods of the Phase 1 clinical trial. Body weight and neutralizing antibodies to romiplostim were found to be important predictors of apparent volume of distribution and linear elimination constant, respectively. Within the framework of the conducted modeling, population estimates of PK/PD parameters were obtained, which were in agreement with literature data for the reference romiplostim. Additionally, values of intersubject variability, previously unreported for romiplostim in a healthy subject population, were derived. Covariate analysis, conducted during model development, as well as visual diagnostics and model-based simulations, demonstrated the absence of significant differences in PK and PD between GP40141 and romiplostim-ref.
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Biosimilares Farmacéuticos , Proteínas Recombinantes de Fusión , Humanos , Voluntarios Sanos , Biosimilares Farmacéuticos/farmacocinética , Trombopoyetina , Receptores FcRESUMEN
Immune thrombocytopenic purpura (ITP) is an autoimmune disorder determined by immune-mediated platelet demolition and reduction of platelet production. Romiplostim is a new thrombopoiesis motivating peptibody that binds and stimulates the human thrombopoietin receptor the patent of which was registered in 2008. It is used to treat thrombocytopenia in patients with chronic immune thrombocytopenic purpura. Romiplostim is a 60 kDa peptibody designed to inhibit cross-reacting immune responses. It consists of four high-affinity TPO-receptor binding domains for the Mpl receptor and one human IgG1 Fc domain. Escherichia coli is a good host for the fabrication of recombinant proteins such as romiplostim. The expression of a gene intended in E. coli is dependent on many factors such as a protein's inherent ability to fold, mRNA's secondary structure, its solubility, its toxicity preferential codon use, and its need for post-translational modification (PTM). This review focuses on the structure, function, mechanism of action, and expressive approach to romiplostim in E. coli.
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Púrpura Trombocitopénica Idiopática , Receptores Fc , Proteínas Recombinantes de Fusión , Humanos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Escherichia coli/genética , Patentes como Asunto , Plaquetas , Trombopoyetina/farmacologíaRESUMEN
Romiplostim is indicated for immune thrombocytopenia (ITP), though is often used off-label for other indications such as chemotherapy-induced thrombocytopenia (CIT) and thrombocytopenia post hematopoietic stem cell transplantation (HSCT). Although romiplostim is FDA approved at a starting dose of 1â mcg/kg, it is often initiated at 2-4â mcg/kg depending on the severity of thrombocytopenia in clinical practice. Given the limited data, but interest in higher doses of romiplostim for indications other than ITP, we aimed to assess our inpatient romiplostim utilization at NYU Langone Health.This was a single-center, retrospective review of 84 adult patients from January 2019 to July 2021. The top three indications were ITP (51, 60.7%), CIT (13, 15.5%), and HSCT (10, 11.9%). The median initial romiplostim dose was 3.8â mcg/kg (range, 0.9-10.8). 51% of patients achieved a platelet count of ≥50 × 109/L by the end of week 1 of therapy. For patients achieving goal platelets by the end of week 1, the median dose of romiplostim was 2.4â mcg/kg (range, 0.9-10.8). There was 1 episode of thrombosis and 1 episode of stroke.We found that higher than FDA-recommended initial doses should be considered to achieve a platelet response. It appears to be safe to initiate romiplostim as higher doses, and to increase doses by greater increments than 1â mcg/kg in order to achieve a platelet response. Future prospective studies are needed to confirm the safety and efficacy of romiplostim in off-label indications and should evaluate clinical outcomes such as bleeding and need for transfusions.
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Hemostáticos , Púrpura Trombocitopénica Idiopática , Trombocitopenia , Adulto , Humanos , Fibrinolíticos , Hemostáticos/uso terapéutico , Receptores de Trombopoyetina , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Trombocitopenia/tratamiento farmacológico , Trombocitopenia/inducido químicamente , Receptores Fc/uso terapéutico , Trombopoyetina/uso terapéutico , Proteínas Recombinantes de Fusión/efectos adversos , Centros Médicos Académicos , Resultado del TratamientoRESUMEN
Chemotherapy-induced thrombocytopenia (CIT) is a common complication of antineoplastic therapy, resulting in antineoplastic therapy dose reductions, treatment delays, treatment discontinuation, and morbid bleeding events. Despite several decades of research into thrombopoietic growth factors in CIT, there are presently no available U.S. FDA- or EMA-approved agents to treat CIT. However, a respectable body of evidence has been published evaluating the thrombopoietin receptor agonists (TPO-RAs) for the management and prevention of CIT in patients with solid tumors, and critical studies are ongoing with the TPO-RAs romiplostim and avatrombopag. When employed in the appropriate patient population and used properly, TPO-RAs can successfully and safely manage CIT for extended periods of time with minimal apparent risks. This comprehensive review discusses the evidence for TPO-RAs in CIT in patients with solid tumors, provides detailed guidance for their use in the clinic, and discusses ongoing essential clinical trials in management of CIT.
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Antineoplásicos , Neoplasias , Trombocitopenia , Humanos , Trombocitopenia/inducido químicamente , Trombocitopenia/tratamiento farmacológico , Receptores de Trombopoyetina/agonistas , Antineoplásicos/efectos adversos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , RiesgoRESUMEN
Thrombocytopenia is a common adverse effect of chemotherapy. The development of chemotherapy-induced thrombocytopenia (CIT) is influenced by cancer type and therapy, occurring in approximately one-third of patients with a solid tumor diagnosis and half of all patients with a hematologic malignancy. CIT may complicate the administration of chemotherapy, leading to therapeutic delays or dose reductions. This guidance document, presented by the International Society on Thrombosis and Haemostasis (ISTH) Subcommittee on Hemostasis and Malignancy, provides a comprehensive summary of the evidence and offers direction on the use of thrombopoietin receptor agonists (TPO-RAs) in various settings of CIT, including solid tumors, acute myeloid leukemia, stem cell transplant, and lymphoma. Studies have shown that TPO-RAs can improve platelet counts in CIT, but the clinical benefits of TPO-RA in terms of reducing bleeding, limiting platelet transfusion, avoiding chemotherapy delay, or dose reduction are uncertain. Further research is needed to optimize the selection of appropriate indications and study design to manage thrombocytopenia following chemotherapy.
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Antineoplásicos , Leucemia Mieloide Aguda , Trombocitopenia , Trombosis , Humanos , Trombocitopenia/inducido químicamente , Trombocitopenia/diagnóstico , Trombocitopenia/terapia , Trombosis/inducido químicamente , Trombosis/prevención & control , Trombosis/complicaciones , Antineoplásicos/efectos adversos , Hemostasis , Trombopoyetina/uso terapéutico , Trombopoyetina/efectos adversos , Proteínas Recombinantes de Fusión/uso terapéuticoRESUMEN
INTRODUCTION: Chemotherapy-induced thrombocytopenia (CIT) is a significant challenge in cancer treatment, often leading to dose reductions and reduced number of cycles. The limited effectiveness of platelet transfusions in managing CIT highlights the need for alternative treatments. Thrombopoietin receptor agonists (TPO-RA), including romiplostim, eltrombopag and avatrombopag, have shown potential in increasing platelet counts in CIT patients, necessitating a comprehensive analysis of their efficacy. METHODS: This meta-analysis followed the Preferred Reporting Items for Systemic Reviews and Meta-analysis guidelines, searching Ovid databases up to 5 October 2023. The primary metric of interest was platelet count changes post-TPO-RA administration in CIT patients. RESULTS: From the initial 867 studies obtained, 7 studies were selected based on the inclusion criteria. The analysis included 348 patients. A significant association was found between TPO-RA administration and platelet count increase, with a combined-effect increase of 69.52 ± 2.24 × 109/l. Subgroup analysis based on Romiplostim use suggested an increase of approximately 70.11 ± 39.07 × 109/l, while non-Romiplostim TPO-RAs showcased an increase of about 68.09 ± 82.58 × 109/l. CONCLUSIONS: The meta-analysis demonstrates the effectiveness of TPO-RAs in managing CIT. Further research comparing platelet increases across standardised TPO-RA regimens is recommended to refine treatment strategies. This analysis provides valuable insights for clinicians in tailoring CIT treatment using TPO-RAs.
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Introduction: Immune thrombocytopenic purpura (ITP) can be induced by several drugs but there are few case reports of ITP induced by clopidogrel. Second-line treatment with thrombopoietin receptor agonists (TPO-RA) presents solid evidence and should be considered in patients in need of elective surgery who are poor responders to steroids. Case description: We report the case of a 79-year-old male who developed severe immune thrombocytopenic purpura after initiating treatment with clopidogrel. Because he needed elective orthopaedic surgery and he did not respond to corticotherapy and immunoglobulin, second-line treatment with romiplostim was initiated with a significant increase in platelet count. Discussion and conclusion: Clopidogrel can induce ITP and this diagnosis should be considered in patients who present with isolated thrombocytopenia. First-line therapy of ITP is not always successful; second-line treatment with TPO-RA has a high response rate and should be considered in patients in need of elective surgery who have failed to respond to first-line therapy. LEARNING POINTS: Clopidogrel can cause immune thrombocytopenic purpura (ITP); although there are some published cases in literature, it is a rare adverse effect.ITP induced by clopidogrel should be considered in the differential diagnosis of patients experiencing isolated thrombocytopenia.Second-line treatment of ITP with thrombopoietin receptor agonists (TPO-RA) presents solid evidence and should be considered in patients in need of elective surgery who are poor responders to steroids.