RESUMEN
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.
Asunto(s)
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
The only way to prevent immune thrombocytopenia (ITP) from becoming refractory would be to restore tolerance to platelets at an early phase of the disease. Numerous immune alterations probably accumulate in chronic ITP; thus, the chances of cure decrease significantly with time. Currently, sustained remission off treatment (SROT) is a clinical definition describing patients who can discontinue their ITP treatment without risk and maintain a state of remission. Different treatment strategies are presently being evaluated with the goal of attaining SROT, mostly combining drugs targeting the innate and/or the adaptive immune system, the inflammation state, so as increasing the platelet load. In this sense, thrombopoietin receptor agonists (TPO-RAs) have shown promising results if used as upfront treatment. TPO-RAs seem to exhibit immunomodulation and immune tolerance properties, increasing not only the platelet antigen mass but also increasing the transforming growth factor-ß concentration, and stimulating regulatory T and B lymphocytes. However, more immunological studies are needed to establish accurate molecular alterations in ITP that are potentially reversed with treatments.
Asunto(s)
Púrpura Trombocitopénica Idiopática , Trombocitopenia , Humanos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Suiza , Inmunomodulación , PlaquetasRESUMEN
Defining immune thrombocytopenia (ITP) in two age groups-children and adults-overlooks the specific clinical features and needs of adolescents and young adults (AYAS). We previously reported a high risk of chronic disease at 12 months (50%); however, data on the course of chronic ITP, the risk of refractoriness and treatment strategies in AYAS are limited. Data from patients aged 12-25 years with chronic primary ITP at 12 months were extracted from three large registries between 2004 and 2021. Clinical and laboratory data were evaluated until 48 months of follow-up (FU). Refractory ITP was defined as the administration of ≥3 different lines of therapy. A total of 427 AYAS (64% female) with chronic ITP were included. Overall, 7% and 14% were classified as 'refractory' at 12 and 48 months of FU respectively. The proportion of males was greater in the refractory group than in the non-refractory group (43% vs. 35%). AYAS with refractory disease displayed lower median platelet counts, more bleeding and a higher need for treatment at initial diagnosis and FU than non-refractory patients. This study reveals that refractory ITP is uncommon in AYAS; however, AYAS with refractory ITP display a high disease burden at all time points, including at initial diagnosis.
Asunto(s)
Púrpura Trombocitopénica Idiopática , Trombocitopenia , Masculino , Humanos , Adolescente , Femenino , Adulto Joven , Púrpura Trombocitopénica Idiopática/epidemiología , Púrpura Trombocitopénica Idiopática/terapia , Recuento de Plaquetas , Costo de Enfermedad , Sistema de RegistrosRESUMEN
Thrombopoietin receptor agonists (TPO-RAs) stimulate platelet production, which might restore immunological tolerance in primary immune thrombocytopenia (ITP). The iROM study investigated romiplostim's immunomodulatory effects. Thirteen patients (median age, 31 years) who previously received first-line treatment received romiplostim for 22 weeks, followed by monitoring until week 52. In addition to immunological data, secondary end-points included the sustained remission off-treatment (SROT) rate at 1 year, romiplostim dose, platelet count and bleedings. Scheduled discontinuation of romiplostim and SROT were achieved in six patients with newly diagnosed ITP, whereas the remaining seven patients relapsed. Romiplostim dose titration was lower and platelet count response was stronger in patients with SROT than in relapsed patients. In all patients, regulatory T lymphocyte (Treg) counts increased until study completion and the counts were higher in patients with SROT. Interleukin (IL)-4, IL-9 and IL-17F levels decreased significantly in all patients. FOXP3 (Treg), GATA3 (Th2) mRNA expression and transforming growth factor-ß levels increased in patients with SROT. Treatment with romiplostim modulates the immune system and possibly influences ITP prognosis. A rapid increase in platelet counts is likely important for inducing immune tolerance. Better outcomes might be achieved at an early stage of autoimmunity, but clinical studies are needed for confirmation.
Asunto(s)
Púrpura Trombocitopénica Idiopática , Humanos , Adulto , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Inmunomodulación , Tolerancia Inmunológica , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/uso terapéuticoRESUMEN
Current immune thrombocytopenia (ITP) guidelines target children and adults, leading to oversimplification. Adolescents and young adults (AYAS) comprise a separate group with distinct health and psychosocial issues. This study aimed to describe the clinical presentation and therapeutic strategies of ITP among AYAS. We analyzed data from two large ITP registries (PARC-ITP; CARMEN-France) and included newly diagnosed ITP patients (aged 12-25 years) with an initial platelet counts of <100×109/L. Patients with secondary ITP or non-immune thrombocytopenia (n=57) and pregnant women (n=10) were excluded. Of the 656 cases of AYAS with primary ITP registered from 2004 up to 2021, 12-month follow-up data were available for 72%. The initial median platelet count was 12×109/L. In 109 patients (17%), the diagnosis was incidental, without documented bleeding. Apart from gynecological bleeding, the clinical and therapeutical characteristics of females and males were similar. Platelet-enhancing drugs were reported in 66%, 45%, and 30% of patients at diagnosis, 1-6 months, and 6-12 months after diagnosis, respectively. Corticosteroids were the preferred treatment at all time points. At 12 months, 50% of all patients developed chronic ITP. In the subgroup of patients with initial severe thrombocytopenia (<20×109/L), those receiving frontline treatment had a higher remission rate at 1 year than those who followed an initial watch-and-wait strategy (53% and 32%; P<0.05). Our analysis indicates that the remission rate at 1 year may be associated with the initial treatment strategy. This hypothesis must be confirmed in prospective studies.
Asunto(s)
Púrpura Trombocitopénica Idiopática , Trombocitopenia , Masculino , Niño , Humanos , Femenino , Adolescente , Adulto Joven , Embarazo , Púrpura Trombocitopénica Idiopática/terapia , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Estudios Prospectivos , Recuento de Plaquetas , Hemorragia/diagnósticoRESUMEN
Sialoblastoma is a rare congenital malignant tumor of the salivary glands. A case of a submandibular sialoblastoma in a 1.5-year-old child is presented. A comparative analysis on 79 pediatric cases reported in the literature suggests a less aggressive behavior for submandibular sialoblastoma in comparison with other sites. Classically, diagnosis is confirmed by open biopsy, but fine-needle aspiration may offer an alternative with reduced morbidity. Expression of AFP and high levels of Ki-67 have been associated with poor prognosis. Whilst early surgical resection with negative margins is widely accepted as first-line treatment, there is no consensus on therapy of recurrence and follow-up. MRI and sonography represent valid tools for the follow-up, which is usually restricted to 3-5 years.Conclusion: Submandibular sialoblastomas may have a different biological profile in comparison with parotid tumors with the absence of metastasis and much lower rate of recurrence. Comprehensive diagnostics should include additional options such as fine-needle aspiration and markers to assess cell proliferation and AFP. Literature suggests that surgery alone is sufficient for the treatment of tumors with low malignancy. Follow-up should be tailored according to the tumor site and might be limited to 3-5 years. What is Known: ⢠Sialoblastoma is a rare congenital malignant tumor with an unpredictable clinical outcome. What is New: ⢠Sialoblastoma of submandibular origin seems to have a less aggressive behavior in comparison with other sites. ⢠Fine-needle aspiration and markers to assess proliferation index (i.e., suggestive of potential more aggressive course/malignancy) should be strongly considered in the diagnostic work-up. ⢠Radical surgery as first-line therapy and a 3-5-year follow-up are acceptable for tumors with a low malignancy.
Asunto(s)
Neoplasias Glandulares y Epiteliales/diagnóstico , Neoplasias de la Glándula Submandibular/diagnóstico , Humanos , Lactante , Neoplasias Glandulares y Epiteliales/congénito , Neoplasias de la Glándula Submandibular/congénitoRESUMEN
Comparative clinical studies of children and adults with immune thrombocytopenia (ITP) are poorly covered in the literature. However, the accepted classification of ITP-childhood ITP and adult ITP-results in considerable differences in treatment protocols and practice guidelines. The analysis of the Pediatric and Adult Registry on Chronic ITP (PARC-ITP) of patients at first presentation demonstrated fewer differences in clinical and laboratory findings at initial diagnosis between children and adults than expected. The present report of 2-year follow-up data supports the hypothesis that there are common aspects of childhood and adult ITP. Data of 3360 children and 420 adults were collected during the time of 2004 until 2015 at initial diagnosis. Follow-up information was available for 51% and 33% of children and 66% and 49% of adults at 12- and 24-months, respectively. Similarities were found in unexpected areas of ITP, such as the rate of late remission at 12 and 24 months, reported bleeding sites, platelet count in bleeders, and the frequency of treated patients with persistent or chronic ITP. Differences were confirmed for the overall rate of remission and treatment modalities. Unexpected differences were found in the percentage of nonbleeders, with more adults in the nonbleeder group. More studies are needed to investigate different age groups with the aim to optimize their management.
Asunto(s)
Púrpura Trombocitopénica Idiopática/clasificación , Púrpura Trombocitopénica Idiopática/patología , Adulto , Factores de Edad , Niño , Enfermedad Crónica , Estudios de Seguimiento , Hemorragia , Humanos , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Púrpura Trombocitopénica Idiopática/terapia , Inducción de RemisiónRESUMEN
BACKGROUND: Leishmaniasis is endemic in many countries worldwide, with a prevalence of 12 million people infected, and an estimated annual incidence of 500 000 visceral leishmaniasis cases. In Europe visceral leishmaniasis is considered endemic mainly in the Mediterranean countries and cases in non-endemic European countries north of the Alps have primarily been reported in returning travellers. The incubation period is typically described between 6 weeks to 6 months. The cases presented highlight the occurrence of longer incubation periods and illustrate the individual variability for progression from infection to disease. CASE PRESENTATION: We report the cases of 18-months-old twin girls living at the German-Swiss border, who developed visceral leishmaniasis 7 and 15 months after travelling to Tuscany. They presented with fever of unknown origin and pancytopenia. Both had splenomegaly and in the first case haemophagocytic lymphohistiocytosis or leukaemia was initially included in the differential diagnosis. Diagnosis of visceral leishmaniasis was confirmed by presence of intracytoplasmic localised leishmania parasites on bone marrow aspirate and/or positive leishmania serology. Both girls responded well to treatment with liposomal amphotericin B. The mother and two older siblings remained uninfected, while the father was diagnosed to be an asymptomatic carrier. CONCLUSION: Visceral leishmaniasis is an important differential diagnosis for fever of unknown origin and pancytopenia in young children living in countries with endemic disease and highlights the importance of obtaining a detailed travel history. Hemophagocytic lymphohistiocytosis and acute leukaemia present with similar symptoms and consequently are important differential diagnoses. Factors determining progression from infection to disease are not fully understood but younger age seems to be an important risk factor. Screening of siblings from affected individuals therefore may be warranted.
Asunto(s)
Anfotericina B/uso terapéutico , Leishmaniasis Visceral/diagnóstico , Leishmaniasis Visceral/tratamiento farmacológico , Antiprotozoarios/uso terapéutico , Diagnóstico Diferencial , Enfermedades en Gemelos , Enfermedades Endémicas , Femenino , Fiebre/etiología , Humanos , Lactante , Italia , Linfohistiocitosis Hemofagocítica/diagnóstico , Masculino , Pancitopenia/etiología , Esplenomegalia/diagnóstico , ViajeRESUMEN
Factor X deficiency (FXD) is a rare bleeding disorder, which can result in severe bleeding symptoms such as intracranial hemorrhage (ICH). The most common bleeding symptoms are epistaxis and gum bleeding. ICH is reported in 9-26% of all patients with FXD, mostly during the first month of life. Here, we present a rare case of a male presenting with ICH at the age of 20 months as the first manifestation of FXD. Secondary prophylaxis with factor X substitution once weekly prevented further bleeding.
Asunto(s)
Deficiencia del Factor X , Factor X/administración & dosificación , Hemorragias Intracraneales , Deficiencia del Factor X/complicaciones , Deficiencia del Factor X/diagnóstico , Deficiencia del Factor X/tratamiento farmacológico , Deficiencia del Factor X/patología , Humanos , Lactante , Hemorragias Intracraneales/diagnóstico , Hemorragias Intracraneales/etiología , Hemorragias Intracraneales/patología , Hemorragias Intracraneales/prevención & control , MasculinoRESUMEN
Transient myeloproliferative disorder (TMD) is a clonal proliferation of megakaryoblasts, typically occurring in newborns with Down syndrome. It is believed that TMD occurs in the presence of GATA1 mutation together with trisomy 21. However, a limited number of patients with TMD but without Down syndrome have been reported, all with a blast population with numeric or rarely structural chromosome 21 abnormalities. We present the first case of a newborn boy with a TMD without trisomy 21 and without any of the mentioned molecular or cytogenetic abnormalities. This case report suggests that unknown disease mechanisms may provoke or mimic TMD. This case report is followed by a concise review of the literature discussing the different entities and pathomechanisms of TMD and acute megakaryocytic leukaemia in patients with or without Down syndrome.
Asunto(s)
Síndrome de Down/diagnóstico , Síndrome de Down/patología , Reacción Leucemoide/diagnóstico , Reacción Leucemoide/patología , Células Progenitoras de Megacariocitos/patología , Síndrome de Down/genética , Síndrome de Down/terapia , Humanos , Recién Nacido , Reacción Leucemoide/genética , Reacción Leucemoide/terapia , Masculino , Células Progenitoras de Megacariocitos/metabolismo , Transfusión de PlaquetasRESUMEN
BACKGROUND: Tumor-associated fibroblast growth factor 23 (FGF-23)-induced hypophosphatemic rickets is a rare but known pediatric entity first described in 1959. It results from local production of phosphatonins by benign and malignant mesenchymal tumors. CASE-DIAGNOSIS/TREATMENT: We report an 8-year-old boy with tumor-associated hypophosphatemic rickets due to paraneoplastic FGF-23 secretion from a benign mesenchymal pelvic-bone tumor. Excessive FGF-23 production was visualized by immunohistochemistry in the resected tumor. Phosphate wasting stopped immediately after tumor resection. We reviewed 26 reports of pediatric patients with tumor-induced hypophosphatemic rickets; paraneoplastic FGF-23 secretion was documented in only three of them. All tumors developed inside bone, were benign in 21/26 cases, and were localized in femur/tibia (13/26), radius/ulna/humerus (7/26), pelvis (4/26), rib (1/26), and craniofacial (1/26) bones. Mean interval between onset of signs and/or symptoms and diagnosis was 34 months. CONCLUSIONS: In patients with hypophosphatemic rickets acquired beyond infancy, radiologic investigations for bone tumors need to be performed rapidly. In contrast to biochemical screening for increased circulating FGF-23 levels, immunohistochemical confirmation of FGF-23 production in resected tumor tissue can be regarded as being well established.
Asunto(s)
Neoplasias Óseas/complicaciones , Factores de Crecimiento de Fibroblastos/biosíntesis , Raquitismo Hipofosfatémico/etiología , Neoplasias Óseas/metabolismo , Niño , Factor-23 de Crecimiento de Fibroblastos , Humanos , Inmunohistoquímica , MasculinoRESUMEN
Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by congenital abnormalities and chromosomal breakages with the occurrence of hematological and solid malignancies. FA is the most common type of inherited bone marrow failure and poses tremendous challenges. FA patients are uniquely hypersensitive to hematopoietic stem cell transplantation (HSCT) conditioning agents due to the underling chromosomal instability. HSCT has shown important progress in the last years, especially after the introduction of fludarabine and the reduction of cyclophosphamide in the preparative regimen. For patients with HLA-identical-related donors HSCT should be performed as first-line therapy, for patients with alternative donors HSCT remains a therapy with increased morbidity and mortality.
Asunto(s)
Anemia de Fanconi/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Acondicionamiento Pretrasplante/métodosRESUMEN
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.
Asunto(s)
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
PURPOSE: Langerhans cell histiocytosis (LCH) is a rare disease characterized by dysregulated proliferation of myeloid marrow progenitors and subsequent organ infiltration. While LCH is associated with a favorable prognosis, some survivors may develop chronic health conditions (CHC) because of the disease. In this study, we aimed to assess the spectrum and prevalence of CHC among LCH survivors compared with siblings and identify factors associated with the development of CHC. METHODS: The Swiss Childhood Cancer Survivor Study sent questionnaires to all ≥ 5-year LCH survivors registered in the Swiss Childhood Cancer Registry and diagnosed between 1976 and 2015. Siblings also received similar questionnaires. We compared CHC prevalence between LCH survivors and siblings and used logistic regression to identify determinants of CHC. RESULTS: A total of 123 LCH survivors participated in the study, with a response rate of 69%. Median time since diagnosis was 13 years (interquartile range 9-20). Among LCH survivors, 59% had at least one CHC. Cardiovascular (13% vs. 6%), endocrine (15% vs. 2%), musculoskeletal (22% vs. 13%), and digestive (15% vs. 8%) CHC were more common among LCH survivors compared to siblings (all p < 0.05). Factors most strongly associated with the occurrence of CHC were multisystem LCH, multifocal bone involvement, and involvement of the pituitary gland. CONCLUSIONS: More than half of long-term LCH survivors suffered from one or more CHC and were affected considerably more than siblings. IMPLICATIONS FOR CANCER SURVIVORS: LCH survivors in follow-up care should be screened especially for cardiovascular, endocrine, musculoskeletal, and digestive conditions.
RESUMEN
The pathogenesis of immune thrombocytopenia (ITP) is increasingly being elucidated, and its etiology is becoming more frequently identified, leading to a diagnostic shift from primary to secondary ITP. The overlap between autoimmunity, immunodeficiency, and cancer is evident, implying more interdisciplinarity in daily care. This mini-review is based on an expert meeting on ITP organized by the Intercontinental Cooperative ITP Study Group and presents the challenges of hematologists in understanding and investigating "out of the box" concepts associated with ITP.
RESUMEN
Primary immune thrombocytopenia (ITP) in children is a diagnosis of exclusion, but cases of secondary ITP and nonimmune thrombocytopenia (non-IT) are generally difficult to recognize in a timely fashion. We describe a pediatric population with a revised diagnosis of secondary ITP or non-IT within 24 months of follow-up. Data were extracted from the Pediatric and Adult Registry on Chronic ITP, an international multicenter registry collecting data prospectively in patients with newly diagnosed primary ITP. Between 2004 and 2019, a total of 3974 children aged 3 months to 16 years were included. Secondary ITP and non-IT were reported in 113 patients (63 female subjects). Infectious (n = 53) and autoimmune (n = 42) diseases were identified as the main causes, with median ages at diagnosis of 3.2 years (interquartile range: 1.2; 6.7 years) and 12.4 years (interquartile range: 7.6; 13.7 years), respectively. Other causes included malignancies, aplastic anemia, immunodeficiency, and drug use. Patients with malignancy and aplastic anemia had significantly higher initial platelet counts (37 and 52 × 109/L) than did those with infection or autoimmune diseases (12 and 13 × 109/L). Characteristics of patients with secondary ITP due to infection were similar to those of children with primary ITP at first presentation, indicating similar mechanisms. Significant differences were found for age, sex, comorbidities, initial bleeding, sustained need for treatment, and disease persistence for the remaining noninfectious group compared with primary ITP. Based on our findings, we propose a diagnostic algorithm that may serve as a basis for further discussion and prospective trials.
Asunto(s)
Púrpura Trombocitopénica Idiopática , Trombocitopenia , Adolescente , Adulto , Niño , Errores Diagnósticos , Femenino , Humanos , Estudios Prospectivos , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/epidemiología , Sistema de RegistrosRESUMEN
Hemolytic-uremic syndrome (HUS) is a leading cause of acute renal failure in childhood. In its typical presentation, it is preceded by an episode of diarrhea mostly due to Shiga-toxin-producing Escherichia coli. There is important geographical variation of many aspects of this syndrome. Nationwide data on childhood HUS in Switzerland have not been available so far. In a prospective national study through the Swiss Pediatric Surveillance Unit 114 cases (median age 21 months, 50% boys) were reported between April 1997 and March 2003 by 38 pediatric units (annual incidence 1.42 per 10(5) children < or =16 years). Shiga-toxin-producing E. coli were isolated in 32 (60%) of tested stool samples, serotype O157:H7 in eight. Sixteen children presented with only minimal renal involvement, including three with underlying urinary tract infection. Six patients presented with atypical hemolytic-uremic syndrome, and six with HUS due to invasive Streptococcus pneumoniae infection. Mortality was 5.3%, including two out of six children with S. pneumoniae infection. The severity of thrombocytopenia and the presence of central nervous system involvement significantly correlated with mortality. In conclusion, childhood HUS is not rare in Switzerland. Contrasting other countries, E. coli O157:H7 play only a minor role in the etiology. Incomplete manifestation is not uncommon.
Asunto(s)
Síndrome Hemolítico-Urémico/epidemiología , Encefalopatías/etiología , Niño , Preescolar , Escherichia coli/aislamiento & purificación , Femenino , Estudios de Seguimiento , Síndrome Hemolítico-Urémico/complicaciones , Síndrome Hemolítico-Urémico/microbiología , Síndrome Hemolítico-Urémico/mortalidad , Humanos , Lactante , Recién Nacido , Masculino , Estudios Prospectivos , Streptococcus pneumoniae/aislamiento & purificación , Suiza/epidemiología , Trombocitopenia/etiologíaRESUMEN
Fc fusion proteins and Fc fusion peptides or peptibodies are chimeric molecules composed of an active pharmacological protein or peptide and the Fc fragment of an immunoglobulin. The primary aim of this drug construct is to prolong the half-life of the active component. This molecular architecture is seen in drugs, such as etanercept, romiplostim, and the recombinant factor VIII (efmoroctocog alfa). A considerable number of Fc fusion proteins and peptibodies are currently in pre-clinical and clinical development. The isolated effect of the Fc fragment has been studied intensively during last years, but is still poorly understood in the clinical setting and in relation with the active drug and underlying disease. In this short review, we will propose new hypotheses of possible immunomodulatory functions of the Fc fragment of romiplostim in patients with primary immune thrombocytopenia.