Platelet production, clearance and distribution in patients with idiopathic thrombocytopenic purpura

Isaka, Yoshinari; Kambayashi, Jun-ichi; Kimura, Kazufumi; Matsumoto, Masayasu; Uehara, Akira; Hashikawa, Kazuo; Kamada, Takenobu; Imaizumi, Mitsuyoshi; Ashida, Keiichi; Nakayama, Hirofumi; Matsushita, Koji; Furukawa, Toshiyuki

doi:10.1016/0049-3848(90)90291-j

Cited by 15 publications

(16 citation statements)

References 16 publications

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“…[1][2][3][4][5] A growing body of evidence suggests that ITP is not only a disease of autoantibody-mediated platelet destruction but also a disease of impaired platelet production. [6][7][8] Suboptimal platelet production is thought to be a direct effect of autoantibodies on the megakaryocyte, 9,10 which may be affected further by failure to substantially increase circulating thrombopoietin (TPO) levels despite often marked thrombocytopenia. [11][12][13][14] Treatments for patients with ITP have focused either on inducing short-term increases in platelet counts, through administration of agents such as steroids, intravenous immunoglobulin (IVIG), and intravenous anti-D, [15][16][17][18][19][20] or on long-term maintenance of platelet counts through splenectomy or other treatments such as rituximab, danazol, azathioprine, or even prolonged steroid treatment.…”

Section: Introductionmentioning

confidence: 99%

Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP

Bussel

Kuter

Pullarkat

et al. 2009

Blood

398

383

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Chronic immune thrombocytopenic purpura (ITP) is characterized by low platelet counts and mucocutaneous bleeding. In previous studies romiplostim (AMG531), a thrombopoiesis-stimulating protein, increased platelet counts in most patients with chronic ITP. This ongoing, long-term open-label, single-arm study investigated safety and efficacy in patients who completed a previous romiplostim study and had platelet counts less than 5 ؋ 10 9 /L. One hundred forty-two patients were treated for up to 156 weeks (mean, 69 weeks). Platelet responses (platelet count > 50 ؋ 10 9 /L and double baseline) were observed in 87% of all patients and occurred on average 67% of the time in responding patients. In 77% of patients, the romiplostim dose remained within 2 g/kg of their most frequent dose at least 90% of the time. Ninety patients (63%) received treatment by selfadministration. Treatment-related serious adverse events were reported in 13 patients (9%). Bone marrow reticulin was observed in 8 patients; marrows were not routinely performed in this study, so the true incidence of this event cannot be determined. Severe bleeding events were reported in 12 patients (9%). Thrombotic events occurred in 7 patients (5%

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Section: Introductionmentioning

confidence: 99%

Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP

Bussel

Kuter

Pullarkat

et al. 2009

Blood

398

383

View full text Add to dashboard Cite

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“…Increased platelet destruction, whether immunological (ITP) or consumptive (e.g., consumptive coagulopathy, haemolytic uremia syndrome, vasculitis), was characterized by accelerated platelet turnovers with corresponding increases in megakaryocyte mass. Table I shows platelet turnover data based on autologous thrombokinetic measurements from seven studies involving 218 patients with untreated ITP (Branehog, 1975;Branehog et al, 1975;Stoll et al, 1985;du P Heyns et al, 1986;Ballem et al, 1987;Isaka et al, 1990;Louwes et al, 1999). These results showed that increased platelet production rates are uncommon in ITP patients, with most exhibiting either depressed or normal platelet production rates.…”

Section: Platelet Turnover In Itp Patientsmentioning

confidence: 99%

Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production

Nugent

McMillan

Nichol³

et al. 2009

Br J Haematol

237

158

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SummaryChronic immune thrombocytopenia (ITP) is a haematological disorder in which patients predominantly develop skin and mucosal bleeding. Early studies suggested ITP was primarily due to immune-mediated peripheral platelet destruction. However, increasing evidence indicates that an additional component of this disorder is immune-mediated decreased platelet production that cannot keep pace with platelet destruction. Evidence for increased platelet destruction is thrombocytopenia following ITP plasma infusions in normal subjects, in vitro platelet phagocytosis, and decreased platelet survivals in ITP patients that respond to therapies that prevent in vivo platelet phagocytosis; e.g., intravenous immunoglobulin G, anti-D, corticosteroids, and splenectomy. The cause of platelet destruction in most ITP patients appears to be autoantibody-mediated. However, cytotoxic T lymphocytemediated platelet (and possibly megakaryocyte) lysis, may also be important. Studies supporting suppressed platelet production include: reduced platelet turnover in over 80% of ITP patients, morphological evidence of megakaryocyte damage, autoantibody-induced suppression of in vitro megakaryocytopoiesis, and increased platelet counts in most ITP patients following treatment with thrombopoietin receptor agonists. This review summarizes data that indicates that the pathogenesis of chronic ITP may be due to both immune-mediated platelet destruction and/or suppressed platelet production. The relative importance of these two mechanisms undoubtedly varies among patients.

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“…21 Because romiplostim and eltrombopag bind to different sites on the TPO-R and the 2 molecules have not yet been directly compared, the relevance of switching from one TPO-RA to the other in clinical practice has not been A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia Mehdi Khellaf, 1 Jean-François Viallard, 2 Mohamed Hamidou, 3 Stéphane Cheze, 4 Françoise Roudot-Thoraval, 5 François Lefrere, 6 Olivier Fain, 7 Sylvain Audia, 8 Jean-François Abgrall, 9 Jean-Marie Michot, 10 Charles Dauriac, 11 Sophie Lefort, 12 Emmanuel Gyan, 13 Mathilde Niault, 14 Jean-Marc Durand, 15 Laetitia Languille, 1 David Boutboul, 16 Philippe Bierling, 17 Marc Michel, 1 and Bertrand Godeau…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5][6] ITP pathophysiology has long been considered to be only a matter of accelerated platelet destruction by platelet-bound antibodies but there is strong evidence to show that it is also associated with impaired platelet production. [7][8][9][10][11] Most therapies commonly used to treat ITP (e.g. corticosteroids, intravenous immunoglobulins (IVIg), immunosuppressants and splenectomy) are mainly active by reducing the destruction of antibody-coated platelets.…”

Section: Introductionmentioning

confidence: 99%

A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia

et al. 2013

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Romiplostim and eltrombopag, the first thrombopoietic receptor-agonists with demonstrated efficacy against immune thrombocytopenia in prospective controlled studies, were recently authorized in most countries for adults with chronic immune thrombocytopenia. So far, no data are available about the potential contribution of switching from romiplostim to eltrombopag or vice versa in terms of efficacy or tolerance. Efficacies and tolerance profiles were evaluated for 46 patients who sequentially received both drugs, switching from one to the other. The reasons for switching were: lack of efficacy for 23 patients, platelet-count fluctuations for 11, side effects for 4, and 8 patients' preferences. For 50-80% of the patients, switching from romiplostim to eltrombopag or eltrombopag to romiplostim effectively impacted the platelet count, with fluctuations disappearing in 54% and side effects resolved in 100%. In 80% of the patients, the 2 thrombopoietic receptor-agonists achieved similar response patterns. Our results confirmed that switching from one thrombopoietic receptor-agonist to the other could be beneficial in clinical practice for patients with severe chronic immune thrombopenia who failed to respond or experienced adverse events to the first. (Clinical Trials.gov identifier: NCT01618734). A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia Design and Methods PatientsAll patients followed by specialists in the network of National ITP Referral Centers who have been sequentially treated with the TPO-RAs, romiplostim and eltrombopag, were enrolled. Inclusion criteria were: 1) age 18 years or over; 2) primary ITP diagnosed according to the current definitions; 4,22 3) previous romiplostim and eltrombopag treatment, regardless of the switching sequence, with at least three months of follow up with each molecule. Patients treated for secondary ITP were excluded.The trial protocol was approved by the Henri-Mondor University Hospital Institutional Review Board and Ethics Committee; all patients received a written information form before screening and data analysis. Treatment designAccording to the European Medicines Agency authorization of the 2 TPO-RAs, patients received a weekly subcutaneous injection of romiplostim, usually started at 1 mg/kg/week, or daily oral eltrombopag, at a starting dose of 50 mg/day; the dose was then adjusted, as needed (up to a maximum 10 mg/kg/week and 75 mg/day, respectively) based on the patient's platelet count.Patients could continue to receive concurrent ITP therapies, including rescue interventions, defined as any agent administered to transiently increase the platelet count, e.g. IVIg, corticosteroids, anti-IgD and/or platelet transfusions. The need to increase the dose of concurrent ITP medication to levels above those used at baseline was also considered a rescue intervention. Assessments and outcome measuresThe following characteristics were recorded on a standardized form by the same investigator (MK): age, gender; and ITP ...

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Platelet production, clearance and distribution in patients with idiopathic thrombocytopenic purpura

Cited by 15 publications

References 16 publications

Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP

Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP

Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production

A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia

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