Short Term Treatment With Thrombopoietin-Receptor Agonists For Patients With Immune Thrombocytopenic Purpura (ITP) Before Splenectomy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1086-1086 ◽  
Author(s):  
Yosef Kalish ◽  
Galia Spectre ◽  
David Varon
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenic Purpura ◽  
Complete Blood Count ◽  
Conflicts Of Interest ◽  
Short Term Treatment ◽  
Thrombocytopenic Purpura ◽  
Thrombopoietin Receptor Agonists ◽  
Receptor Agonists ◽  
Short Course ◽  
Thrombopoietin Receptor

Abstract The thrombopoietin-receptor agonists (romiplostim and eltrombopag) were approved recently as treatments for patients with immune thrombocytopenic purpura (ITP). Splenectomy remains a common second line treatment for ITP with the highest remission rate compared with alternative therapies. It has been reported that splenectomy can be safely performed in patients with a platelet count of 40-50,000 per cubic millimeter but many patients do not reach these values. Intravenous immune globulins (IVIG) are often used before splenectomy in order to increase the platelet count before surgery. The aim of this study was to determine whether a short course of thrombopoietin-receptor agonists can be used as a reliable and safe treatment to increase the platelet count in patients with ITP before splenectomy. Between 2010 and 2012, fifteen patients with ITP, all refractory to steroids, were scheduled for splenectomy. Treatment with thrombopoietin-receptor agonists (romiplostim or eltrombopag) was started 3 weeks before splenectomy. Eight patients received eltrombopag at a dose of 50 mg/day orally until 3 days before splenectomy. For romiplostim, a subcutaneous injection of 3 mcg/kg was given weekly to 7 patients. The last injection was given one week before splenectomy. Complete blood count was repeated every week and the dose of romiplostim was adjusted (up to 10 mcg/kg or down to 1 mcg/kg) based on the platelet count increment. Response was defined as a platelet count of 50,000 or more per cubic millimeter. Mean platelet count before treatment was 11,000±8,000 cells per cubic millimeter. All patients, except one patient on romiplostim, responded to the treatment with a mean platelet count of 74± 25 cells per cubic millimeter on the day of splenectomy (p<0.01). Similar effect was noticed among responders of the two drugs. Four patients from the romiplostim group responded to a 3 mcg/kg dose. Two patients responded to increased doses of 7 and 10 and 10 mcg/kg. One patient did not respond to 10 mcg/kg of romiplostim but later responded to IVIG. The two drugs were well tolerated with no side effects except for mild liver function abnormalities in one patient in the eltrombopag group. No thromboembolic complications or excessive bleeding were reported for these patients. In summary, we report that a short course of thrombopoietin-receptors agonists can effectively and safely increase the platelet count in steroid resistant ITP patients before splenectomy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Balancing Therapy with Thrombopoietin Receptor Agonists and Splenectomy in Refractory Immune Thrombocytopenic Purpura: A Case of Postsplenectomy Thrombocytosis Requiring Plateletpheresis

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Jacquelyn Zimmerman ◽  
Kelly J. Norsworthy ◽  
Robert Brodsky
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Treatment Options ◽  
First Line ◽  
Thrombocytopenic Purpura ◽  
Thrombopoietin Receptor Agonists ◽  
Receptor Agonists ◽  
Autoimmune Destruction ◽  
Thrombopoietin Receptor ◽  
Line Of Therapy ◽  
The Ideal

Immune thrombocytopenic purpura (ITP) causes thrombocytopenia through the autoimmune destruction of platelets. Corticosteroids remain the first line of therapy, and traditionally splenectomy has been the second. While the availability of thrombopoietin receptor agonists (TPO-RAs) has expanded treatment options, there is little data for the ideal management of these agents in preparation for splenectomy. Thrombocytosis has been reported after splenectomy in patients treated with TPO-RA preoperatively, with one prior case requiring plateletpheresis for symptomatic thrombocytosis. We present a case report and review of the literature pertaining to this complication and provide recommendations for preventing postsplenectomy thrombocytosis in ITP patients on TPO-RAs.

A Prospective Multicenter Single-Arm Study of Low-Dose Decitabine in Adult Patients with Immune Thrombocytopenia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3744-3744
Author(s):  
Hai Zhou ◽  
Ping Qin ◽  
Chenglu Yuan ◽  
Haiyan Zhang ◽  
Zhencheng Wang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Intravenous Immunoglobulin ◽  
Immune Thrombocytopenia ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
End Points ◽  
Thrombopoietin Receptor Agonists ◽  
Receptor Agonists ◽  
Thrombopoietin Receptor

Abstract Introduction: Approximately 30% of patients with immune thrombocytopenia (ITP) fail to respond to the first- and/or second-line treatments (corticosteroids, intravenous immunoglobulin, rituximab, splenectomy, and thrombopoietin-receptor agonists). For those patients, the management is challenging. Decitabine (DAC), a demethylating agent with a dual mechanism of action: the demethylating effect leading to cell differentiation at low dose and cytotoxic activity leading to cell death at high concentration, has been used in the management of myelodysplastic syndrome (MDS) with a considerable platelet response during the past decade. Recent studies proved that low-dose DAC was sufficient to show a therapeutic effect with no obvious cytotoxicity. Our previous and other studies have demonstrated that low-dose DAC could promote megakaryocyte maturation and platelet production. These findings suggest a possible therapeutic role of low-dose DAC in the management of ITP. We hereby present the preliminary results of a prospective, multicenter, open-labeled study evaluating the efficacy and safety of low-dose DAC for ITP patients. Methods: ITP patients, who failed to respond to corticosteroids, intravenous immunoglobulin, rituximab, and/or thrombopoietin-receptor agonists from 9 centers, were enrolled in the study. The study protocol was approved by the ethics committee on medical research of each participating site. All patients provided written informed consent in accordance with the Declaration of Helsinki. DAC was given intravenously at 3.5mg/m2 for 3 days/cycle for 3 cycles with a 4-week interval between cycles. The primary end points were complete response (CR), response (R), overall response (OR). All the criteria were consistent with the standardization of terminology, definitions and outcome criteria in immune thrombocytopenia proposed by the international working group (RodeghieroF, et al. Blood, 2009, 113:2386-2393). Secondary end points were bleeding scores, time to response (TTR), duration of response and adverse events. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events, version3.0. This clinical trial was registered at http://clinicaltrials.gov as NCT 01568333. Results: A total of 20 ITP patients were recruited. The clinical characteristics were shown in Table 1. At the end of the 12th week of the initial treatment, CR was achieved in 1 patient (5%) and R was achieved in 9 patients (45%). The OR rate was 50%. During the follow-up period, 1 patient initially stabilized at R and subsequently improved to CR at the 20th week. Therefore, CR, R and OR rates were 10% (2/20), 40% (8/20) and 50% (10/20), respectively. In patients who achieved CR and R, the median (range) TTR was 22 days (8-38 days). The median (range) follow-up time was 24 weeks (13-40 weeks). The platelet counts of patients who achieved CR and R were shown in Figure 1. The follow-up of our study is in progress. Adverse events were observed in 2 patients, one had nausea and the other was mild fever. No adverse events exceeded grade 1. Conclusion: Although the sample size is small, with a relatively short follow-up period limited by now, our study suggests that low-dose DAC is effective and safe in the management of ITP patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Thrombopoietin Receptor Agonists: Clinical Use and Evaluation of Treatment Efficacy

2020 ◽  
Vol 10 (4) ◽  
pp. 236-243
Author(s):  
A. G. Solodovnikov ◽  
E. Yu. Sorokina ◽  
E. I. Morkovin
Keyword(s):  
Platelet Count ◽  
Healthy Volunteers ◽  
Treatment Efficacy ◽  
Reference Drug ◽  
Orphan Status ◽  
Thrombopoietin Receptor Agonists ◽  
Pharmacodynamic Marker ◽  
Receptor Agonists ◽  
Thrombopoietin Receptor ◽  
Number Of Patients

Idiopathic thrombocytopenic purpura (ITP), or primary immune thrombocytopenia, is an orphan disease associated with thrombocytopenia. One of the most recent and promising approaches to ITP treatment is the use of thrombopoietin receptor agonists (TPO-RAs). The scope of TPO-RA use is expanding rapidly, which stimulates the development of both innovator and generic (or biosimilar) medicines. The aim of the paper was to assess TPO-RA role in ITP treatment, methodological approaches to TPO-RA development, and feasibility of using the platelet count as a pharmacodynamic marker in bioequivalence studies of peptide TPO-RAs in healthy volunteers. Clinical development of new medicines for the treatment of thrombocytopenia includes comparative, parallel-group trials lasting about a year. The standard approach to bioequivalence studies, which is based on the results of comparative pharmacokinetic studies, can be used in marketing authorisation applications for generic non-peptide TPO agonists, while peptide TPO agonists have to comply with specific requirements for biosimilar products. The orphan status of ITP does not affect the development strategy and study design, but it limits the number of patients that could be included into the study. In the absence of valid surrogate biomarkers of efficacy, demonstration of comparable clinical efficacy of the biosimilar and reference drug is usually required in a randomised, parallel, preferably double-blind comparative study. On the other hand, clinical comparability of the biosimilar and reference drug can also be demonstrated in comparative pharmacodynamic studies, if the selected biomarker is a well-established and valid surrogate marker which correlates with patient clinical outcome. Platelet count is a key parameter in both diagnosis of diseases associated with low platelet levels and assessment of treatment efficacy. Therefore, it can be used as a pharmacodynamic marker in bioequivalence studies of biosimilar peptide TPO-RAs. It was concluded that such studies could be performed in healthy volunteers, and not in patients, whose participation in clinical trials is limited due to the orphan status of ITP.

Mycoplasma Pneumonia Infection - a Possible unrecognized Cause for Immune Thrombocytopenic Purpura

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4555-4555
Author(s):  
Shraga Aviner ◽  
Daniel London ◽  
Shulamith Horowitz ◽  
Menachem Schlesinger ◽  
Gilles Lugassy
Keyword(s):  
Platelet Count ◽  
Clinical Diagnosis ◽  
Intracranial Hemorrhage ◽  
Immune Thrombocytopenic Purpura ◽  
Complete Blood Count ◽  
Case Reports ◽  
English Literature ◽  
Severe Bleeding ◽  
Thrombocytopenic Purpura ◽  
Mycoplasma Pneumonia

Abstract Mycoplasma pneumonia (M. pneumonia) is usually not considered among the several pathogens that induce immune thrombocytopenic purpura (ITP). We report a case of a child with a clinical diagnosis of severe ITP (as defined by the American Society of Hematology panel guidelines of 1994), that was associated with M. pneumonia pneumonia, and reviewed the few cases described in the English literature. A 7-year-old girl was admitted to the pediatric department with 1 day history of fever, purpura and petechiae on her legs, buttocks, arms, face, hard palate, oral mucous membranes and lips. Crepitations were heard over both lungs’ lower fields. Complete blood count revealed WBC of 22.3×103/ μL, Hemoglobin of 11.1 gr/dL, and platelet count of 2×103/μL. Red cells appeared normal on blood film with no features of microangiopathy. A chest X-ray demonstrated right middle lobe infiltrate. Presumptive diagnoses of ITP and RML pneumonia were made and treatment was initiated with one dose of IVIG 0.8 g/kg and daily IV Ceftriaxon at 50 mg/kg. Twelve hours after the IVIG administration, platelet count was 1.2×103/μL. Bone marrow examination revealed normal cellularity with young megakaryocytes, compatible with the diagnosis of ITP. Since there was no response to IVIG, Methylprednisolone 4 mg/ kg for 4 days was started. An extensive search of the literature for ITP or thrombocytopenia and pneumonia retrieved only 7 case reports. In all cases M. pneumonia was the only identified pathogen. Therefore, clarithromycin 15 mg/kg/d was added to the treatment regimen, prior to obtaining the serology results. Thereafter severe hemoptysis developed; the patient was admitted to the PICU and received 4 units of platelets and a second dose of IVIG. Hemoptysis resolved after another day, when the platelet count started to increase gradually, only to drop after the cessation of steroids. A second course of steroids at the same dose was begun and tapered off gradually over 21 days, while the platelet count steadily increased, exceeding 150×103/μL at 4 weeks from presentation. A positive Mycoplasma IgM titer at diagnosis and a 1:160 titer at 2 months confirmed the clinical diagnosis. The child is by now 20 months after the event with normal CBC. Several features of the 8 cases described (including our case) distinguish them from “classic” ITP: Thrombocytopenia occurred concomitantly with the infection as opposed to a few days to a few weeks interval between infection and ITP. Severe bleeding in 4 out of 8 patients including 2 with fatal intracranial hemorrhage in contrast to around 3% severe bleeding and around 1‰ fatal intracranial hemorrhage in “classic” ITP. Three of the authors who looked for specific anti-platelet antibodies were unable to demonstrate it, whereas such antibodies are found in many patients with ITP. Several mechanisms are suggested to explain these differences; though it remains unclear whether Mycoplasma associated thrombocytopenia represents a subset of ITP or constitutes a separate entity. We conclude that M. pneumonia should be looked for in any case of pneumonia and thrombocytopenia or ITP, and early specific anti-Mycoplasma therapy should be initiated to rapidly eliminate the causative agent. This may enhance recovery of the platelet count and decrease the rate of complications.

Rituximab Treatment in Childhood Chronic Immune Thrombocytopenic Purpura (ITP).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4461-4461 ◽  
Author(s):  
Ji Yoon Kim ◽  
Kun Soo Lee ◽  
Hyoung Jin Kang ◽  
Hoon Kook ◽  
Hong Hoe Koo ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenic Purpura ◽  
Medical Records ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
New Treatment ◽  
Lost To Follow Up

Abstract Abstract 4461 Background Immune thrombocytopenic purpura (ITP) is characterized by mucocutaneous purpura and thrombocytopenia caused by circulating anti-platelet auto-antibodies. ITP is usually self-limited in children, but around 20% of patients will develop chronic ITP. The conventional treatments for children chronic ITP include intravenous immunoglobulin (IVIG), corticosteroid therapy, anti-D immune globulin, or splenectomy. Some children with chronic ITP are refractory to these treatments and nowadays begun to try new treatment agents such as rituximab. Rituximab as a monoclonal antibody to CD-20, has shown promising reports to these patients with refractory chronic ITP in adults groups and a few children groups. We investigated this study to evaluate the efficacy of rituximab for childhood chronic ITP in Korea. Methods We reviewed the questionnaires and medical records about the clinical progresses and results in thirteen children from eight clinical institutes, retrospectively. Complete response (CR) was considered if the platelet count was > 100,000/uL. Results Thirteen patients with chronic thrombocytopenia who had been treated with rituximab were investigated. Two patients were lost to follow-up after rituximab. Finally eleven patients were evaluated including one patient with Evans syndrome. Median age was 6.5 year (range, 0.5 ∼ 15.4). Median platelet count at baseline was 13,700/uL (3,000∼46,000). All patients had been treated with conventional therapy including IVIG and steroids. One had done splenectomy. Median follow-up duration was 2.8 years (1.1-5.9). Among 11 patients, CR was achieved in 3 patients (27%). Their platelet count prior to rituximab were < 10,000/uL. They were treated as the regimen of 375 mg/m2/dose weekly for 4 doses. Time from the first rituximab dose to achievement of complete response was 3.9, 4.9 and 5.7 weeks respectively. One patient who was relapsed 6months after the first course of rituximab was received second course of rituximab using the same regimen and achieved a new CR at 9.3 weeks after. There were no reports about severe complication or interruption of medication. Conclusions Therefore, we suggest that rituximab is effective treatment choice in childhood refractory chronic ITP and well tolerated. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Use of the Platelet Indices for Differential Diagnosis of Pediatric Immune Thrombocytopenic Purpura ( ITP )

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4935-4935 ◽  
Author(s):  
Hisaya Nakadate ◽  
Akira Ishiguro ◽  
Kimikazu Matsumoto
Keyword(s):  
Differential Diagnosis ◽  
Platelet Count ◽  
Blood Cell ◽  
Immune Thrombocytopenic Purpura ◽  
Conflicts Of Interest ◽  
Large Cell ◽  
Blood Parameters ◽  
Thrombocytopenic Purpura ◽  
Platelet Indices ◽  
Cell Analyzer

Abstract Introduction The prognosis of pediatric immune thrombocytopenic purpura (ITP) has a favorable prognosis, but it is difficult to predict the course of this disease at the time of diagnosis. Recent advances of automated blood cell analyzer enable to measure platelet indices such as mean platelet volume (MPV), platelet size deviation width (PDW) and platelet-large cell ratio (P-LCR). These have brought about some information for thrombocytopenia. We studied the significance of such platelet indices in the differential diagnosis of immune thrombocytopenic purpura (ITP) and their ability to discriminate the clinical courses of ITP. Methods Ninety-three patients were enrolled this study at our institution from 2004 to 2006. Their ages ranged from 1 to 17 years (media 4.3 years). Of 93, patients were divided into two goups for analysis, according to the diagnosis of ITP. 34 were diagnosed as ITP and 59 were diagnosed various blood diseases other than ITP. In these 59 non-ITP patients, five were with thrombocytopenia (platelet count < 100.0 x 109/L), the other without thrombocytopenia. Of 34 ITP patients, 29 were acute subtype and 5 were chronic. The Sysmex-XE2100 automated blood cell analyzer (Sysmex, Kobe, Japan) was used to measure the blood parameters, including the platelet indices. Results According to MPV, PDW and P-LCR, there were no significant differences between ITP patients and non-ITP. In children with ITP, there were significant inverse correlations between the platelet count and evaluated parameters, MPV (R2=0.376), PDW (R2=0.26) and P-LCR(R2=0.338). But no significant correlations were found between the platelet count and these evaluated platelet indices in non-ITP. Also, we have found all platelet indices were significantly higher in chronic ITP than in acute ITP. In particular, PDW (9.910 vs 13.080) and P-LCR (21.071 vs 33.220) showed marked differences between the two groups. Conclusions ITP is considered as a result of hyper-destruction of platelets. Increase of platelet count is regarded as decrease of destruction of platelets. Our data suggested that platelet indices, MPV, PDW and P-LCR showed the useful information for the degree of platelet destruction and the ability to predict the clinical courses of ITP. Disclosures No relevant conflicts of interest to declare.

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