Thrombopoietin Levels May Predict Responsiveness to Therapy with Thrombopoietin Agonists Among Patients with Immune Thrombocytopenic Purpura,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3288-3288 ◽  
Author(s):  
Robert Makar ◽  
Olga S. Zhukov ◽  
Mervyn A. Sahud ◽  
David J. Kuter

Abstract Abstract 3288 INTRODUCTION: Thrombopoietin (TPO) is the major regulator of platelet production. In prior clinical studies, thrombopoietin levels have been shown to vary inversely with circulating platelet mass and with the rate of platelet production. Thus, TPO levels may help distinguish between the various disorders of thrombocytopenia. In addition, the introduction of TPO agonists has created an interest in predicting the response of patients to these agents. Determining TPO levels may help predict such treatment responses. METHODS: Sera from 121 patients with a history of abnormal platelet counts were tested using a novel, commercially available ELISA assay that measures TPO levels. The TPO assay detected TPO levels as low as 7 pg/mL and was linear for levels up to 2000 pg/mL. The coefficient of variation ranged from 27% near the lower limit of detection to 9% at a TPO concentration of 669 pg/mL. The reference range for TPO was established in serum samples from 118 apparently healthy individuals (58 males and 60 females) and was 7–99 pg/mL. The Wilcoxon test was used to compare continuous variables and the Fisher's exact test was used to compare categorical variables. RESULTS: The patient population included 40 patients with a consumptive thrombocytopenia (38 with primary or secondary immune thrombocytopenic purpura (ITP), 2 with thrombotic thrombocytopenic purpura), 34 patients with myeloproliferative disorders (23 with essential thrombocytosis, 9 with polycythemia vera, 2 with an ill-defined myeloproliferative disorder), and 47 patients with hypoproliferative thrombocytopenia (29 with chemotherapy-related thrombocytopenia, 19 with primary or secondary bone marrow failure syndromes). Among the 38 patients with ITP, 11 were taking TPO agonists (9 on romiplostim, 2 on eltrombopag), 19 were taking immunomodulatory agents (16 on steroids alone or in combination with other therapies, 2 on azathioprine, 1 on danazol), and 12 were off ITP-specific therapy when the TPO level was measured. 9 out of 38 (24%) patients with ITP had undergone splenectomy and/or been previously treated with rituximab. The median serum TPO level in patients with consumptive thrombocytopenia was 64.5 pg/mL (interquartile range, 48.5–97.5 pg/mL) and the corresponding median platelet count was 68,000/μL (interquartile range, 27,000–144,500) (Figure). While patients with myeloproliferative disorders had similar TPO levels [median 87.0 pg/mL (38.0–125.5)], their platelet counts were significantly higher than those of patients with consumptive thrombocytopenia [median 549,500/mL (431,250–693,000] (P <0.0001). Contrastingly, comparable platelet counts [median 61,000/μL (31,000–118,000)] were observed among patients with hypoproliferative thrombocytopenia, but serum TPO levels were significantly higher than those of patients with consumptive thrombocytopenia [844 pg/mL (409.5–1551.5), P <0.0001]. Among 22 evaluable patients meeting diagnostic criteria for primary or secondary ITP who had taken a TPO agonist for at least 1 month, serum TPO levels appeared to predict responsiveness to the drug. A clinical response to a TPO agonist was defined as achieving a platelet count ≥50,000/μL after starting the drug and maintaining it at or above that count in ≥50% of subsequent complete blood counts from initiation until discontinuation of the drug, loss to follow-up, or 6 months had passed, whichever was longest, without the need for recurrent rescue therapy. Whereas 14 out of 16 (88%) ITP patients with a TPO level <99 pg/mL met our definition for a clinical response to treatment with a TPO agonist, only 1 out of 6 patients (17%) with a TPO level >99 pg/mL responded (P <0.005 for the difference in clinical response to TPO agents.) CONCLUSIONS: TPO levels may have diagnostic utility in discriminating between patients with hypoproliferative and consumptive thrombocytopenia. High TPO levels among patients with ITP may predict a poor clinical response to treatment with TPO agonists. Further studies are required to confirm these data. Disclosures: Zhukov: Quest Diagnostics: Employment. Sahud:Quest Diagnostics: Employment. Kuter:Quest Diagnostics: Consultancy, Research Funding.

Blood ◽  
1981 ◽  
Vol 57 (4) ◽  
pp. 809-811 ◽  
Author(s):  
BS Morse ◽  
D Giuliani ◽  
M Nussbaum

Abstract Platelet-associated IgG (PAIgG) was measured by a simple radial immunodiffusion technique using washed solubilized platelets and commercially available immunoplates. Subjects with normal platelet counts had PAIgG levels of 1.5--7.0 fg/platelet. Subjects with idiopathic immune thrombocytopenic purpura (ITP) had levels ranging from 5.7 to 70.5 fg/platelet. All patients with recurrent ITP and 85% of patients with acute ITP had elevated PAIgg. Elevated PAIgG was also found in 17% of patients with recovered ITP, 40% of patients with SLE and thrombocytopenia, 57% of patients with thrombocytopenia occurring during the course of septicemia, and 100% of patients with IgG myeloma in whom the serum IgG level was clearly elevated, regardless of the platelet count. The results are similar to reports that used more complex techniques.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3933-3933
Author(s):  
Yongqiang Zhao ◽  
Baolai Hua ◽  
Nong Zou ◽  
Shujie Wang ◽  
Tienan Zhu

Abstract Thrombopoietin (TPO) is the key regulator of megakaryocytepoiesis and platelet production. TPO binds to its specific receptor, c-Mpl, on the surfaces of megakaryocytes, and may promote the proliferation, differentiation and maturation of megakaryocytes, and finally increase the circulating platelet count. The role of TPO in the pathogenesis of idiopathic thrombocytopenic purpura (ITP) is not certain. Plasma concentrations of TPO in ITP patients were similar to or little lower than that in healthy subjects. Therefore it is possible that supplemental TPO could significantly promote platelet production and increase platelet counts in ITP patients. Here, we report the result of multiple cycles of recombinant human thrombopoietin (rhTPO) therapy in a patient with refractory ITP. The patient, a 42-year-old woman, was admitted to our department on December 30, 2003. She had suffered from chronic ITP for more than 4 years. The patient had been treated with glucocorticosteroids, immunosuppressive agents and splenectomy. No sustained response could be achieved. The diagnosis of chronic refractory ITP was made. There were petechiae and gingival bleeding on admission. Liver and spleen were not palpable. Hemoglobin was 142g/L, white blood cell count 7.6×10 9/L, platelet count 15×10 9/L. Bone marrow aspiration revealed that erythroid and myeloid development were normal, megakaryocytes were increased in number and no dysplastic features. After an informed consent was obtained from the patient, rhTPO (Sunshine Pharmaceutical Corporation, China) was administrated subcutaneously at dosage of 1.0 μg/kg, daily for 14 days or until platelet count sustained more than 50×109/L. Anti-rhTPO antibodies were determined weekly by ELISA. Three cycles of rhTPO therapy was given with 6, 13 and 8 dosing for each cycle. The platelet counts before each cycle were all less than10×109/L and increased above 50×109/L on day 5, 11 and 8 of rhTPO administration, respectively. The peak platelet counts of 456, 130 and 82×109/L were reached on day 9, 15 and 13 for each cycle. Then platelet count decreased gradually. The durations of platelet count more than 50×109/L in 3 cycles were 13, 7 and 10 days respectively. No increase of WBC count and Hb level occurred. No liver and kidney function damage, abnormal coagulation functions or thrombosis developed during the treatment. rhTPO antibodies were not detectable. The result indicated that rhTPO could transiently increase peripheral platelet counts of the patient with chronic refractory ITP. It was uncertain why peak platelet counts declined and durations of platelet count more than 50×109/L shortened when multiple cycles of rhTPO were given.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3517-3517
Author(s):  
Gregory Cheng ◽  
Michael Tarantino ◽  
Terry Gernsheimer ◽  
Oliver Meyer ◽  
Andres Brainsky ◽  
...  

Abstract Abstract 3517 Poster Board III-454 BACKGROUND Eltrombopag (PROMACTA®; GlaxoSmithKline, Collegeville, PA, USA) is an oral, small molecule (565 Da), thrombopoietin receptor agonist that has been approved in the United States for the treatment of patients with chronic immune thrombocytopenic purpura (ITP). It is also being studied in thrombocytopenic patients with chronic liver disease, hepatitis C, myelodysplastic syndromes, and cancer. Withdrawal of treatments that stimulate platelet production may theoretically result in recurrent thrombocytopenia below pretreatment levels (below baseline). OBJECTIVE: To determine whether worsening of thrombocytopenia (ie, platelet count decrease below baseline) occurs after discontinuation of eltrombopag in patients with chronic ITP. METHODS: The lowest median platelet counts during the first 4 weeks posttherapy were compared with median baseline platelet counts. Data from 369 patients treated in 3 randomized, double-blind, placebo-controlled studies were analyzed: TRA100773A and TRA100773B were 6-week studies, and RAISE was a 6-month study. For all 3 studies, a baseline platelet count <30,000/μL was required. Platelet counts, bleeding events, and the use of ITP medication were examined in the 4 weeks following the discontinuation of eltrombopag or placebo. A transient decrease in platelet counts (ie, worsening of thrombocytopenia) was defined as a platelet count below 10,000/μL and at least 10,000/μL below each patient's baseline platelet count (Bussel N Eng J Med 2006). RESULTS: Using pooled data from the 3 studies, no decreases below baseline median platelet counts (placebo, 16,300/μL; eltrombopag, 16,000/μL) were observed compared to the lowest median platelet counts within the first 4 weeks posttherapy (placebo, 14,000/μL; eltrombopag, 17,000/μL). Across the pooled studies, a total of 10/128 (8%) of placebo-treated patients and 20/241 (8%) of eltrombopag-treated patients had a transient decrease in platelet counts in the 4 weeks following discontinuation or interruption of treatment. None of the 10 placebo-treated patients had bleeding events associated with posttreatment platelet nadirs. Three of the 20 eltrombopag-treated patients had bleeding events and/or rescue treatment associated with the platelet nadir in the 4-week posttreatment period. One patient discontinued eltrombopag after achieving platelet counts >200,000/μL following on-therapy rescue medication (corticosteroid 0.5 mg/kg/day); 9 days after discontinuing study medication, the patient had grade 1 gum bleeding and resumed daily corticosteroids at an increased dose. The second patient had grade 3 menorrhagia and was administered vincristine (patient had a history of similar symptoms). The third patient had Henoch-Schoenlein purpura, interrupted eltrombopag due to platelet counts >400,000/μL, and 7 days after holding eltrombopag had a platelet count of 2000/μL, experienced grade 1 mouth hemorrhage and grade 2 petechiae, and did not require rescue medication. The patient continued in the study for the full 6 months and following permanent discontinuation of eltrombopag, this patient did not experience a transient decrease in platelet counts or any bleeding. CONCLUSION: Across 3 placebo-controlled studies, the incidence of transient decreases in platelet counts following discontinuation or interruption of study medication was similar in patients receiving eltrombopag or placebo. Therefore, these decreases may be unrelated to study medication and may represent normal fluctuations in platelet counts in patients with chronic ITP. Transient platelet count decreases were generally not associated with bleeding events. Disclosures: Cheng: GlaxoSmithKline: Research Funding. Tarantino:GlaxoSmithKline: Speakers Bureau; Lundbeck: Speakers Bureau; Baxter: Membership on an entity's Board of Directors or advisory committees. Gernsheimer:GlaxoSmithKline: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Meyer:GlaxoSmithKline: Consultancy, Honoraria. Brainsky:GlaxoSmithKline: Employment. Stone:GlaxoSmithKline: Employment.


2018 ◽  
Vol 5 (5) ◽  
pp. 1719
Author(s):  
Olia Sharmeen ◽  
Mohammod Hasanur Rashid ◽  
Md Abdur Rouf ◽  
Afiqul Islam

Background: Established treatment option for immune thrombocytopenic purpura (ITP) are intravenous immunoglobulin (IVIg), anti-D immunoglobulin’ and high dose intravenous methyl prednisolone (HIVMP). The present study was undertaken to compare the efficacy of subcutaneous bolus anti-D over HIVMP in the treatment of ITP.Methods: A randomized clinical trial was conducted on a total 20 children with ITP, presented with extensive bleeding manifestation and platelet count <20 × 109/L;10 children received single dose subcutaneous anti-D (75 microgram/kg) and 10 children received HIVMP (30 mg/kg/dose) for 3 consecutive days. Patients were monitored for response to treatment and adverse events, platelet count and hemoglobin label were done in all patients at 24-hour, 48-hour, 72 hour, 1st week, 2nd week, 1st month, 2nd month and 3rd month after treatment to observe the change. Response rate define as a platelet count over 20 × 109/L within 72 hours of treatment. All the data were analyzed with the help of SPSS software version 16.0.Results: By 24 hours of treatment 40% patient of anti-D and 10% patients of HIVMP group had platelet count >20 x109/L, by 72 hours 90% patients of both group achieved complete response (P =1.750). In HIVMP group the rate of remission gradually decreasing but in anti-D group it was persistently remain high. In anti-D group hemoglobin concentration decreased in 80% cases (P=0.023) but rate of decrease was not significant. New hemorrhage or significant extension of hemorrhage did not observe in any group.Conclusions: A single dose of subcutaneous anti-D raised platelet count in children with ITP more rapidly and effectively than HIVMP (30 mg/kg/dose) with an acceptable safety profile.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4003-4003 ◽  
Author(s):  
Jun Ho Jang ◽  
Hyeoung Il Kim ◽  
Hyun Woo Lee ◽  
Seok Yun Kang ◽  
Joon Seong Park ◽  
...  

Abstract BACKGROUND: Helicobacter pylori has clearly been implicated in the pathogenesis of gastric and duodenal ulcers, gastritis, and gastric malignancy. Remarkably, eradication of H. pylori from the gastric mucosa has been associated with improvement of systemic disease, including Sjögren’s syndrome, rheumatoid arthritis, autoimmune thyroid disease, and immune thrombocytopenic purpura (ITP). PURPOSE: To investigate the relationship between Helicobacter pylori infection and the clinical features of idiopathic thrombocytopenic purpura (ITP), and to examine the effects of H. pylori eradication on platelet counts. METHOD: A 13C urea breath test (UBT) for H. pylori infection was performed in a 25 consecutive patients with ITP at Ajou University School of Medicine, Suwon, Korea. Patients who tested positive for H. pylori received standard eradication therapy if their platelet count was &lt; 50 x 109/L. RESULTS: H. pylori infection was detected in 18 patients (72%) and eradication therapy was successfully administered to all infected patients. H. pylori infection was not associated with dyspepsia or other clinical or laboratory features. Platelet responses were observed in 6 (33%) of these patients, which lasted for more than 4 months in 4 patients. Platelet associated antibody and anti platelet antibody were negative to all patients. CONCLUSION: H. pylori eradication may improve the platelet counts in some of adults (33%) in whom the ITP is of recent onset.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1077-1077
Author(s):  
Eri Tanaka ◽  
Shuji Hayashi ◽  
Katsumichi Fujimaki ◽  
Hiroyuki Fujita

Abstract Refractory Immune Thrombocytopenic Purpura (ITP) is a difficult disease to treat effectively and the mortality approaches nearly 10% over 10 years. Moreover, the side effect profile of chronic steroid administration is undesirable due to the multi-systemic actions of these drugs. Recently, it has been reported in the literature that Rituximab is effective treatment for chronic ITP and it has been used at a dose of 375mg/m2 weekly for up to four weeks, as with lymphoma therapy. Rituximab is an expensive treatment, but according to previous data, patients treated with this drug have responded with increased and sustained platelet counts following only one infusion. Based on this, we treated five refractory ITP patients with single-dose Rituximab and all responded well. Patient 1 is with a 15 year history of ITP and Patient 2 is with a 34 year long history of ITP. Following treatment with Rituximab, although there was an interval of up to 7 months, both eventually responded well. Patient 3 is a 93 year old male who presented to our hospital with an acute presentation of ITP which involved severe gastrointestinal bleeding and this proved to be refractory to both steroids and intravenous immunoglobulins, but responded very quickly to Rituximab within 24 days. Patient 4 is a 75 year old female with diabetes mellitus and three-vessel coronary artery disease who presented with a bleeding diathesis. She was treated with steroids, intravenous immunoglobulins, danazol and azathioprine but with no response. Single-dose Rituximab was effective within 20 days with an improvement in platelet counts. Patient 5 is a 51 year old male with a six year history of ITP who presented to our hospital with massive intraabdominal and gastrointestinal bleeding and after Rituximab therapy his platelet count responded appropriately after 45 days. These patient responses were not associated with prior response to therapy, age, previous splenectomy, duration of ITP or platelet count. All patients tolerated treatment well except one patient who developed SLE-nephrotic syndrome 15 months later although it cannot be proven that such therapy induced this collagen-vascular diseases because Rituximab can be used to actually treat such conditions. Three patients remained in remission for more than one year after just one dose of the Rituximab therapy. Even from our small number of refractory ITP patients treated with Rituximab, it is our experience that single-dose treatment is also effective in some cases of refractory ITP and its effect may continue to provide long-term remission whereby it is now possible to decrease and even stop long-term steroid treatment in such patients.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4686-4686
Author(s):  
Yun Ling ◽  
Xiangshan Cao ◽  
Xinyu Qian

Abstract Abstract 4686 Immune thrombocytopenic purpura (ITP) is an autoimmune disorder. A corticosteroid, usually prednisone is often the first line treatment for ITP. However, the problem is that about 70 percent of adult patients experience a relapse after discontinuation of corticosteroids. And approximately 20–30% of patients with chronic ITP do not respond to corticosteroids therapy. Rituximab has been proven effective in refractory chronic ITP, but the timing of response is slower than expected, at least three months might be necessary to observe an effect. And the response duration to rituximab remains relatively short in some patients. So, sometimes it is necessary to use combination therapy including rituximab, according to different patient conditions. Here, we report an 82-year-old man with chronic ITP who had thrombocytopenia (platelet count <10 × 109/L) for more than 6 months and relapsed on a prednisone taper. He presented sustaining blood-tinged sputum, bleeding in skin and steroid-induced diabetes, the result of short-term prednisone. He didn't want splenectomy and other immune suppressive drugs. His blood glucose got control after insulin therapy. We gave the patient intravenous infusions of rituximab 375 mg/m2 weekly for 4 weeks combined with dexamethasone (10 mg intravenously weekly for 4 weeks). After first dose of dexamethasone followed by rituximab, within 24 hours his platelet count had increased to 65 × 109/L and bleeding symptoms were significantly improved. During the next 3-week period of treatment, his platelet counts fluctuated between 30 × 109/L and 60 × 109/L. And then the platelet count dropped back to a minimum of 19 × 109/L. Consider the slow responses to rituximab and prevention of bleeding, we still gave the patient maintenance therapy with 15mg prednisone daily and he had been no bleeding. Two months after starting rituximab and dexamethasone, his platelet counts began to gradually recover to normal. Although we need to further observe the patients's duration of response, this case suggests that combination therapy of rituximab and corticosteroids may be a promising treatment for refractory chronic ITP. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
1981 ◽  
Vol 57 (4) ◽  
pp. 809-811
Author(s):  
BS Morse ◽  
D Giuliani ◽  
M Nussbaum

Platelet-associated IgG (PAIgG) was measured by a simple radial immunodiffusion technique using washed solubilized platelets and commercially available immunoplates. Subjects with normal platelet counts had PAIgG levels of 1.5--7.0 fg/platelet. Subjects with idiopathic immune thrombocytopenic purpura (ITP) had levels ranging from 5.7 to 70.5 fg/platelet. All patients with recurrent ITP and 85% of patients with acute ITP had elevated PAIgg. Elevated PAIgG was also found in 17% of patients with recovered ITP, 40% of patients with SLE and thrombocytopenia, 57% of patients with thrombocytopenia occurring during the course of septicemia, and 100% of patients with IgG myeloma in whom the serum IgG level was clearly elevated, regardless of the platelet count. The results are similar to reports that used more complex techniques.


2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Ayrton Bangolo ◽  
Mohamed Ahmed ◽  
Ali Atoot ◽  
Ashraf Mahmoud ◽  
Chibuzo Agbakwuru-Onyike ◽  
...  

Secondary immune thrombocytopenic purpura (ITP) associated with Helicobacter pylori (H. pylori) infection has been described in the literature. It appears to have a geographic distribution; mostly encountered in countries with a higher prevalence for H. pylori such as Italy or Japan. H. pylori eradication has been recommended in the management of ITP with studies showing improvement in the platelet count in some patients. Substantial platelet count increases in patients with severe thrombocytopenia (platelet counts <30 × 103 microliter), however, are uncommon with H. pylori treatment alone. Here, we present a 34-year-old Hispanic male with worsening chronic thrombocytopenia that resolved following eradication of his H. pylori infection. Herein, we highlight a rare and reversible cause of secondary ITP. With this case report, we hope to encourage physicians to include H. pylori testing in the evaluation of thrombocytopenia.


Sign in / Sign up

Export Citation Format

Share Document