Chronic immune thrombocytopenic purpura

2009 ◽  
Vol 29 (01) ◽  
pp. 76-79 ◽  
Author(s):  
M. Ruggeri ◽  
F. Rodeghiero
Keyword(s):  
Platelet Count ◽  
Growth Factors ◽  
Immune Thrombocytopenic Purpura ◽  
New Drugs ◽  
New Paradigm ◽  
Open Label ◽  
Thrombocytopenic Purpura ◽  
Normal Volunteers ◽  
Increase Platelet Count ◽  
New Generation

SummaryFirst generation thrombopoietic growth factors (rhTPO and PEG-rHuMGDF), investigated in the early 2000s, proved effective in increasing platelet count in normal volunteers, in thrombocytopenia due to chemotherapy and also in a few cases of immune thrombocytopenic purpura (ITP). These agents did not complete their clinical development since one of them induced antibodies in the recipients that cross reacted with endogenous thrombopoietin (TPO), thus causing thrombocytopenia. This promoted the ingenious design of a new generation of thrombopoietic growth factors having no sequence homology with natural TPO. The two main agents are romiplostim, a peptibody already approved for clinical use in USA and eltrombopag, a non-peptide, orally active small molecule. In open label and placebo-controlled trials both agents proved to predictably increase platelet count in normal volunteers and in patients with ITP. With appropriate dosages (1–10 µg/kg weekly sub cutaneously for romiplostim; 50–75 mg/die per os for eltrombopag ) a platelet increase becomes significant after 7–10 days and peaks between 10–14 days. By dis -continuing treatment, platelet count returns to baseline level in 10–15 days. The response rate with both agents is above 70–80%, also in patients that had undergone several lines of treatment, or that have failed splenectomy. The response is maintained during the treatment, but is almost invariably lost even after several months of successful administration. Due to the lack of a curative potential and to the incomplete knowledge of long-term side effects, the place of these new drugs in the management of ITP is still unsettled and their use is best restricted to refractory patients or in preparation of splenectomy. It seems however that a new paradigm in the treatment of ITP has been established where the focus is not on reducing platelet consumption but on increasing platelet production.

Safety and Efficacy of Laparoscopic Splenectomy in Patients with Refractory Immune Thrombocytopenic Purpura. A Long-Term Survey

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4548-4548
Author(s):  
Nicola Cascavilla ◽  
Matteo Scaramuzzi ◽  
Michele Nobile ◽  
Matteo Dell’Olio ◽  
Antonietta Pia Falcone ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenic Purpura ◽  
Laparoscopic Splenectomy ◽  
New Drugs ◽  
Thrombocytopenic Purpura ◽  
Safety And Efficacy ◽  
Haematological Response ◽  
Short And Long Term

Abstract Background: Despite the popularity of splenectomy has decreased dramatically in the past few years, the surgical approach remains the best therapy for patients with refractory Immune Thrombocytopenic Purpura (ITP) in terms of high and durable rate of response (Vesely et al, Ann Intern Med2004; 140: 112). The recent introduction of anti-CD20 antibodies and thrombopoietins of second generation such as AMG 531 and Eltrombopag may have a relevant role (Kuter et al, Lancet2008; 371: 362) but their long-term safety and efficacy have not been still established. In parallel with new drugs, there has been an evolution in the surgery of splenectomy as well (Dolan et al, Am J Hematol2008; 83: 93). Actually, the laparoscopic surgery is considered the standard approach and the ITP represents the most common indication in 50–80% of all the laparoscopic splenectomies. Methods: The aim of this study is to evaluate the long-term complete and partial haematological response (CR + PR), as well as the short and long-term complications, of 40 patients (30 females and 10 males; median age: 38 years - range 6–71) with unresponsive ITP after one or more medical approaches and underwent laparoscopic splenectomy at our Institution from 1999 through 2006. The 40 patients accounted for 22.2% of 181 patients diagnosed in those years. An abdominal CT scan to evaluate the presence of accessory spleens was performed in all cases. All patients received meningococcal, pneumococcal and haemophilus influenzae vaccine one week before splenectomy. For 4 or 5 days before splenectomy the patients were treated with high doses of intravenous Immunoglobulins. Anti-thrombotic prophylaxis was performed with low molecular weight heparin (LMWH) for 10 days and afterwards with cardioaspirin (ASA) if the platelet count exceeded 500x10E9/L. Results: No cases required conversion to laparotomic splenectomy. An accessory spleen was found in 2 patients (5%). Immediate haematological response rate was of 100%. At date, after a median follow-up of 78 months (range 28–112 months), 36 patients (90%) remain in CR or PR with a platelet count more than 50x10E9/L and 2 patients are taking ASA. Four patients (10%) relapsed; out of which, 2 patients have a platelet count less than 10x10E9/L. Short and long-term mortality rate was 0%. Immediate postoperative complications rate was 5%: we observed 2 cases of hemoperitoneum related to a trocar’s tube and to an active bleeding, respectively, both resolved with new laparoscopic approach. The mean postoperative hospital stay was 4,5 days (range 4–8). Neither cases of bacterial sepsis in the postoperative or during the follow-up time, nor cases of splenic-portal vein thrombosis (SPVT) and no cases of neoplasms occurred. Conclusions: Our experience suggests that laparoscopic splenectomy is an excellent approach to patients with refractory ITP in terms of safety, efficacy and costs. With respect to laparotomic splenectomy, the use of laparoscopy is likely to make the splenectomy even safer and therefore suitable for a larger number of patients. Undoubtedly there is a great expectation for the new drugs (Rodeghiero et al, Am J Hematol2008; 83: 91) and we agree that only controlled comparative clinical trials (Vianelli et al, Haematologica2005; 90: 72) will be able or not to say a final word and to challenge the role of splenectomy.

Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk

Blood ◽  
2009 ◽  
Vol 113 (14) ◽  
pp. 3154-3160 ◽  
Author(s):  
Anna Podolanczuk ◽  
Alan H. Lazarus ◽  
Andrew R. Crow ◽  
Elliot Grossbard ◽  
James B. Bussel
Keyword(s):  
Clinical Trial ◽  
Platelet Count ◽  
Immune Thrombocytopenic Purpura ◽  
Disease Models ◽  
Phase 2 ◽  
Open Label ◽  
Thrombocytopenic Purpura ◽  
Phase 2 Clinical Trial ◽  
Persistent Response ◽  
Refractory Itp

Abstract To determine whether inhibition of Syk would be useful in FcγR-dependent cytopenias such as immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia, mouse models were used to evaluate efficacy of R406, an inhibitor of Syk function, in treating cytopenia. Both disease models responded favorably to treatment, with amelioration of ITP being more dramatic. Thus, phase 2 clinical trial was initiated to study the effects of Syk inhibition in humans with ITP. Sixteen adults with chronic ITP were entered into an open-label, single-arm cohort dose-escalation trial beginning with 75 mg and escalating as high as 175 mg twice daily. Doses were increased until a persistent response was seen, toxicity occurred, or 175 mg twice daily was reached. Eight patients achieved persistent responses with platelet counts greater than 50 × 109/L (50 000 mm3) on more than 67% (actually 95%) of their study visits, including 3 who had not persistently responded to thrombopoietic agents. Four others had nonsustained responses. Mean peak platelet count exceeded 100 × 109/L (100 000 mm3) in these 12 patients. Toxicity was primarily GI-related with diarrhea (urgency) and vomiting; 2 patients had transaminitis. In conclusion, inhibition of Syk was an efficacious means of increasing and maintaining the platelet count in half the patients with chronic refractory ITP. (ClinicalTrials.gov, no. NCT00706342).

scholarly journals Metastatic Breast Cancer with Extensive Osseous Metastasis Presenting with Symptomatic Immune Thrombocytopenic Purpura and Anemia: A Case Report and Review of the Literature

2015 ◽  
Vol 8 (2) ◽  
pp. 256-263 ◽  
Author(s):  
Jiaxin Niu ◽  
Teresa Goldin ◽  
Maurie Markman ◽  
Madappa N. Kundranda
Keyword(s):  
Breast Cancer ◽  
Platelet Count ◽  
Metastatic Breast Cancer ◽  
Immune Thrombocytopenic Purpura ◽  
English Literature ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated

Background: Immune thrombocytopenic purpura (ITP) is a rare acquired bleeding disorder with an estimated incidence of 1 in 10,000 people in the general population. The association of ITP with breast cancer is an even rarer entity with very limited reports in the English literature. Case Presentation: We report a case of a 51-year-old female with no significant past medical history who presented with sudden onset of malaise, syncope, gingival bleed and epistaxis. She was found to have severe thrombocytopenia (platelet count 6,000/μl) and anemia (hemoglobin 7.2 g/dl). Her workup led to the diagnosis of metastatic ductal breast cancer with extensive bone metastasis. Bone marrow biopsy demonstrated myelophthisis which was initially thought to be consistent with her presentation of thrombocytopenia and anemia. Therefore, the patient was started on hormonal therapy for the treatment of her metastatic breast cancer. After 3 months of therapy, she did not improve and developed severe mucosal bleeding. Her clinical presentation was suspicious for ITP and immune-mediated anemia, and hence she was started on steroids and intravenous immunoglobulin. The patient had a dramatic response to therapy with normalization of her platelet count and hemoglobin within 2 weeks. Conclusion: To our knowledge, this is the first reported case of metastatic breast cancer presenting with symptomatic ITP and anemia, and both symptoms are postulated to be immune-mediated.

scholarly journals Anti-RH immunoglobulin therapy for human immunodeficiency virus-related immune thrombocytopenic purpura

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1499-1502 ◽  
Author(s):  
E Oksenhendler ◽  
P Bierling ◽  
Y Brossard ◽  
C Schenmetzler ◽  
PM Girard ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Platelet Count ◽  
Immune Thrombocytopenic Purpura ◽  
Specific Interaction ◽  
Immunoglobulin Therapy ◽  
Thrombocytopenic Purpura ◽  
Immunodeficiency Virus

Abstract The potential hazards of steroids in human immunodeficiency virus (HIV)- infected patients led us to evaluate the effectiveness and safety of anti-D and anti-c Ig in 17 adults with severe HIV-related immune thrombocytopenic purpura (platelet count less than 20 x 10(9)/L). The 14 Rh+ patients received 12 to 25 micrograms/kg of anti-D IgG intravenously on two consecutive days. A significant platelet rise above 50 x 10(9)/L was obtained in nine patients. Repeated boosters were performed in six cases and were effective in all cases. The 3 Rh- patients had a good response after they were given 20 mL x 2 of plasma containing potent anti-c antibodies. Therapy was well tolerated, and only one patient had significant hemolysis. These data suggest that anti-Rh IgG can be effective and safe in HIV-related thrombocytopenic purpura and that a specific interaction between the RBC antigens and the anti-Rh antibodies is required.

scholarly journals Quantitation of platelet-associated IgG by radial immunodiffusion

Blood ◽  
1981 ◽  
Vol 57 (4) ◽  
pp. 809-811 ◽  
Author(s):  
BS Morse ◽  
D Giuliani ◽  
M Nussbaum
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenic Purpura ◽  
Radial Immunodiffusion ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Normal Platelet ◽  
Serum Igg ◽  
Acute Itp ◽  
Igg Level

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.

scholarly journals An open-label, unit dose-finding study of AMG 531, a novel thrombopoiesis-stimulating peptibody, in patients with immune thrombocytopenic purpura

2006 ◽  
Vol 135 (4) ◽  
pp. 547-553 ◽  
Author(s):  
Adrian Newland ◽  
Marie T. Caulier ◽  
Mies Kappers-Klunne ◽  
Martin R. Schipperus ◽  
Francois Lefrere ◽  
...  
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Dose Finding ◽  
Open Label ◽  
Thrombocytopenic Purpura ◽  
Finding Study ◽  
Dose Finding Study ◽  
Unit Dose

Treatment Patterns and Splenectomy Failure Rates in Patients with Chronic Immune Thrombocytopenic Purpura in Canada: A Retrospective Chart Review

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4565-4565
Author(s):  
Joseph Mikhael ◽  
Alan Tinmouth ◽  
Tazmin Merali ◽  
Mo Amin ◽  
Wendy Lam
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenic Purpura ◽  
Chart Review ◽  
Retrospective Chart Review ◽  
Initial Therapy ◽  
Second Line ◽  
First Line ◽  
Bleeding Events ◽  
Thrombocytopenic Purpura ◽  
Line Therapy

Abstract Background: In clinical practice there is little consensus on treating patients with chronic immune thrombocytopenic purpura (ITP) beyond first line therapy with steroids. Objectives: Describe the demographic and disease characteristics of adult ITP patients who receive treatment; Obtain the treatment approach for patients with ITP beyond first line treatment with steroids, with an emphasis on splenectomy; and Evaluate adverse bleeding outcomes associated with ITP. Methods: A retrospective chart review of ITP patients after initial therapy with steroids was conducted. Ten physicians (oncologists and hematologists) were recruited from across Canada and each physician provided at least 5 ITP cases for review. A total of 51 cases were reviewed and patients (> 18 years old) were required to have had more than 1 course of steroids as treatment to be eligible. Results: The average age of patients at diagnosis was 42 (range 3 to 82 years); 37 (73%) of the patients were female, and 37 (73%) were Caucasian. The median platelet count upon presentation was 5×109/L. Median lines of therapy after initial therapy was 3 (range 0 to 6). Second line therapies varied, but most commonly patients underwent splenectomy (43%), followed by continued steroid treatment (16%), steroids plus IV Ig (16%), IV Ig alone (14%), immunosuppressant alone (2%), and anti-D plus steroids (2%). Of the patients reviewed, 40 (78%) eventually underwent splenectomy. Of the 40 splenectomized patients, 27 were splenectomized within the first year of diagnosis and 35 underwent splenectomy during the first 5 years. In addition, 62 of the splenectomies were laparoscopic, and the median hospital stay for all procedures was 5 days (range 1 to 60 days). Immediate failure of splenectomy occurred in 18% of patients, and the one- and five- year relapse/failure rates (defined as platelet count < 30×109/L) were 38% and 55%, respectively. Other therapies following splenectomy included IV Ig, azathioprine, cyclosporine, danazol, mycophenolate, rituximab, vincristine, cyclophosphamide, and anti-D. Only 6% of IV Ig use was for chronic maintenance therapy and 74% of use was for urgent therapy. A total of 61 bleeding events occurred, of which 10 were major (upper GI, mouth, rectal, and nose). Major bleeding events required hospitalization of the patient with an average length of stay of 5 days (range 2 to 14 days). Conclusions: Notwithstanding several limitations, the retrospective chart review suggests that there is wide variation in long-term therapy for patients with chronic ITP in Canada. Splenectomy was the most widely used second line therapy, although 18% of the patients were non-responders and the five-year relapse/failure rate was 55%.

Platelet Counts Following Eltrombopag Discontinuation in Patients with Chronic Immune Thrombocytopenic Purpura.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3517-3517
Author(s):  
Gregory Cheng ◽  
Michael Tarantino ◽  
Terry Gernsheimer ◽  
Oliver Meyer ◽  
Andres Brainsky ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenic Purpura ◽  
Research Funding ◽  
Rescue Medication ◽  
Study Medication ◽  
Bleeding Events ◽  
Thrombocytopenic Purpura ◽  
Baseline Platelet Count ◽  
Platelet Counts ◽  
Transient Decrease

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.

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