Combination immunosuppressant therapy for patients with chronic refractory immune thrombocytopenic purpura

Abstract Treatment options for patients with chronic refractory immune thrombocytopenic purpura (ITP) are limited. Because combination immunosuppressant therapy appeared to be effective in ITP and other disorders, we used this approach in patients with particularly severe and refractory ITP. In this retrospective, observational study, we determined the response (platelet count above 30 × 109/L and doubling of baseline) among 19 refractory ITP patients. Treatment consisted of azathioprine, mycophenolate mofetil, and cyclosporine. The patients had failed a median of 6 prior treatments, including splenectomy (in all except 1). Of 19 patients, 14 (73.7%) achieved a response lasting a median of 24 months, after which time 8 (57.1%) relapsed. Of the 8 relapsing patients, 6 responded to additional treatments. Of the 14 patients who achieved an initial response, 2 (14.3%) remained in remission after eventually stopping all medications. Severe adverse events did not occur. Combination immunosuppressant therapy can produce a rise in the platelet count that is sometimes sustained in refractory ITP patients.

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Immune Thrombocytopenic Purpura in Pregnancy- A Prospective Observational Study in a Tertiary Care Centre

Bangladesh Journal of Obstetrics & Gynaecology ◽

10.3329/bjog.v34i1.56670 ◽

2019 ◽

Vol 34 (1) ◽

pp. 15-21

Author(s):

Tabassum Parveen ◽

Firoza Begum ◽

Nahreen Akhter ◽

Nigar Sultana ◽

Khairun Nahar

Keyword(s):

Platelet Count ◽

High Risk ◽

Observational Study ◽

Immune Thrombocytopenic Purpura ◽

Platelet Transfusion ◽

Prospective Observational Study ◽

Thrombocytopenic Purpura ◽

Neonatal Thrombocytopenia ◽

Itp In Pregnancy ◽

In Pregnancy

Objectives: Immune thrombocytopenic purpura (ITP) in pregnancy necessitates management of two patients, the mother and the newborn. Complications like maternal bleeding, fetal and neonatal thrombocytopenia demands appropriate and timely therapy. This prospective observational study was designed to explore and summarize the current approach to the investigation, diagnosis, management and outcome of ITP in pregnancy. Materials and Methods: Women with ITP admitted in the Fetomaternal Medicine Department of Bangabandhu Sheikh Mujib Medical University (BSMMU) from 2009 -2017, were included in the study. Total number of high risk pregnancy during that period were 7704 among them 20 cases were pregnancy with Immune Thrombocytopenic Purpura (ITP). Patients were managed under joint supervision of the fetomaternal medicine specialist and the hematologist. Prednisolone was considered as a first line drug in management protocol. Platelet transfusion was considered if there were symptoms or count <20X109/L at any stage of pregnancy or <50 X109 / L in late pregnancy without symptoms. Platelet count of newborn was performed at birth and repeated on day four and count<150X109/L was considered as neonatal thrombocytopenia. Results: Frequency of ITP among high risk patients was found 2.5/1000 live birth, most were preexisting (75%). Almost all cases (95%) were treated with prednisolone. Commonest clinical presentations were gum bleeding (70 %) and purpuric rashes (60%). Though during pregnancy, severe thrombocytopenia (<50 X109/L) was found in 7 patients (35%) but none was at the time of delivery, as drugs and/or platelet transfusion was considered to make delivery process safe. Platelet transfusion needed in 77.7% cases in a range of 1-75 units. Primary PPH noted in 3 cases (17%), increased bleeding during surgery in 5 patients (33%) and one patient needed ICU support. Neonatal thrombocytopenia noted in 5 cases (28%). Though 2 of the neonates needed NICU admission but none needed platelet transfusion and all the babies were discharged healthy. Conclusion: This study documents that pregnancy with ITP need close monitoring, require agents to raise the platelet count and repeated platelet transfusion to maintain reasonable safe platelet count. There are chances of PPH, capillary oozing during surgery. However good outcome is possible for most women, fetus and neonates with appropriate and timely therapy. Bangladesh J Obstet Gynaecol, 2019; Vol. 34(1): 15-21

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Safety and Efficacy of Thrombopoietin Analogs in the Treatment of Chronic Thrombocytopenic Purpura in Children: A Systematic Review

Blood ◽

10.1182/blood-2021-151173 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4215-4215

Author(s):

Usman Ali Akbar ◽

Vivek Soorya Sathya Moorthy ◽

Sudeep Yadav ◽

Saman Bahram ◽

Adnan Mehboob Qureshi ◽

...

Keyword(s):

Clinical Trials ◽

Platelet Count ◽

Placebo Group ◽

Observational Study ◽

Immune Thrombocytopenic Purpura ◽

Research Funding ◽

Pediatric Population ◽

Platelet Response ◽

Thrombocytopenic Purpura ◽

Double Blinded

Abstract Introduction Immune thrombocytopenic purpura (ITP) is an autoimmune disorder consisting of low platelet count, purpura, and hemorrhagic episodes, caused by antiplatelet autoantibodies. Children who develop chronic or refractory ITP are at risk of bleeding after failing first-line therapies. Thrombopoietin analogs -Eltrombopag and romiplostim are safe and effective treatment options. Thrombopoietin receptor agonists (TPO-Ras) improve platelet production by activating the thrombopoietin pathway. They also stimulate megakaryocytes and hematopoietic stem cells. We analyzed the efficacy and toxicity of romiplostim and eltrombopag in chronic immune thrombocytopenic purpura in the pediatric population (1-17 years). Materials/Methods Following the PRISMA guidelines, we performed a comprehensive literature search on Pubmed, Embase, Cochrane Library, Web of Science, and Clinicaltrials.gov. We used the following keywords, "Thrombopoitein analogs", "TPOs", "Immune thrombocytopenic purpura", "Eltrombopag" and "Romiplostim" MeSh terms from the inception of data till 06/17/2021. We screened initial results from the search of 358 articles focusing on the pediatric population and finally included 9 clinical trials and 1 observational study. We excluded all case reports, case series, preclinical trials, review articles, and meta-analyses. We extracted the data for efficacy (platelet response, baseline platelet count, and Platelet count at first response) and safety (Bleeding or Grade ≥ 3 Adverse Events). Results: Romiplostim A total of 185 patients were analyzed in five clinical trials and 1 observational study employing Romiplostim in the treatment group. Platelet response (PR) (platelet count >50 × 109/L) has been reported in all the studies. In 3 randomized double-blinded control trials by Bussel 2011, Elfaly 2011, and Tarantino 2016, Romiplostim achieved a platelet response of 81.69% vs 12.9% in the placebo group. The other three studies reported substantial platelet response as stated in table 1. In all the studies 25 participants had a prior splenectomy. The most common side effects reported in the studies were bleeding (56.75%), headache (58.64%), contusion (50.76%), and epistaxis (49.23%). Clinically significant bleeding (grade 2-4) was reported by 2 studies in Romiplostim vs placebo group (71.08% vs 96%). Eltrombopag A total of 246 patients were analyzed in five clinical trials and 1 observational study. In a randomized double-blinded multicenter study by Grainger et al., Eltrombopag achieved a PR of 39.68% vs 3.4% in the placebo group. Other clinical trials reported a PR of 55.85% whereas the observational study by Neuner et al. reported a PR of 72% in the patient population. Clinically significant bleeding was reported by Grainger et al. and was 47 % in the eltrombopag group vs 7% in the placebo group. Fifteen patients in all the studies had a prior splenectomy. Conclusion: Thrombopoietin analogs such as romiplostim and eltrombopag show substantial platelet response and are associated with minimal side effects. However, more randomized clinical trials are needed to compare their head-to-head efficacy and safety in the treatment of chronic immune thrombocytopenic purpura in pediatric patients. Figure 1 Figure 1. Disclosures Anwer: Janssen pharmaceutical: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Allogene Therapeutics: Research Funding; BMS / Celgene: Honoraria, Research Funding.

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A Meta-Analysis on the Use of Intravenous Gamma Globulin and Corticosteroids in Children with Acute Immune Thrombocytopenic Purpura.

Blood ◽

10.1182/blood.v106.11.4000.4000 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4000-4000

Author(s):

Mary N. Chua ◽

Tintin Manuela ◽

Jesus N. Sarol ◽

Antonio D. Ligsay

Keyword(s):

Platelet Count ◽

Adverse Events ◽

Immune Thrombocytopenic Purpura ◽

Fixed Effects ◽

Gamma Globulin ◽

Treated Group ◽

Risk Difference ◽

Oral Steroid ◽

Thrombocytopenic Purpura ◽

Treatment Groups

Abstract To determine the difference in proportion of patients who achieved a rise in platelet count and to determine the risk difference of adverse events in patients with acute immune thrombocytopenic purpura treated with corticosteroids or gamma globulin (IVIG). Medline, EMBASE, Pediatric Hematology and Oncology, Pediatrics and Journal of Pediatrics (all up to 2005) and personal collections of the authors. Systematic search of articles utilizing a search strategy was performed to identify relevant articles according to prior inclusion and exclusion criteria. Fixed effects and random effects models were used to determine summary effect estimates. Difference in proportion of patients who achieved the desired platelet count and risk difference of adverse events between treatment groups. Analysis of 9 randomized controlled trials showed that IVIG produced an additional 12–14% increase in proportion of patients with platelet count >20 x 109/L and 15% increase in proportion of patients with platelet count >50 x 109/L on days 2 to 4. No significant differences were seen between the treatment groups on days 14 and 28 except for platelet count >50 x 109/L. More patients in oral steroid treated group had adverse events compared to IVIG treated group but no differences were noted in the parenteral treated group. IVIG is more effective compared to corticosteroids in raising the platelet count during the early part of treatment. IVIG and parenteral steroids shows less adverse events as compared to oral steroid.

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Single Dose of Anti-CD20 Monoclonal Antibody (Rituximab) Treatment in Adults with Refractory Immune Thrombocytopenic Purpura (ITP).

Blood ◽

10.1182/blood.v108.11.1077.1077 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1077-1077

Author(s):

Eri Tanaka ◽

Shuji Hayashi ◽

Katsumichi Fujimaki ◽

Hiroyuki Fujita

Keyword(s):

Platelet Count ◽

Single Dose ◽

Gastrointestinal Bleeding ◽

Immune Thrombocytopenic Purpura ◽

Intravenous Immunoglobulins ◽

Thrombocytopenic Purpura ◽

Platelet Counts ◽

History Of ◽

Refractory Itp

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.

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

Blood ◽

10.1182/blood-2008-07-166439 ◽

2009 ◽

Vol 113 (14) ◽

pp. 3154-3160 ◽

Cited By ~ 157

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).

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Efficacy and Safety of a Combination of Thrombopoietin Receptor Agonist with an Immunosuppressant Therapy for the Management of Multirefractory Adult ITP: Results from a Retrospective, Multicenter, Observational Study

Blood ◽

10.1182/blood-2020-143031 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 12-13

Author(s):

Etienne Crickx ◽

Guillaume Moulis ◽

Marc Ruivard ◽

Bouchra Asli ◽

Jean Pierre Marolleau ◽

...

Keyword(s):

Platelet Count ◽

Mycophenolate Mofetil ◽

Observational Study ◽

Median Duration ◽

Research Funding ◽

Biological Data ◽

Efficacy And Safety ◽

Immunosuppressant Therapy ◽

Multicenter Observational Study ◽

Thrombopoietin Receptor

Introduction Multirefractory adult ITP, defined as no response to splenectomy, rituximab, and thrombopoietin receptor agonists (TPO-Ra), is associated with high morbidity and mortality. In a previous study, we have shown that combining an immunosuppressant therapy with one TPO-Ra could be a promising therapeutic strategy for managing patients with multirefractory ITP. Objective The aim of this study was to assess the efficacy and safety of such combination in multirefractory ITP on a larger series of patients. Patients and methods We conducted a retrospective, multicenter, observational study in France. Adult patients treated by a combination of a TPO-Ra with an immunosuppressant therapy (i.e., mycophenolate mofetil, azathioprine, ciclosporin, everolimus, or cyclophosphamide) for chronic (> 12 months) or persistent (> 3 months) multirefractory ITP, were included through the national reference center for adult immune cytopenia (CERECAI) network. Multirefractory ITP was defined as disease not responding to rituximab, to splenectomy (or contraindication to splenectomy), and to the 2 TPO-Ras licensed in France (romiplostim and eltrombopag) administered at the maximal approved dose. Clinical and biological data were retrospectively collected using a standardized form. Complete response (CR) was defined by a platelet count >100 x109/L and response (R) by a platelet count between 30-100 x109/L with at least a 2-fold increase from baseline, according to the international recommendations. Results Thirty-one patients (65% female, median age 57 years [range 23 - 82]) were included. Five (16%) of them had secondary ITP (Evans syndrome (n=2), systemic lupus (n=1) with antiphospholipid syndrome (APS), primary APS (n=1), and Waldenstrom macroglobulinemia (n=1). Four patients had a monoclonal gammopathy of undetermined significance, and 11 (35%) had antinuclear antibodies (titer >1/160) without definite clinical autoimmune disease. All patients had previously received corticosteroids and 16/31 (52%) were corticosteroid-refractory. Previous treatments lines also included intravenous immunoglobulin (28/31, 90%) and at least one immunosuppressant therapy (16/31, 52%). Splenectomy was performed in 25 patients (81%), and not performed in the remaining 6 patients because of advanced age and comorbidities (n=3), underlying APS (n=2), or patient refusal (n=1). At the time of treatment combination initiation, median ITP duration was 57 months [3 - 393], with 28/31 (90%) chronic ITP and 3/31 (10%) persistent ITP. Bleeding symptoms were present in 23 patients (74%) and the median platelet count was 10 x109/L [range 1 - 35]. The combination regiment included eltrombopag (n=18) or romiplostim (n=13), associated with either mycophenolate mofetil (n=15), azathioprine (n=12), cyclophosphamide (n=2), ciclosporine (n=1), or everolimus (n=1). Median duration of combination therapy was 12 months [range 1 - 103]. Nineteen patients (61%) had no therapeutic intervention other than the combined treatment, while 10 patients were also given corticosteroids (either short course of high dose steroids [n=5], or on a long-term at low dose [n=5]), and/or hydroxychloroquine (n=5). Overall, 81% of patients (25/31) achieved at least a R, including 19/31 (61%) CR. Among responders, the median time to response was 30 days [range 7 - 270], and the median duration of the response was 12 months [4 - 55]. Response rates were similar in patients who did not receive concomitant corticosteroids (59% CR, 12% R), and in patients that were previously exposed to immunosuppressant therapy given alone (63% CR, 25% R). Regarding safety, 13/31 (42%) patients experienced at least one adverse event potentially related to treatment, including 7 severe adverse events. Three patients without APS but who were splenectomized had a thromboembolic event, including 3 deep vein thrombosis/pulmonary embolism, and 1 cerebral venous thrombosis; Three patients had an infection (one cholecystitis, one herpes zoster, and one dental abscess). After a median follow-up of 18 months [6-103], one patient died (from a previously diagnosed adenocarcinoma). Conclusion In summary, these data show that most of the patients managed for multirefractory ITP may benefit from the combination of TPOra with an immunosuppressant therapy by achieving a durable response. The safety profile of this combination in this population seems acceptable. Disclosures Moulis: Novartis SAS: Membership on an entity's Board of Directors or advisory committees, Other: meeting attendance grant, Research Funding; Amgen: Other: meeting attendance grant; Grifols: Research Funding. Michel:Bioverativ: Consultancy; Rigel: Consultancy; Alexion Pharmaceuticals: Consultancy. Godeau:LFB: Honoraria; Amgen: Research Funding; Amgen: Honoraria; Novartis: Honoraria. Mahevas:GSK: Research Funding. OffLabel Disclosure: Some immunosuppressant drugs were given off-label for adult ITP.

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Rituximab Is Effective in Refractory Adult Immune Thrombocytopenic Purpura Associated with Chronic Lymphocytic Leukemia.

Blood ◽

10.1182/blood.v104.11.3952.3952 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3952-3952

Author(s):

Thein H. Oo ◽

Neela Natarajan

Keyword(s):

Platelet Count ◽

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Immune Thrombocytopenic Purpura ◽

Peripheral Blood ◽

Lymphocytic Leukemia ◽

High Dose ◽

Thrombocytopenic Purpura ◽

Platelet Counts ◽

Refractory Itp

Abstract Chronic lymphocytic leukemia ( CLL ) is the commonest leukemia in the western world. 2% of CLL patients present with immune thrombocytopenic purpura ( ITP ). Corticosteroids, intravenous immune globulins ( IVIG ) and splenectomy have been the mainstay of treatment of ITP. Rituximab is the monoclonal antibody against CD-20 antigen expressed on the B-lymphocytes. It has established its role in the treatment of many B-cell malignancies in the last one decade. Due to its B-cell depletion capability, interests in employing rituximab in the treatment of many autoimmune diseases have grown in the last few years. Recently, many small case reports/series and a few small trials have reported the efficacy of rituximab in the treatment of refractory ITP. However, not much is known about its efficacy in the ITP associated with CLL. Here, a patient with CLL initially presenting with ITP is described. A 67-year-old white female with a past history of hysterectomy for fibroids and hypertension presented with rectal bleeding and multiple ecchymoses. Physical examination was unremarkable except for skin eccymoses on the extremities and abdomen. Colonscopy revealed hemorrhoids only. Computerized tomograms showed no lymphadenopathy or other abnormalities. Here laboratory data were as follows; hemoglobin 5.8g/dl, WBC 29,400/mm3, platelet 13,000/mm3, lymphocyte 52%, neutrophil 45%, monocyte 2.5%. Chemistry profile was unremarkable. Her blood group was O, Rh-negative. She was initially treated at another institution with packed Red Blood Cells, prednisone 1.5mg/kg qd and daily IVIG 0.4g/kg for 5 days for presumed ITP. Platelet transfusions did not raise the platelet counts. She remained profoundly thrombocytopenic and was subsequently transferred to our hospital. Review of the blood smear revealed anisopoikilocytosis, few tear-drop RBCs, many small-to-medium sized mature lymphocytes, occasional smudge cells, large platelets, few Pseudo-Pelgar-Huet cells but no blasts. Given moderate absolute lymphocytosis ( 15,200/mm3 ), blood film findings and profound thrombocytopenia, a working diagnosis of CLL-associated ITP was entertained. Peripheral blood flow cytometry showed lymphocytes positive for CD5, CD19, CD20 (dim ) and CD23, kappa/lambda ratio of 248:1. Bone marrow biopsy showed moderate lymphocytosis with the same immunophenotype as peripheral blood. Megakaryocytes were abundant. The diagnosis was confirmed. She was treated with a course of high dose methylprednisone, 2 courses of IVIG 1g/kg x 2days with very transient response. Due to this, she underwent splenectomy but her platelet counts remained low. She required another 5 courses of IVIG resulting in brief responses over the next 3 weeks. She was subsequently put on po danazol 200mg bid with short-lived responses. Eventually, she received iv rituximab 375mg/m2 weekly for 4 weeks. She achieved complete remission within 1 month. Two months later, she transferred her care to another facility. Review of the literature showed 1 case report of CLL-associated refractory ITP successfully treated with rituximab and the response duration was 6 months. Three CLL patients with refractory fludarabine-associated ITP also responded to rituximab. Of them, two achieved a platelet count over 100,000/mm3 and 1 achieved a platelet count of 72,000/mm3 within 4 weeks. Duration of responses ranged from 6 to 17 months. Those results together with our case suggest rituximab is an alternative agent for the treatment of CLL-associated ITP. Its potential in ITP associated with B-cell lymphoid malignancies should be explored further.

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Efficacy and Safety of a New Intravenous Immunoglobulin Product in Patients with Chronic Immune Thrombocytopenic Purpura.

Blood ◽

10.1182/blood.v110.11.1307.1307 ◽

2007 ◽

Vol 110 (11) ◽

pp. 1307-1307

Author(s):

Tadeusz Robak ◽

Abdulgabar Salama ◽

Lidia Kovaleva ◽

Yaroslava I. Vyhovska ◽

Simon Davies ◽

...

Keyword(s):

Platelet Count ◽

Adverse Events ◽

Intravenous Immunoglobulin ◽

Primary Endpoint ◽

Immune Thrombocytopenic Purpura ◽

Efficacy And Safety ◽

Platelet Response ◽

Thrombocytopenic Purpura ◽

Platelet Counts ◽

Chronic Itp

Abstract Background Intravenous immunoglobulin (IVIG) is an accepted treatment for immune thrombocytopenic purpura (ITP). A new liquid 10% human IgG preparation stabilized with proline at a pH of 4.8 (trade name: Privigen) was recently developed. It can be stored at room temperature and is therefore always ready to use. Here we report its efficacy and safety in patients with chronic ITP. Patients and Methods Fifty-seven patients with chronic ITP and a platelet count below 20 x 109/L were included in this open-label, single arm, multi-center Phase III trial. IVIG was given at a dose of 1 g/kg on 2 consecutive days at a maximum infusion rate of 4 mg/kg/min. A subset (56.1%) of the patients received premedication (acetaminophen or diphenhydramine) to avoid adverse events. The primary endpoint was the platelet response rate, defined as the percentage of patients showing an increase in platelet count to ≥50 x 109/L within 7 days of the first infusion. Secondary endpoints included platelet counts at specified time points, time to platelet response, duration of platelet response, and regression of hemorrhages at different bleeding sites. Safety was evaluated by the frequency and severity of adverse events. Results The primary endpoint, an increase in platelet counts to ≥50 x 109/L, was achieved by 81% of the subjects (95% CI: 69–89%). The highest median platelet count (149 x 109/L) was observed on day 8. Median time to response was 2.5 days, with 43% of subjects responding within 1 day. Median duration of platelet response (days with platelet count ≥ 50 x 109/L) was 15.4 days. Regression rates for various bleeding sites ranged from 78% to 100%. Regression of bleeding correlated with increases in platelet counts. Adverse events were reported in 52 (91%) subjects. The most common adverse event was headache (67%), the incidence and severity of which was attenuated by premedication with acetaminophen/diphenhydramine. There were 3 serious adverse events, one of which (aseptic meningitis) was considered related to the study medication. Conclusions The present study has shown the safety and significant efficacy of a novel, 10% liquid, ready for use IVIG preparation, in patients with chronic ITP. A rapid increase in platelet counts to a level where severe bleeding episodes become more unlikely was seen in the majority of patients, as expected with IVIG given at 1 g/kg on 2 consecutive days. The increase in platelet counts was associated with a regression of bleeding. Adverse events were generally mild to moderate in severity, corresponded to those expected with IVIG, and could be prevented with premedication.

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Catastrophic anti-phospholipid syndrome with Libman-Sacks endocarditis following eltrombopag therapy for immune thrombocytopenic purpura: A case report

Lupus ◽

10.1177/09612033211065140 ◽

2021 ◽

pp. 096120332110651

Author(s):

Sara Dichtwald ◽

Avraham Meyer ◽

Nisim Ifrach

Keyword(s):

Case Report ◽

Adverse Events ◽

Lupus Erythematosus ◽

Immune Thrombocytopenic Purpura ◽

Intravenous Immunoglobulins ◽

Young Female ◽

The European Union ◽

Positive Serology ◽

Thrombocytopenic Purpura ◽

Refractory Itp

Background Immune thrombocytopenic purpura (ITP) is an autoimmune disease, with accelerated destruction of platelets, estimated to affect 1.6–3.9 in 100,000 adults every year in the European Union. Glucocorticoids and intravenous immunoglobulins are common drug therapies. In refractory cases, drugs that enhance thrombopoiesis may be used. Eltrombopag is a thrombopoietin receptor agonist, known to increase platelet count in patients with refractory ITP. Thrombotic adverse events have been described in association with Eltrombopag administration. Case report A young female patient of Ethiopian ancestry with systemic lupus erythematosus, triple Antiphospholipid (APLA) positive serology and refractory ITP who received Eltrombopag and 2 weeks later developed catastrophic APLA syndrome with severe Libman-Sacks endocarditis of the mitral and aortic valves, multiple intracerebral infracts and arterial thrombosis of the left upper limb. Conclusion Eltrombopag is a salvage drug, used in refractory ITP. Thrombotic adverse events, some of which may be life-threatening, are a possible complication, especially in high-risk patients.

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Incidence and outcomes of refractory immune thrombocytopenic purpura in children: a retrospective study in a single institution

Scientific Reports ◽

10.1038/s41598-021-93646-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Masataka Ito ◽

Hiroshi Yagasaki ◽

Koji Kanezawa ◽

Katsuyoshi Shimozawa ◽

Maiko Hirai ◽

...

Keyword(s):

Platelet Count ◽

Retrospective Study ◽

Intravenous Immunoglobulin ◽

Steroid Therapy ◽

Immune Thrombocytopenic Purpura ◽

Response Rate ◽

Ivig Therapy ◽

Single Institution ◽

Thrombocytopenic Purpura ◽

Refractory Itp

AbstractTreatment of children with refractory immune thrombocytopenic purpura (ITP) is challenging and poorly established. We retrospectively reviewed the clinical data of 87 patients under the age of 16 years who were diagnosed with ITP from April 1998 to March 2017 in our institution. Refractory ITP was defined as a platelet count of < 50 × 109/L at 14 days after receiving intravenous immunoglobulin (IVIG) and prednisolone. We presumed that there was a pathophysiological overlap between refractory ITP and refractory thrombocytopenia (RT): a subtype of refractory cytopenia of childhood (RCC). Immunosuppressive therapies including anti-thymocyte globulin and cyclosporine (CsA) have been adopted for children with RCC in Japan. Thus, from 2009 onwards, we changed the diagnosis from refractory ITP to RT and introduced CsA for refractory ITP/RT. Nine of 42 patients developed refractory ITP in the 1998–2008 group, who received conventional treatments such as IVIG and steroid therapy. Eight of 45 patients developed refractory ITP in the 2009–2017 group, who received CsA with or without IVIG therapy. The response rate at three years after diagnosis was significantly higher in the 2009–2017 group (98%) than in the 1998–2008 group (83%) (p = 0.019). In conclusion, our strategy of introducing CsA for refractory ITP/RT contributed to better outcomes.

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