Thrombopoietin Receptor Agonist (ELTROMBOPAG) for Chronic Immune Thrombocytopenic Purpura (ITP) Treatment: 21 Patients in Only One Center

Abstract Abstract 4658 Introduction ITP management has changed since thrombopoietin receptor agonists (TRAs) were approved for its treatment. Current TRAs are recommended for adults at risk of bleeding who relapse after splenectomy, as well as for those where splenectomy is contraindicated and where, at least, one other therapy has failed. The goal of this paper is to present the results of the treatment and follow-up of 21 patients treated with Eltrombopag in our Centre during the last year. Patients We present 21 patients diagnosed with chronic ITP according to the American Society of Hematology guidelines. 7 of them were males and 14 females. The median age was 70 years (range from 26 to 81 years). Previous splenectomy was undergone in 3 patients. 10 patients had previously received two or more therapies for ITP. 11 patients received TRAs as second line treatment. Results On average, platelet counts at the beginning of the treatment with Eltrombopag were 23.000/μL. All patients started with the same doses (50 mg) except one of them who started with 25 mg. Patients only received concurrent ITP therapy (corticosteroids and intravenous immunoglobulins) when platelet counts were under 20,000/μL or bleeding occurred. 8 patients needed rescue medications throughout the treatment with Eltrombopag (7 of them only once). Eltrombopag was withdrawn in a total number of 8 patients due to different reasons: 4 patients were considered as non-responders (3 of them didn't achieve a certain platelet count to prevent major bleeding and, in the fourth one, reducing or suspending the concurrent ITP therapy was not possible. One of these non-responders received Romiplostin and a good response was achieved). In one patient, the therapy was withdrawn due to liver toxicity and in another one, at patient's request. Finally, Eltrombopag was withdrawn in 2 patients because a sustained platelet counts was held. Conclusion TRAs are safe, effective and well-tolerated for those patients who relapse after splenectomy or when splenectomy is contraindicated. In our experience, TRAs could be also useful in other diseases like HCV or HIV associated thrombocytopenia. Eltrombopag and Romiplostin bind in different places to the TPO receptor (TPO-R). This circumstance, together with the different activation pathways, may explain that some non-responders to Eltrombopag could respond to Romiplostin and viceversa. Disclosures: No relevant conflicts of interest to declare.

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Adding Slow Release Tetracosactide Acetate to Eltrombopag Improves Haematological Response in ITP Patients with Platelet-Count Fluctuation

Blood ◽

10.1182/blood-2018-99-118518 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2449-2449

Author(s):

Francesco Iuliano ◽

Eleonora Iuliano ◽

Marco Rossi

Keyword(s):

Platelet Count ◽

Zinc Phosphate ◽

Conflicts Of Interest ◽

Self Administration ◽

Baseline Platelet Count ◽

Adult Rheumatoid Arthritis ◽

Thrombopoietin Receptor ◽

Thrombopoietin Receptor Agonist ◽

Therapeutic Doses

Abstract Background and aim Tetracosactide Acetate (SR-TA) stimulates the release of corticosteroids such as cortisol from the adrenal gland. It is absorbed on to a zinc phosphate complex which ensures the sustained release of the active substance from the intramuscular injection site. SR-TA is currently used in the management of ulcerative colitis and Crohn's disease, juvenile/adult rheumatoid arthritis and osteoarthrosis. However, its properties indicate that this compound may be particularly useful in patients unable to tolerate oral glucocorticoid therapy or where normal therapeutic doses of glucocorticoids turned to be ineffective. Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist that has been shown efficacy and safety in chronic immune thrombocytopenia (ITP) patients not responding to previous therapy. Based on these premises, we treated with a combination of Eltrombopag and SR-TA selected ITP patients undergoing a platelet count fluctuation despite a standard eltrombopag dose was given . Material and methods A total of 6 adult patients, female (60%),median (range) age 37 (28 - 54) years, median (range) baseline platelet count 31 (28 - 46) × 109/L, median of 3 (2 - 4) prior ITP therapies, received a combo of Eltrombopag 50 mg by mouth daily and SR-TA 1 mg intramuscularly daily until the target platelet count of 50× 109/L was reached, then a dose of 1mg of SR-TA was given every 3 days; in responding patients , i.e. without platelet count fluctuation, the dose was further reduced to 1mg per week. Results 5 out of six patients responded to treatment reaching and maintaining the platelet count between 50× 109/L and 100× 109/L. After a median follow-up of 6 months with combo treatment, all patients maintained their response. Self-administration was started by 100% of patients (6/6). No adverse events have been observed. Our experience has shown that eltrompopag/SR-TA combo is effective and safe in maintaining the platelet count above 50x109/L in those patients not reaching this target with the TPO mimetic alone. Disclosures No relevant conflicts of interest to declare.

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Immune Thrombocytopenia Associated to Low-Dose Alemtuzumab Therapy in Chronic Lymphocytic Leukemia: A Single Retrospective Center Experience

Blood ◽

10.1182/blood.v120.21.4598.4598 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4598-4598

Author(s):

Gianluigi Reda ◽

Francesco Maura ◽

Giuseppe Gritti ◽

Daniele Vincenti ◽

Mariarita Sciumé ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Disease Progression ◽

Cumulative Dose ◽

Immune Thrombocytopenia ◽

Low Dose ◽

Conflicts Of Interest ◽

Autoimmune Disorder ◽

Intravenous Immunoglobulins ◽

Lymphocytic Leukemia ◽

Platelet Counts

Abstract Abstract 4598 Immune thrombocytopenia (ITP) is a common autoimmune complication in chronic lymphocytic leukemia (CLL), occurring in up to 5% of patients. The occurrence of alemtuzumab-associated ITP have been rarely reported in CLL and it has never been reported so far as a significant event complicating alemtuzumab treatment in clinical trials. Recently, a new distinctive form of secondary ITP occurring in 6 out of 215 patients with relapsing-remitting multiple sclerosis treated with alemtuzumab in a randomized, controlled phase II trial has been reported (Cuker et al, Blood 2011). We investigated the incidence of ITP in a cohort of 64 consecutive patients treated with low-dose alemtuzumab for relapsed/refractory CLL from 2003 to 2010. Subcutaneous alemtuzumab was administered at the dose of 10 mg three times a week, up to 18 weeks. ITP was documented in 12/64 patients: in 3 patients (4.7%) ITP developed before alemtuzumab treatment and no relapses of the autoimmune disorder were observed during the treatment; in 9 patients (14.8%, with an incidence of 5.7 events/100 patient-year) ITP developed after alemtuzumab treatment. Median time to ITP from initial alemtuzumab exposure was 12 months (range 1–42 months). Concomitant hemolytic anemia (Evans syndrome) was observed in one patient. At ITP onset, median platelet counts were 11×109/L (range 3–70) and anti-platelet antibodies (Capture P® Method, ImmucorGamma, Norcross GA, USA) were found in 7 of the 8 patients tested. No patients showed severe or life-threatening bleeding. Three of nine patients who developed ITP after alemtuzumab therapy, experienced CLL progression requiring chemo-immunotherapy after 3, 4 and 13 months from ITP onset, respectively. One patient achieved a partial remission of CLL with ITP resolution, while the other two died of disease progression. In the remaining six cases, ITP was not associated with disease progression and was treated with corticosteroids and/or intravenous immunoglobulins. Five patients achieved normal platelet counts, while one patient did not respond. Low-dose alemtuzumab (theoretical cumulative dose 540 mg, equal to half of the classic cumulative dose and one-third of the individual dose) is an effective, safe and well tolerated treatment for CLL, as reported by several recent studies (Cortelezzi et al, Leukemia 2009; Brit J Haematol 2011). In our cohort of CLL patients treated with alemtuzumab, the incidence of ITP was 14.8% that is almost three times higher than previously reported in CLL. These data may indicate a role of T-lymphocyte dysregulation induced by alemtuzumab in the pathogenesis of ITP. Our data also suggested the importance of monitoring platelet counts during follow-up in patients treated with low-dose alemtuzumab for both haematological and non-haematological diseases. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood.v128.22.3744.3744 ◽

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.

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Treatment of Immune Thrombocytopenia (ITP) with Eltrombopag - Results of the 4 th Interim Analysis of the German Non-Interventional Trial RISA

Blood ◽

10.1182/blood-2021-146809 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3150-3150

Author(s):

Oliver Meyer ◽

Rudolf Schlag ◽

Thomas Stauch ◽

Bastian Fleischmann ◽

Marcel Reiser ◽

...

Keyword(s):

Platelet Count ◽

Interim Analysis ◽

Receptor Agonist ◽

Immune Thrombocytopenia ◽

Bleeding Complications ◽

Bleeding Events ◽

Interventional Trial ◽

Platelet Counts ◽

Thrombopoietin Receptor ◽

Thrombopoietin Receptor Agonist

Abstract Background: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder with increased platelet destruction and impaired platelet production. Patients present with bleeding complications of various severity. Another common symptom of ITP is fatigue, which can severely affect patient's quality of life. Eltrombopag (EPAG) is an oral thrombopoietin receptor agonist, which is proved to be effective and safe in the treatment of ITP. In Europe, it is approved for the therapy of patients who were diagnosed with ITP at least 6 months ago and who have not responded to other treatments. Here we present data from the 4 th interim analysis of the RISA study. Methods: RISA is a prospective multicenter non-interventional trial in Germany. It was launched in December 2015, and it will be continued until December 2023. In accordance with the inclusion criteria, adults with persisting or chronic pITP (primary ITP) have been enrolled. Patients with pre-treatment could only be included if it was terminated 4 weeks prior to the patient's consent to participate in the study. Exclusion criteria comprised pregnancy, hepatitis C infection and severe aplastic anaemia. Dosage of EPAG and treatment of patients follows the SmPC and the routine of treating physicians. According to the study protocol, patient questionnaires must be completed at 0,1,3,6,9,12,18 and 24 months. Fatigue is assessed using the FACIT-F score, which includes a score range from 0 to 52, with score values <30 indicating severe fatigue. Statistical elaboration is predominantly descriptive. Calculations of confidence intervals and significance values are performed only for explorative purposes. Results: Data cutoff for this 4 th interim analysis was 23.02.2021. 275 patients were enrolled. 261 of them received at least one dose of EPAG and completed one post baseline assessment. Mean duration of participation was 5.2 years. Mean±SD age was 62.7±17.6 years. 54.8% of the patients were female. Median (range) duration of ITP at baseline was 5.3 (0.0-44.9) years. Comorbidity was present in 80.5% of all patients. 79 (28.7%) patients completed all scheduled visits before data cutoff. Median treatment duration was 395.0 days. Treatment with EPAG was carried out at a median dosage of 50 mg daily. In 255 patients, baseline platelet counts were available. The proportion of patients with a platelet count ≥50x10 9/L was 30.6% at baseline. With EPAG treatment, it increased to 75.4% within the first month (N=224) and to 89.0% within 24 months (N=73) from baseline. 12.6% of the patients who completed at least one assessment visit after baseline were pre-treated with the thrombopoietin receptor agonist romiplostim. Within this subgroup as well, platelet counts responded well to EPAG treatment. In 35.6% of patients, at least one bleeding event had occurred in the 12 months prior to baseline. During EPAG therapy, the incidence of bleeding events per patient year was reduced from 1.40 before baseline to 0.60 and 0.13 within the first and second treatment year respectively. This corresponds to a relative reduction in bleeding events of 57% and 91% respectively. Over the entire two years treatment period, the average incidence of bleeding events per patient year accounted for 0.44, which is 69% below the incidence at baseline. Bleeding events were mostly of low severity. (Tab.) Median FACIT-F score was 37.0 at baseline (N=202; mean 36.0±11.0) and 42.5 after 24 months (N=48; mean 38.1±12.1). This difference was not statistically significant. According to exploratory calculations, severity of fatigue was not correlated to platelet count, hemoglobin concentration or incidence of bleeding events. Discussion: In line with previously published randomized controlled trials (Birocchi et al. Platelets 2021), this non-interventional study confirmed the effectiveness of EPAG in adults with persistent or chronic ITP in a routine care setting. During treatment with EPAG, the prevalence and severity of thrombocytopenia, as well as the incidence of bleeding events, decreased. We could also confirm that fatigue is a significant issue in patients with ITP. A FACIT-F score of 37.0 is comparable to average score values in cancer patients (Montan et al. Value Health 2018). Under treatment with EPAG, we observed a decrease in fatigue that was clinically relevant but not statistically significant. Further research is needed to explore possible additional effects of EPAG, for example on fatigue. Figure 1 Figure 1. Disclosures Meyer: Swedish Orphan Biovitrum: Consultancy, Honoraria; Grifols: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Stauch: Novartis: Honoraria, Research Funding; Amgen: Honoraria. Willy: Novartis Pharma: Current Employment.

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Cerebral Venous Thrombosis in a Patient with Immune Thrombocytopenia, an Apparent Paradox

Case Reports in Oncology ◽

10.1159/000507389 ◽

2020 ◽

Vol 13 (2) ◽

pp. 588-594 ◽

Cited By ~ 2

Author(s):

Maimoonah A. Rasheed ◽

Arwa E. Alsaud ◽

Sania Razzaq ◽

Afraa Fadul ◽

Mohamed A. Yassin

Keyword(s):

Venous Thrombosis ◽

Cerebral Venous Thrombosis ◽

Immune Thrombocytopenia ◽

Intravenous Immunoglobulins ◽

Apparent Paradox ◽

Multiple Line ◽

Thrombopoietin Receptor ◽

Thrombopoietin Receptor Agonist ◽

Venous Infarcts ◽

Low Platelet Count

We present a paradoxical case of immune thrombocytopenia (ITP) that presented with cerebral venous thrombosis. A 39-year-old female patient diagnosed with chronic ITP, who failed treatment on multiple-line agents, was started on eltrombopag (thrombopoietin receptor agonist), which she was not compliant to. The patient later developed extensive cerebral venous thrombosis, along with venous infarcts, and intracranial and subarachnoid hemorrhage. She was treated with intravenous immunoglobulins as well as steroid therapy and was simultaneously started on anticoagulation. The patient improved clinically and radiologically. This case is among few reported cases which signify that patients with ITP are inherently prone to thrombosis despite low platelet count and treating these patients can be a dilemma. Judicious use of anticoagulation and immunosuppressive therapy is recommended based on available evidence pending further recommendations and guidelines about treatment of thrombosis in ITP.

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Eltrombopag monotherapy can improve hematopoiesis in patients with low to intermediate risk-1 myelodysplastic syndrome

Haematologica ◽

10.3324/haematol.2020.249995 ◽

2020 ◽

Vol 105 (12) ◽

pp. 2785-2794 ◽

Cited By ~ 3

Author(s):

Alana Vicente ◽

Bhavisha A. Patel ◽

Fernanda Gutierrez-Rodrigues ◽

Emma Groarke ◽

Valentina Giudice ◽

...

Keyword(s):

Myeloid Leukemia ◽

Liver Toxicity ◽

Primary Efficacy ◽

Phase 2 ◽

Elevated Plasma ◽

Predictors Of Response ◽

Thrombopoietin Receptor ◽

Thrombopoietin Receptor Agonist ◽

Grade 3 ◽

Robust Response

Myelodysplastic syndromes (MDS) are a group of clonal myeloid disorders characterized by cytopenia and a propensity to develop acute myeloid leukemia (AML). The management of lower-risk (LR) MDS with persistent cytopenias remains suboptimal. Eltrombopag (EPAG), a thrombopoietin receptor agonist, can improve platelet counts in LR-MDS and tri-lineage hematopoiesis in aplastic anemia (AA). We conducted a phase 2 dose modification study to investigate the safety and efficacy of EPAG in LR-MDS. EPAG dose was escalated from 50 mg/day, to a maximum of 150 mg/day over a period of 16 weeks. The primary efficacy endpoint was hematologic response at 16-20 weeks. Eleven of 25 (44%) patients responded; five and six patients had uni- or bi-lineage hematologic responses, respectively. The predictors of response were presence of a PNH clone, marrow hypocellularity, thrombocytopenia with or without other cytopenia, and elevated plasma thrombopoietin levels at study entry. The safety profile was consistent with previous EPAG studies in AA; no patients discontinued drug due to adverse events. Three patients developed reversible grade-3 liver toxicity and one patient had increased reticulin fibrosis. Ten patients discontinued EPAG after achieving a robust response (median time 16 months); four of them reinitiated EPAG due to declining counts, and all attained a second robust response. Six patients had disease progression not associated with expansion of mutated clones and no patient progressed to AML on study. In conclusion, EPAG was well-tolerated and effective in restoring hematopoiesis in patients with low to intermediate-1 risk MDS. This study was registered at clinicaltrials.gov as #NCT00932156.

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Methylprednisolone Versus Intravenous Immunoglobulin As Initial Therapy In Adult Immune Thrombocytopenia

Blood ◽

10.1182/blood.v122.21.3557.3557 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3557-3557

Author(s):

Ik-Chan Song ◽

Deog-Yeon Jo ◽

Yoon Seok Choi ◽

Hyo-Jin Lee ◽

Hwan-Jung Yun ◽

...

Keyword(s):

Intravenous Immunoglobulin ◽

Immune Thrombocytopenia ◽

Conflicts Of Interest ◽

Complete Response ◽

Early Response ◽

Adult Patients ◽

Term Outcome ◽

Long Term Outcome ◽

Platelet Counts

Abstract Background Both intravenous methylprednisolone (methyl-Pd) and intravenous immunoglobulin (IVIg) have been used as standard initial therapies in adult patients with immune thrombocytopenia (ITP). Nonetheless, few studies have addressed whether there are differences in clinical efficacy between these two treatments. In this study, we compared platelet responses, toxicities, and bleeding-related mortality associated with these two treatments in adult ITP. Patients and Methods Adult patients newly diagnosed with ITP, with platelet counts of less than 20,000/mL, were prospectively enrolled. Patients with comorbidities such as diabetes and uncontrolled cardiovascular disorders and who were pregnant were excluded. Patients who entered the study between 1993 and 2002 received intravenous methyl-Pd therapy (10 mg/kg/day for 3 days) followed by oral Pd (1 mg/kg/day). Patients who entered the study between 2003 and 2008 received IVIg (400 mg/kg/day for 5 days) together with oral Pd (1 mg/kg/day). After 6 weeks, the prednisolone began to be tapered in both arms. Early response and maintenance of response were assessed at 7 days and 6 months after treatment, respectively, based on the outcome criteria proposed by an international working group (Blood 2009). Results Of 87 patients enrolled, 77 (88.5%) were eligible for analysis. Initial platelet counts did not differ between the two groups. Early responses occurred in 30 of 39 patients (76.9%) receiving methyl-Pd versus 33 of 38 patients (86.6%) receiving IVIg (p = 0.187). Maintenance of response was observed in 28 patients (71.8%) in the methyl-Pd arm and 23 patients (60.5%) in the IVIg arm (p = 0.187). The time to a complete response in the IVIg arm (6 days; range, 1–35 days) was shorter than that in the methyl-Pd arm (13.5 days; range, 2–29 days) (p = 0.002). Side effects were mild and tolerable in both arms. Five years after treatment initiation, 5 patients (12.8%) and 7 patients (18.4%) were still under salvage treatment in the methyl-Pd and IVIg arms, respectively. During a median follow-up of 98 months (range, 33-228 months) in the methyl-Pd arm and 71 months (range, 52-180 months) in the IVIg arm, 19 patients (48.7%) and 18 patients (47.4%) patients required one or more salvage treatments, respectively (p = 0.906). No bleeding-related death was observed in either group during the follow-up period. Conclusion These results indicate that neither the early response rate nor the long-term outcome differs between methyl-Pd and IVIg treatments. IVIg, however, more rapidly induces a complete response than methyl-Pd. Disclosures: No relevant conflicts of interest to declare.

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Increased FVIII and Anti-Phospholipid Antibodies Do Not Modify the Clinical Course of Chronic Immune Thrombocytopenia

Blood ◽

10.1182/blood.v124.21.5013.5013 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5013-5013

Author(s):

Meet Kumar ◽

Maitryee Bhattyacharyya ◽

Shyamali Datta

Keyword(s):

Platelet Count ◽

Lupus Anticoagulant ◽

Immune Thrombocytopenia ◽

Clinical Course ◽

Conflicts Of Interest ◽

Age Groups ◽

Platelet Counts ◽

Bleeding Score ◽

Chronic Immune Thrombocytopenia

Abstract INTRODUCTION: Immune thrombocytopenia is a heterogenous disease with majority patients having a mild bleeding phenotype and one-fourth being asymptomatic. Bleeding episodes are usually seen in patients with platelet counts typically <30,000/cumm. There is no study till date to identify patients with platelet count <30,000/cumm and at high risk for bleeding. Although patients who harbor anti phospholipid antibodies have a higher risk of arterial and venous thrombosis, it is not known whether presence of acquired thrombophilia modifies the clinical course of bleeding in low platelet count ITP patients. We evaluated the role of FVIII and lupus anticoagulant in modifying the clinical course of such patients. MATERIALS AND METHODS: Patients of all age groups with persistent and chronic immune thrombocytopenia were eligible for study enrolment. Patients with acute ITP and secondary ITP were excluded. Eligible patients were evaluated with baseline parameters, ITP bleeding score (ITP-BAT, version 1.0 by IWG on ITP) at baseline and then at every visit and FVIII and lupus anticoagulant at baseline and repeat at six months.Patients were called for monthly scheduled visits if platelet counts were >30,000/cummand more frequently at lower platelet counts. Patients with any evidence of underlying infection or raised c-reactive protein and procalcitonin were deferred evaluation.All patients were treated as per institutional protocol to avoid treatment bias. Patients were followed up for one year. We finally calculated the average bleeding scores of all patients at different platelet counts (for eg. average of skin, mucosal and organ bleeding scores of all patients that had platelet counts <10,000/cumm, 10-30,000/cumm etc) and analysed it with FVIII and anti-phospholipid antibody levels. RESULTS: A total of 45 patients were enrolled with M:F=1:3.2. Median age of patients is 28years (3-72 years). Two patients were excluded (both progressed to SLE) and another two were lost to follow-up. Median duration from ITP diagnosis to study enrolment was 62.4months (8-590 months). Median follow-up of all patients was 14.2 months (13.2-16.4 months). Nine patients had persistent and 32 patients had chronic ITP. ITP-BAT could differentiate intensity of bleeding at different platelet counts by means of bleeding scores (Table 1). Correlation of bleeding scores with prothrombotic markers could not establish a disease course modifying relationship between the two (Table 2). CONCLUSION: Presence of high FVIII and anti phosphoilipid antibodies donot modify the bleeding risks in patients with ITP and low platelet counts. Table 1Platelet count (x109/cumm)Total episodesAverage bleeding scoreP value<1014S2.4 M1.4 O0 0.00210-3015S1.4 M0.9 O030-6018S0.3 M0.1 O0>600S0 M0 O0 Table 2 Platelet count <10,000/cumm Platelet count 10-30,000/cumm N Av BS P= N Av BS P= FVIII>150 5 S2.5M1.1O0 0.02 6 S1.1M0.8O0 0.1 FVIII<150 9 S2M0.7O0 11 S1.4M0.6O0 LA1:LA2>2 1 S2.2M1.5O0 0.03 S1.1M0.8O0 0.2 LA1:LA2<1 12 S2.6M1.2O0 S1.2M0.6O0 Table 3 Platelet count 30-60,000/cumm Av BS P= FVIII>150 4 S0.9M0.1O0 0.2 FVIII<150 11 S0.3M0.1O0 LA1:LA2>2 Nil LA1:LA2<1 9 S1.1M0.4O0 Disclosures No relevant conflicts of interest to declare.

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Effectiveness of Lusutrombopag in Patients with Mild to Moderate Thrombocytopenia

Digestive Diseases ◽

10.1159/000504044 ◽

2019 ◽

Vol 38 (4) ◽

pp. 329-334 ◽

Cited By ~ 1

Author(s):

Yuki Tsuji ◽

Hideto Kawaratani ◽

Koji Ishida ◽

Daisuke Kaya ◽

Takuya Kubo ◽

...

Keyword(s):

Adverse Reaction ◽

Platelet Count ◽

Liver Disease ◽

Chronic Liver Disease ◽

Small Molecule ◽

Receptor Agonist ◽

Common Complication ◽

Platelet Counts ◽

Thrombopoietin Receptor ◽

Thrombopoietin Receptor Agonist

Aims: Thrombocytopenia is a common complication among patients with chronic liver disease (CLD). To increase platelet counts, lusutrombopag, a small-molecule, second-generation thrombopoietin receptor agonist, was developed in September 2015. Lusutrombopag is mainly used in patients with platelet counts <50,000/µL. However, its usefulness in patients with platelet counts ≥50,000/µL remains unknown. We studied the effectiveness of lusutrombopag administration in patients with platelet counts of ≥50,000/µL. Methods: We evaluated 36 patients who received lusutrombopag for CLD. Changes in platelet counts were evaluated. A treatment response was defined as an increasing platelet count ≥20,000/µL from baseline after drug administration. The differences related to these changes between platelet counts ≥50,000 and <50,000/µL were evaluated. Results: Of the patients, 25 had platelet counts ≥50,000/µL. The increase in platelet count and the date in which it reached a maximum did not significantly differ between the groups. The effectiveness of lusutrombopag did not significantly differ between the groups. In both groups, no adverse reaction was observed during lusutrombopag administration. Conclusion: In this study, we showed the effectiveness of lusutrombopag, which had no complications. This study is the first to report that the effectiveness of lusutrombopag was the same for patients with platelet counts ≥50,000/µL and <50,000/µL.

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