Concomitant Idiopathic Thrombocytopenic Purpura Research Articles

Thrombocytopenia and Coronary Artery Disease, the Existing Dilemmas

Abstract Background: Platelets play a pivotal role in the pathogenesis of acute coronary syndrome (ACS) and acute or chronic complications following percutaneous coronary intervention (PCI) as well. Platelet inhibition is a cornerstone treatment in the management of these patients. Thrombocytopenia in patients with ACS is uncommon. Idiopathic thrombocytopenic purpura (ITP) is a rare phenomenon; nevertheless, some case series presenting concomitant ACS and ITP have been described in the literature. The safety of antiplatelet therapy and PCI in patients who have ACS and thrombocytopenia is limited. Case summary: We present a case of a 60-year-old patient with ITP who was admitted with unstable angina pectoris. On admission, the platelet count was 23 × 109/L. Coronary CT angiography revealed severe stenosis in the mid portion of RCA. After one-week treatment with high-dose Prednisolone, the platelet count recovered, and coronary catheterization was performed. Successful PCI to the RCA with drug-eluting stent was performed. The patient was discharged on dual antiplatelet therapy. Conclusion: The case suggests that PCI is a suitable treatment for ITP patients with ACS. Hemostasis is the major concern in managing these patients. The treatment strategy may be based on platelet function rather than platelet count alone. Further analysis of antiplatelet therapies as mono or dual therapy are needed.

Intravenous Iron for the Treatment of Steroid-Refractory Idiopathic Thrombocytopenic Purpura

Introduction: Idiopathic thrombocytopenic purpura (ITP) is an acquired platelet disorder that is often caused by antibodies against platelet's antigens. Steroids are effective first therapy for ITP. Steroid-refractory ITP is rare and warrant further investigation and treatment. While iron deficiency anemia (IDA) usually presents with thrombocytosis, there are a few reported cases of IDA presenting with unexplained ITP.Objective: We aim to determine whether the use of intravenous (IV) iron improves platelet count in patients with concomitant steroid-refractory ITP and IDA.Methods: We identified five patients with IDA who presented to the St. John Hospital and Medical Center between 1/2010 and 12/2017 with unexplained profound thrombocytopenia. They were initially treated with steroids without success. All patients were then treated with a single infusion of iron dextran to replenish their iron stores.Results: All five patients were African American females of childbearing age and with a history of menorrhagia. All patients had profound iron deficiency defined as iron saturation less than 20% and ferritin less than 15 ng/dL. Four of these patients had profound thrombocytopenia defined as platelets count below 30,000/mm3(table 1). Other causes of thrombocytopenia were ruled out. With IV iron, all patients achieved complete and durable resolution of their thrombocytopenia lasting for at least 6 months (table 2).Conclusion: The exact mechanism of thrombocytopenia that occurs in patients with IDA is unknown. However, it is suggested that it may be related to the alteration in the activity of iron-dependent enzymes in the cells responsible for megakaryopoiesis and thrombopoiesis. We suggest that patients who present with concomitant steroid-refractory ITP and IDA should receive a trial of IV iron before proceeding with more aggressive therapy such as splenectomy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Primary Percutaneous Coronary Intervention by a Stentless Technique for Acute Myocardial Infarction with Idiopathic Thrombocytopenic Purpura: A Case Report and Review of the Literature

A 78-year-old man who had been diagnosed with idiopathic thrombocytopenic purpura (ITP) was admitted to our hospital with chest pain, cold sweating and nausea. An electrocardiogram and echocardiogram revealed an ST elevated acute lateral myocardial infarction. He underwent an immediate cardiac catheterization. An occluded left circumflex artery was detected by coronary angiography. Reperfusion was performed successfully by non-slip element balloon angioplasty alone, without stenting, to avoid prolonged dual anti-platelet therapy. In this report we discussed the management strategies of acute myocardial infarction in a patient with concomitant ITP.

Concomitant Immune Thrombocytopenic Purpura and Crohn’s Disease

The coexistence of immune (idiopathic) thrombocytopenic purpura (ITP) and Crohn’s disease (CD) is rare. We performed a review of cases of concomitant ITP and CD in the English and Japanese literature. Among 17 identified cases of concomitant ITP and CD, ITP was initially diagnosed in four cases and CD was initially diagnosed first in six cases. Simultaneous diagnoses were reported in the remaining seven cases. No fatalities were reported in any of the 17 cases. However, resistance or transient responses to standard therapies, such as glucocorticoids or intravenous immunoglobulin (IVIG), and splenectomy for the treatment of ITP were reported in a number of concomitant cases. Moreover, the administration of anti-tumor necrosis factor (TNF)-alpha antibodies was a commonly considered pharmacological therapy in cases of concomitant ITP and CD.

Reversal of Idiopathic Thrombocytopenic Purpura [ITP] with Fecal Microbiota Transplantation [FMT

Purpose: Regarded as an autoimmune disorder, Idiopathic Thrombocytopenic Purpura is characterized by persistent fluctuating thrombocytopenia of unknown cause resulting in platelet destruction. Current treatments include corticosteroids, and other immunosuppressive medications, or splenectomy. The risk of serious morbidity/mortality is substantial, with life-threatening hemorrhagic events and death estimated at being 60 percent above expected mortality rate1. We report an unexpected finding in a patient with long-standing ulcerative colitis (UC) and ITP in whom FMT for UC resulted in a ‘cure' of her concomitant ITP. This response suggests an underlying infection of the gut microbiota as a possible etiology in this disorder. Methods: Case: A 39 year old female presented for opinion and management of her chronic, relapsing UC, diagnosed in 1984. The patient also had concomitant idiopathic thrombocytopenic purpura since 1995. Due to difficult-to-control UC and frequent relapses the patient was offered FMT prior to colectomy. Prior to undergoing FMT in January 1999, the patient's mean platelet levels were consistently beneath the lower limit of normal (mean 96.18, range 62-133). In the months following FMT the patient experienced an abrupt rise in her platelet count with a mean of 127 (range 56-188) which then normalized upwards to lie consistently within the upper limits of the normal range (mean 190, range 153-259) from March 2004 where they remain today. The patient also experienced a marked reduction in UC symptoms, passing 2-3 semi-formed stools daily, without bleeding or urgency. Results: We believe this is the first case of immune-mediated ITP successfully reversed using FMT. Transient thrombocytopenia has been reported secondary to infections with Helicobacter pylori, Campylobacter jejuni, Yersinia enterocolitica and Mycobacterium tuberculosis, all absent in this patient. Success of FMT in this ‘autoimmune' condition, traditionally etiologically unrelated to the gastrointestinal tract, suggests this therapy may be beneficial in other socalled ‘autoimmune' conditions and prompts us to reconsider the mechanisms behind ‘autoimmune disorders'. Conclusion: Our finding that ITP can be reversed by FMT points to an underlying GI infective cause. The success of this procedure in this ‘autoimmune' condition highlights the potential of FMT in other diseases previously thought to be ‘autoimmune'.

Platelet response to Helicobacter pylori eradication therapy in adult chronic idiopathic thrombocytopenic purpura seems to be related to the presence of anticytotoxin-associated gene A antibodies

The aims of this study were to assess the prevalence of Helicobacter pylori infection in chronic idiopathic thrombocytopenic purpura adult patients and investigate the platelet response after eradication. To minimize the confounding effect of concomitant idiopathic thrombocytopenic purpura therapies, patients were eligible for the prospective study if they had 20-100 x 10/l platelets, and no requirement for treatment for thrombocytopenia or no change of doses of ongoing medications for at 3 months before inclusion.Helicobacter pylori infection was assessed in 62 patients using a stool antigen test, and the infection was present in 52% of patients. Immunoglobulin G antibodies against the cytotoxin-associated gene A protein were detected in 53% of infected patients. All patients underwent sampling for specific platelet autoantibodies, 37.5% of H. pylori-positive and 33% of H. pylori-negative patients had detectable platelet autoantibodies. Sixteen eligible H. pylori-positive patients were submitted to the eradication therapy and followed in the prospective study. We considered 14 H. pylori-negative patients as control group. Platelet response was defined as an incremental increase above 50% from baseline platelet count. A positive response was observed in 43% patients after 6 months of follow-up. Eradicated responder and nonresponder patients were comparable for all main clinical features but not for anticytotoxin-associated gene A antibodies (83 vs. 12.5%, P = 0.026).Given the good cost-benefit ratio, we believe that all idiopathic thrombocytopenic purpura patients should be screened for H. pylori infection and eradication treatment should be considered, particularly for patients who are also found positive for anticytotoxin-associated gene A antibodies.

Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial

Eltrombopag is an oral, non-peptide, thrombopoietin-receptor agonist that stimulates thrombopoiesis, leading to increased platelet production. This study assessed the efficacy, safety, and tolerability of once daily eltrombopag 50 mg, and explored the efficacy of a dose increase to 75 mg. In this phase III, randomised, double-blind, placebo-controlled study, adults from 63 sites in 23 countries with chronic idiopathic thrombocytopenic purpura (ITP), platelet counts less than 30 000 per muL of blood, and one or more previous ITP treatment received standard care plus once-daily eltrombopag 50 mg (n=76) or placebo (n=38) for up to 6 weeks. Patients were randomly assigned in a 2:1 ratio of eltrombopag:placebo by a validated randomisation system. After 3 weeks, patients with platelet counts less than 50 000 per microL could increase study drug to 75 mg. The primary endpoint was the proportion of patients achieving platelet counts 50 000 per microL or more at day 43. All participants who received at least one dose of their allocated treatment were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00102739. 73 patients in the eltrombopag group and 37 in the placebo group were included in the efficacy population and were evaluable for day-43 analyses. 43 (59%) eltrombopag patients and six (16%) placebo patients responded (ie, achieved platelet counts >/=50 000 per microL; odds ratio [OR] 9.61 [95% CI 3.31-27.86]; p<0.0001). Response to eltrombopag compared with placebo was not affected by predefined study stratification variables (baseline platelet counts, concomitant ITP drugs, and splenectomy status) or by the number of previous ITP treatments. Of the 34 patients in the efficacy analysis who increased their dose of eltrombopag, ten (29%) responded. Platelet counts generally returned to baseline values within 2 weeks after the end of treatment. Patients receiving eltrombopag had less bleeding at any time during the study than did those receiving placebo (OR 0.49 [95% CI 0.26-0.89]; p=0.021). The frequency of grade 3-4 adverse events during treatment (eltrombopag, two [3%]; placebo, one [3%]) and adverse events leading to study discontinuation (eltrombopag, three [4%]; placebo, two [5%]), were similar in both groups. Eltrombopag is an effective treatment for managment of thrombocytopenia in chronic ITP.

Oral Eltrombopag for the Long-Term Treatment of Patients with Chronic Idiopathic Thrombocytopenic Purpura: Results of a Phase III, Double- Blind, Placebo-Controlled Study (RAISE)

INTRODUCTION: Eltrombopag (PROMACTA®/REVOLADE®; GlaxoSmithKline, Collegeville, PA, USA) is a first-in-class, oral, small molecule, non-peptide, thrombopoietin receptor agonist being studied for the treatment of thrombocytopenia related to a variety of conditions.METHODS: RAISE was a 6-month, randomized, double-blind, placebo-controlled, phase III study that evaluated the efficacy and safety of eltrombopag in previously treated adults with chronic idiopathic thrombocytopenic purpura (ITP) with platelet counts <30,000/μL. It was estimated that approximately 189 patients randomized 2:1 (eltrombopag:placebo) would provide sufficient statistical power. Patients were stratified by splenectomy status, use of baseline ITP medication, and platelets □15,000/μL. Patients initiated treatment with eltrombopag 50 mg (or matching placebo) once daily, and the dose was individualized based upon each patient's platelet response, from a maximum of 75 mg once daily to 25 mg once daily or less frequently. Patients could reduce concomitant medications and receive rescue therapy as dictated by local standard of care. The primary endpoint was the odds of responding (platelets 50,000 to 400,000/μL) during the treatment period for patients receiving eltrombopag relative to placebo. Bleeding symptoms were prospectively evaluated using the WHO Bleeding Scale: Grade 0 = no bleeding, Grade 1 = mild bleeding, Grade 2 = moderate bleeding, Grade 3 = gross bleeding, and Grade 4 = debilitating blood loss.RESULTS: One hundred ninety-seven patients (eltrombopag, 135; placebo, 62) were enrolled in RAISE, and baseline characteristics were balanced: in both arms ~50% of patients had platelet counts □15,000/μL, ~50% were receiving concomitant ITP therapies, ~35% were splenectomized, and >15% had received at least 3 prior ITP medications. Patients who received eltrombopag were 8 times more likely to achieve platelet counts 50,000 to 400,000/μL during the 6-month treatment period compared with patients on placebo (OR [95% CI] = 8.2 [4.32, 15.38]; P <0.001). Baseline median platelet counts were 16,000/μL in both groups and never exceeded 30,000/μL in the placebo group. In contrast, platelets rose to 36,000/μL after 1 week in the eltrombopag group (Figure 1) and subsequently ranged from 52,000 to 91,000/μL for the remainder of the study. Median platelet counts returned to near baseline 2 weeks after stopping eltrombopag. Patients responded to eltrombopag regardless of splenectomy status, use of baseline ITP medications, or baseline platelet counts. Significantly fewer patients treated with eltrombopag had any bleeding (WHO Grades 1–4; P <0.001) or clinically significant bleeding (WHO Grades 2–4; P <0.001) throughout the trial compared with patients treated with placebo. More patients in the eltrombopag group (59%) stopped or dose-reduced their concomitant ITP medications than in the placebo group (32%; P = 0.016). Patients in the eltrombopag group (19%) required less rescue therapy compared with the placebo group (40%; P = 0.001) during the treatment phase of the study. The overall incidence of adverse events (AEs) was similar between the eltrombopag (87%) and placebo groups (92%), and the AEs were mostly mild to moderate. Headache was the most common AE in both groups (30%). Of note, 2 steroid-associated AEs (dyspepsia and peripheral edema) were significantly less likely to occur in the eltrombopag group compared with the placebo group. A higher incidence of hepatobiliary laboratory abnormalities were reported in the eltrombopag group (13%) compared with the placebo group (7%). There were no clinical or laboratory symptoms suggestive of bone marrow fibrosis. One death due to brain stem hemorrhage was reported in the placebo group.DISCUSSION: Long-term eltrombopag therapy significantly increased platelet counts, decreased bleeding symptoms, allowed for a reduction or discontinuation of baseline ITP therapies, and reduced the use of rescue ITP medications compared with placebo. Eltrombopag was well-tolerated, with a similar safety profile to placebo, and is an important new treatment option for patients with chronic ITP. [Display omitted]

Oral Eltrombopag Treatment Reduces the Need for Concomitant Medications in Patients with Chronic Idiopathic Thrombocytopenic Purpura.

INTRODUCTION: Eltrombopag (PROMACTA®/REVOLADE®; GlaxoSmithKline, Collegeville, PA) is the first oral, small molecule, non-peptide thrombopoietin receptor agonist developed as a treatment for thrombocytopenia of various etiologies, including chronic idiopathic thrombocytopenic purpura (ITP). In 2 placebo-controlled studies totaling over 200 patients with chronic ITP, eltrombopag has demonstrated a significant increase in platelet counts and a reduction in clinically relevant bleeding after up to 6 weeks of treatment. EXTEND is an ongoing open-label, phase III extension study to assess the long-term safety and efficacy of oral eltrombopag. Although the primary objective of this study was to raise platelet counts to a safe level (≥50,000/μL), the ability of eltrombopag treatment to allow patients to reduce concomitant ITP medications and avoid the adverse events associated with those therapies was also of interest.METHODS: Adult patients with previously treated chronic ITP who completed a prior eltrombopag study were eligible to participate in EXTEND. Eltrombopag treatment was initiated at 50 mg once daily and then adjusted to maintain platelet counts ≥50,000/μL and <400,000/μL, with doses between 75 mg once daily and 25 mg once daily or less often than once daily, if necessary. The effect of eltrombopag treatment on the ability of patients to reduce and/or discontinue baseline concomitant ITP medications was evaluated.RESULTS: As of the clinical cut-off date (January 7, 2008), 207 patients (median age, 50 years; 67% female) had received eltrombopag. At baseline, 69 (33%) patients reported the use of ITP medications; of these, 65 patients had at least 1 post-baseline visit by the clinical cut-off date and were evaluable for response status. Eighty percent (52/65) of these patients responded to eltrombopag with a platelet count of ≥50,000/μL during the study. Forty-eight percent (33/69) of patients attempted to reduce or discontinue their concomitant ITP medications during the study. Seventy percent (23/33) of these patients discontinued or had a sustained reduction of their baseline ITP medication and did not require any subsequent rescue treatment as of the clinical cut-off date; of these, 65% (15/23) had maintained the discontinuation or reduction for at least 24 weeks as of the clinical cut-off date. Sixty-one percent (20/33) of patients discontinued at least 1 baseline ITP medication, and 55% (18/33) discontinued all baseline ITP medications, without subsequent rescue treatment. Discontinued or reduced medications included prednisone (n = 11); prednisolone (n = 8); danazol (n = 5); and azathioprine, dexamethasone, mycophenolic acid, and oxymetholone (n = 1 each). Only 12% (8/69) of patients increased the dose of concomitant ITP medication from baseline.CONCLUSION: In this study, long-term therapy with oral eltrombopag allowed 80% of patients with chronic ITP who were also receiving a concomitant ITP medication at baseline to maintain elevated platelet counts sufficient to permit a reduction in the use of concomitant ITP medications without the need for rescue therapy.

Eltrombopag Delivers Clinical Benefit in Chronic Idiopathic Thrombocytopenic Purpura (ITP) Patients Not Achieving Platelet Counts ≥50,000/μL - Data from the EXTEND Study.

INTRODUCTION: Eltrombopag (PROMACTA®/REVOLADE®; GlaxoSmithKline, Collegeville, PA) is the first oral small molecule, non-peptide thrombopoietin receptor agonist shown to increase platelets and reduce bleeding symptoms during placebo-controlled trials in chronic ITP patients. EXTEND is an ongoing, open-label study designed to assess the long-term safety and clinical benefit of eltrombopag in patients with chronic ITP. While eltrombopag has been shown to raise platelet counts above the recognized goal of ≥50,000/μL in the majority of patients, it unknown whether patients who do not achieve this level of elevation derive other clinical benefit from eltrombopag therapy.METHODS: For this analysis, patients who were enrolled in EXTEND for at least 6 weeks were evaluated to determine what percentage achieved platelet counts ≥50,000/μL from baseline platelet counts ≤30,000/μL. Furthermore, clinical benefit, in terms of doubled platelet counts, reduced bleeding symptoms, or reduced concomitant ITP medication use, was evaluated in the subgroup of patients who did not achieve platelet counts ≥50,000/μL during the study. Bleeding symptoms were prospectively evaluated using the WHO Bleeding Scale: Grade 0 = no bleeding, Grade 1 = mild bleeding, Grade 2 = moderate bleeding, Grade 3 = gross bleeding, and Grade 4 = debilitating blood loss.RESULTS: Of the 117 patients with baseline platelet counts ≤30,000/μL evaluated, 91 patients (78%) achieved platelet counts ≥50,000/μL at least once during the study; whereas, 26 patients (22%) did not achieve platelet counts ≥50,000/μL. The majority of patients not achieving platelet counts ≥50,000/μL had baseline platelet counts ≤15,000/μL (96%, n = 24/26); however, 69% of all patients with baseline platelet counts ≤15,000/μL on study for at least 6 weeks achieved platelet counts ≥50,000/μL. The majority of patients not achieving platelet counts ≥50,000/μL during the study doubled their platelet count from baseline at least once (62%, n = 16/26). Among patients whose platelet counts doubled, the median baseline platelet count was 4,000/μL, compared to the median maximum platelet count of 29,000/μL achieved during treatment with eltrombopag. Nineteen of the 26 patients not achieving platelet counts ≥50,000/μL had bleeding symptoms at baseline (WHO Grades 1–4). The majority of the 19 patients with bleeding symptoms at baseline reduced their bleeding symptoms during treatment with eltrombopag (68%, n = 13/19). Eleven of the 26 patients not achieving platelet counts ≥50,000/μL were receiving concomitant ITP medications at baseline. Five of the 11 (45%) were able to reduce or discontinue at least 1 baseline concomitant ITP medication while receiving eltrombopag. A total of 24 of the 26 patients (92%) not achieving platelet counts ≥50,000/μL during the study derived clinical benefit (doubling of platelet count, reduction in bleeding, and/or reduction in use of concomitant ITP medications) following treatment with eltrombopag.CONCLUSION: Approximately 80% of evaluated patients with baseline platelet counts ≤30,000/μL achieved platelet counts ≥50,000/μL during the study. In the subgroup of patients who did not achieve platelet counts ≥50,000/μL, clinical benefit was achieved by 92% of patients and consisted of doubled platelet counts, reduced bleeding symptoms, and/or reduced concomitant medication use.

Long-Term Safety and Efficacy of Oral Eltrombopag for the Treatment of Subjects with Idiopathic Thrombocytopenic Purpura (ITP): Preliminary Data from the EXTEND Study.

Idiopathic thrombocytopenic purpura (ITP) is a disease caused by inadequate platelet production as well as increased platelet destruction. Eltrombopag is a first-in-class, oral, non-peptide platelet growth factor that increases platelet counts by interacting with the thrombopoietin receptor on megakaryocytes and their precursors. Accordingly, in two completed 6-week, randomized, double-blind, placebo-controlled studies of adult subjects with chronic ITP, eltrombopag produced a substantial dose-dependent increase in platelet counts. EXTEND is an ongoing, open-label extension study designed to assess the long-term safety and efficacy of oral eltrombopag. Subjects previously enrolled in an eltrombopag study are eligible to enroll in EXTEND after an intervening washout period of at least 4 weeks. Subjects are administered a starting dose of 50 mg/day (which could be increased to 75 mg/day at any time after 3 weeks) in order to reach a platelet count of ≥50,000/uL (stage 1). Then, concomitant ITP medications, if taken at study entry, are tapered to a minimal dose or discontinued entirely (stage 2), whilst maintaining a platelet count of ≥50,000/uL. Eltrombopag is then titrated to a minimal effective dose (25–75 mg/day) required to maintain platelet counts of 50,000/uL-200,000/uL (stage 3). Eltrombopag is continued for as long as the subject continues to benefit (stage 4). Bleeding incidence and severity is assessed using the WHO bleeding scale (Grade 0–4). As of August 6, 2007, data were available on 96 subjects. Ninety-four subjects were administered eltrombopag. Evaluable subjects (n=89) had a median treatment duration of 151 days (2–333 days). At baseline, 42 (44%) subjects had a platelet count ≤15,000/uL, 60 (63%) had evidence of bleeding (WHO Grade 1-4), 44 (46%) were splenectomized, and 35 (36%) were receiving concomitant ITP treatment. Of the sixty-one subjects who entered into the study with a platelet count <30,000/uL, 43 (73%) achieved a platelet count of ≥50,000/uL while on study; 10 of the 61 subjects had at least one count ≥400,000/mL during the study. Of the 94 subjects who received at least one dose of eltrombopag, 78 (83%) reported at least one adverse event; 30 (32%) reported a drug-related adverse event (AE). Most AEs were mild in severity with the most common being headache (20%). Twelve (13%) subjects reported a serious adverse event. Two deaths were reported (traffic accident and hypovolaemic shock), both not related to study medication. To date, these findings of the EXTEND study suggest that eltrombopag is well tolerated and sustains increased platelets counts during long-term treatment.Stage DescriptionSubjects enteringMedian Platelet counts (/uL)WHO Grade 2–4 Bleeding n (%)Stage 1eltrombopag administered9416,00025 (27%)Stage 2tapering ITP con meds17143,5004 (24%)Stage 3titrating eltrombpag to maintain platelet counts46108,5003 (7%)Stage 4treating with eltrombopag long-term27104,0001 (4%)