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

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3424-3424 ◽  
Author(s):  
Patrick F. Fogarty ◽  
James B Bussel ◽  
Gregory Cheng ◽  
Mansoor N Saleh ◽  
Balkis Meddeb ◽  
...  
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Phase Iii ◽  
Term Therapy ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Once Daily ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Rescue Treatment

Abstract 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.

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)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 400-400 ◽  
Author(s):  
Gregory Cheng ◽  
Mansoor N Saleh ◽  
James B Bussel ◽  
Claus Marcher ◽  
Sandra Vasey ◽  
...  
Keyword(s):  
Placebo Group ◽  
Rescue Therapy ◽  
Phase Iii ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Double Blind ◽  
Thrombocytopenic Purpura ◽  
Once Daily ◽  
Double Blind Placebo ◽  
Platelet Counts

Abstract 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 &lt;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 &gt;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 &lt;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 &lt;0.001) or clinically significant bleeding (WHO Grades 2–4; P &lt;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. Figure 1. Median platelet counts.a&#x2028; BL, median baseline value.&#x2028; aError bars represent the 25th to 75th percentiles for each treatment group. Figure 1. Median platelet counts.a&#x2028; BL, median baseline value.&#x2028; aError bars represent the 25th to 75th percentiles for each treatment group.

Safety and Efficacy of Long-Term Treatment with Oral Eltrombopag for Chronic Idiopathic Thrombocytopenic Purpura.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3432-3432 ◽  
Author(s):  
James B Bussel ◽  
Gregory Cheng ◽  
Mansoor N Saleh ◽  
Balkis Meddeb ◽  
Christine Bailey ◽  
...  
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Term Treatment ◽  
Thrombocytopenic Purpura ◽  
Once Daily ◽  
Safety And Efficacy ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Long Term Treatment ◽  
Previously Treated

Abstract INTRODUCTION: Eltrombopag (PROMACTA®/REVOLADE®; GlaxoSmithKline, Collegeville, PA) is the first oral, small molecule, non-peptide thrombopoietin receptor agonist under investigation for the treatment of thrombocytopenia due to various causes, including idiopathic thrombocytopenic purpura (ITP). Chronic ITP is characterized by autoantibody-induced platelet destruction and reduced platelet production, leading to chronically low peripheral platelet counts. Eltrombopag treatment has previously demonstrated a significant increase in platelet counts and a reduction in clinically relevant bleeding symptoms in 2 placebo-controlled trials evaluating a total of >200 patients with chronic ITP 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 in ITP patients that have previously completed an eltrombopag trial. METHODS: 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 in order 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. Patients who achieved platelet counts ≥ 50,000/μL during treatment with eltrombopag were considered responders. Bleeding events 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: At the time of this analysis, 207 patients (median age, 50 years; 67% female) had received eltrombopag on this study. At baseline, 33% were receiving concomitant ITP medication and 40% were splenectomized. The majority of patients (70%) enrolled with baseline platelet counts <30,000/μL, followed by 18% and 12% with baseline platelet counts from ≥ 30,000/μL to ≤ 50,000/μL, and >50,000/μL, respectively. The duration of eltrombopag treatment ranged from 3 to 523 days. Seventy-nine percent (159/201) of patients achieved a platelet count ≥ 50,000/μL, and 24% (18/75) of patients who had received eltrombopag for at least 25 weeks maintained platelet counts ≥ 50,000/μL continuously for ≥ 25 weeks. Patients responded to eltrombopag regardless of splenectomy status (non-splenectomized: 78%, splenectomized: 81%) and use of baseline concomitant ITP medications (no baseline ITP medications: 79%, baseline ITP medications: 80%). Median platelet counts remained ≥ 50,000/μL throughout the observation period of the study (Figure 1) with only 3 exceptions, when the median platelet counts remained >40,000/μL. At baseline, 59% of patients reported bleeding symptoms (WHO Grades 1–4) compared with approximately 30% at months 1, 3, and 6. Adverse events (AEs) were reported in 150 patients (72%) while on therapy, the majority of which were mild to moderate. Headache (15%) was the most commonly reported on-therapy AE, followed by upper respiratory tract infection (13%), diarrhea (10%), and nasopharyngitis (9%). Six thromboembolic events were reported during the study. No clinically relevant effects of eltrombopag on patient bone marrow were detected. Thirty-nine serious AEs were reported by 17 patients (8%) while on therapy +1 day. Four deaths were reported in the study (2 deaths on therapy and 2 deaths >30 days after the last dose of eltrombopag); none were considered related to study medication. CONCLUSION: Oral eltrombopag is effective at raising platelet counts and decreasing bleeding symptoms during long-term treatment, regardless of splenectomy status or the use of baseline ITP medications. Eltrombopag is well tolerated during long-term treatment in patients with previously treated chronic ITP. Figure 1. Median platelet counts.a
 BL, median baseline value.
 aDotted line indicates 50,000 platelets/μL. Figure 1. Median platelet counts.a
 BL, median baseline value.
 aDotted line indicates 50,000 platelets/μL.

scholarly journals Abnormal platelet function and arachidonate metabolism in chronic idiopathic thrombocytopenic purpura

Blood ◽  
1981 ◽  
Vol 58 (2) ◽  
pp. 326-329 ◽  
Author(s):  
MJ Stuart ◽  
JG Kelton ◽  
JB Allen
Keyword(s):  
Platelet Aggregation ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Platelet Function ◽  
Bleeding Time ◽  
Bleeding Tendency ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Arachidonate Metabolism

Abstract We observed several patients with chronic idiopathic thrombocytopenic purpura (ITP) whose bleeding times were more prolonged than would have been expected from their platelet counts. To investigate this further, we performed in vivo and in vitro platelet function studies, assessed arachidonate metabolism, and measured platelet-associated IgG (PAIGG) in seven patients with chronic ITP. The bleeding times of three of the patients were prolonged for greater than 7 min, and all of these patients had impaired platelet aggregation and abnormal platelet arachidonic acid metabolism as reflected by increased production of the lipoxygenase product HETE and a concomitant decrease in cyclooxygenase products, TXB2 and HHT (p less than 0.001). The abnormalities noted were not due to concomitant drug ingestion, since they were present on repeated evaluation. There was no relationship between the platelet count and the bleeding time; however, there was a significant inverse correlation between the bleeding time and TXB2 production in all patients evaluated (r = 0.81; p less than 0.05). There was no relationship between the level of platelet-associated IgG and any parameter of platelet aggregation or arachidonate metabolism. The abnormalities noted should be looked for in the individual patient with chronic ITP, since the bleeding tendency is exacerbated by the superimposed impairment of platelet function even at platelet counts of greater than 50,000/cu mm, levels generally regarded as “safe”.

scholarly journals Abnormal platelet function and arachidonate metabolism in chronic idiopathic thrombocytopenic purpura

Blood ◽  
1981 ◽  
Vol 58 (2) ◽  
pp. 326-329 ◽  
Author(s):  
MJ Stuart ◽  
JG Kelton ◽  
JB Allen
Keyword(s):  
Platelet Aggregation ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Platelet Function ◽  
Bleeding Time ◽  
Bleeding Tendency ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Arachidonate Metabolism

We observed several patients with chronic idiopathic thrombocytopenic purpura (ITP) whose bleeding times were more prolonged than would have been expected from their platelet counts. To investigate this further, we performed in vivo and in vitro platelet function studies, assessed arachidonate metabolism, and measured platelet-associated IgG (PAIGG) in seven patients with chronic ITP. The bleeding times of three of the patients were prolonged for greater than 7 min, and all of these patients had impaired platelet aggregation and abnormal platelet arachidonic acid metabolism as reflected by increased production of the lipoxygenase product HETE and a concomitant decrease in cyclooxygenase products, TXB2 and HHT (p less than 0.001). The abnormalities noted were not due to concomitant drug ingestion, since they were present on repeated evaluation. There was no relationship between the platelet count and the bleeding time; however, there was a significant inverse correlation between the bleeding time and TXB2 production in all patients evaluated (r = 0.81; p less than 0.05). There was no relationship between the level of platelet-associated IgG and any parameter of platelet aggregation or arachidonate metabolism. The abnormalities noted should be looked for in the individual patient with chronic ITP, since the bleeding tendency is exacerbated by the superimposed impairment of platelet function even at platelet counts of greater than 50,000/cu mm, levels generally regarded as “safe”.

Long-Term Treatment of Chronic Immune Thrombocytopenic Purpura with Oral Eltrombopag: Results From the EXTEND Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 682-682 ◽  
Author(s):  
Mansoor N. Saleh ◽  
James B. Bussel ◽  
Gregory Cheng ◽  
Balkis Meddeb ◽  
Bhabita Mayer ◽  
...  
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Advisory Committees ◽  
Thrombocytopenic Purpura ◽  
Once Daily ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Equity Ownership

Abstract Abstract 682 INTRODUCTION: Eltrombopag (PROMACTA; GlaxoSmithKline, Collegeville, PA) is the first oral, small molecule, thrombopoietin receptor agonist approved in the US for the treatment of chronic immune thrombocytopenic purpura (ITP). Eltrombopag is also being evaluated for the treatment of thrombocytopenia due to other causes (eg, hepatitis C, MDS). Chronic ITP is characterized by autoantibody-induced platelet destruction and reduced platelet production, leading to chronically low platelet counts. Eltrombopag has been shown to significantly increase platelet counts and reduce clinically relevant bleeding symptoms in 3 placebo-controlled ITP trials evaluating a total of 429 patients. EXTEND is an ongoing open-label, phase 3 extension study to assess the long-term safety and efficacy of eltrombopag in chronic ITP. METHODS: 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 between ≥50,000/μL and <200,000/μL, with doses between 75 mg and 25 mg once daily (or less often if necessary). Patients who achieved platelet counts ≥50,000/μL were considered responders. Bleeding events were prospectively evaluated using the World Health Organization (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. Bone marrow (BM) biopsy was required after 1 year on treatment. RESULTS: At the time of this analysis, 299 patients (median age 50 years; 66% female) had received eltrombopag (240, 126, 48, and 17 patients exposed for ≥6, 12, 18, and 24 months, respectively). The median duration of eltrombopag treatment was 204 days and ranged from 2–861 days. At baseline, 33% were receiving concomitant ITP medication and 38% had been splenectomized. The majority of patients (70%) had baseline platelet counts <30,000/μL, followed by 17% and 13% with baseline platelet counts from μ30,000/μL to <50,000/μL, and μ50,000/μL, respectively; all had baseline platelet counts <50,000/μL at the time of entry into their previous study. Overall, 86% of patients (257/299) achieved a platelet count μ50,000/μL. Splenectomized and non-splenectomized patients responded equally well (89% and 82%, respectively). Patients responded to eltrombopag regardless of baseline use of concomitant ITP medications (no baseline ITP medications and baseline ITP medications: 86% each). Median platelet counts increased to μ50,000/μL by week 2, and remained μ50,000/μL throughout the observation period of the study (Figure 1). Patients on treatment for μ6 months or μ12 months achieved platelet counts of μ50,000/μL and 2x baseline for 69% (18/26 weeks) and 71% (37/52 weeks) of the time on treatment, respectively. At baseline, 56% of patients reported bleeding symptoms (WHO grades 1–4) compared to 27%, 21%, 40%, and 25% at 6, 12, 18, and 24 months, respectively. Adverse events (AEs) were reported in 248 patients (83%) while on therapy, the majority being mild to moderate. The most common AEs reported were headache (23%), upper respiratory tract infection (17%), nasopharyngitis (17%), fatigue (13%), arthralgia (12%), and diarrhea (11%). Five deaths were reported: 2 occurred on therapy and 3 occurred more than 30 days posttherapy; none considered related to study medication. A total of 24 patients (8%) met any of the hepatobiliary laboratory abnormality screening criteria (ALT ≥3x ULN, AST ≥3x ULN, total bilirubin >1.5x ULN, or alkaline phosphatase >1.5x ULN). Thirteen patients (4%) experienced 16 thromboembolic events (TEEs); 11/13 (85%) experienced the event at a platelet count lower than the maximum platelet count achieved during eltrombopag treatment. Platelet counts proximal to the TEEs ranged from 14,000–407,000/μL. Eighty-six BM biopsies were performed. No clinically relevant effects of eltrombopag on BM were detected. CONCLUSION: Oral eltrombopag treatment for up to 2 years effectively raised platelet counts, decreased bleeding symptoms, and was generally well-tolerated in chronic ITP. Disclosures: Saleh: GlaxoSmithKline: Speakers Bureau; Amgen: Speakers Bureau. Bussel:Genzyme: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc: Research Funding; Sysmex: Research Funding; Scienta: Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees. Cheng:GlaxoSmithKline: Research Funding. Mayer:GlaxoSmithKline: Employment. Bailey:GlaxoSmithKline: Employment. Aivado:GlaxoSmithKline: Employment.

scholarly journals Subarachnoid Haemorrhage Complicating Resistant Idiopathic Thrombocytopenic Purpura: A Case Report

2014 ◽  
Vol 4 (2) ◽  
pp. 105-107
Author(s):  
Farhana Afroz ◽  
Hasna Fahmima Haque ◽  
Samira Rahat Afroze ◽  
Muhammad Abdur Rahim ◽  
Aparna Rahman ◽  
...  
Keyword(s):  
Case Report ◽  
Autoimmune Disease ◽  
Subarachnoid Haemorrhage ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Conservative Management ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Chronic Itp

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease where low platelet counts predisposeto various bleeding tendencies; intracranial haemorrhageis one of them. It is a rare and devastating complication of ITP, mostly presenting as intracerebral (ICH) or subarachnoid haemorrhage (SAH). Here, we report a 32-year-old splenectomized chronic ITP patient on corticosteroid and azathioprine, in whom spontaneous SAH developed. In this case, conservative management resulted in clinicoradiological improvement and showed eventual favourable out-come.Birdem Med J 2014; 4(2): 105-107

Abnormalities In Platelet Arachidonic Acid Metabolism In Chronic Idiopathic Thrombocytopenic Purpura

1981 ◽  
Author(s):  
M J Stuart ◽  
J G Kelton ◽  
J B Allen
Keyword(s):  
Arachidonic Acid ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Inverse Correlation ◽  
Arachidonic Acid Metabolism ◽  
Thromboxane B2 ◽  
Bleeding Tendency ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Platelet Thromboxane

Patients with chronic idiopathic thrombocytopenic purpura (CITP) have been described to have bleeding times (B.Ts) that were shorter than would be predicted by their platelet counts. This phenomenon was explained by the presence in CITP of a young platelet population with increased hemostatic competence (NEJM 287:155, ’72). In contradistinction, we have observed patients with CITP to have a bleeding tendency at platelet counts >75,000/cu mm. We therefore evaluated B.Ts and platelet arachidonic acid (AA) metabolism in 7 patients with CITP who demonstrated increased amounts of platelet associated IgG (PAIgG >3fg per platelet) and compared them to 20 healthy controls. 3/7 patients with CITP and platelet counts of >75,000/cu mm demonstrated marked prolongations in their B.Ts. (10’, 12’ and 14’, normal <7’). Marked abnormalities in the metabolism of AA through the cyclo-oxygenase (Thromboxane B2 and HHT) and lipoxygenase (HETE) pathways were also observed in patients with CITP. Platelets in CITP synthesized less amounts (p <0.005) of Thromboxane B2 (10.3 ± 3.1%) in comparison to controls (22.9 ± 1.8). Values for HHT were decreased (23.7 ± 4.9 vs 39.7 ± 1.9; p<0.005), while HETE production was increased (59.5 ± 7.8 vs 30.7 ± 1.8; p<0.001). No correlation was observed between PAIgG and platelet Thromboxane B2 formation. However, an inverse correlation (r=0.81, p<0.05 was observed between the B.T. and platelet Thromboxane B2 formation in patients with chronic ITP. We have demonstrated platelet dysfunction and impaired Thromboxane B2 formation in CITP. This association should be investigated in the individual patient, since the bleeding tendency in these patients is exacerbated by the superimposed impairment in platelet function.

scholarly journals Therapy of chronic idiopathic thrombocytopenic purpura in adults [see comments]

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2309-2317 ◽  
Author(s):  
P Berchtold ◽  
R McMillan
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Clinical Studies ◽  
Morbidity And Mortality ◽  
Cooperative Group ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Therapeutic Approaches ◽  
Group Setting ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Large Numbers

Abstract Chronic ITP is a common hematologic illness. Approximately three fourths of the patients respond to corticosteroids or splenectomy and need no further treatment. Patients refractory to these two therapeutic approaches are relatively resistant to present forms of treatment and are at much greater risk for morbidity and mortality. Future clinical studies evaluating therapy in this refractory group would be best performed in a cooperative group setting in which large numbers of patients could be treated in a prospective randomized manner.

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