Autoimmune Platelet Destruction: Idiopathic Thrombocytopenic Purpura

1982 ◽  
Vol 8 (02) ◽  
pp. 83-104 ◽  
Author(s):  
John Kelton ◽  
Steven Gibbons
1996 ◽  
Vol 76 (06) ◽  
pp. 1020-1029 ◽  
Author(s):  
Laurent Macchi ◽  
Gisèle Clofent-Sanchez ◽  
Gérald Marit ◽  
Claude Bihour ◽  
Catherine Durrieu-Jais ◽  
...  

SummaryIn idiopathic thrombocytopenic purpura (ITP), autoantibodies reacting with antigens on the platelet membrane bring about accelerated platelet destruction. We now report PAICA (“Platelet-Associated IgG Characterization Assay”), a method for detecting autoantibodies bound to specific membrane glycoproteins in total platelet lysates. This monoclonal antibody (MAb) capture assay takes into account the fact that antibodies on circulating platelets may be translocated to internal pools as well as being on the surface. A total of twenty ITP patients were examined by PAICA, and the results compared with those obtained by measuring (i) serum antibodies bound to paraformaldehyde-fixed control platelets by ELISA, (ii) IgG bound to the surface of the patient’s own platelets by flow cytometry (PSIgG), (iii) total platelet-associated IgG (PAIgG) by ELISA and (iv) serum antibodies reacting with control platelets by MAIPA (“Monoclonal Antibody-specific Immobilization of Platelet Antigens”). Of twelve patients with elevated PAIgG, nine had increased PSIgG yet eleven reacted positively in PAICA. Of these, eight possessed antibodies directed against GP Ilb-IIIa, two against GP Ib-IX and one patient possessed antibodies directed against GP Ilb-IIIa and GP Ia-IIa respectively. Only seven of the patients possessed serum antibodies detectable by MAIPA. PAICA was also able to detect platelet-associated c7E3 (the chimeric form of Fab fragments of the MAb 7E3) following its infusion during antithrombotic therapy, when it proved more sensitive over a seven-day period than a MAIPA assay adapted for assessing surface-bound antibody. We propose that PAICA provides added sensitivity to the detection of platelet-associated antibodies in immune thrombocytopenias or following therapy with humanized MAbs.


Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 1024-1032 ◽  
Author(s):  
R He ◽  
DM Reid ◽  
CE Jones ◽  
NR Shulman

Abstract The characteristic decreased recovery and survival of transfused platelets in nonalloimmunized patients with idiopathic thrombocytopenic purpura (ITP) suggest that plasma antiplatelet autoantibodies (autoAbs) are present in almost all cases. Studies emphasizing reactions of IgG autoAbs with platelet glycoprotein (GP) IIb/IIIa indicate that less than 50% of ITP patients have detectable serum Abs, and that many of these Abs may not be pathogenic because they are directed against epitopes in the cytoplasmic domain of GPIIIa (Fujisawa et al, Blood 77:2207, 1991 and 79:1441, 1992). We evaluated the contribution of Ig classes other than IgG to the overall incidence of serum Abs in 47 patients with chronic ITP and the frequency of reactions with GPs IIb/IIIa, Ib/IX, IV, and Ia/IIa. Abs were further characterized by their reactions with cytosolic or exosolic GP epitopes and their titers and apparent affinities. Using immunobead techniques we found (1) anti- GPs in 85% of sera; (2) IgA and IgG Abs each in 68%, together in 51%; (3) IgM agglutinins in 15%, always with another Ab class; (4) GP Ib/IX, IIb/IIIa, IV, and Ia/IIa targets in 83%, 81%, 38%, and 28% of cases, respectively; (5) 93% of positive sera reactive with more than one GP; but GP IV or Ia/IIa never the sole target; (6) Abs against cytosolic epitopes on one or more of GPs IIIa, Ib alpha, and IIb beta in 66% of sera, always accompanied by Abs against exosolic epitopes of the same or a different GP; (7) autoAbs against cytosolic GP epitopes in 38% of 16 patients recovered from posttransfusion purpura and drug purpura; and (8) evidence that serum ITP Abs, often high-titered, saturate platelets less than alloAbs against the same GPs. Whereas Abs against external GP epitopes are a distinctive marker for ITP in 80% of patients, Abs against internal GP epitopes are likely a secondary phenomenon of platelet destruction and not pathogenic. Anti-GPs against exosolic epitopes were also found in eluates of patients platelets', suggesting that they have pathogenic significance.


2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Huimin Wu ◽  
Robert Paulino ◽  
Qi Shi ◽  
Sandhya Samavedam ◽  
Indupriya Pallekonda ◽  
...  

INTRODUCTION Chronic idiopathic thrombocytopenic purpura (ITP) is classified as a bleeding disorder that involves autoimmune platelet destruction. Cerebral venous sinus thrombosis in association with chronic ITP is rarely reported in medical literature. CASE PRESENTATION A 70-year-old female with a history of chronic ITP, on prednisone, and coronary artery disease presented with a four-day history of vomiting and diarrhea. Platelet count at the time of admission was 25×10 9 /L. She was treated with i.v normal saline. Platelets fell to 12×10 9 /L and intravenous immunoglobulin (IVIG) was started. Six days later, the patient developed confusion and right sided weakness. Repeat platelet count was 13x10 9 /L. MRI of the brain showed bilateral cortical infarcts suggesting sagittal vein involvement. MRV confirmed thrombosis of the posterior portion of the sagittal sinus. Bone marrow aspirates and core biopsy done to rule out other hematological disorders showed tri-lineage hematopoiesis with adequate marrow megakaryocytes. Hypercoagulable work up was unremarkable. ITP was treated with rituximab and romiplostim. Repeat MRV after 2 weeks showed no new thrombosis or hemorrhage. DISCUSSION ITP is occasionally associated with venous thrombosis. The paradoxical occurrence of venous thrombosis in the setting of ITP is poorly understood. Previous data postulates that platelet destruction releases humoral factors and microparticles, which may increase thrombotic events by the activation of thrombin and other coagulation factors. Other possible mechanisms include endothelial damage by autoantibodies directed against antigens on platelets and endothelial cells. More recently, reports have described IVIG-induced arterial and venous thrombotic complications. Treatment of thrombosis in the setting of ITP is complex and requires in-depth risk/benefit assessment. Our case highlights the dilemma of stroke treatment and prevention predicated on antiplatelet therapies for patients with ITP. Additional studies on chronic ITP associated with thrombosis are needed to establish preventive and treatment guidelines.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1325-1325
Author(s):  
Ewout Houwerzijl ◽  
Henk Louwes ◽  
Wim Sluiter ◽  
Jan Smit ◽  
Edo Vellenga ◽  
...  

Abstract The thrombocytopenia in ITP is predominantly caused by autoantibodies that recognize antigens on platelets and megakaryocytes resulting in accelerated platelet destruction and a decreased platelet production rate (PPR). ITP patients with a predominantly suppressed PPR might respond differently to therapy than patients with predominantly peripheral platelet destruction. Tests and/or patient characteristics that can make a distinction between a reduced platelet half life and a reduced PPR could therefore influence diagnostic and therapeutic strategy in ITP. Therefore, in the present study the predictive value of clinical and platelet kinetic parameter for treatment outcome in idiopathic thrombocytopenic purpura (ITP) was investigated. Seventy-five patients with severe ITP (platelets ≤20 × 109/L) were studied. Median age was 46 (range 16–89) years and 34 (45%) patients were males. Median platelet count was 8 (1–20) × 109/L. The mean platelet life was 1 (0.1–6.5) days, and the PPR 160 (2–4670) × 109/day (normal 223 (100–355) × 109/day, p = 0.7). PPR was decreased (<100 × 109/day), normal (100–355 × 109/day) and increased (>355 × 109/day) in 33%, 48%, and 19% of the patients, respectively. All patients started with prednisone at diagnosis (1 mg/kg/day). Initial complete and partial response (CR/PR) was 84% and a durable CR/PR (defined as CR/PR for ≥6 months without treatment) was attained in 44% of the patients. Apart from a higher proportion of patients with a decreased PPR in the group that responded to prednisone therapy (p=0.03), there were no significant differences regarding clinical and platelet kinetic parameters between responders and nonresponders. A durable CR/PR was noticed in 64% of the patients with a decreased PPR (median follow-up of 81 months (18–92)), compared to 34% of the patients with normal or increased PPR (median follow-up 141 (10–284) months (HR: 0.47 [95% CI (0.24–0.92)], p = 0.03). Splenectomy was performed in 32% of the patients with decreased PPR and in 62% of patients with normal or increased PPR (p = 0.03). In addition, patients with a decreased PPR showed significantly less splenic sequestration and a significantly longer mean platelet life than patients with a normal or increased PPR, which underscores that in these patients peripheral destruction of platelets contributes relatively less to thrombocytopenia than suppressed platelet production. Thirty-nine of 42 nonresponders to prednisone underwent splenectomy. Durable CR/PR postsplenectomy was reached in 74%. There were no significant differences with regard to patient characteristics between responders and nonresponders to splenectomy. In conclusion, ITP patients with suppressed PPR have a significant higher durable CR/PR rate to prednisone therapy and are less frequently exposed to splenectomy, than those with a normal or increased PPR.


2008 ◽  
Vol 99 (01) ◽  
pp. 4-13 ◽  
Author(s):  
Maria Laura Evangelista ◽  
Elisa Stipa ◽  
Francesco Buccisano ◽  
Adriano Venditti ◽  
Sergio Amadori ◽  
...  

SummaryIdiopathic thrombocytopenic purpura (ITP) is characterized by a low platelet count, which is the result of both increased platelet destruction and insufficient platelet production. Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP, several abnormalities involving the cellular mechanisms of immune modulation have been identified. Conventional treatments for ITP aim at reducing platelet destruction, either by immunosuppression or splenectomy. Two new thrombopoietic agents, AMG 531 and eltrombopag, have been used in clinical trials to stimulate platelet production in ITP patients not responsive to standard treatments. These new molecules bear no structural resemblance to thrombopoietin, but still bind and activate the thrombopoietin receptor. This review will focus on the pathophysiology and treatment of ITP in adults, highlighting recent advances in both fields.


2021 ◽  
Vol 12 (2) ◽  
pp. 166-166
Author(s):  
Aswathi Raj ◽  
Amina Asfiya ◽  
Malcolm Pinto ◽  
Manjunath Shenoy M ◽  
Spandana P Hegde ◽  
...  

Idiopathic thrombocytopenic purpura is a disorder with a myriad of possible clinical presentations. The mechanism of thrombocytopenia involves both increased platelet destruction and impaired platelet production. The patient can manifest a wide range of symptoms: from asymptomatic or minimal gingival bleeding to profuse bleeding from any site. The disease may first present itself to the dermatologist in cutaneous findings such as petechiae, purpura, and mucosal manifestations in the form of gingival bleeding and hemorrhagic bullae. The diagnosis of idiopathic thrombocytopenic purpura is mostly done by exclusion. In this report, we present two cases with characteristic oral manifestations, who were diagnosed, on investigation, with idiopathic thrombocytopenic purpura. The patients were successfully treated with immunosuppressive therapy. The report aims to raise awareness that would help in enabling prompt referral to the appropriate specialty, especially because of the rarity of this presentation.


2016 ◽  
Vol 51 (3) ◽  
pp. 203 ◽  
Author(s):  
Jefri Pratama Susanto

Idiopathic thrombocytopenic purpura is a autoimmune disease characterized thrombocytopenia casued by excessive platelet destruction. However, both platelet destruction and reduced thrombopoietin level are occurred in some cases. Therefore, new management of ITP is emerged which target is to increase platelet production rate via eltrombopag or romiplostim as the thrombopoietin receptor agonist (TPO-RA). Eltrombopag is given orally while romiplostim is given subcutaneously or intravenously and dose adjustment is depend on platelet count. Both eltrombopag and romiplostim is indicated in minimal response glucocorticoid or intravenous immunoglobulin or splenetomy treatment.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3927-3927 ◽  
Author(s):  
Gregory Cheng

Abstract Idiopathic thrombocytopenic purpura (ITP) is a disease of inadequate platelet production and increased platelet destruction. Two randomized, double-blind, placebo-controlled trials (TRA100773 A/B) reported that eltrombopag, the first-in-class, oral, platelet growth factor, results in a dose-dependent increase in platelet counts in adult patients with chronic ITP. After treatment of eltrombopag was stopped, platelet counts returned to baseline levels in most patients within 2 weeks, reflecting the normal platelet lifespan (range, 10–14 days). This abstract presents data on two patients enrolled in TRA100773 A/B in whom a prolonged platelet count elevation was observed after cessation of eltrombopag treatment. A 79-year old Asian female (Patient 1) was diagnosed with ITP in September 2003. Prior ITP therapy included prednisolone and Danazol simultaneously in 1997. Prednisolone was stopped after 10 months. Danazol was continued until March 2005 (Day -50). The patient relapsed in March 2005 and received dexamethasone (5 days), IVIg (once), vincristine, and cyclosporin A without a significant response. Eltrombopag treatment was started in May 2005 leading to an increase in platelet counts that remained elevated above 100,000/uL after treatment with eltrombopag was discontinued (Table). Patient 2, a 49-year old Asian female, was diagnosed with ITP in 1997. She relapsed after two courses of dexmethasone 40 mg, QD × 4, administered in September 2003 with a 3-month response and in January 2006 with a 1-month response. Therapy with eltrombopag was initiated in March 2006. As was seen with Patient 1, platelet counts increased after administration of eltrombopag and remained elevated after cessation of eltrombopag (Table). To the best of our knowledge, this is the first report of an ongoing prolonged elevation of platelet counts after cessation of thrombopoietic medication, such as eltrombopag. Platelet Counts (/uL) Patient 1 Patient 2 *Eltrombpag withdrawn in both patients. Screening 26,000 69,000 Day 1 26,000 26,000 Day 8 193,000 136,000 Day 15* 591,000 283,000 Day 22 664,000 --- Day 50 --- 260,000 Day 57 330,000 116,000 Day 71 112,000 100,000 Day 85 116,000 111,000


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