scholarly journals Spectrum of Ig classes, specificities, and titers of serum antiglycoproteins in chronic idiopathic thrombocytopenic purpura

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 1024-1032 ◽  
Author(s):  
R He ◽  
DM Reid ◽  
CE Jones ◽  
NR Shulman
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Cytoplasmic Domain ◽  
Platelet Glycoprotein ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Secondary Phenomenon ◽  
Almost All ◽  
Posttransfusion Purpura ◽  
Detectable Serum

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.

scholarly journals Spectrum of Ig classes, specificities, and titers of serum antiglycoproteins in chronic idiopathic thrombocytopenic purpura

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 1024-1032 ◽  
Author(s):  
R He ◽  
DM Reid ◽  
CE Jones ◽  
NR Shulman
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Cytoplasmic Domain ◽  
Platelet Glycoprotein ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Secondary Phenomenon ◽  
Almost All ◽  
Posttransfusion Purpura ◽  
Detectable Serum

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.

scholarly journals Extracellular epitopes of platelet glycoprotein Ib alpha reactive with serum antibodies from patients with chronic idiopathic thrombocytopenic purpura

Blood ◽  
1995 ◽  
Vol 86 (10) ◽  
pp. 3789-3796 ◽  
Author(s):  
R He ◽  
DM Reid ◽  
CE Jones ◽  
NR Shulman
Keyword(s):  
Escherichia Coli ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Fusion Proteins ◽  
Synthetic Peptides ◽  
Immunoaffinity Chromatography ◽  
Platelet Glycoprotein ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Protein Fragment ◽  
Thrombocytopenic Purpura ◽  
Insight Into

Glycoproteins (GPs) IIb/IIIa and Ib/IX are principal targets of autoantibodies (autoAbs) in idiopathic thrombocytopenic purpura (ITP). Platelet-associated Abs against GPIIb/IIIa primarily recognize discontinuous or nonlinear epitopes (Fujisawa et al, Blood 81:1284, 1993). This study focused on whether Abs against the extracellular domain of GPIb/IX might react with short linear amino acid (aa) sequences of GPIb alpha. Complementary DNAs (cDNAs) coding for two overlapping fragments of GPIb alpha were amplified, cloned into pFLAG.2 plasmids, and expressed in Escherichia coli DH5 alpha competent cells as FLAG fusion proteins, which were purified by anti-FLAG immunoaffinity chromatography. Of 16 selected ITP sera containing anti- GPIb/IX, 6 reacted in microtiter radioimmunoassays (RIAs) with recombinant protein fragment 2 (aas 240 to 485); 1 also with fragment 1 (aas 1 to 247). When synthetic peptides corresponding to 4 segments of fragment 2 with high antigenic indices (P1 to P4) were used as targets in RIAs, all 6 sera reacted with P2 (aas 326 to 346); 1 also reacted with P4 (aas 389 to 412). P2 was shown to be present on the surface of intact platelets by adsorption studies, and anti-P2 was detected in direct eluates of platelets from ITP patients. Glycocalicin in solution effectively competed with immobilized P2 for anti-P2; P2 in solution was a less effective competitor. Epitope scanning with a panel of synthetic 15-mer peptides localized the P2 epitope to the sequence, TKEQTTFPP. Epitope definition may offer insight into the pathophysiology of and more specific treatments for ITP.

Abstract 171: Acute Sagittal Sinus Thrombosis in an Elderly Patient with Chronic Idiopathic Thrombocytopenic Purpura

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Huimin Wu ◽  
Robert Paulino ◽  
Qi Shi ◽  
Sandhya Samavedam ◽  
Indupriya Pallekonda ◽  
...  
Keyword(s):  
Platelet Count ◽  
Venous Thrombosis ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Sinus Thrombosis ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Sagittal Sinus ◽  
History Of

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.

PAICA: A Method for Characterizing Platelet-Associated Antibodies - Its Application to the Study of Idiopathic Thrombocytopenic Purpura and to the Detection of Platelet-bound c7E3

1996 ◽  
Vol 76 (06) ◽  
pp. 1020-1029 ◽  
Author(s):  
Laurent Macchi ◽  
Gisèle Clofent-Sanchez ◽  
Gérald Marit ◽  
Claude Bihour ◽  
Catherine Durrieu-Jais ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Flow Cytometry ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Antithrombotic Therapy ◽  
Membrane Glycoproteins ◽  
Serum Antibodies ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Capture Assay ◽  
Specific Membrane

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.

Acute kidney injury and nephrotic syndrome associated with eltrombopag therapy in chronic idiopathic thrombocytopenic purpura

2021 ◽  
Vol 14 (4) ◽  
pp. e241462
Author(s):  
Suchi Anindita Ghosh ◽  
Jean Patrick ◽  
Kyaw Zin Maw
Keyword(s):  
Acute Kidney Injury ◽  
Renal Failure ◽  
Nephrotic Syndrome ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Kidney Injury ◽  
High Dose ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Antibody Screen ◽  
Auto Antibody

A 77-year-old man was admitted with severe acute kidney injury and nephrotic syndrome. He was started on eltrombopag for chronic idiopathic thrombocytopenic purpura 6 weeks earlier. An ultrasound of the kidneys was normal and an auto-antibody screen was negative. The use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient’s development of acute renal failure and eltrombopag therapy. Literature review identified only one other case of nephrotic syndrome and acute kidney injury associated with eltrombopag therapy in which a kidney biopsy revealed focal segmental glomerulosclerosis. Due to the challenges faced during the prevailing SARS-CoV-2 pandemic and persistent low platelet counts a renal biopsy was not undertaken. On stopping eltrombopag, the patients renal function stabilised and he successfully went into remission following treatment with high dose corticosteroids and diuretics. This report of a serious case of reversible renal failure and nephrotic syndrome after treatment with eltrombopag may serve to inform clinicians about the possible severe renal adverse effects of eltrombopag before its commencement for future use.

Autoantibodies to αIIbβ3 in patients with chronic immune thrombocytopenic purpura bind primarily to epitopes on αIIb

Blood ◽  
2001 ◽  
Vol 97 (7) ◽  
pp. 2171-2172 ◽  
Author(s):  
Robert McMillan ◽  
Jennifer Lopez-Dee ◽  
Joseph C. Loftus
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Cho Cells ◽  
Chinese Hamster ◽  
Surface Proteins ◽  
Platelet Glycoprotein ◽  
Beta Chain ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Platelet Surface ◽  
Chronic Immune Thrombocytopenic Purpura

Abstract Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disease caused by platelet destruction resulting from autoantibodies against platelet surface proteins, particularly platelet glycoprotein IIb/IIIa (αIIbβ3). To localize the auto-epitopes on platelet αIIbβ3, the binding of autoantibodies to Chinese hamster ovary (CHO) cells expressing either αIIbβ3 or αvβ3was studied. Thirteen of 14 ITP autoantibodies bound only to CHO cells expressing αIIbβ3. Because these 2 integrins have the same beta chain (β3), these results show that most epitopes in chronic ITP are dependent on the presence of glycoprotein αIIb.

Aplastic Anemia and Idiopathic Thrombocytopenic Purpura with Antibody to Platelet Glycoprotein llb/llla Following Resection of Malignant Thymoma

1993 ◽  
Vol 90 (1) ◽  
pp. 42-45 ◽  
Author(s):  
Hikaru Kobayashi ◽  
Kiyoshi Kitano ◽  
Fumihiro Ishida ◽  
Hiroshi Saito ◽  
Hideharu Miyabayashi ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Platelet Glycoprotein ◽  
Thrombocytopenic Purpura ◽  
Malignant Thymoma
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