scholarly journals Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr- labeled platelets differ

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 86-92
Author(s):  
P Heyns A du ◽  
PN Badenhorst ◽  
MG Lotter ◽  
H Pieters ◽  
P Wessels ◽  
...  
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Severe Disease ◽  
Reticuloendothelial System ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Antiplatelet Antibody ◽  
Thrombocytopenic Purpura ◽  
Computer Assisted Image ◽  
The Difference

Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr- labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.

scholarly journals Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr- labeled platelets differ

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 86-92 ◽  
Author(s):  
P Heyns A du ◽  
PN Badenhorst ◽  
MG Lotter ◽  
H Pieters ◽  
P Wessels ◽  
...  
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Severe Disease ◽  
Reticuloendothelial System ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Antiplatelet Antibody ◽  
Thrombocytopenic Purpura ◽  
Computer Assisted Image ◽  
The Difference

Abstract Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr- labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.

Mannose Labeled Liposome-Encapsulated Doxorubicin Is Effective in the Management of Experimental Immune Thrombocytopenic Purpura Model Mice.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3995-3995
Author(s):  
Yoji Ishida ◽  
Kazunori Murai ◽  
Syugo Kowata ◽  
Tatsuo Oyake ◽  
Ryo Suzuki ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Intravenous Injection ◽  
Immune Thrombocytopenic Purpura ◽  
Mannose Receptor ◽  
Reticuloendothelial System ◽  
Peritoneal Macrophages ◽  
Thrombocytopenic Purpura ◽  
Murine Macrophages

Abstract Immune thrombocytopenic purpura (ITP) is an autoimuune disease in which platelet antibodies cause increased platelet consumption. The destruction of platelets is mediated by the reticuloendothelial system (RES), especially hepatic and splenic macrophages. The depletion of these cells was carried out by the intravenous injection of mannose labeled liposome-encapsulated doxorubicin (mannose-DXR-liposome). The reason why mannose labeled liposome was used was that the macrophage expressed mannose receptor on the surface. Therefore, mannose-DXR-liposome is considered to be phagocyted specifically by macrophages. In this study, we evaluated the effects of mannose-DXR-liposome in a mouse model of ITP. In vitro experiments: Murine peritoneal macrophages were obtained by the intraperitoneal injection of thioglycolate (TGC) to ddY mice. The uptake of fluorescence by peritoneal macrophages was measured using rhodamine-liposome by flow cytometry. The macrophages were incubated with mannose labeled rhodamine-liposome (mannose(+)-rhodamine-liposome) or mannose unlabeled rhodamine-liposome (mannose(−)-rhodamine-liposome) for 30 min at 37 °C. After washing with PBS, they were applied for flow cytometry. Rhodamine fluorescence intensity in macrophages was higher in mannose(+)-rhodamine-liposome treatment than that in mannose(−)-rhodamine-liposome treatment (Figure 1). The viability of peritoneal macrophages was measured by MTT assay after 30 min incubation with DXR-liposome. The viability in the treatment with mannose(+)-DXR-liposome was much less than that in the treatment with mannose(−)-DXR-liposome (Figure 2). In vivo experiment: Anti-mouse platelet serum (APS) was injected intraperitoneally to ddY mice at 24 hr after intravenous injection of mannose(+)-DXR-liposome or mannose(−)-DXR-liposome. Platelet count was measured at 12 hr after APS injection. It was 89.3 ± 22.1 x104 / μl (n=6) in mannose(+)-DXR-liposome treatment, while 4.5 ± 2.0 x104 / μl (n=8) in mannose(−)-DXR-liposome treatment. The platelet counts were 3.2 ± 0.5 x104 / μl (n=4), 96.1 ± 15.0 x104 / μl (n=4) or 99.3 ± 26.2 x104 / μl (n=4) in mice with only APS administration, mannose(+)-DXR-liposome+saline or mannose(−)-DXR-liposome+saline administrations instead of APS, respectively. These in vivo data indicated that APS induced thrombocytopenia was not observed in mice treated with mannose(+)-DXR-liposome, because of the destruction of macrophages by mannose(+)-DXR-liposome administration. These in vitro and in vivo results strongly suggest that mannose(+)-DXR-liposome treatment specifically delete the macrophages and can be effective in the management of experimental ITP model mice. Figure 1 The Uptake of Rhodamine –liposome by Murine Macrophages. Figure 1. The Uptake of Rhodamine –liposome by Murine Macrophages. Figure 2. The Viability of Murine Macrophages after incubation with Doxorubicin-liposome. Figure 2. The Viability of Murine Macrophages after incubation with Doxorubicin-liposome.

Kinetics, Redistribution And Fate Of Indium-111-Labelled-Platelets In Patients With Aortic Aneurysms

1981 ◽  
Author(s):  
A duP Heyns ◽  
M G Lötter ◽  
P N Badenhorst ◽  
F de Kock ◽  
H Pieters ◽  
...  
Keyword(s):  
Imaging System ◽  
Reticuloendothelial System ◽  
Aortic Aneurysms ◽  
Whole Body ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Normal Limits ◽  
Geometrical Mean ◽  
Indium 111

Platelets of 7 patients with abdominal aortic aneurysms were labelled with In-lll-oxine prior to surgery. The platelets were reinjected with the patient positioned under a scintillation camera with a computer assisted imaging system. Images were acquisitioned daily, areas of interest selected with the computer, organ radioactivity- quantitated with a geometrical mean method and expressed as a percentage of whole body radioactivity. Platelet survival (PS) in the circulation was determined, and disappearance curves fitted to a gamma function “multiple hit” model.Mean PS was shorthened to 143,2 ± 47h (normal 232<17); the dissappearance curves were exponential in all but the two patients who had PS within normal limits. The surgically removed aneurysms were dissected and radioactivity of different layers measured. In-111-activity was confined to the superficial layers of the aneurysm.These techniques allow quantitative studies of the in vivo distribution of labelled platelets. Platelets are deposited in the aneurysms, this shortens PS, the disappearance curves become exponential, and the major sites of deposition of In-111-activity are in the liver and spleen. This indicates that although platelets are damaged and deposited in the aneurysm, the reticuloendothelial system remains a major site of platelet sequestration.

THE EFFECT OF INTRAVENOUS IMMUNOGLOBULIN ON PLATELET KINETICS IN CHRONIC IMMUNE THROMBOCYTOPAENIC PURPURA (ITP)

1987 ◽  
Author(s):  
P N Badenhorst ◽  
H F Kotze ◽  
A duP Heyns ◽  
M G Lotter ◽  
P Wessels ◽  
...  
Keyword(s):  
Intravenous Immunoglobulin ◽  
Kinetic Studies ◽  
Ivig Therapy ◽  
Reticuloendothelial System ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Significant Difference ◽  
Before And After ◽  
High Doses

Most patients with ITP respond to high doses of intravenous immunoglobulin (IVIg) with a transient increase in platelet count. The effect of IVIg on platelet kinetics was studied in 5 patients with chronic ITP. Autologous platelets were labelled with In-111 and mean platelet lifespan (MPLS) calculated; in vivo distribution and sites of platelet sequestration were determined with a scintillation camera and computer assisted image analysis. The studies were performed before and after treatment with 2 g/kg Sandoglobulin. Two groups of patients were identified: those with a splenic platelet sequestration pattern (spleen-liver In-111-activity ratio >1.4) and those with diffuse sequestration of platelets in the reticuloendothelial system (RES).There was a significant difference in mean platelet counts before and after treatment (p<0.05). Patients with a splenic sequestration pattern responded better to IVIg: the MPLS lengthened and the high spleen-liver ratio decreased. In the diffuse RES sequestration pattern group, IVIg had almost no effect on platelet kinetics. We conclude that platelet kinetic studies identify a subgroup of patients with ITP who will respond to IVIg therapy.

Kinetics And Sites Of Destruction Of Indium-111-Oxine Labelled Platelets In Immune Thrombocytopenic Purpura

1981 ◽  
Author(s):  
A duP Heyns ◽  
P N Badenhorst ◽  
M G Lötter ◽  
F de Kock ◽  
C Herbst ◽  
...  
Keyword(s):  
Imaging System ◽  
Kinetic Studies ◽  
Reticuloendothelial System ◽  
Whole Body ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Thrombocytopenic Purpura ◽  
Indium 111 ◽  
System Acquisition ◽  
In Parenthesis

Kinetics and quantification of the sites of destruction of In-111-oxine labelled autologous platelets was investigated in eight patients with idiopathic thrombocytopenic purpura. The mean platelet count was 17 9 × 109/l; platelets were separated by differential centrifugation and labelled with 5,6 ±2,5 MBq In-111. Whole body and organ In-111-platelet distribution was quantitated with a scintillation camera and a computer assisted imaging system acquisition matrix. Areas of interest were selected with the computer and organ In-111-radioactivity expressed as a percentage of whole body activity. Mean platelet survival was 49,5+29,6h, and the survival curves exponential. Equilibrium percentage organ In-111-radioactivity was (normal values in parenthesis): spleen 33,7±8,8 (31,1 ± 10,2); liver 16,1 ± 9,5 (13,1 ± 1,3); thorax 22,8 ± 3,7 (28,8 ± 5,6). Percentage organ In-111-activity at the time when labelled platelets had been removed from the circulation was: spleen 44,5 ± 16,4 (40 ± 16); liver 16,0 ± 11,5 (32,4 ± 7,2); thorax 19,7±6,0 (17,7 ± 10,3). Thorax activity corresponds to radioactivity in the bony cage of the thorax. Three patterns of platelet sequestration were evident. Three patients had mainly splenic sequestration; two, mainly hepatic sequestration; and three, diffuse reticuloendothelial system sequestration with a major component of platelets destroyed in the bone marrow. Splenectomy was performed in two patients. The pattern of In-111-platelet sequestration was not predictive of response to glucocorticoid therapy or indicative of the necessity for splenectomy. Quantitative In-111-labelled autologous platelet kinetic studies provide a new tool for the investigation of platelet disorders.

scholarly journals Platelet-associated and plasma anti-glycoprotein autoantibodies in chronic ITP

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1040-1045 ◽  
Author(s):  
R McMillan ◽  
P Tani ◽  
F Millard ◽  
P Berchtold ◽  
L Renshaw ◽  
...  
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Platelet Glycoprotein ◽  
Antiplatelet Antibody ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Chronic Immune Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Negative Results ◽  
Well Assay ◽  
Positive Results

Chronic immune thrombocytopenic purpura (ITP) is due to platelet destruction by circulating antiplatelet antibody. Although autoantibodies against the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) complex and GPIb have been demonstrated using various methods, practical assays for detection of platelet-associated or plasma autoantibodies have not been available. We studied 59 patients with chronic immune thrombocytopenic purpura in whom platelet-associated and plasma autoantibodies against the GPIIb/IIIa complex and GPIb were measured using a newly developed immunobead assay and a previously reported microtiter-well assay. Platelet-associated autoantibody was detected using the immunobead assay in 21 of 28 patients (75.0%; 13 with anti-GPIIb/IIIa, 8 with anti-GPIb). Plasma autoantibodies were noted in 34 of 59 patients (57.6%; 21 with anti-GPIIb/IIIa, 11 with anti-GPIb, and 2 with both). Positive results were noted in 30 of 59 patients using the immunobead assay and in only 14 of 59 using the microtiter-well assay, suggesting that solubilization of the platelets prior to antibody addition, as in the microtiter-well assay, alters epitope stability. Of the 31 thrombocytopenic control patients studied, all gave negative results using both assays. We conclude that these clinically adaptable assays allow detection of autoantibodies in most patients with chronic ITP, confirming the presence of an autoimmune process.

scholarly journals Platelet-associated and plasma anti-glycoprotein autoantibodies in chronic ITP

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1040-1045 ◽  
Author(s):  
R McMillan ◽  
P Tani ◽  
F Millard ◽  
P Berchtold ◽  
L Renshaw ◽  
...  
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Platelet Glycoprotein ◽  
Antiplatelet Antibody ◽  
Platelet Destruction ◽  
Thrombocytopenic Purpura ◽  
Chronic Immune Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Negative Results ◽  
Well Assay ◽  
Positive Results

Abstract Chronic immune thrombocytopenic purpura (ITP) is due to platelet destruction by circulating antiplatelet antibody. Although autoantibodies against the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) complex and GPIb have been demonstrated using various methods, practical assays for detection of platelet-associated or plasma autoantibodies have not been available. We studied 59 patients with chronic immune thrombocytopenic purpura in whom platelet-associated and plasma autoantibodies against the GPIIb/IIIa complex and GPIb were measured using a newly developed immunobead assay and a previously reported microtiter-well assay. Platelet-associated autoantibody was detected using the immunobead assay in 21 of 28 patients (75.0%; 13 with anti-GPIIb/IIIa, 8 with anti-GPIb). Plasma autoantibodies were noted in 34 of 59 patients (57.6%; 21 with anti-GPIIb/IIIa, 11 with anti-GPIb, and 2 with both). Positive results were noted in 30 of 59 patients using the immunobead assay and in only 14 of 59 using the microtiter-well assay, suggesting that solubilization of the platelets prior to antibody addition, as in the microtiter-well assay, alters epitope stability. Of the 31 thrombocytopenic control patients studied, all gave negative results using both assays. We conclude that these clinically adaptable assays allow detection of autoantibodies in most patients with chronic ITP, confirming the presence of an autoimmune process.

New Drug Approvals: Romiplostim Management of Immune Thrombocytopenic Purpura

2009 ◽  
Vol 43 (5) ◽  
pp. 914-919 ◽  
Author(s):  
Heather J Ipema ◽  
Michelle Y Jung ◽  
Amy E Lodolce
Keyword(s):  
Immune Thrombocytopenic Purpura ◽  
Data Extraction ◽  
Reticuloendothelial System ◽  
Pharmacokinetic Data ◽  
Open Label ◽  
Double Blind ◽  
Thrombocytopenic Purpura ◽  
Time To Peak ◽  
Study Selection ◽  
Open Label Extension

Objective To review the pharmacology, pharmacokinetics, efficacy, and safety of romiplostim, the first drug approved for use in patients with immune thrombocytopenic purpura (ITP). Data Sources Articles were identified through searches of MEDLINE (1966–January 2009) and International Pharmaceutical Abstracts (1970–January 2009) using the key words romiplostim and AMG 531. Searches were limited to articles published in English. The manufacturer was contacted for additional data. Study Selection And Data Extraction Clinical trials and pharmacokinetic data were selected for review. Data Synthesis Romiplostim is a second-generation thrombopoietic receptor agonist that exerts its therapeutic effect by stimulating megakaryopoiesis. Subcutaneous therapy results in a dose-dependent increase in platelets; however, interindividual variability exists. Time to peak concentration is approximately 14 hours, and the elimination half-life is approximately 3.5 days (range 1–34). Romiplostim undergoes endothelial recirculation and is eliminated by the reticuloendothelial system. The results of 2 Phase 3, randomized, double-blind, placebo-con trolled trials have demonstrated the efficacy of romiplostim for increasing platelet counts in patients with ITP refractory to other therapies, including splenectomy. Effects on platelets were transient and decreased within 2 weeks of discontinuing the drug. Interim results of an open-label extension study revealed that romiplostim has sustained efficacy and tolerability for up to 156 weeks at a dosage range of 1–17 μg/kg/wk (mean 5.9 ± 3.9). The most common adverse effects include headache, fatigue, epistaxis, and contusion. Romiplostim is also under investigation for treatment of thrombocytopenia associated with myelodysplastic syndrome. The drug must be ordered directly from the manufacturer through a limited access program, and weekly subcutaneous injections are given in the clinic setting. Conclusions Romiplostim is effective for the management of ITP in adults refractory to other therapies, including splenectomy.

Kinetics and in Vivo Redistribution of 111Indium-Labelled Human Platelets after Intravenous Protamine Sulphate

1980 ◽  
Vol 44 (02) ◽  
pp. 065-068 ◽  
Author(s):  
A duP Heyns ◽  
M G Lötter ◽  
P N Badenhorst ◽  
H Kotze ◽  
F C Killian ◽  
...  
Keyword(s):  
Imaging System ◽  
Human Platelets ◽  
Computer Assisted ◽  
Scintillation Camera ◽  
Protamine Sulphate ◽  
Normal Volunteers ◽  
Activated Platelets ◽  
Platelet Survival ◽  
Platelet Aggregates

SummaryThe pathogenesis of thrombocytopenia induced by intravenous protamine sulphate was studied in six patients who underwent cardiopulmonary bypass surgery, and in three normal volunteers. Autologous platelets were labelled with 111Indium-oxine. Platelet lifespan was determined. In vivo 111In-platelet localization, organ redistribution and sites of destruction were quantitated with a scintillation camera and a computer-assisted imaging system. Protamine induced a transient thrombocytopenia, maximal 5-10 min after injection, and 30-40 min in duration. The thrombocytopenia was accompanied by a transient accumulation of platelets in the liver. The splenic platelet pool remained unaltered and no platelets accumulated in the lungs. Platelet survival, measured in two volunteers, was slightly longer than normal and fitted a linear function best. There was a severe transient neutropenia during the period of thrombocytopenia. We conclude that protamineinduced thrombocytopenia is caused by hepatic accumulation of "activated" platelets or platelet aggregates, the process is reversible, and in the two normal volunteers studied, platelet survival was not affected.

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