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

Abstract

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.

The interpretation of platelet kinetic studies for the identification of sites of abnormal platelet destruction

“…rapid equilibration, an increased pooling capacity, and a DIP ratio of unity. Values of DIP in ITP estimated from illustrated data in the literature are similar to those reported here: 1.7 (Ries & Price, 1974), 1.5-2 (Aster & Keene, 1969) and 1.4-2.2 (Heyns et al, 1982b) in patients with predominant splenic sequestration: 1-1 -4 (Heyns et al, 1982b) in those with 'diffuse' reticuloendothelial sequestration; and 0.9-1.2 (Heyns et al, 1982b) and 0.5 (Kotilainen, 1969) in those with predominant hepatic sequestration.…”

“…the splenic surface count ratio corrected for pooled activity (i.e. excess counts; Kotilainen, 1969), and, more recently with "lIn labelled platelets, absolute quantitation of activity in the spleen (Klonizakis et al, 1981;Heyns et al, 1980Heyns et al, , 1982b. The approach suggested by Aster & Keene (1969) is the one closest to the approach described in the present study.…”

“…There are three fundamental causes of thrombocytopenia: reduced platelet production reduced platelet life span and, although it is not clear if thrombopoiesis is sensitive to the total circulating platelet population or the blood count, enlargement of the splenic platelet pool. As far as the role of the spleen is concerned, radiolabelled platelet studies have not produced consistent results, and there is some confusion in the literature regarding both accelerated splenic platelet destruction and increased splenic platelet sequestration as causes of thrombocytopenia (Kinlough et al, 1966;Kotilainen, 1969;Aster & Keene, 1969;Najean & Ardaillou. 1971;Cooper et al, 1972;Ries & Price, 1974;Richards & Thompson, 1979;Klonizakis et al, 1981;Heyns et al, 1982a, b).…”

Pathophysiology of HIV related thrombocytopenia: an analysis of 41 patients.

“…This could explain the excellent results obtained by removing the spleen of these patients, although opinions vary as to the correlation between the results of the 11 In labelled platelet studies and the therapeutic response. '3 15 Nearly all of the patients had a low platelet recovery, which shows a rapid decrease in transfused platelets as a result of peripheral destruction. '5 Measurable differences (p < 001) were only found in patients with less than 200 x 106 CD4/1 lymphocytes who showed a recovery of 53% (practically normal) compared with 28% (decreased) in the others.…”

“…We investigated three areas: the spleen; the liver; and the thorax-sternum (bone marrow activity). 15 Finally, to detect HIV-1 infection in megakaryocytes, specific monoclonal antibodies were used against p24 antigen (Chemicom, USA). The study was carried out on 12 biopsy specimens of bone marrow fixed in B5 and paraffin wax, using the avidin biotin alkaline phosphatase technique.…”