indium-oxine and Purpura--Thrombocytopenic--Idiopathic

Topics: Adult; Aged; Aged, 80 and over; Blood Platelets; Female; Humans; Indium Radioisotopes; Male; Middle Aged; Organometallic Compounds; Oxyquinoline; Platelet Transfusion; Purpura, Thrombocytopenic, Idiopathic; Radiopharmaceuticals; Receptors, Thrombopoietin; Young Adult

Splenectomy is a time-honoured well established approach for patients with steroid-resistant immune thrombocytopenia (ITP). However, due to the more recent availability of therapeutic options alternative to splenectomy, such as rituximab and agonists of the thrombopoietin-receptor, the choice of second-line therapy is challenging. Platelet kinetics has been widely used to predict response to splenectomy. We describe the outcome of 70 chronic ITP patients who performed a platelet kinetic study after failure of front-line corticosteroids and subsequently underwent open splenectomy. After a median follow-up from surgery of 20 years, 62 (88.5%) patients responded to splenectomy and 9 patients (13%) relapsed. Achieving a complete response (CR) significantly predicted a higher probability long-term stable response. The pattern of platelet sequestration was predominantly splenic in 52 patients (74%), predominantly hepatic in 12 patients (17%), and diffuse in 6 (9%). Patients with nonsplenic (diffuse and hepatic) sequestration showed significantly lower overall responses compared to patients with splenic captation (P = 0.002). A nonsplenic sequestration significantly correlated with lower CR rate and, among CR patients, predicted an increased risk of relapse. Also, the probability of stable responses in nonsplenic uptake patients was substantially lower than in patients with splenic uptake (85% vs. 50%, P = 0.0083). Platelet life span and platelet turnover did not correlate with response and relapse rate. Overall, splenic sequestration was able to predict not only a better quality, but also a higher durability of the responses. However, it should be enphasized that the response rate and duration of response even in patients with nonsplenic uptake were similar or even superior to those reported in patients treated with rituximab as first option.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Age Factors; Aged; Child; Child, Preschool; Drug Resistance; Female; Follow-Up Studies; Humans; Indium Radioisotopes; Infant; Male; Middle Aged; Organometallic Compounds; Oxyquinoline; Patient Selection; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Radiopharmaceuticals; Splenectomy; Tissue Distribution; Young Adult

Topics: Child; Female; Humans; Male; Organometallic Compounds; Oxyquinoline; Purpura, Thrombocytopenic, Idiopathic; Radionuclide Imaging; Splenectomy; Splenic Diseases

Taking into consideration the existing disagreement in the literature, the aim of this paper was to estimate the value of the initial kinetics of autologous platelets labelled with 111In-oxinate, performed during the first 20 minutes after their intravenous injection. Two hypothesis were tested: 1. Initial 111In-platelet kinetics indicates the platelet sequestration site (in patients with normal mean platelet life span)/destruction site (in patients with shortened mean platelet life span), 2. Initial 111In-platelet kinetics indicates the quality of platelet separation and labelling procedure. We performed initial labelled platelet kinetics in thrombocytopenic patients (in order to test the first hypothesis) as well as in control (healthy) subjects (in order to test the second hypothesis). Thirty-nine persons were investigated: 33 with thrombocytopenia: 25 with shortened mean platelet life span, caused by chronic im mune thrombocytopenic purpura (ITP), eight with normal platelet life span and thrombocytopenia caused by myelodysplastic syndrome (MDS), six healthy, control subjects (C). In all 39 persons platelet blood count on the day of platelet labelling was determined, autologous platelet labelling with 111In-oxinate was performed, general and differential yields of platelet labelling (GYL and DYL), as well as mean labelled platelets life span were determined. Besides that, initial labelled platelets kinetics was performed with initial 111In-platelets accumulation in the liver (IPAL) calculation, as well as the late platelet kinetics for platelet sequestration index and platelet sequestration/destruction site determination. We obtained two types of initial labelled platelets kinetics (not only in the patients with shortened platelet life span, but also in the subjects with normal labelled platelets life span), which differed in the IPAL value and in the ratio of the liver and the heart radioactivity: IPAL < 20% and IPAL>20%. We found statistically significant difference in GYL and DYL between the two groups: IPAL<20% and IPAL > 20%. Both yields were higher in IPAL<20% group. There was no significant difference between the two IPAL groups in the platelet blood count, labelled platelet life span, sequestration index and sequestration site. No correlation could be found between IPAL on one side and platelet blood count, sequestration index, and sequestration site on another. We concluded that initial labelled platelet kinetics could not indicate the platele

Topics: Adult; Blood Platelets; Female; Humans; Indium Radioisotopes; Isotope Labeling; Male; Middle Aged; Organometallic Compounds; Oxyquinoline; Platelet Count; Platelet Transfusion; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia

Immune thrombocytopenic purpura (ITP) is an autoimmune disease related to the presence of elevated levels of platelet-associated immunoglobulin, or autoantibodies. In recent years the importance of macrophage Fc gamma receptors in the uptake of platelets in ITP has been confirmed. Although in patients with ITP the platelet destruction occurs in liver and spleen, in this present experimental mouse model the liver was the principal organ of sequestration of sensitized platelets. The uptake in the spleen, bone marrow, lung, and kidneys was negligible and not different from that in control animals. In addition, the trapped platelets did not return to circulation, and new cells derived from the platelet-storage pool or new thrombocytogenesis were necessary to restore the platelet count. The depletion of splenic and hepatic murine macrophages by liposome-encapsulated clodronate (lip-clod) was studied as a new strategy for ITP treatment. Lip-clod inhibits, in a dose-dependent manner, the antibody-induced thrombocytopenia. Moreover, lip-clod treatment rapidly restored (24 hours) the platelet count in thrombocytopenic animals to hematologic safe values, and despite additional antiplatelet antiserum treatment, mice were able to maintain this level of platelets at least up to 48 hours. The bleeding times in lip-clod-treated animals was not different from those in controls, demonstrating that the hemostasis was well controlled in these animals. The results presented in this study demonstrate that lip-clod treatment can be effective in the management of experimental ITP. (Blood. 2000;96:2834-2840)

Topics: Animals; Autoimmune Diseases; Bleeding Time; Blood Platelets; Clodronic Acid; Dose-Response Relationship, Drug; Drug Compounding; Drug Evaluation, Preclinical; Erythrocyte Count; Immune Sera; Indium Radioisotopes; Leukocyte Count; Liposomes; Liver; Macrophages; Mice; Models, Animal; Organ Specificity; Organometallic Compounds; Oxyquinoline; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Rabbits; Spleen

The purpose of this study was to evaluate the feasibility of a shorter method of performing platelet kinetic studies with respect to the conventional 8-9-day approach.. We studied 41 patients (28 women, 13 men; mean age 52 yr) with primary idiopathic thombocytopenic purpura (ITP) (n = 20), secondary ITP (n = 9), HCV associated thrombocytopenia (n = 9), splenectomy (n = 1) and hairy-cell leukemia (n = 1). The patients were in a steady-state of platelet turnover. Initial platelet counts ranged from 19 to 302 x 10(9)/liter (mean value = 83). Platelet survival times (PST) were measured from the blood radioactivity disappearance curve of 111In-oxine-labeled autologus platelets following the recommendations of the International Committee for Standardization in Haematology: blood samples were taken at 30 min and 2 and 4 hr and thereafter daily for 7 days. PST was calculated by the weighted mean method and ranged from 18 to 219 hr (mean value = 98). PST was also calculated using only the data collected at 2, 48 and 96 hr. If the radioactivity in the blood at 96 hr exceeded 10% of the 2-hr value, the additional point at 168 hr was used.. By using this reduced dataset, we obtained a correlation of r = 0.97 with the PST obtained from the whole dataset. In 24 patients, the difference was between +/- 10 hr and exceeded 1 day in only 4.. About 94% of the data may be recovered with only three or four blood samples and the duration may be shortened to 4 days in a significant proportion of patients (48% of ITP patients). This approach offers the advantages of increased patient throughput, compliance and reduced examination costs.

Topics: Blood Platelets; Cell Survival; Cellular Senescence; Feasibility Studies; Female; Humans; Indium Radioisotopes; Male; Middle Aged; Organometallic Compounds; Oxyquinoline; Purpura, Thrombocytopenic, Idiopathic; Radionuclide Imaging; Thrombocytopenia; Time Factors

Objective determination of regions of interest (ROIs) is a prerequisite for the accurate quantification of radionuclide volume distributions in single photon emission tomographic (SPET) images. In this study, we compared four segmentation methods: fixed thresholding (FT), grey level histogram (GL), region growing (RG) and combined region growing and edge detection (RGE). For this purpose, an elliptical phantom containing two cylinders with varying volumes (8-360 ml) and activities of 111In and 99Tcm (2.9-37 kBq ml-1) was employed. Using these methods, the following correlation was observed between true and measured phantom volumes: 111In, r = 0.95 (FT), 0.73 (GL), 0.93 (RG) and 0.92 (RGE); 99Tcm, r = 0.85 (FT), 0.72 (GL), 0.85 (RG) and 0.89 (RGE). Volume determination with FT and RG was not sensitive to the cut-off frequency used in image filtering. A significant correlation was observed between spleen volumes measured with the different segmentation methods, except GL, when applied to the SPET images of 25 patients administered 111In-labelled platelets. On the basis of these results, FT and RG are recommended for the clinical determination of ROIs, although they can be difficult to apply if the signal-to-noise ratio is very low or highly variable, when a combination of different imaging modalities may be the only accurate solution to the segmentation problem. The RGE method can also produce accurate results, but estimation of parameters is laborious with this method. Before being applied clinically, all segmentation methods tested in this study require phantom measurements for the determination of optimal parameters.

Topics: Humans; Indium Radioisotopes; Liver; Models, Structural; Organometallic Compounds; Oxyquinoline; Purpura, Thrombocytopenic, Idiopathic; Spleen; Technetium; Tomography, Emission-Computed, Single-Photon

The paper presents the new method of platelet labelling, quality control of separation and labelling, as well as the investigation of the 111In oxinate labelled platelets lifespan. Among the 23 investigated persons, there were 4 hematologically healthy persons and 19 ITP patients. Homologous and autologous labellings were done in one and 22 persons, respectively. Determination of the platelet lifespan in healthy subjects enabled the estimation of "in vitro" procedures of separation and labelling, as well as "in vivo" behaviour of the labelled platelets. Our results show that 111In oxinate labelled platelets have normal lifespan (8.9 +/- 0.6 days), which means that the procedure of separation and labelling does not damage them. In the ITP patients the platelet lifespan is shortened (0.4-4.6 days), which confirms the mechanism of thrombocytopenia. In the subject where homologous labelling had been done, we found out the existence of sensibilisation toward the donor platelets, which lead to the correction of therapy.

Topics: Adolescent; Adult; Blood Platelets; Cell Survival; Humans; Indium Radioisotopes; Middle Aged; Organometallic Compounds; Oxyquinoline; Purpura, Thrombocytopenic, Idiopathic

The splenic uptake of thrombocytes and spleen size were studied in 25 patients with idiopathic thrombocytopenic purpura (ITP) using two methods: anterior/posterior scintigraphy and single photon emission computed tomography (SPECT). Various factors (acquisition and reconstruction protocols) influencing the quality of 111In SPECT were studied. The splenic uptake, measured by SPECT, was found to be significantly higher in patients with a high level of autoantibodies in the blood than in patients without such antibodies (37 +/- 6%, n = 8 vs 22 +/- 3%, n = 11, P = 0.04, t-test). The correlation between the spleen SPECT volume and the geometric mean size in anterior and posterior images was 0.80 (P < 0.001). However, the spleen size calculated as geometric mean of anterior and posterior images differed by more than 50% from the SPECT volume in some patients. Based on these observations and on the results of phantom studies it is concluded that a reasonable estimate of the spleen:liver uptake ratio may be obtained using planar imaging, but to estimate the spleen volume and the absolute splenic uptake of platelets SPECT imaging is needed, in spite of the present technical limitations of SPECT.

Topics: Blood Platelets; Humans; Indium Radioisotopes; Models, Structural; Organometallic Compounds; Oxyquinoline; Purpura, Thrombocytopenic, Idiopathic; Spleen; Tomography, Emission-Computed, Single-Photon

ITP (idiopathic thrombocytopenic purpura) causes rapid sequestration and destruction of thrombocytes by the spleen, liver, bone marrow, and reticuloendothelial elements of other organs. The usefulness of multiple radionuclide functional imaging procedures in the management of a 34-year-old woman with chronic ITP, two splenectomies (removal of the initial spleen and then a hypertrophied accessory spleen), and the failure of chemotherapy to control her thrombocytopenia, are discussed. A combination of In-111 oxine autologous platelet imaging, liver/spleen imaging, disofenin (liver/gallbladder) imaging, and glucoheptonate renal imaging demonstrated that her platelets were being sequestered by a markedly enlarged left hepatic lobe extending to the left lateral wall, with a small amount in the kidneys and lungs, and that there was no second accessory spleen.

Topics: Adult; Female; Humans; Imino Acids; Kidney; Liver; Organometallic Compounds; Organotechnetium Compounds; Oxyquinoline; Purpura, Thrombocytopenic, Idiopathic; Radionuclide Imaging; Spleen; Sugar Acids; Technetium Tc 99m Disofenin