The kinetics of short-lived indium-111 radiolabelled platelets

We have studied the kinetics of autologous 111In-labelled platelets in patients with reduced platelet life span (less than 4.5 d), most of whom were thrombocytopenic, and of homologous 111In-labelled platelets in patients with severe thrombocytopenia. Intrasplenic platelet transit time (t) was calculated by compartmental and deconvolution analysis. In patients with a mean platelet life span of less than a few h, compartmental analysis may not be valid and so only deconvolution analysis was applied. There was a close correlation between values of t given by the two approaches (r = 0.88, n = 18, P less than 0.001). In some patients with severely reduced mean platelet life span (MPLS), the deconvolved splenic platelet clearance curves appeared to approach an asymptote, the relative magnitude of which was indicative of the irreversible extraction fraction by the spleen of incoming platelets. In other patients with severely reduced MPLS resulting from abnormal intra-hepatic platelet destruction, the deconvolved splenic curves resembled the normal. The intrasplenic platelet transit time showed no clear relationship with other parameters. It was concluded that platelet pooling within the spleen is normal in patients with reduced platelet life span, including idiopathic thrombocytopenic purpura, even when the predominant site of destruction is the spleen, and that platelets are not delayed in transit through the spleen in preparation for their removal from the circulation and ultimate destruction.     

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

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.     

Detection of arterial thrombi using blood platelets labeled with indium-111

Scintigraphy with Indium 111-labelled platelets was carried out in 62 patients (37 transient cerebral ischaemic accidents, 21 lower limb ischaemic episodes and 4 aortic aneurysms) to detect arterial thrombi. The results of this investigation were compared with the surgical findings and showed this to be a satisfactory method of detecting haematologically active thrombi.     

Kinetics of indium-111-labelled platelets in HIV-infected patients with and without associated thrombocytopaenia.

Seven to 12% of HIV-infected patients have thrombocytopaenia. The pathophysiology of the thrombocytopaenia is not clear. It has been variously suggested that it may be caused by an increased peripheral platelet destruction, a defect in platelet production, or by a combination of these. The aim of the study was to elucidate the pathogenesis of HIV-associated thrombocytopaenia. We determined the mean platelet life span (MPLS) and calculated the turnover of autologous indium-111-labelled platelets in 17 HIV-positive patients, seven with thrombocytopaenia. The sites of sequestration of labelled platelets were quantified. The thrombocytopaenic patients had a very short MPLS (3.0+/-3.8 h) and a marked increase in platelet production (18.2+/-12.6x10(9)/l/h). The majority of these patients (5 of 7) had excessive sequestration of platelets in the spleen. Five of the patients with a normal blood platelet count had a shortened MPLS (109+/-23 h) and increased platelet turnover (3.8+/-1.2x10(9)/l/h), i.e. the increased peripheral platelet destruction was compensated for by increased platelet production. The other five patients with a normal platelet count had normal MPLS (195+/-11 h) and slightly increased platelet production (2.5+/-0.6x10(9)/l/h). We conclude that patients with HIV-associated thrombocytopaenia have increased peripheral platelet destruction. Platelet production is elevated but is insufficient to maintain a normal peripheral platelet count. In these patients platelets are predominantly sequestrated in the spleen. Patients with HIV infection and a normal blood platelet count may also have increased platelet production. This may be an early subclinical phase in the development of full-blown HIV-associated thrombocytopaenia.     

Detection of left atrial thrombi in man using indium-111 labelled autologous platelets

A scintigraphic technique using indium-111 labelled platelets to detect left atrial thrombi was used in 28 patients, 14 of whom had mitral valve disease and 14 combined valve disease. Imaging was performed in the anterior, right anterior oblique (45 degrees), and left lateral views on the day of injection and thereafter at one or two day intervals for a maximum of four days. When scintiphotos obtained in two or three views 72 or 96 hours after the platelet injection showed "hot spot areas" within the left atrial pool and indium-111 activity in these areas did not decrease with time they were interpreted as positive for thrombi. Of 28 patients, seven had positive platelet images by this criterion; of these, three underwent surgery and were found to have left atrial thrombi. One patient died, and a thrombus was found at necropsy. The remaining 21 patients had normal scintiphotos; of these, seven had no thrombi at operation and one had false negative images. The diagnostic accuracy of platelet scintigraphy by this criterion of positivity in the 12 patients in whom surgical or postmortem confirmation of thrombi could be obtained was 92%. These results indicate that this technique is a promising method for detecting active left atrial thrombi.     

Detection of left atrial thrombi in man using indium-111 labelled autologous platelets.

A scintigraphic technique using indium-111 labelled platelets to detect left atrial thrombi was used in 28 patients, 14 of whom had mitral valve disease and 14 combined valve disease. Imaging was performed in the anterior, right anterior oblique (45 degrees), and left lateral views on the day of injection and thereafter at one or two day intervals for a maximum of four days. When scintiphotos obtained in two or three views 72 or 96 hours after the platelet injection showed "hot spot areas" within the left atrial pool and indium-111 activity in these areas did not decrease with time they were interpreted as positive for thrombi. Of 28 patients, seven had positive platelet images by this criterion; of these, three underwent surgery and were found to have left atrial thrombi. One patient died, and a thrombus was found at necropsy. The remaining 21 patients had normal scintiphotos; of these, seven had no thrombi at operation and one had false negative images. The diagnostic accuracy of platelet scintigraphy by this criterion of positivity in the 12 patients in whom surgical or postmortem confirmation of thrombi could be obtained was 92%. These results indicate that this technique is a promising method for detecting active left atrial thrombi.     

A quantitative method to measure human platelet chemotaxis using indium- 111-oxine-labeled gel-filtered platelets

Human blood platelets have been shown to migrate directionally and specifically toward collagen in plasma in vitro. We have developed a new system to monitor this behavior using a linear 7-compartment chamber with 111In-oxine-labeled gel-filtered platelets. The compartments are separated by various Nuclepore and Millipore filter membranes. Radiolabeled platelets suspended in plasma are placed in the central compartment and the other compartments are filled with platelet- free plasma. When collagen is added to an end compartment, platelets migrate toward that end. The degree of this directed movement or chemotaxis can be measured by counting the radioactivity of the contents of each compartment and then comparing the counts from radiolabeled platelets that have moved to the end that holds the chemotactic inducer with those that have randomly migrated to the opposite end, containing only plasma. This assay system allows quantitative comparisons between the chemotaxis-inducing abilities of different substances and permits the study of soluble materials. Experiments to determine the optimal conditions for the procedure are reported, and the advantages of this new method for the investigation of platelet chemotaxis and the identification of chemotaxins are discussed.     

Long-term lung clearance in humans studied with Teflon particles labeled with chromium-51

Six healthy nonsmoking males inhaled 4-micron diameter Teflon particles labeled with chromium-51. Lung retention was measured for approximately 300 days. Three subjects inhaled "high-leaching" particles and three "low-leaching" particles. The high-leaching leaching particles leached 0.26%/day in water at 37 degrees C for the first 100 days and the low-leaching particles 0.065%/day. On an average, urine sampled for 24 h contained 0.13% of the lung burden for the high-leaching particles and 0.02% for the low-leaching particles. Thirty percent of the long-term clearance occurred with a fast phase, with half-times ranging from 4.5-45 days, and 70% with a slow phase, with half-times ranging from 200-2500 days. The fast phase was similar for the high-leaching and low-leaching groups. The slow phase varied widely among the subjects. There was no clear-cut relationship between half-time and type of particle. However, it seems probable that the slow phase was dependent on the degree of leaching, i.e., the half-times for elimination of intact particles from the lung are even slower. The large differences in long-term clearance among subjects indicate that long-term exposure to highly insoluble particles will result in large differences in lung burden. Subjects with a low capacity to eliminate alveolarly deposited particles are thus expected to be more susceptible to diseases in the alveolar part of the lung, i.e., diseases caused by certain insoluble particles.     

Failure of ticlopidine to inhibit deposition of indium-111-labeled platelets on Dacron prosthetic surfaces in humans

In a randomized double-blind trial we sought to determine whether short-term therapy with ticlopidine (250 mg bid for 14 days) inhibited platelet deposition on Dacron aortic bifurcation grafts that had been in place a year or longer. A total of 10 men, 42 to 69 years old, underwent indium-111 platelet imaging during both placebo and drug phases of the trial at 24, 48, and 72 hr after the injection of labeled platelets. Platelet accumulation was quantitated by a graft/blood ratio that compared background-corrected activity of indium-111-labeled platelets in the graft with whole-blood activity of indium-111-labeled platelets. Additionally, blinded qualitative visual analysis of the unprocessed images was used to compare graft area activity with activity in adjacent native arteries. Ticlopidine significantly prolonged the template bleeding time from 5.3 +/- 0.5 to 17.1 +/- 3.1 min (+/- SEM) (p = .003). However, by quantitative analysis there was no significant reduction in platelet deposition in the graft during ticlopidine therapy compared with placebo at 24 hr (graft/blood ratio 2.3 +/- 0.4 vs 2.6 +/- 0.3), 48 hr (3.1 +/- 0.5 vs 3.2 +/- 0.4), or 72 hr (3.9 +/- 0.7 vs 4.0 +/- 0.6) after injection of labeled platelets. By visual analysis, nine patients had positive results for abnormal platelet deposition when on placebo that were unchanged when on ticlopidine. The tenth patient had an equivocal result for abnormal platelet deposition when on placebo and a negative result for abnormal platelet deposition when on ticlopidine.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of indium-111-labelled platelets for scintigraphic localization of gastrointestinal bleeding, with special reference to occult bleeding

Gamma-camera imaging of the abdomen after injection of autologous 111In-labelled platelets was applied for localization of gastrointestinal bleeding in a study of 22 patients. In 15 studies showing scintigraphic signs of bleeding, the clinical presentation included occult bleeding in 6, melaena in 4, and bloody stools in 5. Scintigraphy could be done repeatedly for up to 1 week after a single tracer injection. The time interval between the injection and scintigraphic visualization of bleeding ranged from 10 min to 68 h, being longest in cases of occult bleeding. In most cases the scintigraphic findings were supported by other diagnostic modalities, including surgical removal of presumed sources of bleeding. In seven studies without scintigraphic signs of bleeding a probable source of bleeding was identified by other means in one patient. The 111In-platelet method seems to be a promising method for localization of gastrointestinal bleeding which may prove particularly useful in cases of occult or recurrent bleeding.     

The in vivo kinetics of 111In- and 51Cr-labelled platelets: a comparative study using both stored and fresh platelets

The in vivo kinetics of simultaneously injected 51Cr- and 111In-labelled platelets was investigated in 20 healthy male volunteers. The studies were carried out using both fresh platelets and platelets stored for 5 d at 22 degrees C; the disappearance of platelet-bound radioactivity was measured on whole blood samples as well as platelet pellets. Compared to 111In, the labelling efficiency was notably lower for 51Cr, and a higher amount of 51Cr was bound to contaminating red cells. As regards the fresh platelets, only small dissimilarities were observed in the in vivo kinetics obtained with the two labels. 51Cr yielded a slightly higher platelet recovery and longer T1/2 than 111In, when whole blood samples were used for calculations; no differences were seen when using platelet pellets. When stored platelets were studied, 51Cr gave significantly longer T1/2 and mean life-span (MLS) than did 111In. This difference was present for all mathematical models used for the calculation of MLS, and when whole blood samples as well as platelet pellets were employed. It was demonstrated that the estimation of MLS was also highly dependent upon techniques of blood sampling and curve fitting. Calculation, in which the initial data points were excluded, gave consistently longer MLS (P less than 0.0001), as compared to when all data points were included. Furthermore, when all survival studies were grouped together, calculations using platelet pellets gave a significantly (P less than 0.001) shorter platelet MLS than calculations using whole blood samples. It is concluded that both 51Cr and 111In are acceptable as radiolabels for both fresh and stored platelets. However, it appears that the viability of stored platelets may be influenced by the choice of label, and caution must be taken when these isotopes are used together in dual tracer experiments. Also, our results show that a meticulously standardized processing of blood samples and experimental data is required to enable interlaboratory comparisons of the results.     

Focal myocardial injury following blunt chest trauma: a comparison of indium-111 antimyosin scintigraphy with other noninvasive methods.

The diagnosis of myocardial contusion is often difficult, as traditional methods such as serial electrocardiograms, cardiac enzyme (creatine kinase [CK-MB]) analysis, and echocardiography lack sensitivity and specificity. Recent reports have shown that 111In labelled antimyosin scanning has high sensitivity for detecting cardiac injury. However, no prior studies have been reported for antimyosin imaging with patients suspected of sustaining a cardiac contusion. Accordingly, 17 patients with severe multisystem trauma (intrathoracic vascular injury in eight patients, pneumothorax and pulmonary contusion in 13) underwent antimyosin scintigraphy, echocardiography, 12-lead electrocardiograms, and CK-MB determinations. Arrhythmias were noted in seven patients, four of whom died. All patients has elevated CK levels but CK-MB isoenzyme was greater than 4% in only three. Abnormal ST segments were noted in nine subjects, only one of whom had CK-MB elevation. Echocardiography revealed pericardial effusions in four patients but was technically suboptimal in 53% of the studies. Blinded interpretation of the antimyosin scans revealed only one with focal myocardial uptake; this same patient had the only discrete wall motion abnormality on the echocardiogram and also had ST depression with ectopy but normal CK-MB. Thus in patients with suspected myocardial contusion, echocardiography is frequently limited technically and the electrocardiogram and CK analysis appear to lack diagnostic accuracy. In contrast, monoclonal antimyosin imaging may be performed in patients with trauma without limitation and yields results that are concordant with echocardiograms. In patients with suspected myocardial contusion, focal antimyosin uptake is uncommon despite severe thoracic injury, which suggests that extensive myocardial necrosis is not the primary method of injury.     

Kinetics, in vivo redistribution and sites of sequestration of indium-111-labelled platelets in giant platelet syndromes

Six patients with giant platelet syndrome were examined: four with Bernard-Soulier syndrome (two were asplenic); one with hereditary thrombopathic thrombocytopenia; and one with May-Hegglin anomaly. Autologous platelets were labelled with In-111-oxine and in vivo redistribution and sites of sequestration measured with quantitative imaging. In Bernard-Soulier syndrome platelet survival was normal or moderately shortened; platelet turnover was decreased only in the two patients with thrombocytopenia. In the patients with thrombopathia or May-Hegglin anomaly, platelet survival and turnover was moderately decreased. In those patients with normal-sized spleens, the mean splenic platelet pool consisted of 35.5% of the platelet mass, i.e. normal. The intrasplenic transmit time of the megathrombocytes was prolonged. Splenic blood flow was within normal limits. There was a marked accumulation of platelets in the liver at equilibrium: 15.5-58.8% of whole body radioactivity (normal 9.6 +/- 1.2%). This finding is unexplained. The final sites of sequestration of platelets were mainly in the liver and spleen, similar to that seen in normal subjects. We conclude that there is no inverse relationship between cell size and splenic platelet transit time. Platelet size therefore does not determine the size of the splenic platelet pool. The size of the platelets also does not seem to affect the sites of sequestration at the end of their life span.     

Survival of density subpopulations of rabbit platelets: use of 51Cr-or 111In-labeled platelets to measure survival of least dense and most dense platelets concurrently

The origin of the density heterogeneity of platelets was studied by measuring the survival of density subpopulations of rabbit platelets separated by discontinuous Stractan density gradient centrifugation. When a total population of 51Cr-labeled platelets was injected into recipient rabbits, the relative specific radioactivity of the most dense platelets decreased rapidly. In contrast, that of the least dense platelets had not changed 24 hr after injection, and then decreased slowly. To distinguish between the possibilities that most dense platelets are cleared from the circulation more quickly than least dense platelets or that platelets decrease in density as they age in the circulation, the concurrent survival of least dense and most dense platelets, labeled with either 51Cr or 111In-labeled total platelet populations, determined concurrently in the same rabbits, were identical, calculated from 1 hr values as 100%. However, the 1-hr recovery of 111In-labeled platelets was slightly but significantly less than that of 51Cr-labeled platelets. Therefore, we studied the survival of 51Cr-labeled least dense and 111In-labeled most dense platelets as well as that of 111In-labeled least dense and 51Cr-labeled most dense platelets. Mean 1-hr recovery of least dense platelets, labeled with either isotope (78% +/- 7%, SD) was similar to that of most dense platelets, labeled with either isotope (77% +/- 8%; SD). Mean survival of least dense platelets was 47.3 +/- 18.7 hr (SD), which was significantly less than that of most dense platelets (76.1 +/- 21.6 hr; SD) (p less than 0.0025). These results indicate that platelets decrease in buoyant density as they age in the circulation and that most dense platelets are enriched in young platelets, and least dense in old. Thus, the events that affect platelets as they age in the circulation contribute to platelet density heterogeneity, although they may not be the sole cause of it.