Anthon du P. Heyns

Thromboembolic potential of synthetic vascular grafts in baboons

We have compared in baboons the capacity of two types of synthetic vascular grafts to accumulate thrombus, activate circulating platelets, and generate occlusive platelet microemboli. Grafts were incorporated into femoral arterial-arterial shunts placed unilaterally in 10 baboons; the unoperated contralateral limbs served as controls. The accumulation of indium 111 (111In)-labeled platelets onto the grafts (expanded polytetrafluoroethylene [ePTFE] or knitted Dacron, 4 mm inner diameter) and the appearance of 111In radioactivity in distal microcirculatory beds (calf and foot) were quantified by dynamic scintillation camera imaging. After 1 hour total platelet deposition per graft was higher with Dacron (49.0 +/- 8.0 x 10(9) platelets) than with ePTFE (3.7 +/- 0.6 x 10(9) platelets, p less than 0.01). Platelet counts decreased and beta-thromboglobulin levels increased with Dacron graft placement but were unaffected by ePTFE graft placement (p less than 0.05 and p less than 0.01, respectively). Emboli shed from Dacron grafts were detected as multifocal, irregular, and changing deposits in the calves and feet. Indium 111 platelet activity in the feet distal to the Dacron grafts increased 81.1% +/- 21.4% from baseline values over 1 hour, whereas the activities in the feet distal to the ePTFE grafts were unchanged (p less than 0.05). The increase 111In-platelet radioactivity above the control limb values (excess radioactivity) was higher for the Dacron graft group than for the ePTFE group in both the feet (139.6% +/- 46.9% vs 6.2%, p less than 0.05) and the calves (86.7% +/- 21.7% vs 7.3% +/- 3.6%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Blood platelet kinetics in normal subjects modelled by compartmental analysis

The purpose of this study was to describe the function of platelets throughout their life span by expressing their in vivo distribution and kinetic behaviour in mathematical terms by using multicompartmental analysis. The distribution of indium-111 labelled platelets in five normal subjects was imaged and quantified with a scintillation camera image processing system. Serial blood samples were also obtained. The data were modelled using the SAAM (Simulation Analysis and Modelling) compartmental computer program. Five models were entertained to evaluate the role of platelets that were either functional or injured during collection and their interaction with the liver, spleen and vascular endothelium. Models were evaluated by comparing F values calculated from the least squares estimate obtained from each model. The Dornhorst function was used to describe the sequestration of platelets in the compartmental model. Results indicated that the data could not be satisfactorily simulated when compartments were included that simulated only functional and sequestered platelets (model 1). It was necessary to include compartments that simulated the kinetics of collection-injured plateles in the liver (model 2) and spleen (model 3). The model that simulated the interaction with the vascular endothelium (model 5) showed a visual but not significant improvement in the fitting of the observed data compared to model 3. The mean organ uptake and range indicated in parentheses were calculated at equilibrium. There were 20% (15%–27%) of the injected platelets in the spleen, 10% (8%–11%) in the liver and 70% (64%–75%) in the circulation. The relatively high accumulation of activity in the spleen was as a result of the slow transit time of the functional platelets through the spleen of 5.1 (3.5–6.0) min compared with the transit time through the liver of 0.33 (0.19–0.50) min. The 9% (5%–12%) collection-injured platelets in the spleen and 10% (5%–16%) in the liver had longer transit times than functional platelets. Platelet sequestration was well simulated with the compartmental model. The mean platelet survival time estimated by the compartmental model and standard curve fitting techniques did not differ significantly. A multicompartmental model and reference range for platelet kinetics have been established and may prove to be clinically useful in platelet disease.