Platelet inhibitory drugs: an in vivo method of evaluation in patients.

The measurement of platelet deposition in human thrombi is essential for the evaluation of platelet-inhibitory drugs and prosthetic materials for use in patients. The rate of 111Indium-labelled platelet accumulation on Dacron arterial grafts was measured in 27 patients randomised to take either aspirin and dipyridamole (ASA + DPM) or placebo. Autologous platelets were labelled and re-injected seven days following surgery and the graft thrombogenicity index calculated as the daily rise in the ratio of emissions from the graft over a reference site. The mean (+/- SD) thrombogenicity index in 12 patients undergoing femoro-popliteal bypass was 0.25 +/- 0.09 on placebo and 0.16 +/- 0.07 on ASA + DPM started pre-operatively (p less than 0.05). Post-operative ASA + DPM therapy started two days following platelet labelling in 15 patients with aorto-femoral grafts also significantly reduce thrombogenicity to 0.12 +/- 0.05 compared with 0.25 +/- 0.08 on placebo (p less than 0.01). In the latter patients the ratio of emissions from the graft over reference fell significantly on starting ASA + DPM, suggesting a net loss of platelets from the graft. These results indicate that the rate of in vivo platelet accumulation on Dacron grafts can be quantitated and that ASA + DPM reduced this rate in man.

Platelet accumulation on mature Dacron grafts in man.

Prosthetic graft occlusion is most frequent in the early postoperative period when the luminal surface is highly thrombogenic. It is generally believed that graft maturation ultimately results in a non-thrombogenic surface. The accumulation of 111-indium-labelled autologous platelets in Dacron aortofemoral grafts has been measured 1 week following surgery and at intervals of 6 months to 1 year. Platelets from 9 patients were labelled with 111-indium oxine and re-injected. Isotope emissions over the graft and a reference site (aortic arch) were measured daily for 8 days and gamma camera images taken on alternate days. Graft thrombogenicity was calculated as the daily rise in the graft: reference ratio of emissions. All grafts, regardless of age, accumulated platelets and were imaged by gamma camera. Mean thrombogenicity (+/- s.e.mean) 1 week after surgery was 0.21 +/- 0.04 compared with 0.08 +/- 0.03 at follow-up (P less than 0.01). The platelet survival during the early study was reduced at 6.8 +/- 0.6 days but recovered to a value of 8.6 +/- 0.8 days (P less than 0.01) at follow-up. Further grafts, 2, 5 and 9 years old, were studied and all accumulated platelets, especially near the anastomoses. Platelet accumulation on Dacron grafts does diminish with time but persists beyond the period of altered platelet survival and perhaps indefinitely.

Aspirin and dipyridamole reduce platelet deposition on prosthetic femoro-popliteal grafts in man.

Platelet inhibitory drugs may be used in an attempt to reduce high failure rates in small artery bypass using prosthetic grafts. We evaluated in patients the effects of aspirin and dipyridamole (ASA/DPM) on radiolabelled platelet accumulation on femoro-popliteal grafts of Dacron, polytetrafluorethylene and saphenous vein. Forty-seven patients awaiting femoro-popliteal bypass received, at random and double blind, either ASA/DPM or placebo capsules. On the seventh postoperative day, the 42 remaining patients with patent grafts were injected with autologous 111-Indium labelled platelets. Graft platelet accumulation was expressed as the Thrombogenicity Index (TI), which was defined as the mean daily rise in the ratio of radioactivity over the graft to that over the contralateral thigh. ASA/DPM reduced mean (+/- s.e. mean) TI in Dacron grafts from 0.25 +/- 0.09 on placebo to 0.16 +/- 0.05 (p less than 0.05). Mean TI in polytetrafluorethylene grafts was also significantly lower at 0.06 +/- 0.01 on ASA/DPM compared to 0.16 +/- 0.03 on placebo. Vein grafts, however, accumulated few, if any, labelled platelets and ASA/DPM had no further influence. ASA/DPM reduces platelet accumulation in prosthetic femoro-popliteal grafts in man.

Femoropopliteal bypass grafts--an isotope technique allowing in vivo comparison of thrombogenicity.

Prosthetic femoropopliteal grafts attract platelet thrombus and often occlude in the months following implantation. Hence a technique to measure the in vivo thrombogenicity of different vascular substitutes in patients has been developed. In 28 patients the rate of accumulation of 111-indium-labelled platelets in saphenous vein, polytetrafluoroethylene (PTFE) and double velour Dacron femoropopliteal grafts was studied. One week postoperatively autologous 111In-labelled platelets were injected and the isotope emissions over the graft and contralateral leg counted. Graft thrombogenicity was calculated as the daily rise over 7 days in the ratio of counts over the graft to those over the contralateral leg. Mean thrombogenicity index (+/- s.e.mean) was greatest in the Dacron grafts at 0.24 +/- 0.03 which compared with 0.13 +/- 0.02 in PTFE (P less than 0.05). Saphenous vein was markedly less thrombogenic than either prosthetic graft with a mean index of only 0.025 +/- 0.01 (P less than 0.01). Platelet survival failed to differentiate the three graft materials, demonstrating that the direct measurement of 111In platelet deposition was a more sensitive technique.