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Biomedical subjects

R J Hawker

Publications and source records attributed to R J Hawker.

At least 37 records · Page 2Linked to original sources
PubMed1983

Does 111indium-platelet deposition predict patency in prosthetic arterial grafts?

The relationship between the rate of 111In-platelet deposition on vascular grafts and subsequent thrombosis has been examined in patients undergoing femoropopliteal by-pass. Sixty-seven patients undergoing femoropopliteal by-pass using vein, Dacron or PTFE were randomized to aspirin plus dipyridamole (ASA/DPM) or placebo. Autologous 111In-platelets were injected in the second postoperative week and Thrombogenicity Index (TI) calculated as the mean daily rise in the ratio of radioactivity graft/contralateral thigh. Graft patency was assessed to 1 year. Mean (+s.e.m.) TI at 1 week in 21 grafts that occluded within 12 months was 0.19 +/- 0.018 compared with 0.07 +/- 0.009 in the 38 that remained patient (P less than 0.001). Grafts with a TI less or greater than the median had a 90 per cent or 39 per cent cumulative 1-year patency, respectively (P less than 0.001). In the prosthetic grafts ASA/DPM reduced mean TI from 0.17 +/- 0.02 to 0.11 +/- 0.01 (P less than 0.02) and enhanced 1-year patency from 36 to 67 per cent (P less than 0.05). Following femoropopliteal by-pass TI related to subsequent graft patency. Radiolabelled platelet deposition therefore provides a guide as to how new materials or antithrombotic drugs may influence clinical graft thrombosis. Platelet inhibition reduced both graft thrombogenicity and subsequent occlusion.

Aspirin↗
PubMed1983

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.

Arterial Occlusive Diseases↗
PubMed1983

Dazoxiben examined for platelet inhibitory effect in an artificial circulation.

1 Platelet inhibitory therapy may protect patency in prosthetic arterial grafts. 2 The effect of the thromboxane synthetase inhibitor dazoxiben (UK 37248) on 113Indium-labelled platelet deposition on Dacron arterial grafts was examined in an artificial circulation containing human blood which mimics the haemodynamics of femoropopliteal bypass. The influence of this drug on thromboxane production and platelet reactivity was measured during the experiment. The study was controlled and performed in two parts to assess in vitro and ex vivo drug effect. 3 Both in vitro and ex vivo dazoxiben reduced plasma thromboxane by about 80% and in citrated ex vivo blood increased mean (+/- s.e. mean) platelet aggregation threshold to collagen from control values of 4.8 +/- 1.7 mg/ml to 10.6 +/- 3.3 mg/ml (P less than 0.01). Dazoxiben, however, had no effect on platelet deposition on the arterial grafts. 4 Selective thromboxane inhibition failed to exert an antithrombotic effect in this model.

Adult↗
PubMed1983

Thrombocytosis of active rheumatoid disease.

Two cross-sectional and one longitudinal study of patients with rheumatoid arthritis showed that platelet number correlated with both clinical and laboratory parameters of disease activity, including erythrocyte sedimentation rate, zeta sedimentation ratio, viscosity of plasma and blood, white cell count, liver enzymes, rheumatoid factor, and several acute-phase proteins. There was also an inverse relationship between platelet number and the haemoglobin and serum albumin levels. III Indium-labelled platelet survival was reduced in 4 patients with active rheumatoid arthritis despite a raised platelet count, with labelled platelets being localised to inflamed joints in the 2 patients studied. Platelet aggregation was normal. We suggest that the raised platelet count of active rheumatoid arthritis may be a useful index of disease activity and may represent a bone marrow stress (syndrome) response to shortened platelet survival, with platelet sequestration occurring in areas of synovial inflammation.

Arthritis, Rheumatoid↗
PubMed1983

Indium-labeled platelet uptake in rejecting renal transplants.

The uptake of 111In autologous platelets in transplanted kidneys was measured in 16 patients shortly after operation. Each patient was then observed for two years. When transplant radioactivity had increased, despite treatment for acute rejection, the kidney was ultimately lost because of rejection.

Adult↗
PubMed1982

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.

Aorta, Abdominal↗
PubMed1982

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.

Arterial Occlusive Diseases↗
PubMed1982

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.

Aorta, Thoracic↗
PubMed1982

Dacron arterial grafts: the influence of porosity, velour, and maturity on thrombogenicity.

It has been claimed that the neointimal healing of Dacron arterial prostheses can be enhanced by increasing porosity and including both an internal and an external velour layer. To test this, 24 patients received at random either woven (USCI, DeBakey, C. R. Bard, Inc.) or more porous, double-velour, knitted (Microvel, Meadox Medicals, Inc.) Dacron aortobifemoral prostheses. Graft thrombogenicity was measured using autogenous 111In-labeled platelets shortly following surgery and 6 to 9 months later. The thrombogenicity index was defined as the mean daily rise in the ratio of emissions over the graft to emissions over a reference area (aortic arch) and is a measure of platelet deposition. At early study the mean (+/- SE) thrombogenicity index was similar in woven and knitted graft patients at 0.19 +/- 0.4 and 0.14 +/- 0.2, respectively. In both groups it was lower (P less than 0.05) 6 to 9 months later at 0.06 +/- 0.2 (woven( and 0.08 +/- 0.1 (knitted), with again no difference between materials. Although platelet survival was restored to near normal values in both groups by 6 to 9 months, only one woven graft failed to demonstrate continued platelet accumulation by gamma-imaging. Thrombogenicity in Dacron grafts diminishes in the early months of maturation but is not affected by porosity and velour. Moreover, this thrombogenicity persists beyond the period of altered platelet survival.

Aorta, Abdominal↗
PubMed1981

Imaging of 111In-labelled platelets--a new method for the diagnosis of deep vein thrombosis.

A radionuclide method for detecting established thrombi at all sites in the lower limb would have several advantages. Autologous platelets were labelled with 150 microCi (5.5 MBq) indium-111-oxine and re-injected into patients who were imaged with a gamma camera and data processed by a medical computer. Areas of increased uptake on imaging were correlated with the sites of thrombi identified by bilateral ascending venography. Venography in 27 patients identified 12 unilateral and 5 bilateral thrombi. On the day following the re-injection of labelled platelets, imaging identified thrombi at 13 sites in 24 limbs giving an overall correlation with venography of 84.4 per cent, correlation for the calf and thigh being 79.5 per cent and 89.1 per cent respectively. In the thigh 57.1 per cent of thrombi were identified by imaging and 52.9 per cent in the calf. Activity over thrombi was at least 20 per cent higher than in adjacent areas or at similar sites in the contralateral leg. Herapin therapy is considered to affect the detection of deep vein thrombus adversely by this technique. The technique offers a useful method for the diagnosis of both early and established thrombi at any site in the lower limb.

Blood Platelets↗
PubMed1980

A microcytotoxicity assay using 111indium oxine release from platelets.

A simple, rapid method is described for the labelling of platelets with 111indium oxine for use in a microcytotoxicity assay. The assay described gives low levels of spontaneous lysis, good reproducibility and an end point may be determined by autoradiography as well as by direct measurement of release of 111indium. The labelled platelets, stored at 4 degrees C without further washing, may be used in the assay system for up to 4 days after preparation without loss of reproducibility.

Antibodies↗
PubMed1980

Indium (111In)-labelled human platelets: optimal method.

1. A detailed laboratory method is described for the labelling of human platelets with [111In]indium oxine. The 45 min method is simple, requires on 26 ml of blood and is suitable for routine clinical use. 2. After the labelling and resuspension of the platelets in plasma, aggregation responses to both adenosine diphosphate and collagen were similar to those of normal platelet-rich plasma. Less than 5% of the [111In]indium oxine was released by secretory function of platelets. 3. Labelling efficiencies of 90.1 +/- 4.29% (n = 28) were achieved in 60 s by normal concentrations of plasma-free platelet suspensions. 4. Platelet survival in vivo in healthy volunteer subjects follows a linear function with a survival time of 8.44 +/- 0.18 days.

Blood Platelets↗