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Biomedical subjects

P Coste

Publications and source records attributed to P Coste.

At least 19 recordsLinked to original sources
PubMed2006

[Direct thrombin inhibitors in coronary angioplasty. Value of bivalirudin ].

During coronary angioplasty, the association of platelet inhibitors and antithrombin agents is required to prevent myocardial infarction. Bivalirudine, a synthetic direct thrombin inhibitor, has been widely validated in this context and has shown its efficacy and safety in several comparative studies. It is officially recommended as a replacement of NFH and LMWH associated or not with anti-GPIIb/IIIa agents because at comparable efficacy it causes fewer bleeding complications. In acute coronary syndromes without ST elevation, anti GPIIb/IIIa agents reduce angioplasty-related complications and mortality, especially in high risk patients in salvage situations. In the REPLACE-2 trial the clinical efficacy of bivalirudine (associated only when necessary with anti-GPIIb/IIIa agents) was no less than that of NFH associated systematically with anti-GPIIb/IIIa agents at the time of intervention. The incidents of serious adverse events at 30 days (death, infarctus, emergency revascularisation, major bleeding) in the bivalirudine group was 9.2% versus 10.2% in the NFH group. In a retrospective analysis, these results did not seem to be influenced by the prior administration of clopidogrel. Finally, the one year follow-up results showed a lower mortality in patients treated with bivalirudine (1.9% versus 2.5%), essentially in the high risk sub-groups such as the elderly, the diabetic or the renal failure patients. Clinical trials are underway (ACUITY) to study the interaction of anti GPIIb/IIIa agents with bivalirudine in the first hours of acute coronary syndromes and should confirm a major role of direct anti-thrombin drugs in the safety of angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed2005

[Isotretinoin: compliance with recommendations in childbearing women].

INTRODUCTION: The aim of this survey is to ascertain if the incidence of isotretinoin exposed pregnancies was reduced by the late recommendations of prescription and issue (AMM modification on 06/08/2001 and 25/09/2001). METHODS: All isotretinoin exposed pregnancies registered by the French Regional Drug Monitoring Centres, the Information Centre for Teratogenic Agents and Roche (Roaccutane), Pierre Fabre (Curacné Gé) and Expanscience (Procuta Gé) laboratories, from January 1st, 1999 to December 31st, 2002, were analysed. Enforcement of the strengthening of isotretinoin prescription recommendations was analysed on a sample of 68 prescriptions from 45 pharmacies throughout France. RESULTS: In 4 years, 103 isotretinoin exposed pregnancies (Roaccutane 97 p. 100, Curacné(R) Gé 3 p. 100) during teratogenic risk period, were registered. Pregnancy started less than one month after isotretinoin stopping (37 p. 100), during the treatment (43 p. 100), or was in progress when the treatment was initiated (20 p. 100). The reason of the 22 lacking contraception was known 12 times, i.e. an absence of prescription (6 times), a refusal to take a prescribed contraception (3 times) and a self-medication (3 times). Among the 71 pregnancies whose contraceptive status is known, 48 p. 100 could had been avoided if recommendations had been followed (pregnancies due to a premature stopping or an absence of contraception). The issue of pregnancies is a voluntary termination in 60 cases (87 p. 100). Malformations frequency is 25 p. 100. Incidence of isotretinoin exposed pregnancies remained stable, 0.26/1000 treated women (vs 0.34 after 2001's AMM modifications). Of 68 prescriptions studied, 23 (24 p. 100) carried all the legal warnings, which is close to the previous survey's results. Contraception was in accordance with the recommendations in 78 p. 100 of cases and women learned and applied information given in 38 p. 100 of cases. At last, only 6 patients (9 p. 100) have both a correctly written prescription, a contraception and a time between the pregnancy test date and prescription and issue dates, in accordance with the licence and have had a correct information and understood it. Regarding the previous survey, pregnancy test before treatment was more often prescribed (96 p. 100 vs 88 p. 100). On the other hand, less women knew the necessity to keep on taking contraception one month after isotretinoin stopping (82 p. 100 vs 93 p. 100). CONCLUSION: Despite 3 successive isotretinoin prescription and issue recommendations strengthening in childbearing women, pregnancies can't be totally avoided. Bad compliance concerns the prescription and/or an incomplete or not understood information by the patient who does not scrupulously apply the care and contraception agreement. However, this study does not allow to assess the proportion of issued prescriptions despite their non-accordance with the licence criteria. The National Commission of Pharmacovigilance did not like to limit isotretinoin prescription to dermatologists only. It estimates that the administrative authority must intensify information by dermatologists, general practitioners and pharmacists, about measures to take to avoid an exposure to isotretinoin during pregnancy.

Abnormalities, Drug-Induced↗
PubMed2005

Primary osteoarthritis of hip, knee, and hand in relation to occupational exposure.

AIM: To identify occupations with excess prevalence of osteoarthritis of the knee, hip, and hand in a nationwide survey and to compare occupations with and without excess prevalence with regard to biomechanical stresses and severity of osteoarthritis. METHODS: Patients presenting with osteoarthritis of the knee, hip, or hand were recruited throughout France by their treating physician who collected information on history, including age at onset, occupation, and occupational stresses to joints. Severity was assessed using joint specific functional status questionnaires: Lequesne for the hip and knee and Dreiser for the hand. The distribution of osteoarthritis patients by occupation was compared with the distribution of occupations in all workers in France to obtain prevalence rate ratios. RESULTS: Occupations with the greatest prevalence rate ratio were female cleaners (6.2; 95% CI 4.6 to 8.0), women in the clothing industry (5.0; 95% CI 3.9 to 6.3), male masons and other construction workers (2.9; 95% CI 2.6 to 3.3), and agriculture male and female workers (2.8; 95% CI 2.5 to 3.2). A twofold greater prevalence rate was observed within certain occupations between self-employed and salaried workers. Early onset of osteoarthritis was seen in the more heavy labour jobs with almost 40% of patients reporting their first symptoms before the age of 50. CONCLUSION: The early onset and severity of osteoarthritis in certain occupations warrants an urgent need for occupation specific studies for the development and evaluation of preventive strategies in this leading cause of disability in Western countries.

Adult↗
PubMed2003

Primary osteoarthritis and occupations: a national cross sectional survey of 10 412 symptomatic patients.

AIMS: To describe the age standardised prevalence of symptomatic osteoarthritis (OA) in a nationwide cross sectional survey of 10 412 patients in France, and their functional and work limitations. METHODS: Cases in the survey were compared with their expected counterpart by age, gender, and occupational groupings using data from the 1998 French National Survey on Health Impairment and Disability. RESULTS: Women represented 66.2% of the sample; mean age was 66.2 years. One third of patients had OA of the knee, 16% of the hip, and 12% of the hand; a third had multiple joint OA. Peak prevalence of symptomatic OA was in the 60-69 year category in women and in the 70-79 year category in men. Agricultural workers showed a significant excess prevalence of OA, with an observed to expected (O/E) ratio of 1.7 in women and 2.3 in men. Linear trends in prevalences between white collar, "mixed" collar, and blue collar workers were also significant, with odds ratios respectively of 1.0, 2.9, and 2.6 in women and 1.0, 1.2, and 1.7 in men. Specific excess prevalence was found in women among housekeepers (O/E 4.4), and in men among unskilled labour workers (O/E 10.3) and truck drivers (O/E 6.7). Total work disability was highest among blue collar workers and partial disability among agricultural workers. CONCLUSION: Results contribute to the mounting evidence that OA is potentially aetiologically linked to occupation in a sizeable segment of the population and that OA can no longer be considered an inevitable disease of ageing.

Adult↗
PubMed2002

Surgery for post infarction ventricular septal defect (VSD): risk factors for hospital death and long term results.

OBJECTIVE: Repair of post infarction ventricular septal defect (VSD) is still a challenging procedure with a high risk of recurrence of the VSD and subsequent mortality. The aim of this retrospective study was to assess if technical change in the surgical procedure was followed by an improvement in recurrence of the VSD and operative results. METHOD: This retrospective study from 1971 to 2001 included 85 patients operated on early (<15 days) after the occurrence of a post infarction VSD. Double patch technique was introduced in 1986. A total of 44 variables were studied by a uni- and multivariate analysis. RESULTS: Hospital death occurred in 36 patients. Significant factors for hospital mortality included: preoperative and evolution of the clinical status, right ventricular function and type of repair (one or two patches). Moreover, no recurrence was observed in patients repaired with the double patch technique (P=0.09). None of the studied variables were significant for long term survival. Concomitant CABG was not associated with higher hospital mortality and long-term survival rate was similar in patients with or without concomitant CABG. CONCLUSION: The use of the double patch technique and glue by avoiding recurrence of the VSD played a role in the reduction of the hospital mortality. This technique has to be recommended in the early repair of post infarction VSD. Concomitant CABG can be done safely to control the added risk of an associated coronary artery lesion.

Aged↗
PubMed2002

[Fibrinolysis and thrombosis of mechanical valvular prosthesis: risk stratification by transesophageal echocardiography].

The place of fibrinolysis in the treatment of mechanical valvular prostheses is still much discussed. The aim of this work is to define the role of transoesophageal echocardiography in risk stratification. This monocentric study draws on 49 cases of thrombolysis preceded by transoesophageal echocardiography (average age 62.1 years, 37 mitral, 11 aortic, 1 tricuspid, 1 mitro-tricuspid). There were 41 obstructive thromboses (OT) and 8 non-obstructive thromboses (NOT). Clinical events and the effectiveness of fibrinolysis were studied as a function of the obstructive or non-obstructive character of the thrombosis and the size of the thrombus < 10 mm (n = 33) or > or = 10 mm (n = 16). Complete success was observed in 34 patients (69.4%). Follow up revealed 2 early cerebral haemorrhages (4.1%) of which one was in the NOT group, and six systemic emboli (12.2%) of which one was in the NOT group. There was a relationship between the size of the thrombus and embolus at the limit of significance in favour of an increased risk of embolus for a voluminous thrombus. Furthermore, the mobility of the thrombi went in hand with an increased rate of systemic emboli (p < 0.01). The rate of failure of fibrinolysis and/or complications correlated with the size of thrombus (complete success in 88% of the < 10 mm thrombus group, versus 35% in the > or = 10 mm; p < 0.01). This work underlines the significance of trans-oesophageal echocardiography in the therapeutic choice for valvular prosthesis thrombosis and suggests that the existence of a voluminous thrombus especially if mobile is a contra-indication for fibrinolysis.

Adult↗
PubMed2001

Stent placement compared with balloon angioplasty for small coronary arteries: in-hospital and 6-month clinical and angiographic results.

BACKGROUND: Stenting has been demonstrated to be superior to balloon angioplasty in de novo focal lesions located in large native vessels. However, in small vessels, the benefit of stenting remains questionable. METHODS AND RESULTS: A total of 381 symptomatic patients with de novo focal lesion located on a small coronary segment vessel (<3 mm) were randomly assigned to either stent implantation (192 patients; 197 lesions) or standard balloon angioplasty (189 patients; 198 lesions). The primary end point was the angiographic restenosis rate at 6 months, as determined by quantitative coronary angiography. On intention-to-treat analysis, angiographic success rate and major adverse cardiac events were comparable: 97.9% and 4.6% versus 93.9% and 5.8% in the stent group and the balloon group, respectively. After the procedure, a larger acute gain was achieved with stent placement (1.35+/-0.45 versus 0.94+/-0.47 mm, P=0.0001), resulting in a larger minimal lumen diameter (2.06+/-0.42 versus 1.70+/-0.46 mm, P=0.0001). At follow-up (obtained in 91% of patients), angiographic restenosis rate was 21% in the stent group versus 47% in the balloon group (P=0.0001), a risk reduction of 55%. Repeat target lesion revascularization was less frequent in the stent group (13% versus 25%, P=0.0006). CONCLUSIONS: Elective stent placement in small coronary arteries with focal de novo lesions is safe and associated with a marked reduction in restenosis rate and subsequent target lesion revascularization rate at 6 months.

Angioplasty, Balloon, Coronary↗
PubMed2001

[Fibrinolysis in myocardial infarction with EKG elevation. Optimization of myocardial reperfusion by treatment with antithrombotic agents].

In the case of acute coronary syndrome with prolonged ST elevation on ECG showing an acute coronary obstruction, the urgent institution of fibrinolysis is a widely validated treatment. Since the first placebo controlled studies with streptokinase until the development of bolus administration rt-PA varieties, fibrinolytic agents have lowered mortality. Associated anti-thrombotic drugs are multiplying in parallel. Their association is recognised as necessary in order to avoid early reocclusions which worsen the prognosis of infarction, the fibrinolysis triggering a harmful prothrombotic effect, notably due to the clot thrombin re-exposed during thrombolysis. Aspirin has an essential place formally demonstrated in ISIS 2. Non-fractionated heparin has more complex effects and its administration protocol in association with fibrinolysis has recently been reviewed with a reduction in dosage because prolonged clotting times during fibrinolysis have provoked a distinct increase in the risk of intracranial haemorrhage. The low molecular weight heparins seem to have become the adjuvant treatment of choice following publication of the ASSENT-3 trial. Pentasaccharide seems attractive. The place of hirudine and its derivatives in the acute phase of MI appear limited after the results of the HERO-2 trial, associating hirulog and streptokinase, with the earlier studies also having been disappointing. The GPIIbIIIa blockers in association with a half dose of fibrinolysis do not aggravate the intracerebral haemorrhagic risk before 75 years old and clearly reduce hospital morbidity in infarction, at the price however of an increase in transfusions.

Aspirin↗
PubMed2001

[Anticoagulation in mechanical valve prostheses. A difficult situation].

Although long-term anticoagulant therapy in patients with mechanical valve prostheses is well codified, a number of difficult situations persists because of the high thromboembolic risk. The protocols of anticoagulation suggested in these situations are controversial as there are no large scale prospective therapeutic trials. However, modern protocols take more and more into account the thromboembolic risk in each individual case. The authors review the most common situations: the early postoperative period for which no precise consensus exists in the literature; anticoagulation in extra-cardiac surgery, a common situation for which the protocols remain very debatable; anticoagulation in pregnancy, a special situation because of the risk of embryopathy with oral anticoagulant therapy and the risk of thromboembolism with heparin; anticoagulation in cases of thromboembolic complications; anticoagulation during infectious endocarditis; anticoagulation during serious haemorrhage.

Anticoagulants↗
PubMed2000

Carvedilol for prevention of restenosis after directional coronary atherectomy : final results of the European carvedilol atherectomy restenosis (EUROCARE) trial.

BACKGROUND: In addition to its known properties as a competitive, nonselective beta and alpha-1 receptor blocker, carvedilol directly inhibits vascular myocyte migration and proliferation and exerts antioxidant effects that are considerably greater than those of vitamin E or probucol. This provides the basis for an evaluation of carvedilol for the prevention of coronary restenosis. METHODS AND RESULTS: In a prospective, double-blind, randomized, placebo-controlled trial, 25 mg of carvedilol was given twice daily, starting 24 hours before scheduled directional coronary atherectomy and continuing for 5 months after a successful procedure. The primary end point was the minimal luminal diameter as determined during follow-up angiography 26+/-2 weeks after the procedure. Of 406 randomized patients, 377 underwent attempted atherectomy, and in 324 (88.9%), a </=50% diameter stenosis was achieved without the use of a stent. Evaluable follow-up angiography was available in 292 eligible patients (90%). No differences in minimal luminal diameter (1.99+/-0.73 mm versus 2.00+/-0.74 mm), angiographic restenosis rate (23.4% versus 23.9%), target lesion revascularization (16.2 versus 14.5), or event-free survival (79.2% versus 79.7%) between the placebo and carvedilol groups were observed at 7 months. CONCLUSIONS: The maximum recommended daily dose of the antioxidant and beta-blocker carvedilol failed to reduce restenosis after successful atherectomy. These findings are in contrast to those of the Multivitamins and Probucol Trial, which raises doubts regarding the validity of the interpretation that restenosis reduction by probucol was via antioxidant effects. The relationship between antioxidant agents and restenosis remains to be elucidated.

Adrenergic Antagonists↗
PubMed2000

A comparison of systematic stenting and conventional balloon angioplasty during primary percutaneous transluminal coronary angioplasty for acute myocardial infarction. STENTIM-2 Investigators.

OBJECTIVES: In a multicenter, randomized trial, systematic stenting using the Wiktor stent was compared to conventional balloon angioplasty with provisional stenting for the treatment of acute myocardial infarction (AMI). BACKGROUND: Primary angioplasty in AMI is limited by in-hospital recurrent ischemia and a high restenosis rate. METHODS: A total of 211 patients with AMI <12 h from symptom onset, with an occluded native coronary artery, were randomly assigned to systematic stenting (n = 101) or balloon angioplasty (n = 110). The primary end point was the binary six-month restenosis rate determined by core laboratory quantitative angiographic analysis. RESULTS: Angiographic success (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3 and residual diameter stenosis <50%) was achieved in 86% of the patients in the stent group and in 82.7% of those in the balloon angioplasty group (p = 0.5). Compared with the 3% cross-over in the stent group, cross-over to stenting was required in 36.4% of patients in the balloon angioplasty group (p = 0.0001). Six-month binary restenosis (> or = 50% residual stenosis) rates were 25.3% in the stent group and 39.6% in the balloon angioplasty group (p = 0.04). At six months, the event-free survival rates were 81.2% in the stent group and 72.7% in the balloon angioplasty group (p = 0.14), and the repeat revascularization rates were 16.8% and 26.4%, respectively (p = 0.1). At one year, the event-free survival rates were 80.2% in the stent group and 71.8% in the balloon angioplasty group (p = 0.16), and the repeat revascularization rates were 17.8% and 28.2%, respectively (p = 0.1). CONCLUSIONS: In the setting of primary angioplasty for AMI, as compared with a strategy of conventional balloon angioplasty, systematic stenting using the Wiktor stent results in lower rates of angiographic restenosis.

Angioplasty, Balloon↗
PubMed2000

The French Randomized Optimal Stenting Trial: a prospective evaluation of provisional stenting guided by coronary velocity reserve and quantitative coronary angiography. F.R.O.S.T. Study Group.

OBJECTIVES: We sought to make a prospective comparison of systematic stenting with provisional stenting guided by Doppler measurements of coronary velocity reserve and quantitative coronary angiography. BACKGROUND: Despite the increasing use of stents during percutaneous transluminal coronary angioplasty, it is unclear whether systematic stenting is superior to a strategy of provisional stenting in which stents are placed only in patients with unsatisfactory results or as a bail-out procedure. METHODS: Two hundred fifty-one patients undergoing elective coronary angioplasty were randomly assigned either to provisional stenting (group 1, in which stenting was performed if postangioplasty coronary velocity reserve was <2.2 and/or residual stenosis > or =35% or as bail-out) or to systematic stenting (group 2). The primary end point was the six-month angiographic minimal lumen diameter (MLD). Major adverse cardiac events were secondary end points (death, acute myocardial infarction and target lesion revascularization). RESULTS: Stenting was performed in 48.4% of patients in group 1 and 100% of patients in group 2 (p<0.01). Six months after angioplasty, the MLD did not differ between groups (1.90+/-0.79 mm vs. 1.99+/-0.70 mm, p = 0.39), as was the rate of binary restenosis (27.1% vs. 21.4%, p = 0.37). Among patients with restenosis, 13/32 (40.6%) in group 1 but 100% (25/25) in group 2 had in-stent restenosis (p<0.01). Target lesion revascularization (15.1% vs. 14.4% in groups 1 and 2 respectively, p = 0.89) and major adverse cardiac events (15.1% vs. 16.0%, p = 0.85) were not significantly different. CONCLUSIONS: Systematic stenting does not provide superior angiographic results at six months as compared with provisional stenting.

Aged↗
PubMed2000

[Hematoma of the aortic wall: from diagnosis to treatment].

Haematoma of the thoracic aortic wall is a relatively new concept, the physiopathology of which remains controversial. It results from an haemorrhage of the aortic wall due to rupture of the vasa-vasorum without communication with the arterial lumen. This is a diagnosis of elimination of dissection of the aorta which has been made possible by modern techniques of imaging, such as transoesophageal echocardiography, helicoidal scanner and magnetic nuclear resonance imaging. The prognosis of haematoma of the aortic wall is not as bad as that of dissection of the aorta. Recent studies have shown that the condition may stabilise, regress or progress towards complications of two types: early, dissection or fissuration of the aorta, and late, aortic aneurysm. This is a medico-surgical emergency, the treatment of which is not well codified. However, schematically, haematoma of the aortic wall should be managed in the same way as dissection of the aorta: surgery when the ascending aorta is affected, medical treatment in other cases in the absence of complications.

Aortic Dissection↗
PubMed2000

[Treatment of left atrial thrombosis by low-molecular-weight heparin. A preliminary study of 6 cases].

Left atrial thrombosis is a serious complication of atrial fibrillation because of its embolic potential, especially for the cerebral circulation. These thrombi are usually treated by oral anticoagulation. The authors studied the efficacy and tolerance of a low molecular weight heparin. Enoxaparin, in the treatment of this condition. This was a prospective study carried out over a 1 year period. Patient recruitment came from the transoesophageal echocardiography laboratory: of 15 thrombi detected, 6 were treated by ambulatory Enoxaparin therapy. Five of the 6 patients had no signs of left atrial thrombosis after 3 weeks of Enoxaparin therapy. The left atrial thrombus of the 6th patient remained hyperechogenic and had decreased in length from 27 to 24 mm. No cases of bleeding, haematoma, embolism or thrombopenia were observed with this treatment. This preliminary study shows that low molecular weight heparin may be used as an alternative to classical oral anticoagulation for the treatment of left atrial thrombosis.

Aged↗
PubMed1999

Emergency coronary artery bypass surgery following coronary angioplasty and stenting: results of a French multicenter registry.

This study investigates the influence of coronary stenting on the risk of emergency bypass surgery performed within 24 hr of percutaneous transluminal coronary angioplasty (PTCA) with particular concern for incidence and indication. Since 1995, coronary stenting has been increasingly performed in France during angioplasty procedures, altering significantly the role of emergency bypass surgery. The outcome of elective stenting and widespread use of coronary stenting and its influence on emergency surgery have not been evaluated so far. Through a retrospective (1995) and prospective (1996) registry, we analyzed the incidence, indication and results of emergency bypass surgery performed within 24 hr of PTCA in 68 and 57 centers, respectively, accounting for nearly half of all angioplasty procedures in France. Data were collected through questionnaires consisting of separate forms for every case report that were sent to every center. Over the two years, 26,885 and 27,497 procedures were investigated with a stenting rate of 46% and 64%, respectively. The observed need for emergency surgery was constantly low throughout this period (0.38% and 0.32%, respectively). Indications for surgery included complications directly due to stent in 37% of cases in the 2-year period. Outcome remained poor, with in-hospital mortality in 10% and 17% and myocardial infarction in 27% and 25% of cases, respectively. A comparison of the results in centers with and without surgical facilities showed no differences in outcome, despite a longer time to surgery (359 min +/- 406 min vs. 170 min +/- 205 min, P = 0.0001) and a lower incidence of emergency surgery (0.25% vs. 0.44%, P = 0.0001) in centers without on-site surgery backup. The French multicenter registry reveals an increase in the use of stents together with a dramatic decrease in the incidence of emergency bypass surgery (below 0.5%) following PTCA. There has been a significant evolution in the indication, and stent implantation now accounts for a third of the indications for emergency bypass surgery.

Angioplasty, Balloon, Coronary↗
PubMed1999

Successful radiofrequency ablation of a slow atrioventricular nodal pathway on the left posterior atrial septum.

RF catheter ablation is highly effective in eliminating atrioventricular nodal reentrant tachycardia by targeting the slow pathway in the posteroinferior part of Koch's triangle in the right atrium. We report here a patient in whom "slow-fast" atrioventricular nodal reentrant tachycardia was eliminated only by ablation of the slow pathway in the left atrial posteroseptal region at the level of the mitral annulus after unsuccessful attempts at the traditional site on the right side.

Adult↗
PubMed1999

Expression of markers of platelet activation and the interpatient variation in response to abciximab.

Our study concerns the biological effects of abciximab (c7E3 Fab, ReoPro), a powerful new antiplatelet drug that blocks glycoprotein (GP) IIb-IIIa complexes. Samples were examined from 6 patients with coronary artery disease who received a bolus of abciximab followed by a 10- microg/min infusion for at least 18 hours before percutaneous transluminal coronary angioplasty. Inhibition of ADP-induced PA was maximal for 4 patients but partial (79% and 53%) for 2 others during the infusion. Flow cytometry performed with monoclonal antibodies (PAC-1, AP-6, and F26) specific for the "activated" GP IIb-IIIa complex revealed large decreases in the expression of activation markers on platelets during therapy, but these decreases were less marked when inhibition of ADP-induced PA was incomplete. Residual aggregation was seen for all patients during the infusion when TRAP 14-mer peptide or thrombin was the stimulus. Unblocked GP IIb-IIIa complexes were detected on thrombin-stimulated platelets from the patients by immunoelectron microscopy performed using the monoclonal antibody AP-2. Unblocked GP IIb-IIIa complexes were also detected by flow cytometry when platelets preincubated for 1 hour in vitro with abciximab under saturating conditions were (1) incubated with TRAP 14-mer or (2) permeabilized with Triton X-100. In confirming interpatient variation in the platelet response to a standard dose of abciximab, our results also show that an uninhibited internal pool of GP IIb-IIIa complexes may mediate a residual response to strong agonists.

Abciximab↗