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Biomedical subjects

M Madan

Publications and source records attributed to M Madan.

At least 19 recordsLinked to original sources

Severe thrombocytopenia possibly related to readministration of eptifibatide.

Thrombocytopenia following eptifibatide therapy is a rare event, and acute severe thrombocytopenia following readministration has not been reported. We describe a case of acute severe thrombocytopenia following reexposure to eptifibatide during percutaneous coronary intervention. We continue to monitor platelet counts at 2-4 hr and 16-24 hr following administration of any glycoprotein IIb/IIIa inhibitor. Cathet Cardiovasc Intervent 2001;54:63-67.

Adult↗

Rapid assessment of glycoprotein IIb/IIIa blockade with the platelet function analyzer (PFA-100) during percutaneous coronary intervention.

BACKGROUND: The platelet function analyzer PFA-100 (Dade Behring, Miami, Fla) evaluates platelet function by determining the time to occlusion of an aperture in a membrane coated with collagen and adenosine diphosphate or epinephrine as whole blood flows under shear stress conditions. Platelet aggregation causes aperture occlusion, and results are reported as closure time (CT). Interindividual variability is observed in the level of platelet inhibition achieved with use of the current abciximab dosing regimen (0.25-mg/kg bolus + 10-microg/min infusion for 12 hours). The relationships between specific levels of platelet inhibition and clinical efficacy and safety have not been fully established. METHODS AND RESULTS: We prospectively studied platelet function in 27 patients receiving abciximab during percutaneous coronary intervention. This evaluation included determinations of platelet-rich plasma aggregometry, receptor occupancy studies (D3 assay), and CT measurements at baseline and 10 minutes, 4 hours, 12 hours, and 24 hours after the bolus. All patients received abciximab, aspirin, and heparin; patients undergoing coronary stent implantation received aspirin and ticlopidine after the procedure. CT results were reported within 10 minutes after initiation of testing. For 96% of patients, CT was 300 seconds (maximum CT) immediately after abciximab bolus and remained so throughout the infusion. At 24 hours we observed variable recovery from platelet inhibition and in 72% of patients CT returned to normal (< or =130 seconds). CONCLUSIONS: Findings with the PFA-100 were similar to results observed with platelet aggregometry and receptor occupancy measurements. Most patients treated with abciximab exhibit normalized platelet function at 24 hours despite moderate levels of receptor occupancy, suggesting dissociation between occupancy and function.

Abciximab↗

Efficacy of abciximab readministration in coronary intervention.

Abciximab, an Fab monoclonal antibody fragment that blocks the platelet glycoprotein IIb/IIIa receptor, is increasingly used as an adjunct to coronary intervention. Little is known, however, about the efficacy and safety of readministration of abciximab. This study examined and characterized outcomes of patients receiving abciximab for a second time. From April 1995 to June 1997, 164 consecutive patients were readministered abciximab at our 3 institutions. We retrospectively examined and analyzed in-hospital outcomes in this cohort. The median time to readministration was 95 days. The angiographic success rate of percutaneous intervention was 99.5%. Rates and 95% confidence intervals of in-hospital events were death 2% (0.7% to 6.1%), myocardial infarction 3% (1% to 7%), coronary bypass surgery 0% (0% to 2.2%), and intracranial hemorrhage 2% (0.4% to 5.3%). Severe thrombocytopenia was observed in 4% of patients (1.4% to 7.8%) after readministration. Allergic or anaphylactic reactions were not observed. Major bleeding was associated with excessive concomitant antithrombotic therapy. Patients undergoing readministration of abciximab within 2 weeks of first administration experienced a higher incidence of severe thrombocytopenia (12% vs. 2%, p = 0.046). Thus, abciximab remains clinically efficacious when readministered as an adjunct to percutaneous coronary intervention. However, concomitant heparin administration must be carefully monitored and warfarin therapy should be avoided. Vigilant surveillance for thrombocytopenia should be employed. Reduced dosing may be necessary when abciximab is readministered within days of the initial administration.

Abciximab↗

Design and methodology of the ESPRIT trial: evaluating a novel dosing regimen of eptifibatide in percutaneous coronary intervention.

BACKGROUND: Clinical trials of the glycoprotein (GP) IIb/IIIa inhibitors have shown that these potent antiplatelet agents are effective in reducing the ischemic complications of percutaneous coronary interventions. However, even though stents are now implanted in >75% of percutaneous interventional procedures, only one study, a trial of the monoclonal antibody abciximab, has formally evaluated adjunctive GP IIb/IIIa inhibition in this setting. METHODS AND RESULTS: Eptifibatide, a nonimmunogenic and rapidly reversible inhibitor of the platelet receptor integrin IIb/IIIa, has also undergone evaluation as an adjunct to coronary intervention. In clinical trials performed heretofore, however, it has appeared to have less relative clinical efficacy than the monoclonal antibody abciximab. Since the early seminal trials, it has been recognized that the doses of eptifibatide previously used achieved only 30% to 50% of maximal platelet GP IIb/IIIa integrin inhibition. This is considerably less than the 80% level of receptor inhibition that has been proposed to prevent coronary thrombus formation in animal models and that has been achieved in clinical trials with abciximab. CONCLUSIONS: The Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trial was designed to test the safety and efficacy of a high-dose, "180/2.0/180" double-bolus regimen of eptifibatide (a 180-microg/kg bolus followed 10 minutes later by a second 180-microg/kg bolus of eptifibatide combined with a 2.0-microg/kg per minute infusion) as an adjunct to nonacute percutaneous coronary intervention with stent implantation. In this report, we review the rationale, design, and methods of this clinical investigation.

Angioplasty, Balloon, Coronary↗

Update on Abciximab Readministration During Percutaneous Coronary Interventions.

Abciximab is a monoclonal antibody fragment that blocks the platelet glycoprotein IIb/IIIa receptor and is increasingly used as an adjunct to percutaneous coronary intervention. Because some patients will return for additional revascularization procedures, it is anticipated that abciximab retreatment may be necessary. There exists at least the theoretic potential for immunologic reactions and diminished efficacy upon re-exposure to abciximab. The limited data available regarding abciximab retreatment suggests that readministration is as safe and effective as first-time treatment, provided certain precautions are taken. This review summarizes the available clinical data and provides suggestions for safe abciximab readministration.

Journal Article↗

Hepatobiliary cystadenoma presenting with intermittent inferior vena caval obstruction.

Hepatobiliary cystadenomas are rare benign tumours. They form as multilocular cysts in and around the liver. Their presentation is usually at a late stage when their size causes symptoms. We report a case of a 44-year-old woman presenting with abdominal pain, which was attributed to a multiloculate liver cyst. After intially refusing surgery she relented once intermittent inferior vena caval obstruction had developed. The cyst was found to be a hepatic cystadenoma.

Adult↗

Understanding thrombocytopenia and antigenicity with glycoprotein IIb-IIIa inhibitors.

Platelet glycoprotein (GP) IIb-IIIa receptor antagonists are being used with increasing frequency in the settings of percutaneous coronary interventions and acute ischemic syndromes. The development of thrombocytopenia after GP IIb-IIIa blockade has been observed to some extent with all parenteral GP IIb-IIIa inhibitors studied to date and could potentially limit their effectiveness. The incidence and severity of thrombocytopenia has varied in large clinical trials with GP IIb-IIIa inhibitors, presumably as a consequence of the different structural and pharmacokinetic characteristics of the agents, the dose administered and duration of use, repetition of exposure, and the various drugs coadministered with these agents. Certain baseline characteristics may be predictive. In most cases, severe thrombocytopenia associated with the use of GP IIb-IIIa receptor antagonists was readily reversible with platelet transfusion and was not usually associated with major clinical sequelae. Although the exact mechanisms responsible for thrombocytopenia after GP IIb-IIIa blockade are poorly understood, an immune mechanism is suggested in which the binding of the antagonist to GP IIb-IIIa receptors leads to the exposure of ligand-induced binding sites recognized by preexisting or induced antibodies. Alternatively, the receptor-drug metabolite complex itself may induce an immune response. All patients receiving parenteral GP IIb-IIIa inhibitors should be monitored within 24 hours of initiation of therapy for the development of thrombocytopenia. An algorithm for the detection and management of thrombocytopenia after GP IIb-IIIa inhibitor therapy is proposed.

Algorithms↗

Coronary intervention and glycoprotein IIb/IIIa integrin blockade.

In a few short years, platelet glycoprotein IIb/IIIa receptor antagonists have been developed from laboratory curiosities to critical treatment adjuncts to the successful performance of PCI. With more than 15,000 patients participating in trials of these agents during PCI, it is now clear that glycoprotein IIb/IIIa blockade reduces rates of adverse cardiovascular sequelae after PCI. Abciximab is the most extensively studied agent to date, but trials of other antagonists, particularly eptifibatide and tirofiban, support the utility of this class of therapeutic agents as a whole. This paper examines and interprets the results of large-scale clinical trials of glycoprotein IIb/IIIa inhibition during PCI and reviews directions for future study with this unique class of agents.

Angioplasty, Balloon, Coronary↗

Bleeding complications with platelet glycoprotein IIb/IIIa receptor antagonists.

Platelet glycoprotein (GP) IIb/IIIa receptor antagonists are being used with increasing frequency in the settings of percutaneous coronary interventions and acute ischemic syndromes. The development of bleeding complications following GPIIb/IIIa blockade represents a significant limitation to its effectiveness. Baseline characteristics predictive of future bleeding events in patients receiving platelet GPIIb/IIIa receptor antagonist include older age, low body weight, evolving myocardial infarction, and female sex. In patients undergoing percutaneous coronary interventions with adjunctive GPIIb/IIIa inhibition, the risk of bleeding, particularly from the femoral vascular access site, may be reduced through the use of low-dose, weight-adjusted heparin (70 U/kg), avoidance of postprocedural heparin, and early vascular sheath removal. Strategies to reduce the incidence of bleeding complications in patients receiving GPIIb/IIIa inhibitors are proposed in this article.

Coronary Disease↗

Uncommon mesiodens--a report of two cases.

Mesiodens is a supernumerary tooth with a cone shaped crown and a short root situated between the maxillary central incisors. Supernumerary teeth occur as isolated dental findings or as part of a syndrome. They are frequently discovered when a normal tooth is either delayed in its eruption or displaced often resulting in arch length inadequacy. An early diagnosis allows early intervention, more favourable prognosis and minimal complications. Presented here are two cases of unusual bilateral mesiodens.

Adolescent↗

Cyclospora cayetanensis--an emerging coccidian parasite.

Over the last decade increasing number of enteritis cases have been attributed to infection with a new coccidian sp that was named Cyclospora cayetanensis in 1993. Diarrhoea caused by this agent is clinically indistinguishable from cryptosporidiasis, isosporiasis and microsporidiasis but cyclospora infection are often very prolonged (upto 15 weeks) and may cause severe weight loss. Diagnosis is important because unlike diarrhoea caused by cryptosporidium and microsporidium, treatment with co-trimoxazole is effective. We report here a case of cyclosporiasis, to increase awareness of possibility of cyclospora infection in patients with prolonged diarrhoea. It should be considered in assessment of patients with unexplained prolonged diarrhoeal illness.

Animals↗