Academic Journal
An additional mechanism of action of abciximab: dispersal of newly formed platelet aggregates
| العنوان: | An additional mechanism of action of abciximab: dispersal of newly formed platelet aggregates |
|---|---|
| المؤلفون: | Marciniak, Stanley J. Jr., Mascelli, Mary A., Furman, Mark I., Michelson, Alan D., Jakubowski, Joseph A., Jordan, Robert E., Marchese, Peter J., Frelinger, Andrew L. III |
| المساهمون: | Department of Pediatrics |
| المصدر: | Thrombosis and haemostasis ; 87 ; 6 ; 1020-5 |
| سنة النشر: | 2022 |
| المجموعة: | University of Massachusetts, Medical School: eScholarship@UMMS |
| مصطلحات موضوعية: | Adenosine Diphosphate, Antibodies, Monoclonal, Aspirin, Blood Platelets, Dose-Response Relationship, Drug, Drug Synergism, Fibrinogen, Humans, Immunoglobulin Fab Fragments, Kinetics, Platelet Aggregation, Platelet Aggregation Inhibitors, Platelet Glycoprotein GPIIb-IIIa Complex, Protein Binding, Hematology, Oncology, Pediatrics |
| الوصف: | BACKGROUND: The ability of abciximab to prevent fibrinogen binding to activated platelets indicates it may also promote dissolution of platelet-rich thrombi. The present study examined the capacity of abciximab to reverse platelet aggregation in vitro. METHODS AND RESULTS: Experiments were performed on blood from healthy non-medicated donors. Platelet aggregate formation and disaggregation were monitored turbidimetrically. Platelet-bound fibrinogen was measured by flow cytometry. For disaggregation studies, platelets were first stimulated with either ADP or the 11-mer thrombin receptor activating peptide (TRAP), then varying amounts of abciximab were added at periodic intervals after agonist addition. Platelet disaggregation was detected by comparing the extent of light transmittance at 4 min after addition of either abciximab or saline to PRP. ATP release was simultaneously monitored by chemi-luminescence. When added 1 min after low concentrations of ADP, abciximab rapidly (andlt; 1 min) dispersed platelet aggregates in a dose-dependent manner, with complete disaggregation observed with 6.25 microg/mL of the beta3 antagonist. In contrast, equivalent concentrations of abciximab did not induce appreciable disaggregation to platelets stimulated with TRAP (10 microM). Platelet counts of samples that had undergone complete disaggregation, as assessed by aggregometry, were equivalent to baseline, indicating dispersal of aggregates to single cells. Concentrations of abciximab that produced complete disaggregation induced partial displacement of platelet-bound fibrinogen (52 +/- 8% inhibition of fibrinogen binding at 12.5 microg/ml abciximab). The disaggregation effectiveness of abciximab decreased as the time between ADP and subsequent abciximab addition widened, and as the amount of both dense granule release and agonist stimulation increased. However, pre-treatment of platelets with acetylsalicylic acid (ASA) did not potentiate platelet disaggregation induced by abciximab. CONCLUSIONS: These data indicate that ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | Link to article in PubMed; http://www.schattauer.de/en/magazine/subject-areas/journals-a-z/thrombosis-and-haemostasis/contents/archive/issue/806/manuscript/3152/show.html; Thromb Haemost. 2002 Jun;87(6):1020-5.; 0340-6245 (Linking); http://hdl.handle.net/20.500.14038/43360; https://escholarship.umassmed.edu/peds_hematology/38; 2796526; peds_hematology/38 |
| الاتاحة: | https://hdl.handle.net/20.500.14038/43360 https://escholarship.umassmed.edu/peds_hematology/38 |
| رقم الانضمام: | edsbas.25ECD68E |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |