Therapeutic drug-induced platelet apoptosis: an overlooked issue in pharmacotoxicology

The surfacing of the applied fields of biology such as, biotechnology, pharmacology and drug discovery was a boon to the modern man. However, it had its share of disadvantages too. The indiscriminate use of antibiotics and other biological drugs resulted in numerous adverse reactions including thrombocytopenia. One of the reasons for drug-induced thrombocytopenia could be attributed to an enhanced rate of platelet apoptosis, which is a less investigated aspect. The present essay sheds light on the adverse (pro-apoptotic) effects of some of the commonly used drugs and antibiotics on platelets viz. cisplatin, aspirin, vancomycin and balhimycin. Furthermore, the undesirable reactions resulting from chemotherapy could be attributed at least to some extent to the systemic stress induced by microparticles, which in turn are the byproducts of platelet apoptosis. Thereby, the essay aims to highlight the challenges in the emerging trend of cross-disciplinary implications, i.e., drug-induced platelet apoptosis, which is a nascent field. Thus, the different mechanisms through which drugs induce platelet apoptosis are discussed, which also opens up a new perspective through which the adverse effects of commonly used drugs could be dealt. The drug-associated platelet toxicity is of grave concern and demands immediate attention. Besides, it would also be appealing to examine the platelet pro-apoptotic effects of other commonly used therapeutic drugs.     

Lowering radiation dose for integrated assessment of coronary morphology and physiology: First experience with step-and-shoot CT angiography in a rubidium 82 PET-CT protocol

Background. Reduction of radiation exposure from computed tomography coronary angiography (CTA) will be a key factor for more liberal use in cardiac hybrid positron emission tomography (PET)-computed tomography (CT). We report our initial experience with a new algorithm for low-dose CTA based on a prospectively gated step-and-shoot technique. This limits acquisition to the diastolic phase and minimizes exposure time versus the previous standard of retrospectively gated helical acquisitions. Methods and Results. In 15 consecutive patients referred for integrated functional and morphologic workup by rubidium 82 perfusion PET-CTA, step-and-shoot CTA (SnapShot Pulse; GE Medical Systems) (120 kV, 600–800 mA) was acquired on a 64-slice GE Discovery Rx VCT PET-CT scanner and compared with a group of patients with conventional helical CTA (120 kV, with modulation of the milliampere level) who were matched with regard to clinical variables. Effective dose was estimated from dose-length product. The American Heart Association 15-segment coronary tree model was used to determine study interpretability. Potential for fusion with Rb-82 perfusion PET was tested by use of commercial software. In addition, direct dose measurements were conducted by use of an anthropomorphic phantom for more accurate dosimetry. The dose-length product-derived effective patient dose for step-and-shoot and helical CTA was 5.5±0.1 mSv versus 20.5±3.5 mSv (P<.0001). The mean number of evaluable segments per patient for the best phase of helical CTA was 12.5±2.8 (83.3%±18.7%) versus 13.3±2.2 (88.7%±14.7%) (P=not significant vs helical) for step-and-shoot CTA. Review of multiple phases increased the number for helical CTA to 13.7±1.7 (91.3%±11.3%;P=not significant vs step-and-shoot CTA, for which this was not an option). Semiautomated fusion with corresponding PET was feasible for all studies. Phantom data confirm effective doses of 5.4 mSv for step-and-shoot CTA and 19.6 mSv for helical acquisition. Conclusions. Low-dose prospectively gated CTA reduces radiation exposure by nearly 70% versus the previous standard of helical acquisition, without significant loss in interpretability and integrative potential with Rb-82 perfusion PET. This represents a step toward a broader, routine integration of CTA and perfusion PET for assessment of coronary morphology and physiology by cardiac PET-CT.