Effect of Ado-Trastuzumab Emtansine on Autologous Platelet Kinetics and Function.

PURPOSE: Ado-trastuzumab emtansine (T-DM1) treatment results in grade 3-4 thrombocytopenia in 8%-13% of patients. Prior in vitro studies reported T-DM1 inhibition of megakaryocyte maturation as the cause of decreased platelet production. The current observational study was initiated to evaluate causes of thrombocytopenia in patients with metastatic breast cancer. MATERIALS AND METHODS: Patients with human epidermal growth factor receptor 2-positive metastatic breast cancer (N = 11) were enrolled in this postmarket safety study. 111-Indium- radiolabeled autologous platelet recoveries and survivals as well as serial platelet counts, bleeding time assays, and platelet aggregation responses to a wide range of agonists were performed at baseline (BL) and during two consecutive cycles of the drug (3.6 mg/kg IV once every 3 weeks). RESULTS: Platelet nadirs occurred earlier in cycle 2 than in cycle 1. Average nadir counts (% BL) in cycles 1 and 2 were 116,000/µL (53% ± 6%) and 115,000/µL (51% ± 9%), respectively, with return to BL by D15 in both cycles. BL platelet survival averaged 8.8 (± 0.3) days but progressively shortened to 5.5 (± 0.5) days during cycle 1 and to 4.6 (± 0.3) days during cycle 2 (P < .001 compared with BL for both cycles). Aggregation responses to all agonists decreased during the study, both in cycle 1 and cycle 2. CONCLUSION: Following T-DM1 administration, we observed statistically significant progressive decreases in platelet survivals and decreased platelet function from BL values. In distinction to published in vitro studies, these unexpected results indicate a direct toxic effect of T-DM1 on patients' autologous circulating platelets.

The virtual physical exam in the 21st century.

The modern Western medical encounter follows a strict framework that weaves subjective and objective components into a unifying diagnosis. As health care changes to incorporate new technology, such as virtual health care, the components that lead to diagnosis must likewise evolve. The virtual physical exam has limitations compared with the traditional exam. Despite this limitation, every year more patients are seen virtually with high satisfaction. Data have shown that supplementary real-time patient-provider video telemedicine increases access and extends established patient-physician relationships which will likely fuel increased telemedicine adoption even further. However, to date, there are limited data regarding the validity of the virtual examination compared with the traditional physical exam. In this paper, we review the use of developing technology related to the virtual physical exam.