Artefactual serum hyperkalaemia and hypercalcaemia in essential thrombocythaemia

Aim—To investigate possible abnormalities of serum potassium and calcium levels in patients with essential thrombocythaemia and significant thrombocytosis. Methods—24 cases of essential thrombocythaemia with significant thrombocytosis (platelet count > 700 x 10(9)/litre) had serum potassium and calcium estimations performed at the time of maximum thrombocytosis before treatment, and at the time of low platelet count after treatment with cytoreductive drugs. Selected patients were further investigated with plasma sampling and estimation of ionised calcium and parathyroid hormone. Results—At the time of maximum thrombocytosis six patients had serum hyperkalaemia (> 5.5 mmol/litre) and five had serum hypercalcaemia (> 2.6 mmol/litre). Following treatment and reduction of the platelet count, hyperkalaemia resolved in all cases and hypercalcaemia in four of the five cases. Mean serum potassium and calcium concentrations were raised (p < 0.0001) at maximum thrombocytosis compared with the values when the platelet count was low. Serum potassium and calcium values were significantly correlated at all stages. Measurements on plasma consistently corrected the hyperkalaemia but not the hypercalcaemia. Serum hypercalcaemia was associated with raised ionised calcium and normal parathyroid hormone concentrations. Conclusions—Essential thrombocythaemia with significant thrombocytosis is associated with serum hyperkalaemia and hypercalcaemia. The probable mechanism of hypercalcaemia is the secretion of calcium in vitro from an excessive number of abnormally activated platelets. It is thus likely that the hypercalcaemia is an artefact, as is the hyperkalaemia. Key Words: thrombocythaemia • hypercalcaemia • hyperkalaemi

An Extraterritorial FDA: Could the Food and Drug Administration Apply Its Informed Consent Requirement Abroad Consistent with International Law?

This paper addresses the regulatory challenges wrought by the increasing amount of human subject drug testing conducted in developing countries in support of new drug applications to the Food and Drug Administration. Specifically, it examines the difficulty of enforcing the “informed consent” requirement for ethical scientific research performed in foreign territory. In poorer regions, a lack of government oversight, lower regulatory standards, and barriers to communication have too frequently resulted in allegations of human experimentation performed without its participants’ informed consent. In order to solve this problem, some commentators have suggested that the FDA could apply its human subject protections to foreign clinical research, and enforce them through injunctions or criminal prosecutions. However, the international legal limits on states’ prescriptive jurisdiction may prohibit this exercise of extraterritoriality. After analyzing the proposed extraterritorial regulation of foreign drug testing under the traditional bases and limitations of prescriptive jurisdiction, this paper concludes that such regulation would likely violate international law. However, because nonconsensual clinical research has previously been regarded as a crime against humanity, the FDA might be able to bring criminal prosecutions under the principal of “universal jurisdiction” against investigators or sponsors who conducted studies without their subjects’ informed consent. This analysis offers both positive and normative conclusions regarding the international legal system and the human rights regime