David C. Calverley

Mast cell disease associated with acute myeloid leukemia: Detection of a new c-kit mutation Asp816His

Mast cell disease (MCD), a proliferation of mast cells (MC), is occasionally associated with hematologic malignancies. Neoplastic MC have activating c‐kit mutations. c‐kit is a receptor tyrosine kinase required for the development, proliferation, and survival of MC. Interaction of c‐kit with its ligand stem cell factor induces dimerization, receptor phosphorylation, and signal transduction. The most common c‐kit mutation detected in neoplastic MCD is Asp816Val, which results in ligand‐independent autophosphorylation of the receptor leading to MC proliferation. We describe the rare occurrence of MCD associated with acute myeloid leukemia, report a novel c‐kit mutation Asp816 His, and discuss the pathogenesis of MCD associated with hematologic malignancies. Am. J. Hematol. 65:307–309, 2000.

Antiplatelet therapy in the elderly. Aspirin, ticlopidine-clopidogrel, and GPIIb/GPIIIa antagonists.

Antiplatelet agents including aspirin, dipyridamole, the thienopyridines, and the GPIIb/IIIa antagonists have collectively demonstrated their ability to have a significant impact on the incidence of recurrent MIs, strokes, and other vascular ischemic events in the geriatric population. Low-dose aspirin also seems to be effective and safe for the primary prevention of ischemic heart disease in men considered at high risk. There is no evidence that the recommendations from these studies had increased relevance to younger adults, and the studies considering age as a variable found antiplatelet agents had either similar or increased benefit in older patients. In view of the relatively reduced adverse effects of these agents when compared with their potential therapeutic benefit, it is important that they be considered in all older patients for secondary prevention and in certain high-risk groups for primary prevention of cardiovascular morbidity and mortality.

Antiplatelet therapy. Aspirin, ticlopidine/clopidogrel, and anti-integrin agents.

Aspirin is the most widely employed antithrombotic agent in use today and has a proven role in the prevention and acute management of atherosclerosis-associated arterial thrombotic events. More recently developed antiplatelet agents have been found to have specific prophylactic roles associated with percutaneous coronary intervention and other clinical settings. This article outlines pharmacologic considerations and current clinical knowledge relevant to the use of aspirin, ticlopidine, clopidogrel, and the GPIIbIIIa antagonists in the management of thrombotic disorders.

Aspirin, Prostaglandins and Platelet Function: Pharmacology and Thrombosis Prevention

Since the early 1970’s, there has been significant progress made in de fining the mechanism of action and pharmacology of aspirin, one of the most significant anti-thrombotic agents known. Today, a wealth of studies, extending over the past three decades and ranging from molecular biology to clinical epidemiology, all point to the conclusion that aspirin exerts it’s anti-thrombotic effect via a single specific reaction with cyclooxygenase, an enzyme found in platelets (1–3). The purpose of this chapter is to elucidate mechanisms of platelet function by outlining how aspirin acts on platelets to inhibit its prothrombotic properties; this physiologic information will then be integrated with information from randomized clinical trials that address aspirin’s important role in the prevention of thromboembolic disease.