This trend may be accelerated by anagrelide. This increase in fibrosis appeared to be linked to a drop in hemoglobin as it progressed. Stopping anagrelide (and switching patients to hydroxyurea) appeared to reverse the degree of marrow fibrosis. Thus, patients on anagrelide may need to be monitored on a periodic basis for marrow reticulin scores, especially if anemia develops, or becomes more pronounced if present initially.Less common side effects include: congestive heart failure, myocardial infarction, cardiomyopathy, cardiomegaly, complete heart block, atrial fibrillation, cerebrovascular accident, pericarditis, pulmonary infiltrates, pulmonary fibrosis, pulmonary hypertension, pancreatitis, gastric/duodenal ulceration, renal impairment/failure and seizure. Due to these issues, anagrelide should not generally be considered for first line therapy for essential thrombocytosis. Mechanism of action
Anagrelide works by inhibiting the maturation of platelets from megakaryocytes. The exact mechanism of action is unclear, although it is known to be a phosphodiesterase inhibitor. It is a potent (IC50 = 36nM) inhibitor of phosphodiesterase-II. It inhibits PDE-3 and phospholipase A2. Synthesis
Phosphodiesterase inhibitor with antiplatelet activity. Condensation of benzyl chloride 1 with ethyl ester of glycine gives alkylated product 2. Reduction of the nitro group leads to the aniline and reaction of this with cyanogen bromide possibly gives cyanamide 3 as the initial intermediate. Addition of the aliphatic would then lead to formation of the quinazoline ring (4). Amide formation between the newly formed imide and the ester would then serve to form the imidazolone ring, whatever the details of the sequence, there is obtained anagrelide (5).
Transient hypogammaglobulinemia of infancy is a form of hypogammaglobulinemia appearing after birth, leading to a reduction in the level of IgG, and also sometimes IgA and IgM. (The ratios of immunoglobulins vary rapidly in all infants, and the term dysgammaglobulinemia, although theoretically applicable, is not usually used in this context.) It can result in increased infections, but it can also present without symptoms. Pathophysiology
Normally, a newborns immunoglobulins come from the mother during pregnancy and wane after birth until 3-6 months of age, when the infant begins to start to produce their own IgG. However, in transient hypogammaglobulinemia of infancy, the IgG synthesis is delayed, and the hypogammaglobulinemia is prolonged beyond age 6 months. See also
List of cutaneous conditions

References


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