Attempts to make sense of the antiphospholipid syndrome.

Many investigators have been intrigued by the paradoxical association of a circulating anticoagulant, first called lupus anticoagulant by Feinstein and Rapaport [1], with a tendency to develop thrombosis, as initially described by Walter Bowie [2]. Work in Leuven on this topic started when Luis Carreras, an Argentinian hematologist, joined the laboratory of blood coagulation at this university in 1979. At that time, the head of the laboratory was Marc Verstraete. Luis had a particular interest in antibody-mediated coagulation disorders, and had prepared reviews on thrombosis and thrombocytopenia induced by heparin [3] and on the lupus inhibitor [4]. In Leuven, he joined Jos Vermylen, senior member of the laboratory, and an internist with particular interest in hemostasis, thrombosis and vascular disease. As such, Professor Vermylen was involved in both laboratory research and patient care.

Anagrelide: what was new in 2004 and 2005?

Anagrelide is an established platelet-reducing drug. Although there are gaps in the understanding of its mechanism of action, two randomized comparisons with other drugs used for therapy of patients with essential thrombocythemia (ET) have been performed. Recent progress has been made in this field with the development of better determination techniques, with the characterization of metabolites, and with studies of their mechanism of action on megakaryocytes and platelets. More data are now available from various noncomparative clinical trials on its clinical efficacy and safety. Only few investigations are available that document its long-term effects. Although the drug should not be used during pregnancy, there are a few studies that report that pregnant women have taken this drug without harm to the newborn. Studies have also investigated the effects of anagrelide on platelets, indicating that platelet function is as important as platelet counts in ET. Preliminary analyses of the mechanism of action of anagrelide have revealed that the drug interferes with the signal transduction of the thrombopoietin receptor. Results of the first phase III trial (PT1) that compared anagrelide/aspirin with hydroxyurea/aspirin have sparked an intense discussion, given that the combination of anagrelide and aspirin causes more bleeding complications in the gastrointestinal tract. It has been speculated that the higher number of transient ischemic attacks in this study arm is not caused by thrombotic events but by small bleedings that would be responsible for transient hemorrhagic attacks. More insights are expected from the recently completed ANAHYDRET trial that compared monotherapy with hydroxyurea and anagrelide.

[Coagulation disorders in obstetric patients at gynaecological hospital of Leipzig University, 1961 through 1978 (author's transl)]. / Gerinnungsstörungen im geburtshilflichen Krankengut der Universitäts-Frauenklinik Leipzig von 1961 bis 1978.

Intrapartum coagulopathy was secured from 41 in 69,336 obstetric patients, between 1961 and 1978. Haemostatic disorders, such as v. Willebrand-Jürgens syndrome, idiopathic thrombocytopenia, plasmatic coagulation defects, and hyperfibrinolysis, had been recorded from ten patients even before parturition. The courses of pregnancy, childbirth, and puerperium of those patients are reported, with reference being made to the need for prepartum hospitalisation as well as for target-oriented substitutional therapy and non-invasive delivery control. - Acute intrapartum haemorrhagic syndrome occurred to 31 patients, among them 13 patients with loss coagulopathy. Prophylaxis and therapy of such coagulation disorders are discussed. The deaths of two mothers are analysed. Consumptive coagulopathy, triggered by typical gestational complications, was manifest in the other 18 patients. Prophylaxis and therapy of that severe obstetric coagulopathy are discussed.