Coagulation disorders - recent lessons from clinical conditions.

For clinicians, who are not experienced in hemostasis and thrombosis, coagulation and coagulation disorders remain a ‘book of seven seals’ (1). This may be due, at least in part, to the complexity of the hemostatic apparatus and its interaction with inflammatory processes and immune mechanisms, all of which require detailed theoretical knowledge, practical experience, and continuous medical education (CME). More recently, the use of direct oral anticoagulants, which have specific pharmacological targets and pharmacodynamics distinct from those of vitamin K antagonists, heparins, or the pentasaccharide fondaparinux, has created insecurities and concerns among clinicians. Some of these concerns result from the fact that these novel agents with their superior safety profile impact on standard coagulation screening tests (such as prothrombin time and activated partial thromboplastin time) in a way that is different from conventional anticoagulants. This theme issue of Hämostaseologie should facilitate the readers’ access to several acquired coagulation disorders and assist to overcome fundamental problems of understanding hemostasis or, metaphorically spoken, to ‘break some of the seals’ of hemostasis and thrombosis textbooks. As third part in a series of reviews, the current edition also reflects several highlights of the GTH Congress 2015 (2, 3, 4). In his article, Medcalf provides an upto-date view on fibrinolysis, demonstrating that tissue-type plasminogen activator (t-PA)-mediated conversion of plasminogen into plasmin is not solely designed to remove fibrin deposits and blood clots in a self-regulated proteolytic process (5). Importantly, it is shown that t-PA and plasmin have pleotrophic effects and other substrates than fibrin such as prion proteins, amyloid-β, and misfolded or aggregated proteins. Thus, t-PA can act in a nonfibrinolytic (i.e., plasmin-independent) manner and have multiple effects on cerebral functions (e.g., synaptic plasticity, neurotransmission, visual processing, learning and memory). The author therefore concludes that the “original concept for the fibrinolytic system, being focused on fibrin, is a massive understatement” (5). Tiede et al. report on recent advances in the management of acquired hemophilia A (AHA) (6). At an incidence of about 1.3 cases per million people (7), AHA is a rare but challenging bleeding disorder caused by inhibitory autoantibodies against coagulation factor (F) VIII. Apart from hemostatic management to control active bleeding, immunosuppressive treatment is mandatory in AHA to achieve remission. However, the outcome of AHA remains highly variable. Therefore, clinically valid prognostic factors for remission are urgently required. Recently, the GTH-AH (01/2010) study, a multicenter trial conducted under the leadership of Andreas Tiede, has demonstrated for the first time that residual FVIII activity and inhibitor