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Semin Thromb Hemost 2012; 38(05): 421-424
DOI: 10.1055/s-0032-1315760
Preface
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Thrombotic and Hemorrhagic Syndromes Associated with Autoimmunity and Infection

Massimo Franchini
1   Department of Transfusion Medicine and Hematology, “C. Poma” Hospital, Mantova, Italy
,
Antonio Coppola
2   Department of Clinical and Experimental Medicine, Regional Reference Center for Coagulation Disorders, Federico II University Hospital, Naples, Italy
,
Marcel Levi
3   Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands
,
Emmanuel J. Favaloro
4   Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, New South Wales, Australia
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
02. Juli 2012 (online)

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Welcome to the latest issue of Seminars in Thrombosis & Hemostasis devoted to the analysis of coagulation abnormalities associated with autoimmune and infectious disorders. This issue focuses on the complex interactions between many acquired disorders and the hemostatic system, and which result in hemorrhagic or thrombotic complications. Poor awareness of some of these conditions may cause inappropriate management of affected patients and impact negatively on clinical outcomes. This issue does not address the clinical and laboratory features of disseminated intravascular coagulation or the antiphospholipid (antibody) syndrome, because both have been recently covered in this journal.[1] [2]

The first two articles of this issue discuss the acquired inhibitors (autoantibodies) against coagulation factors, which occur in individuals with previously normal coagulation factor function and thus must be differentiated from those developing in patients with inherited clotting factor deficiencies (i.e., alloantibodies).[3] [4] Although these autoantibodies arise in a variety of clinical settings, they represent a challenge for the diagnostic laboratories, which need to identify specific inhibitors, as well as for hemophilia caregivers, since they may cause life-threatening bleeding. We begin the issue with the article by Coppola and coworkers[3] on acquired hemophilia A, a rare but often severe hemorrhagic disorder due to autoantibodies against coagulation factor VIII (FVIII). In this review, the authors summarize the epidemiology, laboratory and clinical aspects of this bleeding condition. Particular attention is dedicated to the management of such patients, with the presentation of recent data from national and international studies, which have significantly increased knowledge, and led to development of recommendations, in this setting. In the second article, Franchini and coworkers[4] summarize the current literature data on the more rare inhibitors against coagulation factors other than FVIII (i.e., factors I, II, V, VII, IX, X, XI, and XIII) discussing their most important pathogenic, clinical, and laboratory aspects as well as therapeutic approaches.

The next two articles are focused on immune thrombocytopenic purpura (ITP).[5] [6] The first article by Stasi[5] updates the current pathophysiologic mechanisms involved in ITP onset, including abnormalities of cell-mediated immunity and dysfunction of mesenchymal stem cells. The author also underlines the significant advances made by medical therapy in this field with the introduction of rituximab and more recently with the thrombopoietin receptor agonists.[7] The second article on ITP, by Franchini and coworkers,[6] discusses the current evidences on the association between some ITP cases in children and adults and Helicobacter pylori infection. The authors conclude that although the analysis of the existing literature strongly supports such a causal relationship, further in vitro and clinical studies are needed to elucidate the many remaining unclear issues of this association, such as the pathogenic mechanism and the geographical discrepancy of platelet response to eradication therapy.

The following article, by Tsai, is dedicated to new concepts in the pathogenesis, diagnosis, and treatment of thrombotic microangiopathy (i.e., thrombotic thrombocytopenic purpura [TTP] and hemolytic uremic syndrome [HUS]), a clinical syndrome characterized by thrombocytopenia and erythrocyte fragmentation.[8] In recent years, the identification of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency and defective complement regulation as the two major causes of non-infectious thrombotic microangiopathy, has greatly improved our knowledge on the pathogenesis of TTP and HUS, respectively. Thus, while this emerging new pathogenesis-based disease classification requires new diagnostic approaches, it additionally opens up new therapeutic opportunities. This article updates articles published last year in Seminars in Thrombosis & Hemostasis,[9] [10] but with particular emphasis on autoimmune causes of ADAMTS-13 deficiency and defective complement regulation.

In the next article, Prechel and Walenga[11] discuss recent advances in the management of heparin-induced thrombocytopenia (HIT), a potentially life-threatening adverse effect of heparin use.[12] Although the diagnosis and treatment of this condition is particularly difficult and complex, the authors stress that it is crucial to identify HIT as soon as possible to initiate early treatment to avoid thrombosis and improve the clinical outcome.

The next article, by Di Minno and colleagues,[13] evaluates the cardiovascular effects of chronic inflammation in rheumatic disorders and the role of anti-inflammatory agents, especially tumor necrosis factor-α blockers, on rheumatologic and cardiovascular outcomes. The research in this field should be directed to the identification, utilizing clinical and laboratory data, of patient who may be candidates for these expensive treatments. Research should also be directed to the development of educational programs on cardiovascular prevention among specialists and general practitioners, to prevent ischemic events and to achieve optimal inflammation control in rheumatic patients.

The link between inflammation associated with severe infection and hemostatic abnormalities is analyzed by Levi and coworkers in the next article.[14] This interaction is bidirectional because, while proinflammatory cytokines exert an important role in enhancement or inhibition of the different coagulation and fibrinolysis pathways, the activation of the coagulation system may importantly affect inflammatory responses by direct and indirect mechanisms, which also are involved in the development of atherosclerosis and ultimately of arterial thrombosis. Furthermore, besides the general coagulation response to inflammation associated with severe infection, specific infections may affect hemostasis with distinct features, such as hemorrhagic fever or thrombotic microangiopathy. The role of the infections in the pathogenesis of atherothrombosis is then further reviewed by Tufano and colleagues,[15] who have analyzed the often conflicting literature data on specific infectious agents, such as Chlamydia pneumoniae, Porphyromonas gingivalis, Helicobacter pylori, influenza A virus, herpes virus, hepatitis C virus, cytomegalovirus (CMV), and HIV, along with their possible pathogenic mechanisms and the potential role for antimicrobial therapy. The emerging concept is that no single agent is responsible for the effects of infection on atherosclerosis, but that aggregate effects of infections with multiple organisms occur, in the so-called “infectious burden.”

The next two articles analyze the role of viral infections on the development of arterial and venous thrombosis. In the first, Dentali and coworkers[16] discuss the increased risk of cardiovascular events associated with HIV infection and its related treatment (i.e., highly active antiretroviral therapy). The second, by Squizzato and Gerdes,[17] summarizes the more recent in vitro and clinical evidences on the possible pathogenic role of different hepatitis viruses, that is, CMV, Epstein-Barr virus, hepatitis A, B, and C viruses in the occurrence of venous thromboembolism (VTE). Indeed, the procoagulant state associated with hepatotrophic virus-related chronic liver disease may contribute to the development of VTE, in particular portal vein thrombosis, and to the progression of liver fibrosis seen in these patients.

Finally, the last article anticipates a new approach for future issues of Seminars in Thrombosis & Hemostasis, namely the inclusion of articles covering various topics within a single print issue. Thus, the article by Dentali and colleagues[18] is not related to the theme of autoimmunity and infection, but would undoubtedly still be of interest to our readership. Dentali and colleagues[16] have performed a meta-analysis of the existing literature (38 studies) on the association between ABO blood group and the risk of developing VTE. The results are quite impressive, as they demonstrate that non-O blood group is responsible for an approximately twofold increased risk of VTE compared with O blood group, therefore being considered one of the most important genetic risk factors for venous thrombosis.

In conclusion, we believe that the various articles of this issue of Seminars in Thrombosis & Hemostasis, primarily focused on the link between autoimmunity, infection, and hemostasis, will be of particular interest for our readership. We would like, as always, to thank all the authors for the original and comprehensive articles that each respectively provided.