New Therapeutic Agents in Thrombosis and Thrombolysis, 2nd edition.
Arthur A. Sasahara, Joseph Loscalzo, Gary Che Hodes, eds.
707 pp. New York, NY: Marcel Dekker; 2003. $195. ISBN 0-8247-0795-8
The linking of thrombosis with ischemic coronary artery disease launched an all-out offensive against the coagulation system. The second edition of New Therapeutic Agents in Thrombosis and Thrombolysis, edited by Sasahara et al, offers a timely update of the numerous advances in the field since publication of the original edition in 1997. The authors, including leading experts on the subject, provide detailed insight into the evolution of agents used to inhibit coagulation and to lyse its end product, fibrin. The reader finishes with a sound understanding of how humans, by exploiting observations of natural biology, are able to take advantage of the evolutionary features of an interesting array of fellow creatures (ranging from the leech to the vampire bat) to wage the war on thrombosis. The translation of biologic observations into effective new therapies through molecular engineering, detailed biochemical analysis, and finally, well-designed animal and clinical studies makes this book fascinating.
The flow of information is well orchestrated, with an outstanding set of introductory chapters that review the overall coagulation system, the animal models of thrombosis, and the basic principles of clinical trials. These introductory chapters provide a solid framework for the reader’s navigation of subsequent chapters, which address specific classes of drugs with anticoagulant, platelet-inhibitory, and fibrinolytic effects. Although the subject matter of the book is critical for physicians and investigators who specialize in the treatment of circulatory disorders, the use of anticoagulant therapy affects a broad swatch of the medical field, ranging from orthopedic surgery to obstetrics and gynecology. Physicians needing to select anticoagulant therapy would do well to add this book to their library, as it is a valuable reference aid for making informed choices about anticoagulant therapy.
The chapters on the advances in the field of chemically modified low molecular weight heparin (LMWH) and synthetic pentasaccharide agents not only provide a look at the familiar interactions of heparin, but also extend to include the wide array of biologic effects these agents have and how their structural variations can alter physiological effect. After an extensive overview of new anticoagulant agents, there are chapters that address the role of these agents in specific clinical settings. Although there is some redundancy from chapter to chapter regarding the advantages of these new agents, this only serves to reinforce the importance of new developments in the field. The class of direct thrombin inhibitors is well covered in several chapters, with balanced coverage of the successes and failures of these agents relative to heparin-based agents. The impact of activated protein C and the potential benefits of tissue factor pathway inhibitor (TFPI) and soluble thrombomodulin in sepsis and disseminated intravascular coagulopathy (DIC) are extensively covered. Hence, the contributors set the stage for future studies of the use of these agents for other thrombotic disorders.
The section devoted to antiplatelet therapy covers the full range of available therapeutic agents. Again, a well-written and concise introductory overview summarizes the effect of antiplatelet agents. Subsequent chapters review the acronym-rich body of clinical trials and detail the benefits and, where available, the comparative efficacy of the agents being studied. A chapter that addresses the seemingly paradoxical procoagulant, platelet membrane glycoprotein (GP) IIb/IIIa blockers, strengthens the section. The chapter digs deeply into the biology of GP IIb/IIIa antagonism and offers insight into the theories addressing the failures and successes of these agents. The potential role of a key, yet less pursued, pathway involving the inhibition of vonWillebrand Factor (vWF) GP Ib/IX interaction follows. Long-term oral antiplatelet therapies, including approved thienopyridine agents, newer phosphodiesterase inhibitors, and agents not yet in clinical use in the United States, are discussed in detail.
The section about fibrinolysis does a fine job of presenting the importance of first generation fibrinolytic agents and outlining the need for the development of agents that are simpler to administer and that will produce more effective thrombolysis. The authors, in addressing the need for improved agents, dissect the various key functional domains of fibrinolytic agents and describe the impact of novel engineered products in basic biochemical and clinical studies. Relative specificity for fibrin, agent persistence, antigenic considerations, and interaction with natural inhibitors are aptly presented. The section also does a good job of presenting the limits of development, because maintenance fibrin deposition is a key event in maintaining orderly vascular structure. The chapter on the development of Desmondus rotundus salivary plasminogen activator-α1, based on the optimized properties of Desmodus rotundus (vampire bat) saliva for digesting blood clots, is an alluring chapter that seizes the reader’s imagination. This section, though composed of excellent agent-specific chapters that review the mechanics of fibrinolysis, lacks the well-composed drug class-specific overview that is offered as a prelude in the other sections.
The illustrations are plentiful and well done, and the tables should prove invaluable to readers in need of a quick reference. However, I would like to have seen more elaboration on the use of new and current coagulation assay systems and on individualized dosing. As many early trials suggest, individual dosing may be a key step in further refinement of the use of anticoagulant agents. Although the epilogue does address this consideration, the only real shortcoming of the book is that it does not include a more focused review of the principles of individualized dosing across all agents covered. In addition, the chapters are variable in terms of addressing economic considerations, the best being the sections about LMWH. Although this is not a prime focus of the book, it is certainly a major consideration for practicing physicians and for society in general.
As the field continues to evolve at such a rapid pace, it is doubtless that new data will require ongoing updates of this very useful textbook.