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Heparin-Induced Thrombocytopenia

4th Edition, June 20, 2007

Complete Document

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Active, Most Current

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ISBN: 978-1-4200-4508-6
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Product Details:

  • Revision: 4th Edition, June 20, 2007
  • Published Date: June 20, 2007
  • Status: Active, Most Current
  • Document Language: English
  • Published By: CRC Press (CRC)
  • Page Count: 596
  • ANSI Approved: No
  • DoD Adopted: No

Description / Abstract:

Preface to the Fourth Edition

This fourth edition of Heparin-Induced Thrombocytopenia continues to expound on the themes enunciated in the Preface to the First Edition (2000): heparin-induced thrombocytopenia (HIT) is a clinicopathologic syndrome; HIT pathogenesis melds both platelet and coagulation activation-a key to comprehending its prothrombotic nature; and HIT exhibits a strikingly variable frequency in different clinical situations.


We have a better understanding of the diagnostic approach to HIT. The combination of a clinical assessment of pretest probability, together with the results of laboratory testing for the pathogenic HIT antibodies, enables the clinician to stratify patients into risk categories for HIT-associated complications. Clinical scoring systems, such as the 4 T's, are now available and evaluated, which help to standardize this approach. A major achievement is the high negative predictive value of this scoring system, i.e., a low score effectively "rules out" HIT. Further, the diagnostic value of the magnitude of a positive test result for "HIT antibodies" is increasingly appreciated. As well, the high sensitivity of the platelet factor 4 (PF4)-dependent enzyme-immunoassays (EIAs) and washed platelet activation assays (when performed by experienced laboratories) is increasingly accepted. New test concepts, such as the rapid assays, and novel methods for detecting antibodies against several heparin-binding proteins simultaneously by EIA are being introduced. But caution is required: there is growing recognition that HIT may be overdiagnosed, at least when low probability clinical situations and weakpositive EIAs are misinterpreted as indicating clinical HIT. Our selection of the "iceberg model" of HIT for the book's cover is meant to highlight the reality that only a minority of heparin-dependent antibodies have the potential to cause HIT, and that the various laboratory assays differ regarding their usefulness in detecting these pathologic "HIT antibodies."

The pathogenesis of HIT is now better understood, especially the biophysical nature of the PF4/heparin immune complexes. Ultrastructural studies have helped to clarify the basis of the greater immunogenic potential of unfractionated heparin [vis-à-vis low molecular weight heparin (LMWH) and fondaparinux], and have also provided a glimpse into the basis of the paradox of immunization induced by the sulfated pentasaccharide, fondaparinux, while at the same time its inability to form well the conformational changes leading to autoepitope formation on PF4. Still, the future of HIT research remains the unraveling of its unusual immunobiology.

Important new concepts in HIT treatment have evolved. There is emerging consensus that the "package insert" dosing for the direct thrombin inhibitors- particularly lepirudin-is too high. That the dangers of coumarin (warfarin, phenprocoumon, acenocoumarol) use during the acute phase of HIT include not only its potential to induce protein C depletion (thereby predisposing to microthrombosis syndromes such as coumarin-induced venous limb gangrene), but also to predispose to underdosing of direct thrombin inhibitor therapy (through prolongation of the partial thromboplastin time by coumarin). Also new to the fourth edition is the approval of bivalirudin for anticoagulation in percutaneous coronary intervention in patients with acute or previous HIT, an indication previously held only by argatroban. New data on the efficacies of the standard HIT therapies-danaparoid, lepirudin, and argatroban-are also discussed.

The growing use of LMWH results in a shift of patient populations affected by HIT, from post–major surgery to the intensive care setting, where unfractionated heparin (UFH) use still predominates. But, among critically-ill patients, HIT explains only a minority of platelet count declines, reflecting the high frequency of numerous thrombocytopenia-inducing comorbidities. How should such thrombocytopenic patients be managed in whom the diagnosis of HIT is raised, but where the probability is judged to be only low or intermediate? What anticoagulant options are available-and in what doses? An evolving concept in countries in which danaparoid is available is to use this agent in prophylactic doses in this setting of low (or even moderate) probability of HIT (when thrombosis is not present), pending clarification of the diagnosis. This approach could reduce the risk of bleeding associated with therapeutic-dose regimens. And, this edition includes a new chapter describing novel anticoagulants, such as fondaparinux, that could have future roles either for prevention or management of HIT.

HIT comprises a myriad of complexities and counter-intuitions. The new chapter on "paradoxes, myths, and realities" of HIT highlights some of the potential sources of error that can lead to catastrophic outcomes in affected patients and is a fitting conclusion to a topic with paradoxes aplenty.


A multi-author book depends on many contributors. For us, as editors, it was a great pleasure to produce this 4th edition together with our contributing colleagues throughout the world, many of whom became our friends, all dedicated to research and resulting improved clinical management of HIT. We would also like to acknowledge the help of many individuals in this project. Paula Garber was superb in managing this edition on behalf of the publisher. In Hamilton, we wish to thank in particular Maria Adamek, Jo-Ann Sheppard, Jim Smith, Jane Moore, Carol Smith, Di Moffatt, Junior Santos, Rumi Clare, and Dr. Greg Lo; in Greifswald, gratitude is owed to Uta Alpen, Norbert Lubenow, Petra Eichler, Kathleen Selleng, David Juhl, Birgitt Fürll, Ulrike Strobel, Ricarda Raschke, and Carmen Blumentritt, for their invaluable technical and administrative support, for ideas and discussions, and especially for being part of the team dedicated to research in HIT.