PDF herunterladen
Semin Thromb Hemost 2012; 38(07): 641-644
DOI: 10.1055/s-0032-1327775
Preface
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Expert Approaches to Common Bleeding and Thrombotic Problems—Part I

Catherine P. M. Hayward
1   Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
,
Kathryn E. Webert
1   Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
2   Canadian Blood Services, Medical Office, Ancaster, Ontario, Canada, L9K 1S5
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
21. Oktober 2012 (online)

    Lizenzen und Reprints

Welcome to this first of two special issues of Seminars in Thrombosis & Hemostasis devoted to how experts approach common bleeding and thrombotic problems. This issue features expert opinion on the diagnosis and management of common disorders, with discussion of the current evidence and the practical issues that need to be considered for management of thrombotic and bleeding problems. The topics covered span many of the common bleeding and thrombotic problems that result in a hematology referral and include discussion of special populations, such as children and neonates.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] Where there are controversies, or a lack of evidence, the expert contributors to this issue have provided thoughtful advice, sometimes with new evidence.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] All of the articles in this issue discuss clinical management and laboratory testing.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] Currently, many common thrombotic and bleeding disorders can be evaluated by fairly simple investigations that are generally widely available (e.g., determination of the international normalized ratio [INR], D-dimer levels, and measurement of coagulation factor levels).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] However, some investigations for common disorders, such as transmission electron microscopy to diagnose platelet dense-granule deficiency ([Fig. 1]), require an evaluation by expert centers.[14] Additionally, there are gaps in the clinical and laboratory assessment of common bleeding and thrombotic problems, as discussed by the contributors to this issue.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] Taken together, the articles present helpful diagnostic and management reviews, with in-depth discussions of key issues and current evidence. The issue is anticipated to be highly valued by individuals engaged in clinical, laboratory, educational, and research practices.

Zoom Image
Fig. 1 Dense granules in a platelet, visualized by transmission electron microscopy for diagnostic assessment of dense-granule deficiency. The platelet was examined after air drying whole mount preparations of platelets in platelet-rich plasma onto a sample grid. Platelet dense granules are the structures that appear black as their high mineral (calcium) content imparts electron density. The average numbers of these granules in this sample were normal. Dense-granule deficiency is a common bleeding disorder that is associated with reduced numbers of dense granules per platelet. Currently, platelet electron microscopy for diagnosing dense-granule deficiency is restricted to expert laboratories. (Figure prepared by Catherine P. M. Hayward, Karen A. Moffat, and Marnie Timleck, McMaster University, Hamilton, Ontario, Canada.)

In the first article of the issue, Cattaneo discusses the diagnosis and management of high platelet reactivity on treatment with clopidogrel, an inhibitor of the P2Y12 platelet receptor for adenosine diphosphate.[1] He provides expert insights on the issues of inter-individual variability in clopidogrel responses and discusses that about one-third of individuals on clopidogrel therapy exhibit high on treatment platelet reactivity.[1] Cattaneo also outlines the genetic and environmental factors that influence the absorption and/or the extent of clopidogrel metabolism, which is important as metabolism affects the levels of the active metabolite.[1] He gives expert perspectives on the pros and cons of tailored treatment, based on results of laboratory platelet function tests, and the need to develop cost-effective tests with clinical utility before monitoring clopidogrel therapy can be recommended for patient management.[1] Finally, Cattaneo discusses the use of alternative drugs with more uniform and predictable bioavailability with favorable risk–benefit and cost-benefit ratios.[1]

In the second article in the issue, Darvish-Kazem and Douketis discuss the perioperative management of patients having noncardiac surgery who are receiving anticoagulant or antiplatelet therapy, using both evidence-based and practical approaches to the issues that are important for managing these patients.[2] The article discusses how to balance the risks for bleeding, thrombosis, and major cardiovascular events for individuals who need to undergo surgery.[2] Darvish-Kazem and Douketis provide practical recommendations on bridging therapy that is often used to minimize the risks associated with anticoagulation or antiplatelet therapy withdrawal and resumption, including how to manage patients who have undergone stent insertions for treatment of atherosclerotic disease.[2] They highlight several important issues that need to be addressed by future research, including the optimal management of patients on anticoagulant or antiplatelet therapy that need to undergo noncardiac surgery.[2] With the increasing median age of many populations worldwide, these issues represent very common challenges.

In the third article by Eby, the basis of warfarin resistance and the current status of pharmacogenetic-guided dosing of warfarin are discussed.[3] The article reviews the common genetic variants that affect warfarin metabolism and sensitivity, and the impact of using information on genetic variants that affect warfarin dosing, along with clinical parameters, to improve warfarin-dosing accuracy.[3] Eby discusses the current recommendations and challenges to using pharmacogenetic information in practice.[3] He also discusses the studies currently underway that could answer several important questions about using pharmacogenetic information to guide the dosing of oral anticoagulant therapy.[3] Eby also provides some thoughtful comments on whether pharmacogenetic testing could be practically implemented for routine care of patients treated with warfarin.[3]

The fourth article of the issue, by Witt, provides additional perspective on the optimal dosing of vitamin K antagonists.[4] His article provides recommendations on both dosing and appropriate frequency of determining the INR that should be a helpful guide for practitioners that manage treatment with vitamin K antagonists.[4] Witt also provides helpful guidance on when daily low dose vitamin K supplementation may be warranted.[4] He also discusses the relative benefits to patient self-management of vitamin K antagonist therapy compared with management by an anticoagulation service.[4] Like Eby,[3] Witt highlights some of the key issues related to treatment with vitamin K antagonists that have not yet been addressed by research studies.[4]

In the fifth article of this issue, Bates addresses D-dimer assays in diagnosis and management of thrombotic and bleeding disorders.[5] She reviews the principles of D-dimer evaluation by laboratory assays and discusses the diagnostic utility of these assays for excluding venous thromboembolism (VTE) and for diagnosing and monitoring disseminated intravascular coagulation.[5] Bates discusses the importance of assay standardization and test performance, and how to best use D-dimer measurement to guide clinical decisions, based on current evidence.[5] As D-dimer assays are very widely used, this contribution provides laboratories and clinical services with expert guidance on how to use D-dimer results to make clinical decisions.[5]

The sixth article by Monagle discusses the diagnosis and management of venous thrombosis and pulmonary embolism (PE) in neonates and children, special populations that pose practical challenges.[6] Monagle reviews and discusses how the diagnosis and management of venous thrombosis and PE in neonates and children differs from the diagnosis and management of these problems in adults, due to differences in pathogenesis and disease entities.[6] He discusses the best diagnostic strategies and therapies, recent guidelines, and the major challenges that result from gaps in current evidence.[6] Clinicians and laboratory professionals that are involved in diagnosing thrombotic disorders in neonates and children will value this contribution.

In the seventh article of this issue, Hogg et al discuss the diagnosis of VTE, a commonly encountered medical problem.[7] Their review covers the current evidence, and helpful strategies to consider for pretest probability assessments for deep venous thrombosis and PE, in addition to decisions on appropriate laboratory testing and diagnostic imaging, based on probabilities for thrombosis.[7] Hogg et al discuss the advantages and disadvantages of different strategies and provide their expert perspective on which strategies are optimal for the management of patients, who can have a low, moderate, or high pretest likelihood for VTE.[7]

The eighth article, by Goy and Crowther, presents an expert approach to diagnosing and managing anticoagulant related bleeding in patients receiving antithrombotic therapies to reduce their risk of death and disability from arterial thromboembolism and/or VTE.[8] Goy and Crowther discuss the effective antidotes and treatments for older antithrombotic drugs and newer agents, which do not as yet have effective antidotes.[8] Their article contains a thoughtful perspective on the diagnosis and management of anticoagulant-related bleeding, which is timely, given that several novel anticoagulants are now being used that require a different strategy for managing anticoagulant-related bleeding.[8]

In the ninth article of the issue, Rydz and James provide their expert approach to the diagnosis and management of common bleeding disorders.[9] They discuss the challenges to assessment of the bleeding history, the usefulness of bleeding history assessment tools to exclude bleeding disorders, including their negative predictive value.[9] Rydz and James discuss testing for common disorders and when to use directed investigations to investigate bleeding, based on the clinical pattern and family history.[9] They also provide a helpful overview on treatment, rationalizing that it needs to be based on symptom management. This may include the need to replace deficient or defective factors, and to administer other therapies, such as antifibrinolytics (tranexamic acid) and hormone-based therapy, such as oral contraceptives.[9]

In the tenth article of the issue, O'Brien discusses the diagnosis and management of bleeding disorders in children, with emphasis on issues that require special consideration for pediatric patients.[10] She discusses that type 1 von Willebrand disease and mild platelet function disorders are the most common hemostatic defects encountered in clinical practice.[10] She includes a thoughtful discussion on bleeding management and prevention, and that evidence is lacking to guide the management and treatment decisions for children with bleeding problems.[10] O'Brien reviews the current literature and cautions about the potential dangers of desmopressin therapy in children, as the complication of hyponatremia is often underrecognized.[10] The article also highlights some of the troublesome hemostatic challenges for children with bleeding disorders, including epistaxis, dental extractions, tonsillectomies, and menstrual bleeding problems at menarche.[10]

In the eleventh article, Carcao discusses the diagnosis and management of hemophilia A and B in children.[11] He discusses the measurement of factor levels and also genetic testing for hemophilia A and B.[11] Carcao also reviews the literature and discusses the treatment of hemophilia with an emphasis on the treatment of acute bleeds.[11] He also outlines the use of prophylactic factor concentrate therapy to prevent bleeding and the complications associated with its use.[11] Finally, Carcao provides a helpful review on acquired inhibitors in patients with congenital hemophilia with a focus on risk factors associated with their development, treatment of bleeding in patients with inhibitors, and immune tolerance induction therapy to eradicate the inhibitor.[11]

In the twelfth article of the issue, Webert discusses the diagnosis and management of acquired hemophilia A, a disorder seen predominantly in adults that is a rare but important cause of abnormal bleeding.[12] Webert discusses the incidence, disease associations, and when acquired hemophilia should be suspected as a cause of bleeding.[12] She also addresses the appropriate investigations and the goals of treatment, namely to eradicate the inhibitor and to manage bleeding complications, and provides a rational approach to choosing between factor replacement and bypassing agents.[12]

In the thirteenth and final article of this issue, an original research submission, Hayward et al discuss the laboratory investigations for bleeding disorders, using data for several prospective cohorts to illustrate on the common findings among individuals evaluated for bleeding disorders.[13] Their study provides needed estimates for the sensitivity and specificity of common tests and bleeding disorder test panels that are used to diagnose bleeding disorders.[13] It illustrates that coagulation screening tests have acceptable specificity but low sensitivity for common bleeding disorders, reflecting that hemophilia, fibrinogen disorders and other coagulation factor deficiencies/defects are rare among individuals evaluated for bleeding disorders.[13] Hayward et al also provide interesting comparative information on the sensitivity of von Willebrand disease screens and platelet aggregometry for common bleeding disorders.[13] Their data illustrate that abnormalities in coagulation screening tests (particularly for the activated partial thromboplastin time and thrombin time), even among individuals referred for bleeding disorder investigations, often reflect false-positive abnormalities.[13] The authors also use this evidence and experience to provide an expert approach to the laboratory investigation of bleeding disorders.[13] In their approach, they rationalize the use and sequence of tests, based on their sensitivity and specificity, and the nature of the disorder suspected to be the cause of bleeding.[13] The findings of their study, and their evidence-based approach to diagnostic testing for bleeding disorders, challenges some of the common, longstanding practices to investigating bleeding disorder causes.[13]

The collection of interesting expert opinion articles that comprise this issue of Seminars in Thrombosis & Hemostasis, provide helpful guidance on diagnosing, managing, and treating common bleeding and thrombotic problems and highlight where evidence is lacking to guide clinical and laboratory practice. The guest editors of this issue of Seminars in Thrombosis & Hemostasis extend their sincere gratitude to all the authors for their interesting and timely contributions. The many practical tips and expert opinions should be valued by clinicians, laboratories, researchers, educators, and learners worldwide. We hope that readers enjoy the collation of articles on expert approaches to common bleeding and thrombotic problems.