Bleeding Disorders: Diagnosis and Treatment of Hemorrhagic Complications in the Intensive Care Unit
Bleeding is a common problem encountered in the intensive care unit. The differential diagnosis for bleeding in critically ill patients is extensive and intensivists must quickly identify the underlying etiology to provide the most effective therapy. The
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Bleeding Disorders: Diagnosis and Treatment of Hemorrhagic Complications in the Intensive Care Unit Craig D. Seaman and Margaret V. Ragni
Inherited Bleeding Disorders The two most common bleeding disorders likely to be encountered in the ICU setting are von Willebrand disease (VWD) and hemophilia. The essentials necessary for the prompt recognition, diagnosis, and treatment of these disorders are discussed below.
von Willebrand Disease Background VWD is a heterogeneous disease caused by deficient or defective von Willebrand factor (VWF). VWD disease subtypes are associated with specific VWF structuralrelated defects, most of which have a genetic basis. VWD is the most commonly inherited bleeding disorder affecting as many as 1 % of the population [1]. Bleeding is usually mucocutaneous in origin, commonly manifesting as menorrhagia, epistaxis, ecchymosis, or postoperative bleeding. Ascertaining a definitive diagnosis of VWD is difficult as VWD exhibits variable penetrance and clinical severity varies from individual to individual, unrelated to VWF level. Furthermore, VWF levels vary considerably from person to person, even within the same person over time, and are affected by extra genic factors, including stress, trauma, infection, estrogen, and ABO blood types. VWF levels do not always correlate with clinical symptoms; therefore, many affected persons go undiagnosed. C.D. Seaman, MD, MS (*) • M.V. Ragni, MD, MPH Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA e-mail: [email protected] © Springer International Publishing Switzerland 2017 J.S. Lee, M.P. Donahoe (eds.), Hematologic Abnormalities and Acute Lung Syndromes, Respiratory Medicine, DOI 10.1007/978-3-319-41912-1_6
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C.D. Seaman and M.V. Ragni
VWF is a large multimeric glycoprotein synthesized in endothelial cells and megakaryocytes. It is stored in Weibel-Palade bodies in endothelial cells and alphagranules in platelets. Circulating VWF, whose half-life is approximately 12 h, binds to factor VIII (FVIII) providing stability for FVIII and preventing proteolytic degradation of FVIII. VWF binds to subendothelial collagen at the sites of vascular injury. There, it facilitates platelet adhesion by binding to the platelet glycoprotein Ib-IX-V receptor complex. VWF binding leads to platelet activation and aggregation, which is termed primary hemostasis. This process is most effective at high shear rates, where a conformational change in VWF multimers enhances platelet binding [2].
Classification There are several VWD variants, which result in quantitative (types 1 and 3) or qualitative (types 2A, 2B, 2M, and 2N) VWF defects (Table 6.1) [2]. Type 1 VWD is characterized by reduced levels of VWF. This is the most common VWD variant representing roughly 70–80 % of VWD diagnoses [3]. Type 2 VWD variants represent approximately 20–30 % of VWD diagnoses. Type 2A is the most common type 2 VWD variant, while types 2B, 2M, and 2N VWD occur infrequently. Type 2 VWD variants are characteriz
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