Thrombophilias and Acute Pulmonary Thromboembolic Disease
Venous thrombosis can be divided into two groups: hereditary and acquired thrombophilias. In this chapter, we first introduce the inherited thrombophilias, including Factor V Leiden mutation, prothrombin gene mutation, and protein S and C deficiency. Then
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Thrombophilias and Acute Pulmonary Thromboembolic Disease Shani Gunning-Carter, Gregory J. Kato, and Belinda Rivera-Lebron
Inherited Thrombophilias Virchow in the 1800s postulated that changes in the flow of blood, the vessel wall, and blood composition resulted in thrombus formation (Fig. 5.1). It is the changes in the composition of blood that is often referred to as thrombophilia, inherited or acquired. Thrombophilia may be recognized in approximately 50 % of patients with venous thromboembolism (VTE) [1]. Factor V Leiden (FVL), prothrombin G20210A mutation, deficiencies of protein C, protein S, or antithrombin are the most common inherited thrombophilias (Fig. 5.2). Factor V Leiden (FVL), the most common inherited thrombophilia, is prevalent in 4–7 % of the Caucasian American population, 2 % Hispanic-Americans and 1 % African-Americans [2]. It is rare in native African and Asian populations [3]. FVL is characterized by a poor anticoagulant response to activated protein C (APC). APC is a natural anticoagulant that degrades activated factors V and VIII (FVa and FVIIIa). The FVL mutation is due to a single point mutation in the factor V gene affecting the first APC cleavage site of FVa, where arginine is replaced by glutaS. Gunning-Carter, MD Division of Hematology-Oncology, Department of Medicine, Monongahela Valley Hospital, Monongahela, PA, USA G.J. Kato, MD (*) Division of Hematology-Oncology, Department of Medicine, Monongahela Valley Hospital, Monongahela, PA, USA Division of Hematology/Oncology, Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA e-mail: [email protected] B. Rivera-Lebron, MD, MS Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA © 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_5
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HYPERCOAGULABILTY Examples: Thrombophilia Malignancy HIT PNH
BLOOD STASIS Examples: Immobilization Heart Failure VIRCHOW’S TRIAD
ENDOTHELIAL INJURY Examples: Surgery Catheter
Fibrin clot
Fig. 5.1 Virchow’s triad. Virchow’s triad describes the three main factors that predispose thrombosis
FXII
FXIIa
FXI
FXIa
FIX
FIXa
Protein C Thrombomodulin Activated protein C
FVIIIa Protein S FX
FXa FVa
Antithrombin
Thrombin
Fibrin (thrombosis)
Fig. 5.2 Coagulation cascade. The intrinsic pathway of the coagulation cascade includes the most common inherited thrombophilias
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mine at position 506. This mutated cleavage site is less susceptible to proteolytic inactivation by APC, known as APC resistance (APCR). Less common causes of APCR include other rare factor V mutations, antiphospholipid antibodies, increased estrogen states, and cancers. APCR is detected by functional activated partial
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