19: Pulmonary Embolism and Deep Vein Thrombosis

Key Points

• Disease summary:

  • Pulmonary embolism (PE) and deep vein thrombosis (DVT) are a disease continuum of venous thromboembolism (VTE), a complex and serious multifactorial disorder of blood coagulation influenced by genetic and environmental risk factors, and their interactions.

• Clinical presentations:

  • DVT is the formation of a thrombus in one of the deep veins, most commonly the lower extremities; occasionally, DVT can occur in the deep veins of the upper extremity, or in other locations.

  • PE is blockage in one or more pulmonary arteries occurring most commonly as a complication of DVT.

• Differential diagnosis:

  • DVT: cardiovascular disorders, septic arthritis, cellulitis, ruptured popliteal cyst, traumatic injury to a vein or artery

  • PE: any condition with clinical presentation characterized by chest pain, dyspnea, hemoptysis, or syncope

• Monogenic forms:

  • The well-established susceptibility genes for DVT/PE are factor V Leiden, factor II (or prothrombin), SERPINC1 gene (in antithrombin deficiency), PROC gene (in protein C deficiency), PROS1 gene (in protein S deficiency), A1 and B blood groups, and fibrinogen gamma gene.

• Family history:

  • Family history reflects inherited genetic susceptibilities, environmental, cultural, and behavioral factors in VTE. A positive family history is an independent risk factor for VTE, similarly among whites and African Americans, with an almost three times increased risk of VTE for both races. The risk of VTE is even higher among individuals who have a strong family history of VTE, that is, a first-degree relative with a history of VTE before the age of 50 years or a history of VTE among multiple relatives regardless of age. In addition, certain comorbid conditions, such as obesity, diabetes mellitus, hypertension, and cancer, could further increase the risk of VTE associated with a positive family history. Furthermore, there is evidence that only one-third of patients with a positive family history of VTE carry factor V Leiden variants among whites.

• Twin studies:

  • Among white monozygotic twins, the concordance rate with DVT or PE is 22% in males and 0.02% in females.

• Environmental and clinical factors:

  • Advanced age, race (whites and African Americans), previous episodes of VTE, prolonged immobilization, major trauma, spinal cord injury, burns, surgery, central venous catheterization, presence of a pacemaker

  • Female risk factors: pregnancy and postpartum period, estrogen-containing hormonal contraception, hormone replacement therapy

  • Obesity, diabetes mellitus

  • Cancer, myeloproliferative disorders, polycythemia vera, essential thrombocythemia, antiphospholipid syndrome, systemic lupus erythematosus, sickle cell disease

  • Endocrine disorders: thyroid dysfunction, Cushing syndrome, hyperprolactinemia

  • Major medical illness: nephrotic syndrome, inflammatory bowel disease, congestive heart failure, chronic obstructive pulmonary disease, paroxysmal nocturnal hemoglobinuria, disseminated intravascular coagulopathy

• Pharmacogenomics:

  • Although the US Food and Drug Administration (FDA) adapted guidelines for the clinical use of warfarin therapy when genotype information on cytochrome P450-2C9 complex (CYP2C9) and vitamin K-epoxide reductase complex subunit 1 (VKORC1) genes is available, the current recommendations for standard clinical practice do not include genetic testing.

Diagnostic ...