Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Thrombophilia is defined as an acquired or familial disorder associated with thrombosis. The clinical presentation of an underlying thrombophilia may include venous thromboembolism (deep vein thrombosis, pulmonary embolism, superficial vein thrombosis), recurrent miscarriage, and complications of pregnancy (eg, severe preeclampsia, abruptio placentae, intrauterine growth restriction, stillbirth). Other possible clinical presentation includes arterial thrombosis (especially among patients <50 years of age with no other risk factors for atherosclerotic arterial occlusive disease (diabetes mellitus, hypercholesterolemia, hypertension, or tobacco smoking) and aseptic necrosis of bone (eg, femoral head mandible). Demographic or environmental exposures that compound the risk of venous thromboembolism among persons with a thrombophilia include increasing age, male gender, obesity, surgery, trauma, hospitalization for medical illness, malignant neoplasm, prolonged immobility during travel (eg, prolonged airplane travel), oral contraceptive use, estrogen therapy (both oral and transdermal), tamoxifen and raloxifene therapy, and infertility drugs. Central venous catheters and transvenous pacemaker wires increase the risk for upper extremity deep vein thrombosis; this risk is unrelated to thrombophilia.
Inherited thrombophilias include:
-Deficiency due to reduced plasma protein level or dysfunctional protein of:
- Protein C
- Protein S
-Activated protein C resistance due to the factor V R506Q (Leiden) mutation
-Prothrombin G20210A mutation
Acquired thrombophilias include a lupus-like anticoagulant (antiphospholipid antibodies) and disseminated intravascular coagulation/intravascular coagulation and fibrinolysis (DIC/ICF). DIC/ICF may cause thrombotic as well as hemorrhagic events. Positive tests for DIC/ICF can also occur as consequences of thrombosis.
Acquired deficiencies of fibrinogen, protein C, protein S, and antithrombin may be found in conjunction with liver disease (they are produced by the liver) or DIC/ICF and are of uncertain significance with respect to thrombosis risk.
Acquired deficiencies of protein C and protein S are also found in liver patients treated with oral anticoagulants (eg, warfarin, Coumadin) since both of these proteins are dependent upon the action of vitamin K for normal function.
Acquired protein S deficiency also occurs in thrombotic thrombocytopenic purpura, pregnancy or estrogen therapy, nephrotic syndrome, and sickle cell anemia. In acute illness, the level of acute-phase reactants rise (including C4b binding protein, which binds and inactivates protein S in the plasma) and the portion of bound protein S also rises leaving a lower proportion of free protein S. The significance of acquired protein S deficiency with respect to thrombosis risk is unknown.
Evaluating patients with thrombosis or hypercoagulability states
Detecting a lupus-like anticoagulant; dysfibrinogenemia; disseminated intravascular coagulation/intravascular coagulation and fibrinolysis
Detecting a deficiency of antithrombin, protein C, or protein S
Detecting activated protein C resistance (and the factor V R506Q [Leiden] mutation if indicated)
Detecting the prothrombin G20210A mutation
An interpretive report will be provided.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
To obtain the most useful information, this testing is best performed in medically stable patients who are not receiving oral vitamin K inhibitor (eg, warfarin, Coumadin), heparin, low-molecular-weight heparin, hirudin (Refludan), argatroban, fibrinolytic agents (eg, streptokinase, tissue plasminogen activator), or platelet GPIIbIIIa (alpha IIb beta3) inhibitors (abxicimab [ReoPro], tirofiban, aggrastat). However, useful information can be obtained in patients receiving anticoagulation therapy.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
College of American Pathologists Consensus Conference XXXVI: diagnostic issues in thrombophilia. Arch Pathol Lab Med. 2002;126:1277-1433