Thrombophilia

Thrombophilia, or hypercoagulability, is a disorder of hemostasis that predisposes to thrombosis. Thrombophilia may be congenital or acquired. Thrombosis may be defined as cardiovascular disease, including peripheral vascular disease, transient ischemic attack, stroke, angina, or acute myocardial infarction. In the context of the coagulation system, thrombosis is usually defined as venous thromboembolic disease including deep venous thrombosis (DVT) or pulmonary embolism (PE).

Why Perform Thrombophilia Testing?
Circumstantial Thrombophilia Risk Factors
Disease-Related Thrombophilia Risk Factors
Reasons To Order a Laboratory Profile For Thrombophilia
Primary Thrombophilia Laboratory Test Profile
Acute Thrombophilia Test Profile
Lupus Anticoagulant Reflexive Test Profile
Risk of Thrombosis for Acquired Thrombophilia Factors
Prevalence Levels For Congenital Thrombophilia Factors
Risk of Thrombosis for Congenital Thrombophilia Factors

Why Perform Thrombophilia Testing?

* Influences duration and intensity of therapy during thrombosis episode.
* Offers prophylaxis for those at risk prior to surgery or periods during which they are exposed to risk.
* Determines need for alternative laboratory testing when condition affects primary testing mode.
* Not useful during acute episodes.
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Circumstantial Thrombophilia Risk Factors

* Thrombosis risk increases with age
* Previous thrombosis
* Pregnancy, oral contraceptives, hormone replacement therapy
* Immobilization: travel, bedfast, wheelchair
* Diet, obesity = lipids and immobilization
* Orthopedic surgery, neurosurgery
* Trauma, fractures
* Blood group non-O (increased VWF and VIII)
* Smoking
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Disease-Related Thrombophilia Risk Factors

* Autoimmune disorders
   -Lupus erythematosus and other collagen diseases
   -Antiphospholipid syndrome
* Malignancies
   -Adenocarcinoma
   -Myeloproliferative diseases (CML, PV)
   -Acute leukemia, especially M3, M5
   -Paroxysmal nocturnal hemoglobinuria
* Chronic inflammatory disease
   -Chronically elevated factor VIII and fibrinogen
* Congestive heart failure
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Reasons To Order a Laboratory Profile For Thrombophilia

* Venous thrombosis before 40-50 years of age
* Spontaneous or unexplained thrombosis
* Recurrent thromboses
* Thromboses at unusual sites
* Positive family history for thrombosis
* Unexplained abnormal laboratory test such as a prolonged PTT
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Primary Thrombophilia Laboratory Test Profile

Order the following series of assays to assess risk for thrombosis when the patient is not taking an anticoagulant such as Coumadin or heparin and has taken no anticoagulant for at least ten days. Further, the following assays are valid as thrombosis risk predictors only if the patient has not had a thrombotic event in the past six months.Activated protein C resistance (APCR)-perform factor V Leiden mutation assay when the ratio is below the lower limit of the reference interval, indicating resistance
* Lupus anticoagulant testing and anticardiolipin antibodies
* Antithrombin activity-follow up with antithrombin antigen assay when activity is below normal
* Homocysteine
* Factor VIII activity
* Protein C activity-follow up with protein C antigen assay when activity is below normal
* Protein S activity-follow up with protein S total and free antigen assays when activity is below normal
* Prothrombin 20210 mutation
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Acute Thrombophilia Test Profile

Order the following assays to assess risk for thrombosis when the patient is currently taking an anticoagulant such as Coumadin or heparin or has taken an anticoagulant within the last ten days. Further, the following assays are valid as thrombosis risk predictors even if the patient has had a thrombotic event in the past six months.Activated protein C resistance (APCR)-perform factor V Leiden mutation assay when the ratio is below the lower limit of the reference interval, indicating resistance
* Anticardiolipin antibodies
* Prothrombin 20210 mutation
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Lupus Anticoagulant Reflexive Test Profile

Lupus anticoagulant testing requires at least two clot-based assays performed in two stages. Most specialty coagulation laboratories perform the PTT using a low phospholipid reagent such as Diagnostica Stago's PTT-LA®specifically designed to detect lupus anticoagulant and the dilute Russell's viper venom time (DRVVT) test. Coumadin affects the results of the DRVVT and heparin affects the PTT-LA.
* Primary stage of lupus anticoagulant testing: prolonged PTT with failure to correct upon mixing, prolonged PTT-LA, or prolonged DRVVT.
* Confirmatory stage of lupus anticoagulant testing: correction of prolonged PTT-LA, integrated test results such as the Sta-Clot-LA®or DRVVT correction with high phospholipid reagent as in Precision BioLogic DVV-Confirm®.
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Risk of Thrombosis for Acquired Thrombophilia Factors

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Prevalence Levels For Congenital Thrombophilia Factors

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Risk of Thrombosis for Congenital Thrombophilia Factors

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