Excessive Clotting Disorders

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Laboratory Tests

Initial testing is usually performed to determine if a person has or has had a blood clot (thrombotic episode) and, if so, to help determine the person's risk of a repeat thrombotic episode. Although it may be fairly simple to identify that a person has a clot, identification of the underlying cause may take more time and effort. This is because several of the diagnostic tests that need to be done are affected by an existing or recent blood clot and by any anticoagulant therapy that is given. Often, the doctor may have to order a few tests and treat the person's existing blood clot first. Several weeks or months later, when he is able to take the person off of anticoagulant therapy, the doctor can order other tests to finish his evaluation of the cause of the clotting. Follow-up testing is important in helping to determine a person's risk of developing recurrent blood clots.

The table below lists some of the tests in alphabetical order. For detailed information about each test, click on the name of the test to go to the specific article.

Not all of the tests listed in the table are needed for each person with excessive clotting disorders. If somebody has been diagnosed as having a blood clot in a vein (venous thrombosis), the first step is to rule out obvious causes of acquired thrombosis, including malignancy, major surgery (e.g., orthopedic), trauma, immobilization, congestive heart failure, myeloproliferative neoplasms, or nephrotic syndrome. Routine tests including PTT, PT, fibrinogen activity, and D-dimer are generally performed. As to other tests, the following general guide is used to determine what tests should be performed based on patient age and personal and family history.

  • If a person has a first episode of venous thrombosis at an age younger than 50, or has a history of recurrent clotting episodes, or has a parent, sibling or child (first-degree relative) with documented thromboembolism at age younger than 50, then a test panel is often performed, including factor V Leiden mutation and prothrombin gene G20210A mutation, antiphospholipid antibodies (including lupus anticoagulant work-up), homocysteine, protein C, protein S and antithrombin. If results of these tests are not revealing, additional tests may be needed to rule out rare causes of clotting disorders.
  • If a person has a first episode of venous thrombosis at an age older than 50 without known acquired risk factors and there is no personal or family history of recurrent episodes, then a limited test panel is often performed, including factor V Leiden mutation and prothrombin gene G20210A mutation, antiphospholipid antibodies (including lupus anticoagulant) and homocysteine.

The medical and family histories plus laboratory testing may reveal that a person has more than one factor or condition that increases their risk of excessive clotting, and the resulting risk can be cumulative. For example, a person whose laboratory tests indicates the presence of Factor V Leiden mutation will likely be at greater risk if they also are bed-ridden or hospitalized for some time (prolonged immobilization).

Tests for Excessive Clotting

Test DescriptionOrdered When/ToAbnormal Results May Indicate
Anticardiolipin antibodies
(Includes cardiolipin antibody, beta-2 glycoprotein antibody, and lupus anticoagulant)
Detects the presence of one or more of these antibodies To evaluate recurrent blood clots and/or miscarriages Antiphospholipid Syndrome
Antithrombin Activity Measures the activity of antithrombin
To evaluate someone for recurrent blood clots; to detect acquired or inherited deficiency Low activity may increase risk of clots
Antithrombin Antigen Measures quantity of antithrombin When results from the test for activity are consistently low Decreased production or increased use of factor; may increase thrombotic risk
D-dimer Detects or measures the level of a specific type of fibrin degradation product Used to detect and evaluate for the presence of a blood clot  If elevated, indicates recent clotting activity; may be due to acute or chronic condition, such as a thromboembolism or DIC (disseminated intravascular coagulation)
Factor V Leiden mutation (may include activated protein C resistance testing)
Identifies a genetic mutation that results in formation of an activated Factor V that resists degradation by activated protein C When an inherited risk factor is suspected as a cause of a blood clot The presence of the mutation Increases the risk of thrombosis
Fibrinogen Tests measure the function and the amount of fibrinogen As part of an evaluation for a clotting disorder 
If low, may indicate decreased production or increased use; may be elevated with inflammation; it is an acute phase reactant
Flow cytometry Presence of certain surface proteins on blood red cells and white cells When paroxysmal nocturnal hemoglobinuria (PNH) is suspected Increased risk of venous thrombosis (abdominal and cerebral veins)
Homocysteine Measures the level in blood To determine a cause of recurrent blood clots If elevated, increased cardiac risk and risk of thrombosis
Lupus Anticoagulant (LA)
(Panel of tests may include LA-sensitive PTT, Dilute Russell Viper Venom Test (DRVVT), and/or Platelet Neutralization Procedure (PNP))
Panel of tests used to check for Lupus anticoagulant To evaluate someone with recurrent blood clots and/or miscarriages; when results of the PTT are prolonged When PTT or LA sensitive PTT and DRVVT are prolonged, it suggests LA, usually confirmed with additional testing; if present, increased risk of thrombosis
Methylenetetrahydrofolate Reductase (MTHFR) Identifies genetic mutation Used when the homocysteine level is elevated with no clear acquired etiology Presence of the mutation confers an increased risk for developing elevated homocysteine levels
Protein C Activity Function of Protein C To evaluate someone for recurrent blood clots; may be acquired or inherited deficiency or dysfunction Protein C helps regulate blood clot formation by degrading activated Factors V and VIII. If activity is low, there is an increased risk of thrombosis.
Protein C Antigen
Quantity of Protein C Tested when Protein C activity is low. If decreased, may be due to inherited or acquired condition; increased risk of thrombosis
Protein S Activity Function of Protein S As part of an evaluation of recurrent blood clots; may be acquired or inherited deficiency or dysfunction 
Protein S is a cofactor that helps Protein C regulate clot formation.
Protein S Antigen (free and total) Quantity of total and free Protein S Tested when Protein S activity is low. Only free Protein S is available to assist Protein C; total protein S includes free protein S and inactive bound protein S.
Prothrombin 20210 mutation Detects inherited genetic mutation When a person has recurrent blood clots and an inherited risk factor is suspected If present, increases risk of thrombosis
PTT (Partial Thromboplastin Time) Measures the time it takes for a clot to form in a blood sample  As part of an initial workup; screens for lupus anticoagulant; also used to monitor anticoagulant therapy A prolonged PTT suggests need for further tests; may indicate nonspecific inhibitor (such as lupus anticoagulant)

Non-Laboratory Tests

One or more of the following imaging studies may be used to detect the presence of a blood clot and/or examine blood vessels:

  • Ultrasound
  • CT scan (e.g., CT angiography)
  • MRI

For additional details on imaging procedures used to examine blood vessels, visit Radiologyinfo.org.  

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