Hypercoagulable disorders

Laboratory Tests

Although it may be fairly simple to identify that a patient has a clot, identification of the 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 clots first. Several weeks or months later, when s/he is able to take the person off of anticoagulant therapy, the doctor can order other tests to finish their evaluation of the cause of the clotting. Follow-up testing is important in helping to determine a patient’s risk of developing recurrent blood clots.

Initial testing may include: a PT, aPTT, FBC, activated protein C resistance (APCR), Factor V Leiden mutation assay (when APCR is abnormal), homocysteine, anticardiolipin antibodies, and a prothrombin 20210 mutation test. If the aPTT testing is prolonged, lupus anticoagulant testing may be done later, along with protein C, protein S, and antithrombin (III).

In general, testing may include:

Test Measures Ordered When/To Abnormal results may indicate

Anticardiolipin antibodies Presence of antibody Evaluate recurrent blood clots and/or miscarriages Antiphospholipid syndrome

Antithrombin (III) activity Activity of antithrombin Evaluate recurrent blood clots Low activity may increase thrombotic risk

Antithrombin (III) antigen Quantity of antithrombin Activity is consistently low Decreased production or increased use of factor, may increase thrombotic risk

APCR (activated protein C resistance) Resistance to degradation of activated factor V by APC Evaluate recurrent blood clots Need to confirm by checking for Factor V Leiden mutation

D-dimer Level of a specific type of crosslinked fibrin degradation product Evaluate blood clot formation during bleeding and clotting episodes If elevated, indicates recent clotting activity. May be due to acute or chronic condition, such as a thromboembolism or DIC (disseminated intravascular coagulation)

Dilute Russell Viper venom test (dRVVT) Time to clot test, evaluates the common pathway of coagulation. Dilute refers to lipid concentration. Evaluate recurrent blood clots, when aPTT is prolonged, looking for a lupus anticoagulant. When prolonged, suggests lupus anticoagulant may be present, increased risk of thrombosis.

Factor V Leiden mutation Genetic mutation that results in formation of an activated Factor V that resists degradation by APC Recurrent blood clots Increased risk of thrombosis

FDP (fibrin degradation products) Reflection of clotting and fibrinolytic (clot breakdown) activity Evaluate bleeding and clotting If increased, indicates recent blood clot formation and breakdown

Fibrinogen Amount of fibrinogen in the circulation. Evaluate bleeding and clotting If low, may indicate decreased production or increased use, may be elevated with inflammation, it is an acute phase reactant

Homocysteine Level in blood Recurrent blood clots If elevated, increased cardiac risk and risk of thrombosis

Lupus anticoagulant (LA) Panel of tests are used to check for lupus antibody Recurrent blood clots and/or miscarriages, prolonged aPTT When aPTT or LA sensitive aPTT and dRVVT are prolonged it suggests LA, usually confirmed with additional testing; if present, increased risk of thrombosis

LA-sensitive aPTT
(PTT-LA) Time to clot test When lupus anticoagulant (LA) suspected If prolonged and ‘corrects’ to normal when phospholipids added, may be due to LA

Methylene-
tetrahydrofolate reductase (MTHFR) Genetic mutation Homocysteine level is elevated with no clear acquired etiology. Increased risk for developing elevated homocysteine levels.

Platelet neutralisation procedure (PNP) Timed test using either the aPTT or the dRVVT, using platelets as a source of phospholipids Evaluate prolonged aPTT and recurrent blood clots If test corrects to normal with the addition of platelets, may indicate presence of a lupus anticoagulant

Protein C activity Function of Protein C Recurrent blood clots Protein C helps slow down the coagulation cascade 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 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 Recurrent blood clots Protein S is a cofactor, helps protein C

Protein S antigen (free and total) Quantity of total and free protein S When protein S activity low Only free protein S is available to assist protein C; total protein S includes free protein S and protein S bound to C4b-binding protein.

Prothrombin 20210 mutation Genetic mutation Recurrent blood clots Increased risk of thrombosis

PT Time to clot As part of an initial workup for bleeding or clotting, monitor anticoagulant therapy Prolonged PT suggests need for additional tests

aPTT (actvated partial thromboplastin time) Time to clot test, Evaluates the intrinsic and common pathways of coagulation cascade Screens for lupus anticoagulant, monitor anticoagulant therapy Prolonged aPTT suggests need for further tests. May indicate nonspecific inhibitor (such as lupus anticoagulant)