Hypercoagulable disorders


Also known as: Clotting disorders
Last Review Date: November 1, 2019


Laboratory tests

The major aims of managing patients with blood clots is to initiate therapy to resolve the acute blood clot, then to determine what clinical factors (including immobility, smoking, oral contraceptives, pregnancy, hormone replacement therapy), inherited conditions and laboratory abnormalities may have contributed to the formation of the blood clot. Clinicians are then able to determine the long-term risk for the patient of recurrent blood clot formation. It should be noted that laboratory testing is only one component of this process and that interpreting these results and determining the need for further blood thinning may require referral to a haematology specialist.

Tests which may be undertaken to assist the haematologist in determining the risk of recurrent blood clots include: PT, APTT, FBC, activated protein C resistance (APCR), Factor V mutation (Leiden) assay (when APCR is abnormal), homocysteine, cardiolipin antibodies, protein C, protein S, antithrombin and a prothrombin 20210 mutation test. If the APTT testing is prolonged, lupus anticoagulant testing may be performed.

Testing may be affected by the type of anticoagulant medications that a patient is taking and underlying medical conditions including pregnancy. As such, testing may not be completed in one session and may require repeat testing when a patient is not taking anticoagulant medications.

Tests for hypercoagulable disorders
Test Measures Ordered When/To Abnormal Results May Indicate
Cardiolipin antibodies Presence of antibody Evaluate recurrent blood clots and/or miscarriages Antiphospholipid syndrome
Antithrombin activity  Activity of antithrombin Evaluate recurrent blood clots Low activity may increase thrombotic risk
Antithrombin 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 mutation (Leiden)
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 formation 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 mutation (Leiden) 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, increased use, or a functional defect. May be elevated with inflammation as, it is an acute phase reactant
Homocysteine Level in blood Recurrent blood clots If elevated, increased cardiac risk and risk of arterial thrombosis. Also elevated with vitamin B12 or folate deficiency
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 arterial and venous thrombosis
LA-sensitive APTT
(PTT-LA)
Time to clot formation 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 aetiology. 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 an 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
Prothrombin Time (PT) Time to clot formation As part of an initial workup for bleeding or clotting, monitor anticoagulant therapy Prolonged PT is suspicious for a coagulation factor deficiency and suggests the need for additional tests.
Warfarin therapy is monitored with the International Normalised Ratio (INR) which is a test based on the PT. The INR assists medical staff to determine how effective the warfarin is at preventing unwanted clotting.
APTT (actvated partial thromboplastin time) Time to clot formation 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)

Treatment

Your doctor should discuss with you the predisposing conditions which contributed to the blood clot formation and then determine your risk of recurrent blood clots. You will then need to work with your doctor to determine if there is a need for long term anticoagulant therapy to attempt to reduce the risk of recurrent blood clots.

Treatment options for blood clots may involve a combination of injections (heparin, low-molecular weight heparin), tablets (Warfarin, Rivaroxaban, Apixaban, Dabigatran) and compression stockings. There is often an overlapping period between injections of heparin and other forms of treatment. Some of these anticoagulant medicines require ongoing testing in the laboratory to make sure that the level of anticoagulation is appropriate – not so high as to cause bleeding and not too low to allow adequate blood clot resolution.

In general blood clots are treated for a period of time ranging from a few weeks for minor clots to a minimum of 12 months therapy in patients who have a large blood clot and a high risk of recurrent blood clot formation. For patients deemed at high risk of recurrent blood clot, the patient may be recommended to stay on anticoagulation or other medications (Aspirin) life-long.

Other risk factors for recurrent blood clots should also be addressed with the patient including: stopping smoking, changing oral contraceptive preparations and the use of low dose anticoagulants in high-risk situations (prophylaxis).

Those who are on continued anticoagulant therapy will have to plan ahead, with the help of their doctor, when they require procedures and surgeries. These usually involve taking the patient off of their anticoagulant for a short period of time prior to their surgery. However, current recommendations suggest that warfarin does not need to be withheld for dental procedures. Following surgery, most patients, including those who do not have known hypercoagulable disorders, will receive a course of preventative anticoagulation. This is especially true after procedures such as hip or knee replacement surgery that may increase a patient’s risk of clotting, either because of the nature of the surgery itself or because of immobilisation and an extended recovery after the surgery.

Patients who are pregnant and have a blood clot will usually receive subcutaneous anticoagulation with low-molecular weight heparin. Patients who have antithrombin deficiencies may benefit from antithrombin factor replacement when they cannot take anticoagulant therapy (for example, around the time of surgery). Protein C concentrates can be used to temporarily replenish protein C deficiencies, and aspirin therapy (which affects platelet function) may be useful in some instances.


Related pages

On this site
Tests: APTT, antithrombin, FBC, coagulation factors, D-dimer, fibrinogen, anti Xa levelshomocysteine, lupus anticoagulant, proteins C and protein S, PT, PT 20210 and Factor V mutation (Leiden)
Conditions: Bleeding disorders, liver disease, SLE

Elsewhere on the web
healthdirect: Blood coagulation disorders 
American Heart Association: Hypercoagulation 

Web MD – Deep Venous Thrombosis