Thrombosis Risk Tests Health Article

Definition

Thrombosis risk tests check for defects in the anti-coagulant system (hypercoagubility) that can cause a predisposition to thrombosis. The D-dimer test is used to screen for the presence of fibrin associated with deep vein and other forms of thrombosis.

Purpose

The purpose of thrombosis risk tests is to establish whether someone has a predisposition for developing thrombosis or has suffered a thrombotic episode, so that appropriate interventions can be instituted. The most common thrombosis risk tests are the D-dimer test, protein C test, protein S test, factor V Leiden test, prothrombin 1+2 (prothrombin 1.2) test, and the antithrombin test. These tests can be ordered individually but are usually ordered as a part of a panel.

Common indications for testing include:

• venous thrombosis
• pulmonary embolism
• cerebral brain thrombosis
• transient ischemic attack or premature stroke
• peripheral vascular disease
• prior to pregnancy, oral contraceptive prescription, estrogen therapy or major surgery if there is a family history of thrombosis
• relative with known genetic predisposition to thrombosis
• history of thrombosis and presence of a known genetic predisposition to thrombosis
• previous laboratory finding of activated protein C resistance (indication for factor V Leiden DNA test)
• premature myocardial infarction in a female patient (indication for prothrombin DNA test)
• history of multiple unexplained miscarriages

Precautions

Treatment with Coumadin, an anticoagulant, can interfere with the protein C and protein S tests. Ideally, the patient should discontinue treatment with Coumadin two weeks prior to undergoing these tests. If this is not possible then, an alternate panel of risk tests should be used. Alternatively heparin therapy can replace Coumadin therapy for two weeks prior to the tests, although heparin anticoagulant therapy can sometimes result in false positive antithrombin III test results. Protein S assays are not reliable during pregnancy. Heterophilic antibodies and rheumatoid factor are known to cause false positive reactions for D-dimer.

Description

The D-dimer test is the only laboratory test that is used to screen for the presence of deep vein thrombosis. The test is positive only when fibrin has formed. The D fragment of fibrinogen is produced by the action of plasmin on fibrinogen. Thrombin activates factor XIII, which stabilizes the fibrin clot by dimerizing the D fragments. In disseminated intravascular coagulation, pulmonary embolism, deep vein thrombosis, sickle cells disease and other conditions such as post surgical thrombus formation, the D-dimer level will be elevated in serum or plasma. D-dimer is measured by immunoassay, either latex agglutination or enzyme immunoassay (EIA). Latex agglutination is a qualitative assay that is not sufficiently sensitive to screen for deep vein thrombosis. Levels measured by EIA below 200 ng/ml indicate that thrombosis is unlikely in patients with no apparent signs of deep vein thrombosis.

Prothrombin fragment 1.2 (1+2), like D-dimer, is a marker for thrombotic disease. Prothrombin fragment 1+2 (1.2) can be measured by enzyme immunoassay. This fragment is produced when factor Xa activates prothrombin. The prothrombin fragment is increased in persons at risk for thrombotic episodes.

Other thrombosis risk tests check for mutations in the genes or proteins that are involved in the anticoagulant system. The anticoagulant system is designed to regulate coagulation and prevent excess blood clotting. Each anticoagulant protein is produced by a different gene. Each person possesses two copies of each anticoagulant gene. Mutation in an anticoagulant gene can cause it to produce abnormal protein, an increased or decreased amount of normal protein or can cause it to stop producing protein altogether. The common anticoagulant abnormalities (protein S, protein C, antithrombin III, prothrombin and factor V Leiden) are autosomal dominant, since only one gene of a pair needs to be altered to cause an increased risk of thrombosis. Someone with one normal copy of an anticoagulant gene and one changed copy of an anticoagulant gene (heterozygote) will have a moderately increased risk of thrombosis. Someone with both copies of an anticoagulant gene changed (homozygous) will have a significantly increased risk of thrombosis. People who have changes in multiple anticoagulant genes also have a significantly increased risk of thrombosis. There are other genetic and environmental factors that affect the risk of thrombosis, making it difficult to predict the exact risk in an individual with an anticoagulant gene mutation.

In some cases a thrombosis risk test checks for a change in the anticoagulant gene. In other cases, it is not feasible to check for a gene change and the activity of the protein is assayed.