Several tests are used to detect factor V Leiden mutation, including the polymerase chain reaction-based test and the modified activated partial thromboplastin time (aPTT)-based test. The latter can be given to patients who are receiving anticoagulants. The results indicate the ratio of activated protein C (APC), and a finding of <2.0 is considered abnormal.8 The presence of lupus anticoagulant—autoantibodies that bind to phospholipids and proteins associated with the cell membrane—may yield a false-positive result on the modified aPTT test.
While the prothrombin G20210A mutation is linked to elevations in prothrombin, measuring prothrombin levels is not an accurate way to test for this hypercoagulable state. The prothrombin G20210A mutation generally is detected through DNA analysis instead.2,8
Hyperhomocysteinemia is diagnosed by measuring fasting plasma levels of homocysteine. Although the results are not standardized, they generally correlate with the severity of disease (mild, 15-30 μmol/L; moderate, >30-100 μmol/L; severe, >100 μmol/L). However, plasma levels may be falsely elevated during an acute thrombotic episode and decreased by supplementation with folic acid, B6, and B12. The decrease, however, does not indicate a reduction in the risk of thrombosis.
Treatment, yes, but for how long?
Most thrombotic events are initially treated with a combination of a heparin product (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) and warfarin—commonly known as bridging therapy. The heparin is discontinued once the patient’s international normalized ratio (INR) has been maintained at a therapeutic level for more than 24 hours, which usually takes about 5 days. Warfarin therapy, however, should continue for at least 3 to 6 months, depending on the severity and cause of the thrombosis.
Individuals with an AT, protein C, or protein S deficiency may be at increased risk of recurrence, and long-term anticoagulant therapy may be warranted.5 Under current guidelines from the American College of Chest Physicians (ACCP), however, hereditary thrombophilias are not considered to be major determinants of recurrence or a major factor guiding the duration of anticoagulation therapy.10 Practitioners must use their judgment to determine the need for treatment; if anticoagulation therapy is initiated, the duration should be based on an individual assessment of benefit and risk.
Recognizing and responding to acquired risks
Several conditions associated with vessel wall changes and venous stasis—the hallmarks of acquired hypercoagulable states—put patients at increased risk of venous thrombosis. Following is a review of the most likely risk factors, including antiphospholipid antibody syndrome (APS), previously known as lupus anticoagulant syndrome; heparin-induced thrombocytopenia (HIT); pregnancy; trauma; estrogen; and malignancy.
When to test for—and treat—APS
APS, a systemic autoimmune disorder that can result in arterial or venous thrombosis or pregnancy loss and morbidity, is characterized by the presence of autoantibodies. Patients of all ages may be affected by APS, one of the most common acquired hypercoagulability disorders. APS affects an estimated 28% of the general population.2 About 15% of recurrent pregnancy losses and 20% of recurrent thromboses in young adults are attributed to this autoimmune disorder.11
A definitive diagnosis of APS requires a history of either vascular thrombosis or pregnancy morbidity—defined as miscarriage after the 10th gestational week, consecutive fetal losses before the 10th gestational week, or placental insufficiency and premature birth before 34 weeks.11,12 APS testing may be useful in patients with cerebral vein thrombosis, intra-abdominal vein thrombosis, or unexplained recurrent fetal loss.9
In addition to clinical criteria, a diagnosis of APS is based on the presence of plasma antibodies on 2 or more occasions at least 12 weeks apart. APS encompasses 3 types of antiphospholipid antibodies—lupus anticoagulant antibodies, anticardiolipin antibodies, and anti-beta 2-glycoprotein I antibodies—which can be detected with 2 different tests. Coagulation assays are used to identify lupus anticoagulant antibodies because they prolong clotting time; however, immunoassays are used to measure immunologic reactivity to phospholipids to determine the presence of anticardiolipin antibodies and anti-beta 2-glycoprotein I antibodies.11,12
Treatment for APS generally involves anticoagulant therapy for the prevention and treatment of acute thrombotic events, or as prophylaxis during pregnancy. ACCP guidelines call for initiating warfarin therapy with a target INR of 2.5 (range 2.0-3.0) in patients with no other risk factors. In patients who have had recurrent thromboembolic events or have additional risk factors, a target INR of 3.0 (range 2.5-3.5) is suggested.10 LMWH and UFH are also options for use in the event of recurrence or for prophylaxis during pregnancy.11,13,14