Antiphospholipid Antibodies

Synonym/Acronym

anticardiolipin antibody (ACA); anti–beta-₂ glycoprotein 1 (Beta-₂ GP1), apolipoprotein H; lupus anticoagulant (LA, lupus antiphospholipid antibodies, lupus inhibitor phospholipid type).

Rationale

To detect the presence of antiphospholipid antibodies, which can lead to the development of blood vessel problems (thrombosis), systemic lupus erythematosus (SLE), and complications including stroke, heart attack, and miscarriage.

Patient Preparation

There are no food, fluid, activity, or medication restrictions unless by medical direction for ACA and beta-₂ GP1.

There are no food, fluid, or activity restrictions unless by medical direction for LA. Heparin or Warfarin (Coumadin) therapy should be noted on the test request or discontinued before LA specimen collection, with medical direction.

Normal Findings

Method: Enzyme-linked immunosorbent assay (ELISA) for ACA: and beta-₂ GP1: Negative (Less than 15 GPL); Dilute Russell viper venom test time for LA: Ratio less than 1.2 (value of patient sample/value of normal control sample).

Critical Findings and Potential Interventions ⬆ ⬇

Overview ⬆ ⬇

(Study type: Blood collected in a red-top tube for ACA and beta-₂ GP1; blood collected in a completely filled blue-top [3.2% sodium citrate] tube; related body system: Circulatory, immune, and reproductive systems. If the patient’s hematocrit exceeds 55%, the volume of citrate in the collection tube must be adjusted. Fill tube completely. Important note: When multiple specimens are drawn, the blue-top tube should be collected after sterile [i.e., blood culture] tubes. Otherwise, when using a standard vacutainer system, the blue-top tube is the first tube collected. When a butterfly is used, due to the added tubing, an extra red-top discard tube should be collected before the blue-top tube to ensure complete filling of the blue-top tube. Promptly transport the specimen to the laboratory for processing and analysis. The recommendation for processed and unprocessed samples stored in unopened tubes is that testing should be completed within 1 to 4 hr of collection.)

ACA

ACA is one of several identified aPL antibodies associated with antiphospholipid syndrome (APS), an autoimmune disease primarily identified in women of age 30 to 40 years. ACAs are of IgG, IgM, and IgA subtypes produced by cells of the immune system, which react with proteins in the blood that are bound to phospholipid and interfere with normal blood vessel function. IgG and IgM subtypes are primarily used to identify the presence of aPL antibodies. The primary types of problems they cause are narrowing and irregularity of the blood vessels, blood clots in the blood vessels, and miscarriages. ACAs are found in individuals with SLE, lupus-related conditions, infectious diseases, and drug reactions. ACAs are often found in association with lupus anticoagulant, another important aPL.

Beta-₂ Glycoprotein 1

Beta-₂ glycoprotein 1 is another important aPL, believed in some respects to be more specific than ACA because it does not produce false-positive findings in specimens of patients with infectious diseases (e.g., syphilis). The serum of normal individuals contains low concentrations of IgG autoantibodies to beta-₂ GP1. Significantly elevated levels of beta-₂ GP1 antibodies occur in patients with APS and systemic rheumatic diseases (e.g., SLE).

The term lupus anticoagulant is misleading. LAs were first identified between the late 1940s and early 1950s in the sera of some patients diagnosed with SLE. They interfered with phospholipid-dependent coagulation tests such as activated partial thromboplastin time (aPTT) by reacting in vitro with the phospholipids in the test system and hence the label lupus anticoagulant. However, in vivo, LA actually increases the risk of developing blood clots. While the presence of LA is associated with SLE, not all patients with LA have SLE.

Determination of Antiphospholipid Antibody Syndrome

The combination of noninflammatory thrombosis of blood vessels, low platelet count, and history of miscarriage is termed antiphospholipid antibody syndrome. It is documented as present if at least one of the clinical and one of the laboratory criteria are met.

Clinical criteria

Vascular thrombosis: One or more events of arterial, venous, or small vessel thrombosis confirmed by histopathology or imaging studies.
Pregnancy morbidity defined as either one or more unexplained deaths of a morphologically normal fetus at or beyond the 10th wk of gestation; one or more premature births of a morphologically normal neonate before the 34th wk of gestation due to eclampsia, severe pre-eclampsia, or placental insufficiency; or three or more unexplained consecutive spontaneous abortions before the 10th wk of gestation, where maternal and paternal abnormalities have been excluded.

Laboratory criteria (according to recommended procedures)

ACA IgG or IgM detectable at moderately elevated to high levels on two or more occasions at least 12 wk apart (standardized ELISA).
Lupus anticoagulant (LA) detectable on two or more occasions at least 12 wk apart (dilute Russell viper venom time).
Anti–beta-₂ glycoprotein 1 antibody, IgG, or IgM detectable on two or more occasions at least 12 wk apart (standardized ELISA).

Indications ⬆ ⬇

ACA and Beta-₂ GP1

Assist in the diagnosis of APS (e.g., predisposition to formation of blood clots, cause of recurrent miscarriage).

Evaluate an unexplained, prolonged aPTT.
Assist in investigating suspected APS.

Interfering Factors ⬆ ⬇

ACA

Drugs and other substances that may increase anticardiolipin antibody levels include antimicrobials (penicillins), anticonvulsants (phenytoin), antidysrhythmics (procainamide and quinidine), antipsychotics (chlorpromazine), and vasodilators (hydralazine).

Beta-₂ GP1

Drugs and other substances that may decrease beta-₂ GP1 antibody levels include estrogens.

Drugs and other substances that may cause a positive LA test result include calcium channel blockers, chlorpromazine, heparin, hydralazine, hydantoins, isoniazid, methyldopa, phenytoin, phenothiazines, procainamide, quinine, and quinidine.
Heparin will cause falsely prolonged results of some coagulation studies performed in the LA panel.
Placement of a tourniquet for longer than 1 min can result in venous stasis and changes in the concentration of plasma proteins to be measured. Platelet activation may also occur under these conditions, causing erroneous results.
Vascular injury during phlebotomy can activate platelets and coagulation factors, causing erroneous results.
Hemolyzed specimens must be rejected because hemolysis is an indication of platelet and coagulation factor activation.
Icteric or lipemic specimens interfere with optical testing methods, producing erroneous results.
Hematocrit greater than 55% may cause falsely prolonged results because of anticoagulant excess relative to plasma volume.
Incompletely filled collection tubes, specimens contaminated with heparin, clotted specimens, or unprocessed specimens not delivered to the laboratory within 1 to 2 hr of collection should be rejected.

Other Considerations

Cardiolipin antibody is partially cross-reactive with syphilis reagin antibody and lupus anticoagulant. False-positive rapid plasma reagin results may occur.
Note: It has been documented that clot-based detection methods (such as dilute Russell viper venom) for LA testing produce unreliable results when performed on specimens of patients being treated with direct oral anticoagulants (DOACs) such as apixaban, betrixaban, dabigatran, edoxaban, etexilate, or rivaroxaban. If testing on these patients is deemed essential, specimen collection should take place at the time of the drug’s trough level. For additional information regarding current strategies to provide safe patient care for patients receiving DOACs, refer to the study titled “Prothrombin Time and International Normalized Ratio.” ELISA methods for ACA and beta-₂ GP1 are unaffected by DOACs.

Potential Medical Diagnosis: Clinical Significance of Results ⬆ ⬇

Increased In

ACA

Although ACAs are observed in specific diseases, the exact mechanism of these antibodies in disease is unclear. In fact, the production of ACA can be induced by bacterial, treponemal, and viral infections. Development of ACA under this circumstance is transient and not associated with an increased risk of antiphospholipid antibody syndrome. Patients who initially demonstrate positive ACA levels should be retested after 6 to 8 wk to rule out transient antibodies that are usually of no clinical significance.

Antiphospholipid antibody syndrome
Chorea
Drug reactions
Epilepsy
Infectious diseases
Mitral valve endocarditis
Patients with lupus-like symptoms (often antinuclear antibody–negative)
Placental infarction
Pre-eclampsia
Recurrent fetal loss (strong association with two or more occurrences)
Recurrent venous and arterial thromboses
Stroke (in adults under the age of 50 yr)
SLE

Beta-₂ GP1

Antiphospholipid antibody syndrome

Antiphospholipid antibody syndrome (LA are nonspecific antibodies associated with this syndrome)
Fetal loss (thrombosis associated with LA can form clots that lodge in the placenta and disrupt nutrition to the fetus)
Raynaud disease (LA can be detected with this condition and can cause vascular inflammation)
Rheumatoid arthritis (LA can be detected with this condition and can cause vascular inflammation)
SLE (related to formation of thrombi as a result of LA binding to phospholipids on cell walls)
Thromboembolism (related to formation of thrombi as a result of LA binding to phospholipids on cell walls)

Decreased In

N/A

Nursing Implications ⬆

Before the Study: Planning and Implementation

Teaching the Patient What to Expect

Discuss how this test can assist in evaluating the amount of potentially harmful circulating antibodies that can cause blood clots or adversely affect a normal pregnancy.
Explain that a blood sample is needed for the test.

After the Study: Implementation & Evaluation Potential Nursing Actions

Treatment Considerations

Encourage discussions about feelings related to clinical events by listening with caring and concern.
Consider that fatigue can occur from multiple causes and contribute to mobility, activity, and self-care concerns. Some contributory causes to consider are loss of sleep, anemia, or depression. Simple interventions include pacing activities to preserve energy stores, identifying what aggravates and decreases fatigue, and assessing for related emotional factors. Collaborate with physical therapy to splint joints and avoid prolonged periods of inactivity that could exacerbate joint pain and stiffness. Assess the level of active participation in the provision of self-care associated with the activities of daily living.
Interventions/actions include the following: Explain that autoimmune diseases like APS and SLE, if undiagnosed, can be fatal. Assess coping skills, including family and social support. Note that pain management is an important aspect of care requiring a careful assessment of which pain management modality provides the best relief. Discuss what has worked to relieve joint pain in the past. Discuss the effect of pain on personal, social, and professional obligations. Identify activities that may aggravate pain. Discuss interventions such as the application of heat or cold to the best effect. Administer ordered medications such as opioids or anti-inflammatory medication. Assess the level of active participation in the provision of self-care associated with the activities of daily living.

Clinical Judgement

Consider how the emotional impact associated with clinical events can adversely influence health-care choices.

Follow-Up Evaluation and Desired Outcomes

Acknowledges contact information provided for the American College of Rheumatology (www.rheumatology .org/I-Am-A/Patient-Caregiver/ Diseases-Conditions/Antiphospholipid -Syndrome).
Acknowledges contact information provided for the Lupus Foundation of America (www.lupus.org) or the Office on Women’s Health (https://www.womenshealth.gov/lupus/pregnancy-and-lupus).
Seeks a support system or spiritual leader to relieve emotional distress associated with loss of potential child or loss of function secondary to disease process.

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Information ⬇

Critical Findings and Potential Interventions ⬆ ⬇

Overview ⬆ ⬇

Indications ⬆ ⬇

Interfering Factors ⬆ ⬇

Potential Medical Diagnosis: Clinical Significance of Results ⬆ ⬇

Nursing Implications ⬆