Antiphospholipid Syndrome: Testing Algorithm

Antiphospholipid syndrome (APS) is an autoimmune disorder that primarily affects the blood-clotting process. In this syndrome, the immune system produces antibodies that target certain proteins and phospholipids (a type of fat molecule) in the blood. These antibodies can lead to increased clotting, which can cause various health issues, including blood clots in veins and arteries. APS can occur as a primary disorder or in association with other autoimmune conditions, such as systemic lupus erythematosus (SLE).

Symptoms of Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) can present with a wide range of symptoms, which can vary from person to person. The symptoms are primarily related to the increased risk of blood clot formation and can affect various organs and systems in the body. Common symptoms and manifestations of APS include:

Blood Clots: APS is characterized by an increased tendency to develop blood clots (thrombosis). These blood clots can occur in veins (deep vein thrombosis) or arteries (arterial thrombosis), leading to various complications such as:

Deep vein thrombosis (DVT) in the legs or arms
Pulmonary embolism (blood clot in the lungs)
Stroke or transient ischemic attacks (TIAs)
Heart attack
Blood clots in other organs such as the kidneys or liver

Recurrent Pregnancy Complications: APS is associated with pregnancy-related complications, including:

Recurrent miscarriages, especially in the second or third trimester
Stillbirths
Preeclampsia (high blood pressure during pregnancy)
Preterm births

Livedo Reticularis: A mottled or lace-like pattern of discoloration on the skin, often seen on the legs or arms, known as livedo reticularis.

Thrombocytopenia: Some individuals with APS may have low platelet counts (thrombocytopenia), which can lead to an increased risk of bleeding.

Neurological Symptoms: APS can cause various neurological symptoms, including:

Headaches, including migraines
Seizures or epilepsy
Cognitive impairment or memory problems
Visual disturbances

Heart Problems: APS may lead to heart-related issues, such as heart valve abnormalities.

Other Manifestations: Other less common symptoms or manifestations of APS may include:

Skin ulcers or necrosis
Joint pain or arthritis
Gastrointestinal symptoms
Kidney problems, including renal thrombotic microangiopathy

Not everyone with APS will experience all these symptoms, and the severity of symptoms can vary widely. Additionally, APS symptoms can overlap with those of other conditions, making diagnosis and management challenging.

Antiphospholipid Syndrome Testing Algorithm

The testing algorithm for diagnosing antiphospholipid syndrome (APS) involves a combination of clinical assessment and laboratory tests to detect specific antibodies associated with the condition. It's important to note that APS is typically diagnosed when a person has both clinical criteria (such as a history of blood clots or pregnancy complications) and positive laboratory test results.

1. Clinical Assessment

The initial step involves evaluating the patient's medical history, including any history of blood clots (venous or arterial) or pregnancy-related complications (recurrent miscarriages, stillbirths, preeclampsia, etc.).
Clinical symptoms such as livedo reticularis (skin discoloration), thrombocytopenia (low platelet count), and neurological symptoms should also be considered.
APS diagnosis requires the presence of specific clinical criteria, such as a history of arterial or venous thrombosis and/or pregnancy complications. The clinical criteria may vary slightly based on guidelines.

2. Laboratory Tests

Lupus Anticoagulant (LA): This antibody is associated with an increased tendency for blood clotting. It is detected through specialized coagulation tests.
Cardiolipin Antibodies (aCA) IgG and IgM: These are the primary antibodies associated with APS.
Beta-2 Glycoprotein I Antibodies (anti-β2GPI) IgG and IgM: Similar to aCA, these antibodies are also associated with APS.
All the above antibodies are called collectively Antiphospholipid Antibodies (aPL).

3. Confirmatory Testing

Positive test results should be repeated at least 6-12 weeks apart to confirm the presence of persistent antibodies.
If first-line laboratory tests are negative but there is a strong suspension of APS, the following tests should be used:

Additionally, there are other non-criteria antibodies that are the subject of investigation for their value in APS, and especially for identifying SNAPS patients. Patients with high clinical suspicion of having APS, but without the presence of criteria aPL, are suggested to have “seronegative APS” (SNAPS).

Testing for these antibodies shows potential for identifying certain obstetric SNAPS patients, but the routine measurement is currently not recommended as there is a limited added value compared to the current criteria of aPL. These antibodies are:

Reference

Vandevelde A, Devreese KMJ. Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances. J Clin Med. 2022 Apr 13;11(8):2164. doi: 10.3390/jcm11082164. PMID: 35456258; PMCID: PMC9025581.

Vasilis J. Sideris
Biologist
Medical Doctor, Biopathologist (Microbiologist)
Certified Functional Medicine Practitioner, CFMP^®