Antiphospholipid Syndrome (APS)

Jan 3, 2020
12 min read

Updated: Nov 3

Antiphospholipid syndrome (APS) is an autoimmune blood-clotting disorder in which the body produces antibodies that mistakenly attack normal proteins in the blood, triggering excessive clot formation. Affecting both men and women but disproportionately diagnosed in women of childbearing age, APS is a leading cause of recurrent deep vein thrombosis, pulmonary embolism, stroke, and pregnancy loss. Diagnosis relies on detecting antiphospholipid antibodies—lupus anticoagulant, anticardiolipin, or anti-β2 glycoprotein I—confirmed by repeat testing. Long-term management centers on anticoagulant therapies such as warfarin or heparin. For pregnant patients, preventive treatment with low-molecular-weight heparin and low-dose aspirin has significantly improved outcomes. With consistent monitoring and individualized care, most people with APS live full, active lives while effectively preventing future clotting events.

Overview

What is antiphospholipid syndrome?

Antiphospholipid syndrome (APS) is a chronic autoimmune disorder that causes the body’s immune system to mistakenly produce antibodies that increase the risk of abnormal blood clot formation. These clots can develop in veins, arteries, or small blood vessels throughout the body, leading to serious complications such as deep vein thrombosis (DVT), pulmonary embolism (PE), stroke, or heart attack.

In women, APS is a leading cause of recurrent miscarriage, stillbirth, and other pregnancy complications, including preeclampsia and intrauterine growth restriction. Because clotting risk remains lifelong, most people diagnosed with APS require long-term anticoagulation therapy to prevent recurrence.

APS may occur as an isolated condition (primary APS) or in association with another autoimmune disorder, most often systemic lupus erythematosus (SLE).

Symptoms

What are the warning signs and clinical features of antiphospholipid syndrome?

Antiphospholipid syndrome (APS) can remain asymptomatic for extended periods, with many individuals identified only after a thrombotic or obstetric event. Early visible signs, when present, may include mottled or net-like skin discoloration known as livedo reticularis or livedo racemosa, reflecting underlying microvascular changes. In other cases, the first manifestation is an acute thrombotic episode affecting venous, arterial, or microcirculatory vessels.

Common clinical presentations of thrombosis in APS include:

Chest pain or shortness of breath, suggestive of pulmonary embolism
Swelling, redness, or warmth in a limb, consistent with deep vein thrombosis
Sudden, severe headache or visual disturbance, indicating possible cerebral ischemia or stroke
Abdominal or flank pain, reflecting thrombosis in mesenteric or renal vessels
Jaw, neck, or back pain, occasionally linked to reduced coronary or vertebral artery flow

These symptoms warrant urgent medical evaluation, as delayed recognition increases the risk of irreversible tissue injury and recurrent thrombotic events.

Beyond clotting manifestations, APS may produce secondary hematologic and cardiovascular findings that serve as clinical clues. Thrombocytopenia occurs in up to 30% of patients, while Coombs-positive hemolytic anemia is observed in approximately 10%. Cardiac involvement—most frequently valvular thickening or regurgitation of the mitral or aortic valve—has been documented in nearly one-third of patients, according to echocardiographic analyses published in Circulation (2023). These features often precede or accompany thrombotic events and may help identify APS before major complications develop.

Causes

What causes antiphospholipid syndrome, and how do antibodies trigger abnormal clotting?

Antiphospholipid syndrome (APS) develops when the immune system produces antibodies that mistakenly target phospholipid-binding proteins, essential components of normal blood vessel and cell membrane function. These antibodies activate platelets, endothelial cells, and clotting pathways, causing hypercoagulability—a state in which the blood is more likely to clot.

The three principal antibodies associated with APS are:

Lupus anticoagulant (LA)
Anticardiolipin (aCL)
Anti–β2 glycoprotein I (anti–β2GPI)

Diagnosis requires persistent positivity for at least one of these antibodies on two separate tests performed 12 weeks apart, along with a history of vascular thrombosis or pregnancy morbidity.

Some individuals carry antiphospholipid antibodies without ever developing APS, which is a condition known as asymptomatic aPL positivity. However, the likelihood of clinical disease rises when multiple antibodies are present or when they are detected at high titers.

The exact trigger for antibody production remains unclear, but genetic predisposition, environmental stressors, and immune dysregulation are thought to play key roles. Infections, medications, or other autoimmune diseases may initiate the process in genetically susceptible individuals.

Risk Factors

Who is most at risk for developing antiphospholipid syndrome?

Antiphospholipid syndrome (APS) can affect people of any age or background, but epidemiologic and clinical data identify clear patterns of susceptibility. The condition reflects an intersection of immune dysregulation, hormonal influences, and genetic predisposition, with certain groups facing a markedly higher risk of developing antiphospholipid antibodies that drive the disease.

You may be at greater risk if you:

Are female – Women account for nearly 70 percent of all APS diagnoses. This imbalance mirrors other autoimmune disorders and is believed to stem from estrogen’s effect on B-cell activation and immune tolerance. The disorder most often emerges during reproductive years, when hormonal cycling amplifies immune sensitivity.
Are between 30 and 45 years old – APS is most frequently identified during the third and fourth decades of life, often first revealed through vascular or pregnancy-related complications. Obstetric APS commonly presents with recurrent miscarriage, preeclampsia, or placental insufficiency that leads to impaired fetal growth.
Have another autoimmune disorder – Systemic lupus erythematosus (SLE) remains the strongest associated condition. Up to one-third of people with lupus, and smaller proportions with Sjögren’s syndrome or rheumatoid arthritis, test positive for antiphospholipid antibodies. When APS occurs alongside another autoimmune disease, it is classified as secondary APS.
Have a family history of APS or thrombosis – Genetic and familial clustering is well documented. Studies in Blood Advances (2023) found that first-degree relatives of affected patients have significantly higher rates of antiphospholipid antibody positivity, suggesting a shared immune and HLA-mediated susceptibility.
Have experienced environmental or hormonal triggers – In genetically predisposed individuals, infections, medications, major surgery, or hormonal changes such as pregnancy or oral contraceptive use can initiate or unmask the syndrome. These exposures may convert previously silent antibodies into clinically active disease.

While APS can appear without a clear trigger, most cases arise from the convergence of inherited immune vulnerability and external or hormonal stressors. Recognizing these risk factors allows for earlier screening, closer monitoring, and proactive prevention of thrombotic and obstetric complications in high-risk populations.

Complications

What serious health problems can result from antiphospholipid syndrome?

Antiphospholipid syndrome (APS) can cause severe and sometimes life-threatening complications by producing clots that obstruct blood flow to critical organs. The location and size of these clots determine the clinical outcome.

Major complications include:

Stroke: Clots in cerebral arteries may lead to sudden neurological deficits, seizures, or memory impairment. APS is recognized as one of the most common causes of stroke in individuals under 50.
Cardiac Thrombosis: Clots can form in coronary arteries or on heart valves, leading to myocardial infarction, heart failure, or valve dysfunction.
Pulmonary Embolism: Clots that travel to the lungs can cause acute respiratory distress and circulatory collapse.
Renal Thrombosis: Blocked renal veins or arteries can result in hypertension and progressive kidney injury.

In pregnancy, APS is a leading cause of recurrent miscarriage and placental insufficiency, which can restrict fetal growth or cause stillbirth. The clotting process impairs placental blood flow, depriving the fetus of oxygen and nutrients. It also increases the likelihood of preeclampsia and preterm delivery.

A rare but devastating form of the disease, catastrophic antiphospholipid syndrome (CAPS), occurs in fewer than 1% of APS patients. CAPS triggers widespread clotting across multiple organs within days, leading to multi-organ failure. Despite aggressive treatment with anticoagulants, corticosteroids, and plasma exchange, mortality remains as high as 45%, according to The Journal of Thrombosis and Haemostasis (2022).

Life Expectancy

Does antiphospholipid syndrome affect lifespan or long-term health outcomes?

For most patients, antiphospholipid syndrome (APS) does not shorten life expectancy when the condition is properly managed with lifelong anticoagulation and routine medical monitoring. However, the risk of fatal outcomes increases dramatically in cases of unrecognized or untreated thrombosis, particularly when major organs are affected or when CAPS develops.

With early diagnosis, consistent preventive therapy, and close coordination between hematology, rheumatology, and obstetrics specialists, individuals with APS can typically maintain a normal lifespan and quality of life.

Diagnosis

How do healthcare providers diagnose antiphospholipid syndrome?

Antiphospholipid syndrome (APS) is diagnosed through a combination of clinical history and specific antibody testing. Because many individuals with antiphospholipid antibodies never develop symptoms, testing is typically reserved for those who have experienced:

Unexplained venous or arterial blood clots, particularly at a young age or in unusual locations
Recurrent miscarriages or other pregnancy complications such as stillbirth, preeclampsia, or premature birth

Diagnosis requires two sets of blood tests, taken at least 12 weeks apart, to confirm the persistence of antibodies, as temporary antibody levels can occur with infections or inflammation. Your provider will order laboratory tests to detect one or more of the following antibodies:

Lupus anticoagulant (LA)
Anticardiolipin antibodies (aCL)
Anti–β2 glycoprotein I (anti–β2GPI)

To meet formal diagnostic criteria for APS, you must have at least one positive antibody test on two separate occasions plus a documented history of thrombosis or pregnancy morbidity. This protocol, established by the Sydney Classification Criteria, ensures that the diagnosis reflects a chronic autoimmune process rather than a temporary immune response.

Management and Treatment

What are the standard and emerging treatments for antiphospholipid syndrome?

Treatment for antiphospholipid syndrome (APS) focuses on preventing blood clots and reducing pregnancy complications. There is no cure for the condition, but lifelong management with anticoagulation therapy effectively lowers the risk of recurrence and improves outcomes.

Primary therapies include:

Heparin: Heparin, whether unfractionated or low-molecular-weight, is often administered intravenously or by subcutaneous injection during hospitalization or pregnancy. It acts quickly to prevent clot formation and is the first-line therapy for acute events.
Warfarin: A long-term oral anticoagulant that inhibits vitamin K-dependent clotting factors. It remains the standard of care for secondary prevention, with an international normalized ratio (INR) typically maintained between 2.0 and 3.0.
Aspirin: Used alone in mild cases or in combination with other anticoagulants to reduce platelet activation and arterial clot risk.

For pregnant patients, standard anticoagulants such as warfarin are replaced with low-molecular-weight heparin (e.g., enoxaparin) and low-dose aspirin, both of which are considered safe and effective during pregnancy. These medications improve live-birth rates in women with recurrent pregnancy loss due to APS.

In certain high-risk or refractory cases, providers may prescribe immunomodulatory therapies, including:

Intravenous Immunoglobulin (IVIG): Helps regulate abnormal immune responses and reduce antibody activity.
Corticosteroids: Used sparingly to suppress inflammation in patients with overlapping autoimmune diseases such as lupus.

Side Effects and Monitoring

What should patients know about long-term anticoagulation and monitoring requirements?

While anticoagulants save lives, they also increase the risk of bleeding complications. Patients should immediately report:

Prolonged or unexplained bleeding (from gums, nose, or menstrual cycle)
Blood in vomit or stool, which may appear bright red or black and tarry
Severe headaches or abdominal pain, which may indicate internal bleeding
Sudden weakness, paralysis, or vision changes, potential signs of a hemorrhagic stroke

Regular follow-up visits are essential to monitor clotting parameters (INR levels) and ensure safe, therapeutic dosing. With consistent monitoring, appropriate anticoagulation, and coordinated care between hematology and obstetrics specialists, individuals with APS can significantly reduce their risk of recurrent thrombosis and maintain stable, long-term health.

Outlook and Prognosis

What can patients expect after diagnosis and treatment for antiphospholipid syndrome?

With early diagnosis and consistent anticoagulant therapy, most individuals with antiphospholipid syndrome (APS) lead full, active lives. Once blood-thinning treatment begins, the risk of recurrent clots decreases significantly, allowing patients to safely resume daily activities and, in most cases, maintain normal longevity.

Women with APS who are managed under the care of both hematology and obstetric specialists can often experience healthy pregnancies and live births, particularly when treated with low-dose aspirin and low-molecular-weight heparin. Long-term management focuses on careful monitoring and individualized adjustments in therapy to ensure the blood remains within a safe clotting range.

Prevention

Is it possible to prevent antiphospholipid syndrome or reduce clotting risk?

APS is a chronic autoimmune condition, and the antibodies that drive it typically persist for life. While some individuals may never experience another clotting event, most will require lifelong anticoagulation to prevent recurrence. Continuous follow-up and routine blood monitoring remain essential to maintaining the condition's stability and preventing serious complications.

Because the underlying immune trigger that causes antiphospholipid antibodies to form remains unknown, there is currently no way to prevent APS itself. However, individuals who have the antibodies or have been diagnosed with APS can reduce the likelihood of developing clots by avoiding additional risk factors such as smoking, obesity, prolonged immobility, and unmonitored estrogen use.

Living With Antiphospholipid Syndrome (APS)

How can patients manage daily life and maintain vascular health with this disorder?

Living with antiphospholipid syndrome (APS) requires consistent management to prevent clot formation and protect long-term vascular health. While APS is a lifelong autoimmune condition, outcomes have improved substantially due to early detection, targeted anticoagulation, and lifestyle interventions that address modifiable risk factors. According to research published in The Journal of Thrombosis and Haemostasis (2023), patients who maintain stable anticoagulation, manage comorbidities such as hypertension and diabetes, and avoid smoking or estrogen-based therapies have markedly lower rates of recurrent thrombosis.

Regular medical follow-up, adherence to treatment, and informed self-management remain essential. Longitudinal data from Blood Advances (2024) show that patients engaged in structured care programs—those involving multidisciplinary coordination between hematology, cardiology, and primary care—experience better control of clotting risk and fewer hospitalizations. Maintaining vascular health with APS involves more than medication; it requires active participation, ongoing education, and a clear understanding of how daily decisions influence the body’s clotting balance.

How do I take care of myself if I have APS?

The primary goal of living with APS is preventing thrombosis. Adhering to prescribed anticoagulant therapy and maintaining close communication with your healthcare provider are crucial.

Managing other conditions that contribute to clotting risk helps strengthen your overall vascular health. Discuss management plans with your provider if you have:

Diabetes
Hypertension (high blood pressure
High cholesterol
Obesity
Other autoimmune diseases

Smoking dramatically increases clot risk, especially in people with APS. Quitting smoking and avoiding nicotine-containing products can substantially reduce your risk. Similarly, women taking estrogen-based contraception or hormone therapy should review alternative options with their clinician, as these medications can amplify clotting tendencies.

What foods should I avoid if I have APS?

Most people with APS can follow a standard, balanced diet that promotes heart and vascular health. However, if you take warfarin, it’s important to maintain a consistent intake of vitamin K. Large fluctuations in foods rich in vitamin K, such as spinach, kale, and other leafy greens, can interfere with medication effectiveness.

Ask your healthcare provider for personalized dietary guidance, including safe alcohol limits, as alcohol can enhance the effects of anticoagulants and raise bleeding risk.

When should I see my healthcare provider?

Regular checkups are necessary to ensure your anticoagulation levels remain within the therapeutic range and to adjust medication doses as needed. Your provider will also monitor for potential side effects, such as excessive bleeding or bruising.

If you are pregnant or planning to become pregnant, consult your care team early. APS increases the risk of miscarriage and preeclampsia, but preventive care can dramatically improve outcomes.

When should I go to the emergency room?

Seek immediate medical attention if you:

Suspect a blood clot (sudden leg pain, swelling, warmth, or redness)
Experience shortness of breath, chest pain, or coughing up blood
Have uncontrolled bleeding or vomit/stool that appears bloody or black
Develop sudden neurological symptoms, such as weakness, numbness, or vision loss

Does having antiphospholipid syndrome (APS) mean I have lupus?

No. Having antiphospholipid syndrome (APS) does not automatically mean you have lupus. While one of the key laboratory tests used to diagnose APS is called the “lupus anticoagulant” test, it does not confirm lupus itself. The term is historical—it refers to how the antibody behaves in laboratory testing, not to the autoimmune disease systemic lupus erythematosus (SLE).

That said, APS and lupus can occur together. Roughly 30% to 40% of people with lupus also test positive for antiphospholipid antibodies, and those individuals are considered to have secondary APS. In contrast, people who have APS without lupus or another autoimmune condition are said to have primary APS.

Your healthcare provider can determine whether you have lupus by performing specific autoimmune tests, such as the antinuclear antibody (ANA) test, and evaluating your clinical symptoms. Most individuals with APS do not have lupus, but the two conditions may overlap and require coordinated care from both hematology and rheumatology specialists.

Patient-Provider Communication

What questions should you ask your doctor about your diagnosis and care plan?

Open and informed communication with your care team is central to effectively managing antiphospholipid syndrome (APS). Bringing a list of focused, evidence-based questions to each appointment helps ensure that treatment decisions reflect your specific risk factors, comorbidities, and lifestyle. Discussing these points early can also prevent avoidable complications and clarify when to seek urgent care.

Which blood clotting disorder do I have and how was that determined?

Ask your provider to explain which laboratory tests confirmed the diagnosis and whether other conditions were ruled out, such as lupus or inherited thrombophilia.

Which anticoagulant or combination therapy is most appropriate for me?

Different medications have different risks and monitoring needs. Clarify why a particular therapy—such as warfarin, low-molecular-weight heparin, or a direct oral anticoagulant—was selected for your case.

How frequently should I have bloodwork or follow-up evaluations?

Regular monitoring ensures your anticoagulation remains within the therapeutic range and allows timely adjustments if your condition or medication changes.

What precautions should I take if I become pregnant or undergo surgery?

Pregnancy and invasive procedures require special anticoagulation strategies. Discuss any preventive protocols well in advance.

Which symptoms should trigger immediate medical attention?

Review the warning signs of deep vein thrombosis, pulmonary embolism, stroke, or internal bleeding so you know when to seek emergency care.

Patients who engage in proactive discussions and keep written records of their care plans experience fewer complications and greater long-term stability.

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