Blood Clots in Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease (when the body's immune system malfunctions and attacks healthy tissue) characterized by an increased risk of blood clots and pregnancy complications.

APS can occur in healthy individuals or people with an underlying autoimmune disorder like systemic lupus erythematosus (SLE), also known as lupus.

To be diagnosed, a person must have APS antibodies (immune system proteins) in addition to related symptoms like a history of blood clots and/or recurrent miscarriages.

This article reviews what it means to have antiphospholipid syndrome, its symptoms and complications, and how it's treated. Lifestyle habits to help prevent blood clots will also be discussed.

Antiphospholipid Syndrome: Why Does Clotting Happen?

Recurrent blood clots in arteries, veins, or small blood vessels are a cornerstone of antiphospholipid syndrome.

These blood clots are caused by antiphospholipid antibodies, proteins that target, attack, and damage phospholipids within blood vessels. Phospholipids are fatty molecules normally found in cell membranes, including cells that line blood vessels.

The antiphospholipid antibodies found in APS are:

• Lupus anticoagulant
• Anticardiolipin antibodies
• Anti-beta-2 glycoprotein-I antibodies

The exact manner in which these antibodies lead to blood clot formation remains unknown. In fact, not everyone with these antibodies develops blood clots or has pregnancy complications.

Experts suspect a complex combination of genetic and environmental factors is involved. Specifically, genetically susceptible individuals with APS antibodies may develop blood clots when exposed to a trigger like trauma, surgery, or infection. Other factors, like vitamin D deficiency, could also play a role.

Secondary APS

APS is classified as either "primary" or "secondary." Primary APS occurs independently, whereas secondary APS occurs with another autoimmune condition, usually lupus.

The link between APS and lupus is strong. Approximately 50% of people with APS eventually develop SLE.

While not a complete list, other autoimmune diseases associated with secondary APS include;

• Rheumatoid arthritis
• Sjögren's syndrome
• Autoimmune thyroid disease
• Systemic sclerosis

Symptoms and Complications of Antiphospholipid Syndrome

The two hallmark features of antiphospholipid syndrome are blood clots and pregnancy-related problems.

Blood Clots

In antiphospholipid syndrome, blood clots can form in any blood vessel, including the arteries (blood vessels that take oxygen-rich blood away from the heart) and veins (blood vessels that take oxygen-poor blood to the heart).

Blood clots usually only develop at one site, although they can continue to form if not treated. A rare exception is catastrophic APS, in which multiple blood clots form in a short time frame.

The symptoms of APS are caused by the blockage of blood flow, which can impair organ function. They can be mild or severe, depending on the location and extent of the blood clot.

Types of blood clots seen in APS and their associated symptoms include:

• Deep vein thrombosis (DVT) is a blood clot in a large deep vein, usually within the legs. Symptoms include pain, redness, swelling, and warmth of the leg.
• A pulmonary embolus is a blood clot in the main artery of the lungs. Symptoms can include trouble breathing, chest pain, and a rapid heartbeat.
• A transient ischemic attack (TIA), or an ischemic stroke, occurs when blood flow in an artery supplying the brain is blocked. Symptoms may include numbness, weakness, vision changes, or difficulty speaking.
• Livedo reticularis is a blotchy, reddish-blue to purple rash caused by blood clots in the small vessels of the skin.
• Renal vein thrombosis is when a blood clot forms in the blood vessel connecting the kidney to the heart, possibly causing kidney dysfunction.

Other health problems potentially seen in individuals with APS include:

• Thrombocytopenia is low levels of platelets (blood cells involved in normal blood clotting), possibly leading to easy bleeding or bruising.
• Autoimmune hemolytic anemia occurs when a person's immune system attacks their red blood cells, causing unusual tiredness, pale skin, and a fast heartbeat.
• Heart valve abnormalities may occur, including valve thickening and valve nodules (masses of antibodies and clot-like clumps)
• Other neurological symptoms like headache, seizures, vision changes, and cognitive problems may be seen.
• Other skin manifestations like ulcers (open sores) and splinter hemorrhages (red or black streaks under a fingernail or toenail) can occur.
  

Pregnancy-Related Problems

Pregnancy-related complications may occur in antiphospholipid syndrome, including recurrent early miscarriage and fetal loss after 10 weeks gestation.

Late pregnancy complications like premature birth or fetal growth restriction associated with decreased blood flow to the fetus may also occur. The decreased blood flow is usually due to:

• Preeclampsia is the new onset of high blood pressure, usually in the second half of pregnancy.
• Placental insufficiency is impaired blood flow to the placenta resulting in a reduction in a decline in the delivery of nutrients and oxygen to the developing fetus.

Catastrophic Antiphospholipid Syndrome

Antiphospholipid syndrome affects around 1% to 5% of the population, and catastrophic APS—the most devastating form of the disease—affects less than 1% of those individuals.

In catastrophic APS, several blood clots develop in small, medium, and large blood vessels throughout the body quickly. Extensive and rapid blood-clotting can lead to the failure of organs, namely the lungs, kidneys, brain, skin, and heart.

It's unclear exactly how catastrophic APS develops. Similar to typical APS, experts suspect to a trigger like an infection in genetically vulnerable individuals.

Treatment to Manage Antiphospholipid Syndrome

A diagnosis of antiphospholipid syndrome requires the presence of symptoms consistent with APS (e.g., blood clot and/or pregnancy complication) and one or more persistently positive APS antibodies. "Persistently positive" means that at least one of the APS antibodies is present on a blood test taken at two separate times at least three months apart.

Once diagnosed with APS, anticoagulation is the mainstay of treatment. Also known as blood thinners, anticoagulants prevent existing blood clots from getting bigger and new blood clots from forming. 

Anticoagulants used to treat blood clots in APS are:

• Heparin is given as an injection underneath the skin or intravenously (through a vein).
• Low molecular weight heparin (LMWH) is given as an injection underneath the skin. Types of LMWH are Lovenox (enoxaparin), Fragmin (dalteparin), and Innohep (tinzaparin).
• Jantoven or Coumadin (warfarin) is a pill used for the long-term treatment of blood clots. Warfarin requires monitoring with periodic blood tests.

In pregnancy, low-dose aspirin and/or LMWH may be used to prevent blood clots, miscarriage, or late pregnancy-related complications like preeclampsia and placental insufficiency.

Aspirin is not an anticoagulant but rather an antiplatelet drug that helps prevent blood clots by preventing platelets from clumping together.

Warfarin is avoided in pregnancy when possible. It may be restarted soon after delivery and is generally considered safe to take while breastfeeding.

Lifestyle Changes With Antiphospholipid Syndrome

Various lifestyle practices can help reduce the risk of blood clot formation.

Such practices include:

• Avoid smoking.
• Lose weight if experiencing obesity.
• Manage certain chronic health conditions (e.g., diabetes or high blood pressure) that increase the risk of atherosclerosis and subsequent arterial clotting.
• Avoid estrogen-containing birth control methods (estrogen increases the risk of blood clots).
  

Keep in mind too that if taking warfarin, you must undergo regular international normalized ratio (INR) blood tests.

Based on the INR level, your warfarin dose may be adjusted. An INR above the target range carries an increased risk of bleeding, and an INR below the target range carries an increased risk of clotting.

Also, it's essential to maintain a stable intake of vitamin K when taking warfarin, as warfarin blocks a step in the blood-clotting process that depends on vitamin K. Consuming significantly lower or higher amounts of vitamin K can alter the INR, making you more prone to bleeding or clotting, respectively.

Other medications, herbs, or dietary products like alcohol, cannabis, Ginkgo biloba, ginger, and Saint-John's-wort can also interfere with warfarin's effect.

Speak with a healthcare provider before engaging in new dietary habits or taking a new prescription, recreational, or over-the-counter drug, vitamin, or supplement to avoid harmful interactions.

Summary

Antiphospholipid syndrome, or APS, is an autoimmune disease (when your immune system attacks its own tissue) associated with one of three APS antibodies, blood clots, and/or pregnancy-related complications, like recurrent miscarriages.

APS may occur on its own or with another autoimmune disease, namely lupus. While APS cannot be cured, it can be managed well in most cases with blood thinners, such as heparin, warfarin, or aspirin, depending on symptoms and the clinical scenario.