Antiphospholipid Syndrome (Clotting Disorder)

What is Antiphospholipid Syndrome (Clotting Disorder)?

Antiphospholipid antibodies (APLAs) are a type of antibodies, which are proteins produced by our immune system that mistakenly target our own body proteins that bind to fats. This can lead to a condition known as antiphospholipid syndrome (APS), which is a disorder where the immune system attacks various systems in the body. The main way to identify APS is to spot the constant presence of APLAs along with instances of blood clots in arteries or veins, or pregnancy loss.

The lower limbs and the brain’s blood vessels are the most common places for blood clots to form. However, they can occur in any organ. To identify APS, laboratory tests like the Enzyme-Linked Immunosorbent Assay (ELISA) and functional assays are used. There are three known types of APLAs:

• Anticardiolipin antibodies IgG or IgM, detected via ELISA
• Anti-beta-2-glycoprotein-I (anti-β2GPI) antibodies IgG or IgM, also detected via ELISA
• Lupus anticoagulants, detected by tests that study blood clotting functions

What Causes Antiphospholipid Syndrome (Clotting Disorder)?

Antiphospholipid syndrome (APS) can occur by itself, or it can be a secondary condition caused by an autoimmune disease like systemic lupus erythematosus. In fact, in about 40% of cases, APS is linked to an autoimmune disease. Studies have found the presence of APS-related antibodies in 6% of pregnant women, 13.5% of stroke patients, and 9.5% of patients with deep vein clots.

Certain genetic factors, such as mutations in blood clotting factors, can increase the risk of clots linked to APS. Some specific genes have been found to be associated with APS. Infections, especially viral ones, can lead to higher levels of APS-related antibodies compared to bacterial infections. Certain viruses have been linked to the production of these antibodies. Interestingly, a large study found that nearly half of COVID-19 patients were found to have APS; however, these patients didn’t show an increased risk of clot formation.

Certain medications can also stimulate the production of APS-related antibodies. Some people may naturally have low levels of these antibodies that can come and go, which is why a diagnosis usually requires repeated positive tests over a period of 12 weeks.

APS presentations may vary and it can be classified based on symptoms like obstetric issues, blood clot problems, or both. It can even involve life-threatening complications affecting multiple organs.

People are diagnosed with thrombotic APS when they have clotting issues in their arteries or veins and persistent APS-related lab markers. The most common symptom is a deep vein clot. Obstetric APS is diagnosed when there are pregnancy complications, such as premature birth caused by severe high blood pressure during pregnancy, fetal death after 10 weeks, placenta insufficiency, or multiple early pregnancy losses, along with persistent lab markers.

Catastrophic APS is a rare and dangerous form of APS characterized by clotting complications that affect multiple organs, big and small.

Risk Factors and Frequency for Antiphospholipid Syndrome (Clotting Disorder)

APS, or Antiphospholipid Syndrome, is estimated to occur in about 2.1 out of every 100,000 people in the United States, and affects 50 out of every 100,000 people. In Europe, the rates are lower at 1.1 out of 100,000. Asian countries also have lower rates, with South Korea reporting an incidence of 0.75 per 100,000 and prevalence of 6.19 per 100,000.

Certain autoantibodies, or self-targeting antibodies, known as anticardiolipin antibodies, can be found in up to 10% of healthy individuals. Interestingly, the likelihood of having a positive test for these antibodies increases with age. For instance, a study of people over 100 years old without any known autoimmune disease found that more than half were positive for one type of these antibodies, and 21% were positive for another kind. However, very high levels and long-lasting presence of these antibodies are rare in healthy people, seen in less than 1%.

People with systemic lupus erythematosus (SLE), an autoimmune disease, are at a high risk of having a positive test for these antibodies and of experiencing related health issues such as blood clots or pregnancy complications. About half to 70% of SLE patients with positive tests for these antibodies will go on to develop APS.

• APS occurs in about 2.1 in every 100,000 people in the United States and affects 50 in every 100,000 people.
• Rates are lower in Europe and Asia, with South Korea reporting an incidence of 0.75 per 100,000.
• Anticardiolipin antibodies, a type of self-targeting antibody, can be found in up to 10% of healthy people.
• Having these antibodies becomes more common as we age.
• High levels of these antibodies are rare in healthy individuals, seen in less than 1%.
• People with SLE are at high risk of having these antibodies and related health problems like blood clots or pregnancy complications.
• About half to 70% of SLE patients with these antibodies go on to develop APS.
• People with rheumatoid arthritis and couples with a history of frequent miscarriages also show a higher prevalence of these antibodies, at rates of 20% and 14%, respectively.

Signs and Symptoms of Antiphospholipid Syndrome (Clotting Disorder)

Antiphospholipid syndrome (APS) can present symptoms of varying severity, ranging from no symptoms with positive APS test results to severe cases known as catastrophic APS. The disease’s primary characteristics include blood clots and pregnancy complications, though it can also affect other organ systems.

Vascular Thrombosis

APS can cause both artery and vein clots in any organ system. Clots can recur and occur in blood vessels uncommonly related to other clotting causes. The most common vein clots are deep vein thrombosis (DVTs), sometimes leading to lung clots and resulting in high blood pressure in the lungs. Artery clots can occur in any artery size, most commonly in the form of temporary lack of blood flow or stroke. Young patients without other factors related to artery hardening experiencing these symptoms should consider APS as a possible cause.

Pregnancy Morbidity

Pregnancy loss is frequent in APS patients, particularly in later pregnancy stages. Triple positivity, a condition where an individual tests positive for three different antibodies, prior pregnancy loss, previous clots, and SLE, a type of immune system disorder, all increase the risk. APS patients can also experience preeclampsia, fetal distress, premature birth, insufficient placental growth, placental detachment, and HELLP syndrome – a complication of high blood pressure during pregnancy.

Cutaneous Involvement

Many skin symptoms have been reported in APS, though none are specific to the disease. The most common skin symptom is ‘livedo reticularis’. Other skin symptoms include skin ulcerations, particularly in the lower legs, and necrotizing purpura.

Valvular Involvement

• Cardiac valve disorders are common in APS patients, with evidence of thickening, nodules, and abnormal growths on ultrasound imaging.

Hematological Involvement

• The APS typically results in low platelet counts in over 15% of cases.

Neurological Involvement

• Common neurological complications of APS include temporary lack of blood flow or stroke, often recurrent, leading to mental dysfunction, seizures, and multi-portion dementia.

Cardiac Involvement

• Heart attacks and heart clots are potential complications of APS

Pulmonary Involvement

• Pulmonary artery clot from DVT is common and can lead to high blood pressure in the lungs.

Renal Involvement

• High blood pressure, protein in urine, and kidney failure due to small vessel disease are common kidney manifestations of APS.

Catastrophic Antiphospholipid Syndrome

A rare but dangerous complication of APS, Catastrophic Antiphospholipid Syndrome (CAPS), affects fewer than 1% of APS patients, with a high mortality rate. CAPS is defined by clotting in multiple organs in a short period, with the clinical presentation varying depending on the organ involved.

Precipitating Factors for CAPS

• Stopping anticoagulation in diagnosed APS patients, infections, and surgical procedures.

Preliminary Criteria for CAPS Classification

• Affecting 3 or more organs, systems, or tissues
• Symptoms developing simultaneously or within less than 1 week
• Confirmation of small vessel occlusion in at least one organ or tissue
• Confirmation of the presence of APS in lab tests

The presence of all four criteria classifies as definite CAPS, whereas the presence of three criteria with the fourth one being partially fulfilled is considered probable CAPS.

Testing for Antiphospholipid Syndrome (Clotting Disorder)

To diagnose Antiphospholipid Syndrome (APS), doctors use a combination of clinical signs and laboratory tests. The tests look for antiphospholipid antibodies (APLA), which include lupus anticoagulant, and IgG or IgM anticardiolipin or anti-β2GPI antibodies. To confirm APS, a second APLA test should come back positive 12 weeks after the first one. This helps to make sure that the antibodies weren’t a temporary presence. If the repeat test is done sooner than 12 weeks or more than 5 years after clinical signs of APS, the diagnosis might be uncertain.

The Lupus Anticoagulant Test is particularly powerful for predicting risky events during pregnancy. It’s more specific, but less sensitive, than anticardiolipin antibodies for predicting blood clots. Importantly, a positive syphilis test doesn’t count towards diagnosing APS.

Other tests check for anticardiolipin antibodies and anti-β2GPI antibodies, usually performed using a method called ELISA. Higher concentrations of these antibodies are associated with a higher likelihood of blood clots.

Patients may also exhibit low platelet count or anemia. Signs of kidney damage, like renal failure or protein in the urine, could indicate blood clot disease in the small blood vessels of the kidneys. Inflammatory markers may be elevated during an active blood clot event, but are generally normal otherwise.

To accurately diagnose APS, doctors use a set of criteria that take into consideration both clinical and laboratory findings. You might be diagnosed with APS if you meet one of the following criteria: you’ve had one or more cases of blood clots in specific locations, or you have a history of specific pregnancy complications. These complications could include one or more late pregnancy losses, premature birth due to specific conditions, or three or more early pregnancy losses without any other explanation.

Along with these clinical criteria, laboratory criteria includes detection of specific types of antibodies in your blood on two or more occasions, at least 12 weeks apart.

There are also new criteria developed by the American College of Rheumatology and the European Alliance of Associations for Rheumatology (EULAR) that aims to classify APS. These look into more specific clinical and laboratory indications. However, these new criteria are highly specific, making them quite complex.

Treatment Options for Antiphospholipid Syndrome (Clotting Disorder)

Managing Blood Clots (Thrombosis)

The European League Against Rheumatism (EULAR) has provided guidelines for managing a variety of clinical situations related to blood clotting. The correct treatment for patients who test positive for certain blood clotting antibodies, but have no history of clotting or negative pregnancy outcomes, is debatable. These patients need to be re-tested at least 12 weeks after their initial testing to confirm the results.

Patients with a condition called Systemic Lupus Erythematosus (SLE) who test positive for these antibodies are at an increased risk for developing blood clots, thus they are recommended to take hydroxychloroquine, a medication that can help prevent blood clots. Additionally, they may also consider taking low-dose aspirin.

For high-risk patients (those with specific positive antibody tests or persistently high levels of these antibodies), the guidelines suggest:

– Patients with a high risk but no history of blood clots should be treated with low-dose aspirin.
– Patients with SLE and no history of blood clots or pregnancy complications should be considered for preventitive treatment with low-dose aspirin depending on their risk profile.
– If a patient has previously experienced blood clots in their veins, treatment with a medication called warfarin is recommended, typically after an initial treatment with heparin.

If a patient has had their first instance of an unprovoked blood clot in their veins, long-term anti-coagulation (blood-thinning) treatment should be continued. Patients who’ve had an unprovoked deep vein thrombosis and test positive for lupus antibodies have an increased risk of another blood clot if they stop their anti-coagulation treatment.

Direct oral anti-coagulants can be used for blood clots in veins in selected patients, particularly those with a high-risk antibody profile. For arterial (related to arteries) blood clots, warfarin is generally preferred. Low-molecular-weight heparin can be used in patients who can’t take warfarin or in those in whom it isn’t effective.

Pregnancy Management

Pregnant women with positive APLA antibody levels need careful monitoring to ensure both mother and baby’s well-being. Treatments vary depending on individual medical histories.

It’s important to note that warfarin is unsuitable during pregnancy due to potential risk to the fetus. Low-molecular-weight heparin is typically recommended, with different guidelines according to specific histories like previous miscarriages or early deliveries due to complications.

In women with specific obstetric complications that continue despite treatment, increasing the dose or adding additional medications could be considered. The use of intravenous immunoglobulins (IVIG) might be considered in selected cases when other treatments have failed.

Other Manifestations

The role of anti-coagulation hasn’t been firmly established for other symptoms of APS. Patients with low platelet counts may be treated with corticosteroids, IVIG or a medicine known as rituximab. In some cases, surgical removal of the spleen has proven beneficial.

Diagnosing and treating Catastrophic Antiphospholipid Syndrome (CAPS) urgently is crucial due to high mortality rates. Treatment with a combination of medicines is recommended, as well as addressing factors that may have triggered the condition.

Follow-up Monitoring

Patients on anti-coagulants and no other autoimmune disease can follow-up as outpatients once or twice a year. Periodic checks on a range of blood measures are conducted to guide treatment. Repeat testing of blood clotting antibodies is generally not needed unless they’re required for future treatment decisions. Appropriate evaluation based on symptoms should be carried out for patients with specific organ-system problems.

What else can Antiphospholipid Syndrome (Clotting Disorder) be?

When diagnosing a blood clot caused by a condition called antiphospholipid antibody syndrome, the doctor also considers other possible causes. This could include having too much of a substance called homocysteine in your blood, genetic variations known as factor V Leiden and prothrombin mutations, or deficiencies in certain proteins that prevent blood clots (namely protein C, protein S, or antithrombin III).

Moreover, when dealing with kidney damage associated with this syndrome, doctors would consider ruling out similar conditions which might be causing the same symptoms:

• Thrombotic thrombocytopenic purpura, a disorder that causes blood clots in small blood vessels around your body.
• Vasculitis, an inflammation of the blood vessels
• Hemolytic uremic syndrome, a condition that affects blood clotting and damages blood vessels
• Malignant hypertension, which is very high blood pressure that comes on suddenly and quickly
• Lupus nephritis, which is kidney damage caused by an autoimmune disease called lupus

In these cases, often a kidney biopsy (a procedure where a small piece of kidney is removed for testing) is needed to accurately identify the cause of the symptoms.

What to expect with Antiphospholipid Syndrome (Clotting Disorder)

Several studies from Europe have shown a survival rate of 90% to 94% over a 10-year period. Nonetheless, people with Antiphospholipid Syndrome (APS) often face serious health complications. In fact, more than 30% of these patients end up with permanent organ damage, and over 20% experience severe disability 10 years after diagnosis.

Certain factors can indicate a worse outcome, including complications like CAPS, lung hypertension, kidney problems, issues with the central nervous system, and extremity gangrene.

The outlook for both primary and secondary APS is generally the same. However, those with secondary APS, who also have an existing rheumatic or autoimmune disorder, may face worse health complications. Particularly, lupus patients with Antiphospholipid antibodies (APLAs) have a higher risk of developing mental health disorders.

APLAs are commonly elevated in patients with underlying cancer, and a high level of these antibodies is linked to a worse prognosis, irrespective of whether blood clots are present or not.

Possible Complications When Diagnosed with Antiphospholipid Syndrome (Clotting Disorder)

Antiphospholipid antibody syndrome can result in problems with the organs it affects. Some of these complications can include miscarriage, having a stroke, blood clots in the lungs, high blood pressure in the lungs, abnormal heart valves, sudden reduction in blood flow to the heart, blood clots in the intestinal arteries, or liver disease due to the obstruction of small veins in the liver.

People with this syndrome who are undergoing surgery may experience more complications because surgery can increase the risk of harmful blood clots. This emphasizes the importance of setting a clear plan for how to manage their increased risk for blood clot formation using blood thinners before having any surgical procedure.

Common Complications:

• Miscarriage
• Stroke
• Blood clots in lungs
• High blood pressure in lungs
• Abnormal heart valves
• Sudden reduction in blood flow to the heart
• Blood clots in the intestinal arteries
• Liver disease due to obstruction of small veins

Preventing Antiphospholipid Syndrome (Clotting Disorder)

Patients need to be informed about possible complications that can arise from Antiphospholipid Syndrome (APS). It’s crucial they understand when to seek medical help, especially if they experience symptoms that could indicate a Transient Ischemic Attack (TIA). Health practitioners need to explain their prescribed medications and stress the significance of taking them as recommended.

Those who are prescribed warfarin might need regular tests known as INRs, which measure their blood’s ability to clot. Additionally, they may need dietary advice to ensure the food they eat doesn’t interfere with the action of warfarin.