Antiphospholipid Antibody Syndrome (APS)

Antiphospholipid Antibody Syndrome (can also be called Hughes Syndrome) is an autoimmune system disorder in which your immune system mistakenly produces antibodies to certain proteins in your blood. Antibodies are cells that normally attack bodily invaders, such as viruses and bacteria. This disorder can cause clotting within your arteries or veins and a variety of other problems, some life-threatening

Antiphospholipid syndrome may cause clots to form in the large veins of your legs, and sometimes your arms, a condition known as deep vein thrombosis (DVT). Besides pain and swelling in the affected limb, thrombosis carries a risk of the clot breaking off and traveling to your lungs, where it can obstruct blood flow

Blood clots sometimes form in the veins and arteries of various body organs. Damage depends on the extent and location of the clot and which organ it affects. For instance, impaired blood flow to your brain can lead to stroke. Impaired blood flow to your kidneys can cause kidney failure

Pregnant women with antiphospholipid syndrome may have miscarriages or stillbirths. Also, antiphospholipid syndrome often occurs in people, particularly women, who have another immune system disorder, such as lupus

There's no cure for antiphospholipid syndrome, but medications may reduce your risk of developing blood clots

Primary APS - APS without an autoimmune system disorder or Lupus

Secondary APS - People in whom it is found in combination with another autoimmune disorder or lupus

• first identified by Conley in the 1950s or Hughes (1983)
• Bowie first described the association between APLA (APS) and thrombosis in 1964

Who gets Primary APS?

• Frequently men with a low titer ANA
• Found in 2% of people without symptoms
• In children after tonsillectomies or viruses
• Patients with hepatitis or HIV (30%), and
• People with parasite infections like malaria
• Certain medications have also been associated with the onset of APS: Chlorpromazine, procainamide, dilantin, certain antibiotics, cocaine, hydralazine, and quinine

APS is relatively new to the medical community and this may be part of the reason that many doctors do not know of it. Diseases Doctor's Miss – article from Family Circle January 2005

Atherosclerosis and APS might work together to cause more clotting! The antiphospholipid antibodies may cross-react with oxidized low-density lipoproteins.

Researchers in Tel Aviv, Israel, suggest that atherosclerosis may not always be “caused” by the usual factors attributed to it (hypertension, diabetes, inactivity, high cholesterol and triglycerides, etc.) but posit that atherosclerosis may actually be caused by an inflammatory, infectious and/or autoimmune disease. Their patients with advanced atherosclerosis had high levels of the C-reactive protein (inflammation), increased amounts of “sticky”/adhesion molecules on cell surfaces, and elevated cytokines associated with the autoimmune system. . The number of these markers increased with the severity of the atherosclerosis

APS Causes

Symptoms

If you have APS, you may have no symptoms, only a few or many symptoms. (That is why it is called a "Syndrome") All of the symptoms are related to the abnormal clotting of the blood caused by APS

• Thromboses (blood clots) may occur in any sized vessel
• clots are often episodic and unpredictable. They can happen quickly with no real warning, or chronically
• Estrogen containing medications may increase the chance of clotting

Symptoms according to the frequency in the literature

• Venous thrombosi - Phlebitis or DVT (Deep Vein Thrombosis) are caused by clots in the deep veins embedded in the muscles of the lower leg, lower abdomen, or groin. Swelling and pain results, especially in the calf of your leg. In the worst case scenerio, a piece of the clot can break off (an embolism), traveling through the venous system and causing a Pulmonary Embolism
• Venous Thromboses occur in 30% of patients with Primary APS; 42% if with Lupus
• Venous Thromboses can be in the form of Superficial thrombophlebitis
• Thromboses can occur in the leg, arm, kidney, abdomen, eyes, heart, liver, lung, or brain
• Pulmonary Embolisms are clots in a lung
• Symptoms include: shortness of breath and chest pain that worsens when you breathe in; you may cough up a small amount of blood
• Treatment - Coumadin (+Heparin, if needed) with INR levels 3.0-3.5 Individuals with leg vein thromboses may only need to be on Warfarin/ Coumadin for six months unless the problem is chronic or recurrent
• Arterial Thromboses
• Young people with myocardial infarctions (heart attacks) and strokes
• Symptoms include peripheral vascular disease (limb pain and circulation problems), headaches, and graft failures.
• Arterial thromboses may occur in the eyes, heart (chest pains), abdomen, kidney, adrenals and skin
• Arterial thromboses are often thought of as more serious than venous and tend to be less prevalent
• Treatment is usually Coumadin with INR levels of 2-3
• Neurological diseases caused by thrombosis (clotting)
• Stroke — most of the time a fixed, focal deficit
• Many times the results may be reversible
• Large and small vessels of the brain are both affected
• Multiple small white matter infarcts may be present
• Strokes - 10-46% of young patients with stroke, 20% of strokes under 45 years of age, and 10% of stroke patients overall may be compromised by APS.
• With APS, the strokes appear earlier (42-62 years of age) than strokes associated with aging. Recurrence rate - 6-30% per year. Mortality rate - 10% per year
• TIAs (Transient Ischemic Attacks, “mini-strokes”) are characterized by transient memory loss, slight speech disturbances and are often attributed to migraine
• TIA’s and Small Strokes are often progressive in people with APS
• Early onset dementia or multi infarct dementia In these cases there is not necessarily evidence of a stroke. The average age of onset is 52 years
• Memory Loss - from lack of blood flow This type of memory loss may be gradual. You may have more difficulty putting words, sentences, lists, etc. together. Many times the memory loss and brain fog will lessen with blood thinning medications,
• Snedden's Syndrome - Livedo reticularis (a purplish blotchy skin discoloration , often on the knees) plus cerebral ischemic events.
• Epilepsy or Seizures - Petit mal through grand mal - For some patients, once coagulation therapy is started, even long-term seizure activity has been known to stop. Severe and difficult-to-control seizures are infrequent
• Multiple sclerosis features such as pins and needles, problems with balance, giddiness, and visual disturbances may occur with APS
• Thrombocytopenia - low blood platelets - Danazol may be appropriate because reportedly the other meds can’t be taken with Coumadin
• Ocular events — Amaurosis Fagax - The veiling effect mentioned with stroke and TIAs. Generally, your vision diminishes from top to bottom but will eventually return. Neurologists will also include other types of graying of vision in one eye within this category if it appears and disappears. This phenomena is different than visual problems you get with migraine
• REtinal artery and vein thrombosis
• Migraines - Up to 50% of migrainous patients may have APS. - The Hughes Syndrome Organization suggests that if you have migraines as a teenager and they disappear in your 20s, reappearing in the 30s and 40s, APS/Hughes Syndrome may be a factor. - Reportedly, these migraines appear with flashing lights, and speech disturbances. - The headaches may predate the clotting problem by many years
• Miscarriage (Fetal loss) - 38% of patients with Lupus and 25-30% of patients with more than 3 miscarriages have been found in patients with APS. - The loss occurs often late in the pregnancy according to some references, in the first and second trimester in others
• Cardiac valve vegetations and mitral regurgitation are frequent in APS patients
• Primary Pulmonary Disease - 10% of chronic patients with this problem have APS
• Hypertension - labile hypertension associated with strokes and TIAs are a possibility if you have APS. Labile hypertension refers to hypertension that fluctuates frequently and is hard to control. You may have blood pressure spikes that just "show up" and then are gone. - Results in hypertensive cerebrovascular disease
• Skin conditions such as Livedo Reticularis, leg ulcerations, distal ischemia/necrosis, blue-toe syndrome, splinter hemorrhages and porcelain-white scars. Livedo reticularis - blue knees, purplish vein coloration on the back of the wrists or in other areas, especially the knees. The pattern of the rash is lacy and net-like. Your blood pressure may fluctuate with the severity of the Livedo. There is a possible reno-vascular connection so if this happens, you may want your kidney function checked. Primary renal disease is rarely associated. The testing is for the blood pressure connection.
• Others
• Constant fatigue
• Addison's disease
• transverse myopathy
• Gillian Barre Syndrome
• Chorea/ St. Vitus Dance (sudden jerky movements)
• Raynauds Syndrome
• Bowel ischemia, infarctions , gangrene
• Transverse myelitis - a rare form of inflammation of the nervous tissue of the brain or spinal cord
• Rare - catastrophic APAmultiorgan failure due to microthrombi in multiple vascular fields
• Most patients have pre-existing autoimmune disorders

Outside of the Lupus factor, patients with Secondary APS may experience skin reactions to sunlight, joint pains, mouth ulcers, excessive hair loss, dry eyes, cold an bluish fingers, and, sometimes, sharp chest pains