Antiphospholipid syndrome

• Antiphospholipid syndrome (APS) is an autoimmune disorder caused when antibodies.
• It is a disorder caused by the presence of autoantibodies directed against phospholipids, causing a hypercoaguable state.

It leads to increased risk of blood clots, stroke, heart attack, and in women, significant pregnancy-related complications, including miscarriage and still birth.

• The syndrome is often associated with other autoimmune disorders, most commonly systemic lupus erythematosus, and infections, including syphilis and lyme disease.

Venous blood clots in legs due to Antiphospholipid syndrome.

Pathophysiology

It is an auto-immune disease where immune system cells that fight off bacteria and viruses -- mistakenly attack healthy body tissues and organs. 

Blood clots

In APS, specific antibodies activate the inner lining of blood vessels, which leads to the formation of blood clots in arteries or veins. 

Other names

APS is sometimes called “sticky blood syndrome,” because of the increased tendency to form blood clots in the veins and arteries. 

Symptoms

The symptoms of APS are due to the abnormal blood clotting.  Clots can develop in the veins of the legs and lungs, or in the placenta of pregnant women. 

Complications

One of the most serious complications of APS occurs when a clot forms in the brain and causes a stroke. 

Neurological symptoms

• In addition to stroke, the other neurological symptoms include chronic headaches, dementia (similar to the dementia of Alzheimer’s disease), and seizures. 
• Infrequently, individuals will develop chorea (a movement disorder in which the body and limbs writhe uncontrollably), cognitive dysfunction (such as poor memory), transverse myelitis, depression or psychosis, optic neuropathy, or sudden hearing loss.  In pregnant women, clots in the placenta can cause miscarriages. 

Acute thrombotic microangiopathy

Diagnosis

• APS is diagnosed by the presence of a positive antiphospholipid antibody and either a history of blood clots in an artery or vein or a history of multiple miscarriages or other pregnancy problems. 
• Some individuals will have a characteristic lacy, net-like red rash called livedo reticularis over their wrists and knees.
• Antiphospholipid syndrome is tested for in the laboratory using both liquid phase coagulation assays (lupus anticoagulant) and solid phase ELISA assays (anti-cardiolipin antibodies).
• Genetic thrombophilia is part of the differential diagnosis of APS and can coexist in some APS patients. Presence of genetic thrombophilia may determine the need for anticoagulation therapy. Thus genetic thrombophilia screening can consist of:
• Further studies for factor V Leiden variant and the prothrombin G20210A mutation, factor VIII levels, MTHFR mutation.
• Levels of protein C, free and total protein S, factor VIII, antithrombin, plasminogen, tissue plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-1)
• The testing of antibodies to the possible individual targets of aPL such as β₂ glycoprotein 1 and antiphosphatidyl serine is currently under debate as testing for anticardiolipin appears to be currently sensitive and specific for diagnosis of APS even though cardiolipin is not considered an in vivo target for antiphospholipid antibodies.

Lupus anticoagulant

This is tested for by using a minimum of two coagulation tests that are phospholipid-sensitive, due to the heterogeneous nature of the lupus anticoagulant antibodies. The patient on initial screening will typically have been found to have a prolonged APTT that does not correct in an 80:20 mixture with normal human plasma (50:50 mixes with normal plasma are insensitive to all but the highest antibody levels). The APTT (plus 80:20 mix), dilute Russell's viper venom time (DRVVT), kaolin clotting time (KCT), dilute thromboplastin time (TDT/DTT), silica clotting time (SCT) and prothrombin time (using a lupus sensitive thromboplastin) are the principal tests used for the detection of lupus anticoagulant. These tests must be carried out on a minimum of two occasions at least 6 weeks apart and be positive on each occasion, demonstrating persistent positivity, to allow a diagnosis of antiphospholipid syndrome. This is to prevent patients with transient positive tests (due to infection etc.) being diagnosed as positive.

Differentiating from other conditions

Distinguishing a lupus antibody from a specific coagulation factor inhibitor (e.g.: factor VIII) is normally achieved by differentiating the effects of a lupus anticoagulant on factor assays from the effects of a specific coagulation factor antibody. The lupus anticoagulant will inhibit all the contact activation pathway factors (factor VIII, factor IX, factor XI and factor XII). Lupus anticoagulant will also rarely cause a factor assay to give a result lower than 35 iu/dl (35%) whereas a specific factor antibody will rarely give a result higher than 10 iu/dl (10%).

Treatment

Treatment involves preventive anticoagulation. Monitoring IV anticoagulant therapy by the APTT ratio is compromised due to the effects of the lupus anticoagulant and in these situations is generally best performed using a chromogenic assay based on the inhibition of factor Xa by antithrombin in the presence of heparin.

Anticardiolipin antibodies

Anti-cardiolipin antibodies can be detected using an enzyme-linked immunosorbent assay (ELISA) immunological test, which screens for the presence of β₂glycoprotein 1 dependent anticardiolipin antibodies (ACA).

A low platelet count and positivity for antibodies against β₂-glycoprotein 1 or phosphatidylserine may also be observed in a positive diagnosis.