Antiphospholipid Syndrome

Definition

Definition of Antiphospholipid Syndrome
Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS or), often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids that provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, or severe preeclampsia. The syndrome occurs due to the autoimmune production of antibodies against phospholipid (aPL), a cell membrane substance. In particular, the disease is characterised by antibodies against cardiolipin (anti-cardiolipin antibodies) and ß2 glycoprotein I. The term "primary antiphospholipid syndrome" is used when APS occurs in the absence of any other related disease. APS however also occurs in the context of other autoimmune diseases, such as systemic lupus erythematosus (SLE), in which case the term "secondary antiphospholipid syndrome" is used. In rare cases, APS leads to rapid organ failure due to generalised thrombosis; this is termed "catastrophic antiphospholipid syndrome" (CAPS) and is associated with a high risk of death.

Symptoms

Symptoms of Antiphospholipid Syndrome
The presence of antiphospholipid antibodies (aPL) in the absence of blood clots or pregnancy-related complications does not indicate APS (see below for the diagnosis of APS).

Antiphospholipid syndrome can cause (arterial/venous) blood clots (in any organ system) or pregnancy-related complications. In APS patients, the most common venous event is deep vein thrombosis of the lower extremities (blood clot of the deep veins of the legs) and the most common arterial event is stroke. In pregnant women affected by APS, miscarriage can occur prior to 20 week of gestation, while pre-eclampsia is reported to occur after that time. Placental infarctions, early deliveries and stillbirth are also reported in women with APS. In some cases, APS seems to be the leading cause of mental and/or development retardation in the newborn, due to an aPL-induced inhibition of trophoblast differentiation. The antiphospholipid syndrome responsible for most of the miscarriages in later trimesters seen in concomitant systemic lupus erythematosus and pregnancy.

Causes

Causes of Antiphospholipid Syndrome
The cause of primary antiphospholipid syndrome is unknown. However, some factors are associated with developing antiphospholipid antibodies - though not necessarily developing the syndrome. They include:

1. Infections: People with syphilis, HIV infection, hepatitis C and malaria, among others, have a higher incidence of having antiphospholipid antibodies.
2. Medications: Taking certain drugs, such as the high blood pressure medication hydralazine, the heart rhythm-regulating medication quinidine, the anti-seizure medication phenytoin (Dilantin) and the antibiotic amoxicillin may lead to an increased risk.(
3. Genetic predispositions: Although the disorder isn't considered hereditary, research indicates that relatives of people with antiphospholipid syndrome are more likely to have the antibodies.

Diagnosis

Diagnosis of Antiphospholipid Syndrome
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:

1. Further studies for Factor V Leiden variant and the prothrombin mutation, Factor VIII levels, MTHFR mutation.
2. 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 ß2 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.

Treatment

Treatment of Antiphospholipid Syndrome
Often, this disease is treated by giving aspirin to inhibit platelet activation, and/or warfarin as an anticoagulant. The goal of the prophylactic treatment is to maintain the patient's INR between 2.0 - 3.0. It is not usually done in patients who have not had any thrombotic symptoms. During pregnancy, low molecular weight heparin and low-dose aspirin are used instead of warfarin because of warfarin's teratogenicity. Women with recurrent miscarriage are often advised to take aspirin and to start low molecular weight heparin treatment after missing a menstrual cycle. In refractory cases plasmapheresis may be used.

Prognosis

Prognosis of Antiphospholipid Syndrome
The long-term prognosis for APS is determined mainly by recurrent thrombosis, which may occur in up to 29% of patients, sometimes despite antithrombotic therapy.

Prevention

Prevention of Antiphospholipid Syndrome
Consult with your doctor.