Antiphospholipid Syndrome

In the 1950's it was discovered that approximately 10% of patients with systemic lupus erythematosus had circulating lupus anticoagulant which falls under the classification of antiphospholipid antibodies. The presence of these antibodies was associated with an increased risk of thrombosis.Soon thereafter, it was recognized that many patients without autoimmune disorders also possessed the lupus anticoagulants. These other disorders include malignacies, immune thrombocytopenic purpura, infections, and after ingestion of chlorpromazine or procainamide. Also, many normal individuals possess antiphospholipid antibodies. It was also noted that the presence of lupus anticoagulant was also associated with a false positive VDRL test for syphilis (the VDRL test is performed with beef cardiolipin which is a phospholipid). Therefore, in 1983, Harris et al. engineered a test for antiphospholipids using cardiolipin. It is important to note that while the other thrombophilic states discussed are genetic, antiphospholipid syndrome is an acquired state.

I. Anticardiolipin antibodies

A. This is a distinct entity from lupus anticoagulants.

B. Clinical Features

1. Thrombosis and Thromboembolus

The first hypercoagulable process we've discussed to clearly have increased arterial events
Recurrent DVT (intracranial veins, retinal veins, upper extremities, hepatic veins, portal veins, renal veins, inferior vena cava, lower extremities)
Pulmonary embolism
Arterial thrombosis (coronary arteries, retinal arteries, brachial arteries, mesenteric arteries, peripheral arteries, aorta).

2. First thrombotic often occurs in early-mid teenage years.

3. Women may experience recurrent fetal loss, usually in second or third trimester.

4. Migraine headaches, transient ischemic attacks, or Guillain-Barre syndrome is often seen.

5. Mild thrombocytopenia is often seen.

6. There is often a dermatologic condition known as livido reticularis in which the skin appears mottled. This is usually most notable in the lower extremities.

7. There is often a postpartum syndrome, which occurs 2-10 weeks after delivery and consists of fevers, dyspnea, pleuritic chest pain, pulmonary infiltrates, pleural effusions, cardiomyopathy, and arrhythmias.

C. Possible mechanisms for anticardiolipin mediated disease.

1. Interaction with platelets to activate their membrane phospholipids, thus initiating the coagulation cascade.

2. Interference with endothelial release of prostacyclin.

3. Interference with activation of Protein C on thrombomodulin.

4. Interference with Antithrombin III activity.

5. Interference with endothelial release of plasminogen activator.

D. Laboratory Measurements

1. IgG, IgA, and IgM anti-cardiolipin antibodies or anti-phospholipid antibodies can be measured.

2. The presence of any one antibody (G, A or M) is a risk factor for thrombosis.

E. Treatment - short term anticoagulation with heparin and long term anticoagulation with warfarin

II. Lupus Anticoagulants

A. May occur in up to 10% of patients with systemic lupus erythematosus.
B. Also associated with HIV, scleroderma, gastric disease.
C. May be caused by certain drugs.: 1. Chlorpromazine; 2. Procainamide; 3. Fansidar; 4. Phenothiazines

D. Laboratory criteria for diagnosis

1. Abnormal activated prothrombin time (aPT)

2. Prolonged activated partial thromboplastin time (aPTT) which does not correct upon addition of normal pooled plasma.

3. Abnormal dilute Russell Viper Venom test. This is the most sensitive test.

E. Clinical features - similar to anticardiolipin antibodies

1. Thrombosis and thromboembolism (see above)

2. False positive VDRL

3. Thrombocytopenia

4. Recurrent fetal loss

5. Prothrombin deficiency

6. Livido reticularis