Antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease that increases the risk of thrombosis as a result of procoagulatory antibodies. The condition may be idiopathic or acquired secondary to an underlying disease, such as systemic lupus erythematosus. Circulating antibodies deactivate anticoagulatory proteins and activate platelets, thereby inducing a hypercoagulable state. Typical clinical manifestations include recurring venous and arterial thrombotic events such as deep vein thromboses, strokes, or transient ischemic attacks. A severe complication of APS in women is recurrent miscarriages of healthy fetuses. The condition should be suspected in patients with a history of thrombosis or miscarriages. It is confirmed by detecting serum antiphospholipid antibodies (e.g., lupus anticoagulant, cardiolipin antibodies). Acute thrombotic events are treated with low-molecular-weight heparin and high-dose glucocorticoids to eliminate antibodies. In mild cases, long-term management involves prophylaxis with low dose aspirin; for patients at high risk of thrombotic events, warfarin is the drug of choice.

• Primary
  • Idiopathic
  • Associated with genetic marker HLA-DR7
• Secondary
  • Systemic lupus erythematosus (most common cause of secondary APS)
  • Rheumatoid arthritis
  • Neoplasms
  • HIV, hepatitis A, hepatitis B, hepatitis C
  • Bacterial infections (e.g., syphilis, Lyme disease, tuberculosis)

• Formation of procoagulatory antiphospholipid antibodies
  • Antibodies form complexes with anticoagulant proteins, thereby inactivating them (e.g., protein C, protein S, antithrombin III)
  • Antibodies activate platelets and vascular endothelium
• Induction of a hypercoagulable state → ↑ risk of thrombosis and embolism ^[1]

APS usually manifests with recurring thrombotic events that may affect any organ.

• Venous
  • Deep vein thrombosis
  • Pulmonary embolism
  • Livedo reticularis
  • Ulceration (see “Chronic venous insufficiency”)
• Arterial
  • Stroke, transient ischemic attacks
  • Occlusion of organ arteries (e.g., myocardial infarction)
  • Occlusion of distal extremity arteries (ischemia and gangrene)
• Capillaries: splinter hemorrhages
• Pregnancy-related: : recurrent miscarriages and premature births

• History ^[2][3]
  • Arterial or venous thrombosis
  • Recurrent miscarriages (≥ 1)
• Serology: for antiphospholipid antibodies
  • Lupus anticoagulant (LA): leads to a prolonged aPTT
    • Mixing study: The patient's plasma is mixed with normal plasma. If the prolonged aPTT is caused by a lack of clotting factors, the factors contained in the normal plasma will normalize the aPTT. In the presence of lupus anticoagulants, the aPTT will remain unchanged.
    • Dilute Russell viper venom test: Lupus anticoagulant interacts with Russell viper venom, which usually induces the formation of blood clots. As LA binds the venom, this effect is suppressed, resulting in a prolonged aPTT.
  • Anticardiolipin antibodies (IgG and IgM): patients with APS often test false positive for syphilis (positive VDRL or RPR), as the antigen used in syphilis tests is cardiolipin.
  • Anti-β2-glycoprotein antibodies: a group of antibodies that inactivate anticoagulant proteins (e.g., protein C, protein S, antithrombin III) and activate platelets and vascular endothelium, thereby resulting in a hypercoagulable state
• Blood tests
  • Thrombocytopenia
  • Hemolysis, leukocytopenia

The key element of APS treatment is systemic anticoagulation.

• Acute management
  • SC low molecular weight heparin (LMWH) or IV unfractionated heparin
  • In severe cases: high-dose glucocorticoids, plasmapheresis, and/or immunoglobulins
• Secondary prophylaxis
  • Low risk: low-dose aspirin
  • High risk and no desire to become pregnant: long-term treatment with oral warfarin
  • Wish to have children: LMWH PLUS aspirin (prevention of miscarriage)