Antiphospholipid syndrome (APS) is an autoimmune disease associated with increased risk of thrombosis due to the presence of procoagulatory antibodies.

Etiology

• Primary
  • Idiopathic
• Secondary
  • Systemic lupus erythematosus (most common cause of secondary APS)
  • Rheumatoid arthritis
  • Neoplasms

Pathophysiology

• Formation of procoagulatory antiphospholipid antibodies
  • In most cases, the antibodies are formed secondary to autoimmune diseases or infections.
  • Antibodies form complexes with anticoagulant proteins, thereby inactivating them (e.g., protein C, protein S, antithrombin III).
  • Antibodies activate platelets and vascular endothelium, leading to increased binding of platelets
• Induction of a hypercoagulable state → ↑ risk of thrombosis and embolism

Clinical features

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

• Venous
  • Deep vein thrombosis
    • There is diffuse edema and erythema of the right leg and foot. The diameter of the right calf is visibly greater than that of the left.
  • Pulmonary embolism
  • Livedo reticularis
    • Blood clots in capillaries lead to swelling of venules, resulting in a purplish, net-like discoloration of the skin.
  • Ulceration
• 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
  • Caused by thrombosis of placental vessels and possible subsequent placental infarction

Diagnostics

• Coagulation panel: paradoxically prolonged aPTT (caused by lupus anticoagulant, which interfere with in vitro aPTT test)

Antiphospholipid antibodies

• Lupus anticoagulant (LA): antibodies against certain phospholipids in cellular membranes; detection involves a three-step procedure
  • These antibodies inhibit coagulation and therefore prolong aPTT in vitro, but have a procoagulatory effect in vivo.
  1. Screening for phospholipid-dependent coagulation with either:
     • Paradoxical prolonged aPTT
     • Prolonged dilute Russell viper venom time (dRVVT)
  2. Mixing study: The patient's plasma is mixed with normal plasma (which contains clotting factors).
     • aPTT or dRVVT normalize: Presence of lupus anticoagulant ruled out; prolonged aPTT may be due to a lack of clotting factors.
     • aPTT or dRVVT remain prolonged: Lupus anticoagulant may be present.
  3. Confirmation of phospholipid dependence: Phospholipid is added.
     • aPTT or dRVVT normalize: Presence of lupus anticoagulants is confirmed.
     • aPTT or dRVVT remain prolonged: Consider a factor deficiency.
• Anticardiolipin antibodies (IgG and IgM): antibodies against cardiolipin, a phospholipid in cellular membranes
• Anti-β2-glycoprotein antibodies (IgG and IgM): antibodies directed against the cardiolipin ­binding factor β2­ glycoprotein I that have prothrombotic effects