Antiphospholipid syndrome
Antiphospholipid syndrome

Antiphospholipid syndrome

Pathophysiology

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Antiphospholipid antibodies (APS) are autoantibodies that attack phospholipid-binding plasma proteins such as prothrombin, as well as the phospholipids that are expressed on platelets, monocytes and trophoblast cells. This leads to hypercoagulability, complications in pregnancy (particularly recurrent miscarriage).

It is not known what causes the development of these antibodies, but it is proposed to be molecular mimicry from bacterial/viral infection.

It may also occur secondary to other autoimmune conditions such as SLE.

Antiphospholipid antibodies that may be useful to remember include:

  1. Lupus anticoagulant
  2. Anticardiolipin antibodies
  3. Anti-beta2-glycoprotein I antibodies

😷 Presentation

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  • History of VTE
    • Pulmonary embolism
    • DVT
  • History of arterial thrombosis
    • Stroke
    • MI
    • Renal thrombosis
  • Pregnancy complications
    • Recurrent miscarriage
    • Stillbirth
    • Preeclampsia
Livedo reticularis
Livedo reticularis
  • Livedo reticularis - a purple, lace-like rash that gives a mottled purplish discolouration to the skin. It may be blanching or non-blanching. It occurs due to fibrin deposition at the periphery of arterioles.
  • Thrombocytopenia
  • Libmann-Sacks endocarditis - vegetations on the valves of the heart. It is a type of non-bacterial endocarditis. Mostly affecting the mitral valve.
  • Prolonged aPTT

🔍 Investigations

The diagnosis based on the history of thrombosis/complicated pregnancy + detection of antibodies:

  • Lupus anticoagulant - based on coagulation assays.
  • Anticardiolipin antibodies
  • Anti-beta2-glycoprotein I antibodies
  • ANA antibodies, dsDNA, nuclear antigen antibodies - suggests SLE which is associated with the disease.

Other investigations to include are:

  1. FBC - may show thrombocytopenia.
  2. Creatinine and urea - to assess renal function. Microangiopathic thrombosis secondary to APS can sometimes lead to oedema and proteinuria in the patient.

🔢 Criteria

This criteria is not diagnostic but simply may aid diagnosis of APS. It has 2 components:

  1. Clinical criteria - at least 1 must be positive.
  2. Laboratory criteria - at least 1 must be positive on 2 more or occasions at least 12 weeks apart.

Clinical criteria

  • Vascular thrombosis - at least 1 episode of arterial or venous thrombosis that is confirmed.
  • Pregnancy complications
    • 3 or more unexplained spontaneous abortions before week 10 of gestation.
    • 1 or more unexplained deaths of morphologically normal fetus at ≥10 weeks of gestation.
    • 1 or more premature births of morphologically normal fetus before 34th week of gestation.

Laboratory criteria

  • Lupus anticoagulant
  • Anticardiolipin antibodies
  • Anti-beta2-glycoprotein I antibodies

🧰 Management

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Thromboprophylaxis:

Management of the patients can be complex and may involve rheumatology, haematology, and obstetrics.

  • Primary thromboprophylaxis (if the patient has not had a thrombosis and has been diagnosed with APLS) → low-dose aspirin.
  • Secondary thromboprophylaxis requires lifelong warfarin with a target INR of 2-3.
    • If the patient has recurrent VTE whilst on warfarin → add low-dose aspirin and increase INR target to 3-4.
  • Pregnant women are started on LMWHs such as dalteparin or enoxaparin.

🚨 An acute thrombosis should be treated with LMWHs such as dalteparin or enoxaparin.