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Antiphospholipid Syndrome

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Overview

Antiphospholipid syndrome (APS) is an autoimmune disorder characterised by arterial and venous thrombosis, adverse pregnancy outcomes, and raised levels of antiphospholipid (aPL) antibodies. Not all patients with aPL antibodies go on to develop APS.

APS may develop secondary to other autoimmune disorders, particularly systemic lupus erythematosus (SLE).

Epidemiology

  • 30% of people who have systemic lupus erythematosus have aPL antibodies
  • Higher prevalence in black people
  • Most seen in young women of childbearing age with a male: female ratio of 1:3.5
  • Accounts for 20% of recurrent thrombosis in young people
  • Accounts for 15% of cases of recurrent foetal loss

Risk Factors

  • History of systemic lupus erythematosus
  • History of other autoimmune disorders
  • Infections, both self-limiting and chronic:
  • Lymphoma
  • Drug exposure:
  • Intravenous drug use

Presentation

  • Recurrent venous or arterial thrombosis
  • Recurrent foetal loss
  • Features of thrombocytopenia:
    • Petechial rashes
    • Mucosal bleeding
  • Arthralgia
    • Due to possible underlying systemic lupus erythematosus
  • Livedo reticularis
  • Coagulation assays show a prolonged APTT
  • Pulmonary hypertension
  • Pregnancy morbidity:
    • Pre-eclampsia
    • Placental abruption
    • Intrauterine growth restriction

Differential Diagnoses

Inherited thrombophilia

  • Presents with venous thromboembolism at an early age
  • Has a family history of venous thromboembolism

Investigations

Overview

Key investigations include:

  • Autoantibodies:
    • Lupus anticoagulant:
      • Positive on 2 occasions 12 weeks apart
    • Anticardiolipin antibodies:
      • Elevated on 2 occasions 12 weeks apart
    • Anti-beta2-glycoprotein I antibodies:
      • Elevated on 2 occasions 12 weeks apart
    • Anti-nuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA) antibody:
      • Elevated if systemic lupus erythematosus present
  • Coagulation assays:
    • Shows prolonged activated partial thromboplastin time (APTT)
      • This is due to lupus anticoagulant which is a prothrombic antibody in the body, however, it increases coagulation times in laboratory tests
      • This is because it binds to both phospholipids and proteins and may interfere with laboratory tests which require the addition of phospholipids to induce coagulation

Other investigations include:

  • Full blood count:
    • May show thrombocytopenia
  • Urea and electrolytes (U&Es):
    • Sometimes nephropathy may be present due to microangiopathic thrombosis
  • Venous Doppler ultrasound:
    • If DVT suspected
  • CTPA/ventilation-perfusion (V/Q) scan:

Diagnosis

The diagnosis of APS requires at least 1 clinical criterion and 1 laboratory criterion.

Clinical criteria are:

  • 1 or more episodes of vascular thrombosis
  • 1 or more unexplained losses of morphologically normal foetuses at or beyond the 10th week of gestation

Laboratory criteria are (must be positive on 2 or more occasions at least 12 weeks apart):

  • Lupus anticoagulant present
  • Anticardiolipin antibody present
  • Anti-beta2-glycoprotein I antibody

Management

Non-pregnant patients

  • If a patient has not had an episode of thrombosis:
    • Low-dose aspirin as primary thromboprophylaxis
  • If a patient has had an episode of thrombosis, they should be offered lifelong warfarin as secondary thromboprophylaxis:
    • Initially aim for an INR of 2-3
    • If recurrent, increase INR to 3-4 and consider adding low-dose aspirin

Pregnant patients

Management in pregnancy is different to that of the general population:

  • Low-dose aspirin once the pregnancy is confirmed via urinary beta-hCG testing
  • Low molecular weight heparin (LMWH) once the foetal heart is seen on ultrasound until 34 weeks gestation when it is then stopped
  • Return to warfarin post-delivery

Patient Advice

  • Patients with APS are at a much higher risk of arterial and venous thromboses which may cause severe disability and even death
  • Patients should be warned of the signs and symptoms of arterial and venous thromboses. These may be:
  • Patients should minimise risk by:
    • Maintaining a healthy lifestyle and exercising regularly
    • Losing weight if overweight
    • Stop smoking
    • Low-fat/low-cholesterol diet
    • Good blood sugar control
    • Avoid oestrogen-containing medications that can increase the risk of a blood clot

Complications

Prognosis

  • As the severity of APS varies significantly, so does the prognosis
  • It may cause catastrophic and potentially lethal problems such as massive pulmonary emboli and myocardial infarctions

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