Treatment

Pregnant women and patients with positive test results should be managed at specialised centres (1).

Patients should be advised about the importance of a healthy life style even at a young age e.g. - avoid smoking, lose weight, regular exercise, avoiding oral contraception hormone replacement therapy (1).

Antithrombotic agents are considered to be the mainstay in treatment.

• venous thromboembolism
  • initial treatment include unfractionated or low-molecular-weight heparin, overlapped with warfarin therapy
  • the risk of recurrent venous thrombosis can be reduced by 80% to 90% (irrespective of the presence of antiphospholipid antibodies) with moderate-intensity warfarin (adjusted to a target international normalized ratio [INR] of 2.0-3.0)
  • the optimal duration of anticoagulation is unknown (2)
• arterial thromboembolism
  • in patients with single positive antiphospholipid (aPL) antibody test result who have experienced the first ischemic stroke, long term anticoagulation with warfarin or low dose aspirin appear to be helpful in preventing thromboembolic complication
• antithrombotic treatment of APS in pregnancy (2)
  • women who are on long term warfarin therapy should switch to heparin when trying to conceive or on confirmation of conception.
  • in women with antiphospholipid antibodies and a history of severe pre-eclampsia a low dose aspirin (75-80 mg once a day) is recommended
  • for women with APS with recurrent (≥3) pregnancy loss, antenatal administration of heparin combined with low dose aspirin is recommended throughout pregnancy
  • women with aPL should be considered for post-partum thromboprophylaxis(1,2)

The risk that warfarin treatment will result in haemorrhage is 1 in 14 per year (the risk of serious haemorrhage is 1 in 50 per year) - this compares favourably with the annual risk of 1 in 3 for new thrombosis in untreated patients and 1 in 5 in patients treated with aspirin alone or lower doses of warfarin (3)

New treatment strategies (4) - seek expert advice:

• Non-vitamin K oral anticoagulants (NOACs/DOACs):
  • NOACs may become an option in patients with APS and a first VTE, who are usually treated with standard-intensity VKA, if there are contraindications for VKA or poor INR control
    • however an MRHA alert (6) stated:
      • a clinical trial has shown an increased risk of recurrent thrombotic events associated with rivaroxaban compared with warfarin, in patients with antiphospholipid syndrome and a history of thrombosis. Other direct-acting oral anticoagulants (DOACs) may be associated with a similarly increased risk
      • direct-acting oral anticoagulants (DOACs) are not recommended in patients with antiphospholipid syndrome, particularly high-risk patients (those who test positive for all 3 antiphospholipid tests - lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2 glycoprotein I antibodies)
        
• Statins:
  • have pleiotropic properties, such as improving endothelial function, reducing oxidative stress and infl ammation and modulating immune responses - because clinical outcome data are still lacking, statins are not recommended for routine use in APS in the absence of hyperlipidaemia
    
    
• Hydroxychloroquine (HCQ ):
  • several studies have established the anti-inflammatory and antithrombotic properties of HCQ in both APL-positive and APL-negative SLE patients
  • although clinical studies in patients with primary APS are lacking, HCQ can be given as an adjunct therapy to anticoagulation in APS patients with recurrent thrombosis due to its excellent safety profile and lack of associated bleeding
  • HCQ has been shown to be eff ective in obstetric APS, decreasing pregnancy morbidity and increasing the live birth rate
    
    
• Rituximab:
  • a chimeric monoclonal antibody against CD20, is used in several autoimmune diseases that are unresponsive to conventional therapies to achieve peripheral blood B cell depletion. Rituximab has also been successfully used for the treatment of severe cases of APS, including thrombocytopenia, recurrent thrombosis, microthrombotic manifestations, and Catastrophic APS (CAPS) - in the majority of cases, rituximab has been used in combination with other treatment strategies, such as anticoagulation, glucocorticoids, plasma exchange and cyclophosphamide, so the benefi ts cannot be clearly attributed to rituximab alone
    
    
• Eculizumab:
  • a humanized monoclonal antibody that binds the C5 complement fraction - has been applied to refractory cases of APS and CAPS
    
    
• Sirolimus:
  • inhibition of the mammalian target of rapamycin (mTOR) pathway is a promising target in APS
    • observed that the mTOR inhibitor sirolimus might be able to prevent vascular proliferation and to preserve renal allograft function in renal transplant patients with APS nephropathy

Notes:

• people with acute ischaemic stroke associated with antiphospholipid syndrome (5)
  • people with antiphospholipid syndrome who have an acute ischaemic stroke should be managed in same way as people with acute ischaemic stroke without antiphospholipid syndrome

Reference:

• (1) Keeling D et al.Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol. 2012;157(1):47-58.
• (2) Lim W, Crowther MA, Eikelboom JW. Management of antiphospholipid antibody syndrome: a systematic review. JAMA. 2006;295(9):1050-7.
• (3) Baglin TP et al.D. the British Committee for Standards in Haematology (2006) Guidelines on oral anticoagulation (warfarin): third edition - 2005 update British Journal of Haematology 2006; 132 (3): 277-285
• (4) Arachchillage DR, Laffan M. Pathogenesis and management of antiphospholipid syndrome. Br J Haematol. 2017;178:181-95.
• (5) NICE (May 2019). The diagnosis and acute management of stroke and transient ischaemic attacks
• (6) MHRA (June 2019). Direct-acting oral anticoagulants (DOACs): increased risk of recurrent thrombotic events in patients with antiphospholipid syndrome