antiphospholipid syndrome

Last edited 04/2019

Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy complications in the presence of persistent antiphospholipid antibodies (APLA)

This syndrome was first described in 1983-1986 as the association of arterial and venous thrombosis with antibodies directed against phospholipids. (1)

The condition may occur

• in isolation as primary antiphospholipid syndrome - seen in more than 50% of patients (1)
• in association with other autoimmune diseases e.g. - SLE is the commonest associated condition with 20-35% of patients developing secondary antiphospholipid syndrome (1)

Laboratory diagnosis of APLA depends upon the detection of a lupus anticoagulant, which prolongs phospholipid-dependent anticoagulation tests, and/or anticardiolipin (aCL) and anti-beta-glycoprotein-1 (ß2GPI) antibodies

• APLA are primarily directed towards phospholipid binding proteins
• high rate of recurrent thrombosis in APS, especially in triple positive patients (patients with lupus anticoagulants, aCL and anti-ß2GPI antibodies), and indefinite anticoagulation with a vitamin K antagonist is the standard of care for thrombotic APS (2)
• other clinical features, such as thrombocytopenia, Coombs-positive haemolytic anaemia, livedo reticularis, heart valve disease, renal microangiopathy and neurologic disorders are also common in APL-positive patients
• APS can be associated with other autoimmune disorders, such as systemic lupus erythematosus

APS - unlike most of the genetic thrombophilias - is associated with both venous and arterial thrombosis

• thrombosis
  • deep veins of the lower extremities and the cerebral arterial circulation are the most commonly affected venous and arterial sites, respectively
    • more unusual locations can also be affected by thrombosis such as the hepatic veins, visceral veins or cerebral venous circulation - if there is development of thrombosis at an unusual site then this should be prompt for antiphospholipid antibodies
  • catastrophic anti-phospholipid syndrome (CAPS) develops in a small number of patients (<1%)
    • defined as small vessel thrombosis in three or more organs in less than one week in the presence of APLA, with histopathologic confirmation of small vessel thrombosis in the absence of inflammation
    • important differential diagnosis include -thrombotic thrombocytopaenic purpura, haemolytic uraemic syndrome, and disseminated intravascular coagulation (2)
    • CAPS is often triggered by a precipitating event such as infection
  • associated with high (50%) mortality - following complications such as cerebral and cardiac thrombosis, infections and multi-organ failure
  • for patients with CAPS, a combined therapeutic approach that is complex and includes modalities such as anticoagulation, glucocorticoids, plasma exchange and/or intravenous immunoglobulin

Obstetrical morbidity in APS includes:

• (a) One or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation.
• (b) One or more premature births of a morphologically normal neonate before the 34th week of gestation because of eclampsia, severe preeclampsia, or recognized features of placental insufficiency
• (c) Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded.

Treatment usually comprises antithrombotic therapy using antiplatelet and anticoagulant agents

• anticoagulant therapy with vitamin K antagonists remains the mainstay of therapy in patients with thrombotic APS
• aspirin with low molecular weight or unfractionated heparin may reduce the incidence of pregnancy loss in obstetric APS (2)

Reference:

• Cohen D et al. Diagnosis and management of the antiphospholipid syndrome. BMJ. 2010;340:c2541.
• Chaturvedi S, McCrae KR. Diagnosis and management of the antiphospholipid syndrome.Blood Rev. 2017 Nov;31(6):406-417
• Keeling D et al.Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol. 2012;157(1):47-58.
• Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for defi nite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295-306