Only a small proportion of the population, one in every 2000 people, many with an existing diagnosis of Systemic Lupus Erythematosus, develop the antiphospholipid syndrome—a syndrome complex of different autoantibodies that predispose to clotting, both within the venous and arterial systems, and that includes a risk of recurrent foetal loss. The diagnosis requires a demonstration of the serological presence of any one of three antibodies: anti-cardiolipin antibodies; antibodies to beta-2-glycoprotein 1; or the lupus anticoagulant.
Cardiolipin is an important component of the inner mitochondrial membrane, where it constitutes about 20% of the total lipid composition. (The only other place that cardiolipin can be found is in the membranes of most bacteria.) The name ‘cardiolipin’ is derived from the fact that it was first found in animal hearts. It was first isolated from beef heart in the early 1940s. In mammalian cells, but also in plant cells, cardiolipin (CL) is found almost exclusively in the inner mitochondrial membrane where it is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism.
LSBio
- anti-cardiolipin Ab: IgG or IgM antibodies to cardiolipin, a negatively charged and uniquely dimeric phospholipid that plays a role in maintaining the structural integrity of the mitochondrial membrane. This is the antibody that confers positivity to a VDRL test (see Syphilis). There is an increased incidence of ACA in Behcet’s disease.
- IgG or IgM antibodies to beta-2-glycoprotein 1, a binder of cardiolipin and an activator of lipoprotein lipase synthesised in the liver. B2-GP1 is also referred to as Apolipoprotein-H (Apo-H).
- lupus anticoagulant, an immunoglobulin that will cause the aPTT lab test to rise (hence the historical misnomer, “anticoagulant”) even though the protein is a pro-coagulant in-vivo, by nature of its interaction with (it binds) phospholipids on the platelet membrane.
Patients with antiphospholipid syndrome (APS) will present with recurrent VTE, cerebral ischaemic vascular events (TIA/stroke, ocular ischaemia), a verrucous endocarditis, necrotising purpura, and spontaneous miscarriage but can present with pulmonary hypertension, epilepsy, migraine-like syndromes, transverse myelopathy, thrombocytopaenia (common), and/or haemolytic anaemia. The paradox here might be when the aPTT comes back (falsely) elevated.
APS is an acquired condition often but by no means always related to lupus but can (like lupus) be drug-related, especially with the drugs chlorpromazine and hydralazine, associated with opportunistic infection, or in the context of sepsis and a thrombotic microangiopathy.
Manage with:
- anticoagulate this person with heparin; and warfarin (non-pregnant), to an INR of 3
- low-dose aspirin (incl. in pregnancy)
- hydroxychloroquine (Plaquenil): drug treatment of choice for an associated SLE
- immunotherapy: in severe cases – the mab CD20-i rituximab, or even eculizumab
- plasmapheresis
- statins: prevent the antiphospholipid antibody-induced up-regulation of tissue factor
- C/I in pregnancy
References
- Cade, J. F.. Critical Care Compendium: 1001 Topics in Intensive Care & Acute Medicine (p. 37). Cambridge University Press. Kindle Edition.
- Papadakis, Maxine A.; McPhee, Stephen J.; Rabow, Michael W.; McQuaid, Kenneth R. CURRENT Medical Diagnosis and Treatment 2023. McGraw Hill LLC. Kindle Edition.
Image Reference
*Smith, Larry J. Amer Soc Clin Lab Sc. Jan 2017; 30(1):7-14.
**Willis R, Gonzalez EB. Pathogenetic mechanisms of antiphospholipid antibody production in antiphospholipid syndrome. World J Rheumatol 2015; 5(2): 59-68 [DOI: 10.5499/wjr.v5.i2.59]
