Antiphospholipid Syndrome

Antiphospholipid syndrome is a still incompletely understood autoimmune disorder that possesses a highly variable clinical presentation, as virtually any organ or part of the body may be affected by the vascular pathological changes that occur [1]. The symptoms stem from two events - formation of venous (or sometimes arterial) thrombosis and thrombotic microangiopathy (TMA) [1] [2] [3]. Venous thrombosis of the lower extremities is regarded as a frequent finding in patients with antiphospholipid syndrome, whereas pulmonary embolism (developing either from distal thrombi or cardiac valve vegetations) can appear in up to 50% of cases [1]. In addition to the lower extremities, thrombotic changes often affect the subclavian, retinal, and renal arteries [1]. In fact, the kidneys are the primary site where both thrombotic and TMA-related effects of antiphospholipid syndrome are exerted [1] [2]. Occlusion of both larger and smaller renal vessels leads to profound hypertension, proteinuria, and renal insufficiency that presents with anuria [1]. Apart from the kidneys, other organs that are prone to damage are the brain, the heart, the lungs, and the skin [1] [4]. The term "catastrophic antiphospholipid syndrome" is used to describe patients who suffer from life-threatening forms of this disease [1] [5]. Hypertension, hemolytic anemia, disseminated intravascular coagulation (DIC), microthrombotic events involving the heart and the brain, as well as adult respiratory distress syndrome (ARDS), are hallmarks of catastrophic antiphospholipid syndrome, which carries a mortality rate of 50% [1] [4] [5].

The recognition of antiphospholipid syndrome rests on a thorough clinical and laboratory assessment and the diagnostic criteria are comprised of the following:

• Clinical criteria - Pregnancy-related events that raise suspicion toward antiphospholipid syndrome are death of previously healthy fetuses after the 10th week of gestation, premature births due to eclampsia, pre-eclampsia, or insufficiency of the placenta, or unexplained spontaneous abortions before the 10th week of gestation [2] [3] [6] [7]. For this reason, it is imperative for physicians to obtain a detailed history that will reveal these findings. Confirmation of vascular thrombosis in any organ, regardless of vessel size, is the second clinical criteria [2] [3] [6] [7].
• Laboratory criteria - Detection of either lupus anticoagulant (LA), immunoglobulin (Ig) M or IgG anticardiolipin antibodies, or IgM or IgG anti-β2-glycoprotein-1 antibodies on two separate tests that are done 12 weeks apart using standard methods is crucial for identifying antiphospholipid syndrome [2] [3] [6] [7]. Values of anticardiolipin and anti-β2-glycoprotein-1 antibodies should be greater than the 99th percentile [2] [6]. Values of LA may not be accurate in the presence of antithrombic drugs, which implies that their use should be temporarily stopped for proper testing [2].

Although nephropathy, thrombocytopenia, and valvular heart disease are notable findings in these patients, at least one clinical and one laboratory criteria are needed in order to make the diagnosis of the antiphospholipid syndrome [2] [3] [7].

1. Fischer MJ, Rauch J, Levine JS. The Antiphospholipid Syndrome. Semin Nephrol. 2007;27(1):35-46.
2. Lim W. Antiphospholipid antibody syndrome. Hematology Am Soc Hematol Educ Program. 2009:233-239.
3. Chaturvedi S, McCrae KR. The antiphospholipid syndrome: still an enigma. Hematology Am Soc Hematol Educ Program. 2015;2015:53-60.
4. Cervera R, Font J, Gómez-Puerta JA, et al. Validation of the preliminary criteria for the classification of catastrophic antiphospholipid syndrome. Ann Rheum Dis. 2005;64:1205–1209.
5. Asherson RA, Cervera R, Piette JC, et al. Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients. Medicine (Baltimore). 1998;77:195–207.
6. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306.
7. Pengo V, Tripodi A, Reber G, et al. Update of the guidelines for lupus anticoagulant detection: Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2009;7(10):1737–1740.