The antiphospholipid syndrome (APS) is an acquired autoimmune disorder in which antibodies are directed against one or more phospholipid-binding proteins (eg, anti-β2-glycoprotein I, anticardiolipin, and lupus anticoagulant) or their associated plasma proteins, resulting in hyper-coagulation within the microvasculature. APS is characterized by elevated titers of different antiphospholipid antibodies.[i] The proteins normally bind to phospholipid membrane constituents and protect them from excessive coagulation activation. The autoantibodies displace the protective proteins and thus produce pro-coagulant endothelial cell surfaces and cause arterial or venous thrombosis. In vitro clotting tests may paradoxically be prolonged because the anti-protein/phospholipid antibodies interfere with coagulation factor assembly and with activation on the phospholipid components that are added to plasma to initiate the tests.
The lupus anticoagulant is an antiphospholipid autoantibody that binds to protein-phospholipid complexes. It was initially recognized in patients with SLE; however, these patients now account for a minority of patients with the autoantibody. The lupus anticoagulant is suspected if the PTT is prolonged and does not correct immediately upon 1:1 mixing with normal plasma but does return to normal upon the addition of an excessive quantity of phospholipids (done by the hematology laboratory). Antiphospholipid antibodies in the patient plasma are measured by immunoassays of IgG and IgM antibodies that bind to phospholipid-β2-glycoprotein I complexes on microtiter plates.[ii] APS can occur with or without associated rheumatic disease (eg, systemic lupus erythematosus).
The arteriole thrombosis results in venous swelling, creating the typical livedo reticularis skin appearance. In addition, the lower extremities may have purpura, splinter hemorrhages, livedoid vasculopathy, anetoderma-like lesions, Raynaud phenomenon, pyoderma gangrenosum-type ulcers, nail fold ulcers, digital ischemia, or superficial thrombophlebitis. (Photo from Epainassist.com) As the disease progresses, skin necrosis may occur, and if the disorder occurs during pregnancy, there will be fetal demise.[iii] If the thrombosis is in the venules, the result may be a DVT with lower extremity edema, tachypnea due to pulmonary emboli, and ascites.
Asymptomatic individuals in whom blood test findings are positive do not require specific treatment. Prophylactic therapy involves elimination of other risk factors such as oral contraceptives, smoking, hypertension, or hyperlipidemia. For patients with SLE, hydroxychloroquine, an anti-inflammatory that may have intrinsic antithrombotic properties, may be useful. Statins are beneficial for patients with hyperlipidemia. If the patient has a thrombosis, full anticoagulation with intravenous or subcutaneous heparin followed by warfarin therapy is recommended.2,[iv]
Based on the most recent evidence, a reasonable target for the international normalized ratio (INR) is 2.0 –3.0 for venous thrombosis and 3.0 for arterial thrombosis. Patients with recurrent thrombotic events, while well maintained on the above regimens, may require an INR of 3.0–4.0. For severe or refractory cases, a combination of warfarin and aspirin may be used. Treatment for significant thrombotic events in patients with APS is generally lifelong. Because cutaneous manifestations are the first sign of APS in up to 41% of patients, a full medical examination is advised for any patient showing the clinical symptoms in order to identify and treat the underlying pathology.[v]
Conservative wound care is recommended for patients with skin lesions, keeping the wound moist and following wound bed preparation principles. Healing of wounds caused by other etiologies, eg, trauma or spider bites, will be delayed in patients who have APS.
[i] Sammaritano LR. Antiphospholipid syndrome. Best Practice and Research Clinical Rheumatology. 2019. Available at https://doi.org/10.1016/j.berh.2019.101463. Accessed March 15, 2020.
[ii] Alarcon-Segovia D, Deleze M, Oria CV, et al. Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive cases. Medicine. 1989;68(6):353-365.
[iii] Zhang Y, Riddle N, Seminario-Vidal L. Post-partum cutaneous manifestation of antiphospholipid syndrome. Human Pathology: Case Reports. 2019. Available at https://doi.org/10.1016/j.ehpc.2019.200334. Accessed March 15, 2020.
[iv] Falanga V. Cutaneous Wound Healing. London: Martin Dunitz; 2001;247-263.
[v] Silverberg JI, Votava HJ, Smith BL. Antiphospholipid antibody syndrome secondary to trimethoprim/sulfamethoxazole. J Drugs Dermatol. 2012;11(9):1117-1118.