This lecture was conducted during the Nephrology Unit Grand Ground by Nephrology Registrar under Nephrology Division, Department of Medicine in King Saud University. Nephrology Division is not responsible for the content of the presentation for it is intended for learning and /or education purpose only.

Antiphospholipid Syndrome Noor Alhassan

Outlines Definition Pathophysiology Presentation Diagnosis Treatment

Definition APL is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids that provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications.

Common autoimmune SLE % Sjögren syndrome - 42% Rheumatoid arthritis - 33% Autoimmune thrombocytopenic purpura - 30% Autoimmune hemolytic anemia - Unknown Psoriatic arthritis - 28% Systemic sclerosis - 25% Mixed connective-tissue disease - 22% Polymyalgia rheumatica or giant cell arteritis - 20% Behçet syndrome - 20% Infections Syphilis Hepatitis C infection HIV infection Human T-cell lymphotrophic virus type 1 infection Malaria Bacterial septicemia

Pathophysiology

Pathophysiology Autoimmune disease, in which "antiphospholipid antibodies“ anticardiolipin antibodies and lupus anticoagulant react against proteins that bind to anionic phospholipids on plasma membranes (cardiolipin and β 2 glycoprotein I)

Pathophysiology Production of antibodies against coagulation factors, including prothrombin, protein C, protein S Activation of platelets Reaction of antibodies to oxidized low- density lipoprotein

Hypercoagulability and recurrent thrombosis can affect virtually any organ system:

Peripheral venous system CNS Hematologic Obstetric Pulmonary Cardiac Ocular Adrenal Musculoskeletal Dermatologic

Diagnosis At least one clinical criterion and one laboratory criterion

Diagnosis Clinical criteria: Vascular thrombosis Pregnancy morbidity

Diagnosis Laboratory criteria: (1) medium to high levels of immunoglobulin G (IgG) or immunoglobulin M (IgM) anticardiolipin (aCL) (2) anti–beta-2 glycoprotein I (3) Lupus anticoagulant

Activated partial thromboplastin time (aPTT) Serologic test for syphilis (false-positive result) CBC count

Treatment Aspirin/Clopidogrel Heparin/Warfarin In pregnancy > SQ LMWH + low dose ASA Steroids ?

References References Giannakopoulos B, Passam F, Rahgozar S, Krilis SA. Current concepts on the pathogenesis of the antiphospholipid syndrome. Blood. Jan ;109(2): Girardi G, Redecha P, Salmon JE. Heparin prevents antiphospholipid antibody-induced fetal loss by inhibiting complement activation. Nat Med. Nov 2004;10(11): Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. Feb 2006;4(2): Laskin CA, Spitzer KA, Clark CA, Crowther MR, Ginsberg JS, Hawker GA, et al. Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA Trial. J Rheumatol. Feb 2009;36(2): Cervera R, Piette JC, Fornt J. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46(4):

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