Antiphospholipid Syndrome

Antiphospholipid Syndrome (APS), also known as Hughes Syndrome, is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPL) that promote abnormal blood clot formation (thrombosis) in both arterial and venous circulation. APS may occur as a primary condition or develop secondary to other autoimmune diseases, most commonly systemic lupus erythematosus (SLE). Clinically, patients may present with deep vein thrombosis (DVT), stroke, pulmonary embolism, or recurrent pregnancy loss due to placental thrombosis. Persistent detection of lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein I antibodies—confirmed on two or more occasions at least 12 weeks apart—forms the cornerstone of laboratory diagnosis. Early recognition and appropriate anticoagulation therapy are essential to prevent recurrent thrombotic events and improve long-term outcomes in antiphospholipid antibody syndrome.

Antiphospholipid Syndrome (APS) is an acquired, treatable autoimmune thrombophilia characterized by antiphospholipid antibodies that attack phospholipid-binding proteins such as β2-glycoprotein I, prothrombin, and annexin A5. These antibodies disrupt normal hemostasis, leading to arterial and venous thrombosis, thrombocytopenia, and recurrent pregnancy loss.

APS can affect multiple organ systems, making it relevant to hematology, rheumatology, obstetrics, and cardiology. Pathophysiology involves loss of protective annexin A5 from cell membranes, exposing procoagulant surfaces that promote clot formation. In severe cases, catastrophic APS (CAPS) causes widespread microvascular thrombosis and multiorgan failure, resembling DIC, HIT, or TMA. Management includes anticoagulation, high-dose corticosteroids, plasmapheresis, and biologic agents such as rituximab or eculizumab to prevent life-threatening complications.

Clinical manifestations of APS:

• Superficial and deep vein thrombosis, cerebral venous thrombosis, retinal vein thrombosis.
• Signs and symptoms of intracranial hypertension, pulmonary emboli, pulmonary arterial hypertension, and Budd-Chiari syndrome.
• Livedo reticularis.
• Arterial thrombosis – migraines, cognitive dysfunction, transient ischemic attacks, stroke, myocardial infarction, ischemic leg ulcers, digital gangrene, avascular necrosis of bone, retinal artery occlusion, renal artery stenosis, and, infarcts of spleen, pancreas, and adrenals.
• Premature atherosclerosis – a rare feature of APS.
• Coombs-positive hemolytic anemia and thrombocytopenia.
• Libman-Sacks endocarditis.
• The fetal loss does not appear to be explained by thrombosis, but rather seems to stem from antibody-mediated interference with the growth and differentiation of trophoblasts, leading to a failure of placentation.
• Discontinuation of therapy, major surgery, infection, and trauma may trigger Catastrophic APS.

Diagnosis:

One clinical + one laboratory criterion:

Clinical criteria:

• Vascular thrombosis in any tissue or organ.
• Pregnancy morbidity: One or more unexplained deaths of a morphologically normal fetus at or beyond the tenth week of gestation, One or more premature births of a morphologically normal neonate before the thirty-fourth week of gestation because of eclampsia, severe preeclampsia, or placental insufficiency, A 3 or more unexplained consecutive spontaneous abortions before the 10th week of gestation.

Laboratory criteria:

Characteristic laboratory abnormalities in APS include persistently elevated levels of IgG and IgM antibodies directed against membrane anionic phospholipids or their associated plasma proteins or evidence of a circulating anticoagulant.

The confirmed presence of a repeated antiphospholipid (aPL) antibodies – at intermediate or high titres on two or more occasions, 12 weeks apart is a required criterion for the diagnosis of APS:

• Antibodies against cardiolipin – ACL.
• Antibodies against beta 2 glycoprotein I – B2GPI.
• Lupus anticoagulant – LA.

The lupus anticoagulant (LA) is suspected if the APTT 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 in the clinical pathology laboratory). Antiphospholipid antibodies in patient plasma are then directly measured by immunoassays of IgG and IgM antibodies that bind to phospholipid/beta₂-glycoprotein I complexes on microtiter plates.

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