Antiphospholipid syndrome (APS)

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How the diagnosis is reached

A pulmonary embolism at 27 with no cause found, anticoagulation stopped at six months, and now a femoral thrombus: the recurrence is the point, and set beside three early losses and a late fetal death with severe pre-eclampsia it satisfies the clinical criteria for antiphospholipid syndrome. The coagulation results contain the diagnostic paradox: the aPTT is prolonged yet the patient thromboses. That prolongation is a laboratory artefact, the lupus anticoagulant binds the phospholipid reagent used in the assay, and failure to correct on a 50:50 mix with normal plasma indicates an inhibitor rather than a factor deficiency, since simply replacing missing factors would normalise the result. Two further clues are easy to overlook: livedo reticularis, the non-blanching net-like mottling, and mild thrombocytopenia, both recognised features. The reactive VDRL with a negative treponemal-specific test is a false-positive syphilis serology, another classic association, because the VDRL uses a cardiolipin-based antigen. A negative ANA makes secondary lupus unlikely, so this is primary APS. Persistence of all three antibodies at 14 weeks matters: transient positivity is common after infection, so diagnosis requires confirmation at least 12 weeks apart. This patient is triple-positive, which carries the highest recurrence risk and also decides the drug. Anticoagulation is lifelong this time, with a vitamin K antagonist to a target INR of 2 to 3, and a direct oral anticoagulant is specifically the wrong choice: trials in antiphospholipid syndrome, and in triple-positive patients above all, found more recurrent thrombosis on a DOAC than on warfarin. Her obstetric history makes the other half of this immediate. Vitamin K antagonists are teratogenic, so any future pregnancy means switching to low molecular weight heparin with low-dose aspirin, a combination that substantially improves live birth rates, and that plan is worth making now rather than at the first positive test.

Key clinical clues

• Unprovoked VTE at 27, now recurrent, plus three early losses and a late fetal death
• Prolonged aPTT that fails to correct on 50:50 mixing, an inhibitor, not a deficiency
• Paradox of a prolonged clotting time in a patient who thromboses
• Livedo reticularis with mild thrombocytopenia
• False-positive VDRL with negative treponemal-specific testing

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