Heparin-induced thrombocytopenia (HIT) is a well described side effect of heparin therapy. A 12-year-old boy developed deep-vein thrombosis. Risk factors for initial thrombosis are antiphospholipid syndrome and heterozygous mutation for prothrombin G20210A. Anticoagulant therapy with warfarin for 12 months was effective, but discontinuation of warfarin after 12 months resulted in recurrence of thrombosis. Unfractionated heparin (UFH) was initiated during the acute period, but heparin-induced thrombocytopenia developed. Transition from UFH to fondaparinux resulted in successful anticoagulation for a period of platelet recovery. We report a case of HIT developing with a background of prothrombotic genetic risk factors and antiphospholipid syndrome. This case study highlights several difficulties in pediatric HIT cases.