Deep venous thrombosis, protein S deficiency and homozygous Factor XII 46T mutation

We report a 13-year-old adolescent with extensive deep venous thrombosis, protein S deficiency and homozygous Factor XII 46T mutation. The patient awoke at night with pain, swelling and limited movement of his left leg. On arrival in the emergency room the pain had worsened considerably, with increasing oedema and marked cyanosis of the leg. There was no dyspnoea, cough, pleuritic pain or haemoptysis. The patient’s medical history was unremarkable and he was not on any medication. There was no history of thrombogenic situations such as surgery, trauma or immobilisation. He had a family history of superficial thrombophlebitis (grandfather and great-grandmother), deep venous thrombosis and protein S deficiency (father). On physical examination the patient appeared well and not fatigued. His temperature was 36oC, blood pressure 130/60 mm Hg, pulse 90 bpm and 26 breaths per min. The left leg showed marked cyanosis, warmth, swelling and oedema from the ankle to the groin. An important ecchymosis on the front part of the thigh was observed. There were no palpable cord or varicose veins, and distal pulses were positive. The rest of the examination was normal. Laboratory data showed a white cell count of 11600/ mm, differential count without abnormalities, a haemoglobin of 121 g/l and platelets 680000/mm. Routine blood chemistries (glucose, urea, creatinine, sodium, potassium) were in the respective reference ranges. Prothrombin time (PT) was 64%, activated partial thromboplastin time (aPTT) 36 s (control 31 s), fibrinogen 220 mg/dl and D-dimer 700 ng/ml (reference range 0–275 ng/ml). Chest X-ray films, electrocardiogram and echocardiogram were unremarkable and oxygen saturation was 98%. In the ultrasonographic examination of the legs there was evidence of massive deep venous thrombosis of the left leg extending from the left iliac vein to the popliteal region. A venography (Fig. 1) revealed extensive deep venous thrombosis affecting all of the venous drainage of the left leg including the iliac sector. The right leg’s deep venous system was completely permeable. Immediately after the diagnosis the patient started anticoagulant therapy with enoxaparin (1 mg/kg/12 h for 7 days), and secondary long-term anticoagulation with acenocumarol. An hypercoagulability study (Table 1), revealed the patient’s protein S deficiency (free 8%, total 40%), father’s protein S deficiency (free 5%, total 20% ), and the patient’s sister’s protein S deficiency (free 10%, total 41%). All of the patient’s mother’s values were in normal range. Studies of the Factor XII C>T polymorphism revealed that the patient and his sister were homozygous for Factor XII 46T, while his father and his mother were heterozygous for Factor XII C46T. The patient’s evolution has been satisfactory. A venography performed 6 months after diagnosis (Fig. 2) showed complete resolution of the thrombosis. He continues under anticoagulant therapy in excellent medical condition without post-phlebitic syndrome. Venous thromboembolic events (VTE) are significantly less frequent in children (5.3/10000 hospital admissions) [5], than in adults (2.5%–5%) [1]. Nevertheless, they represent a significant source of morbidity and mortality, and are being increasingly diagnosed in children as a result of diagnostic and therapeutic advances. Of VTE in young patients, 95% are secondary to underlying disorders (malignancy, trauma/surgery, R. Perez-Montes (&) AE C. Sedano AE L. Yanez AE A. Iriondo Department of Haematology, Marques de Valdecilla Hospital, Valdecilla Avenue s/n, 39008 Santander, Spain E-mail: hemsbc@humv.es Tel.: +34-942-203816 Fax: +34-942-202559