A 42-year-old Caucasian man presented with a one-year history of worsening vague abdominal pains over the past few months. The pain radiated to his back, and was associated with fever. He did not smoke and his alcohol consumption was 25 units per week.
At the age of 31 years, he had a right spontaneous lower limb deep vein thrombosis (DVT), with post-phlebitic leg swelling. His father had previously had two spontaneous DVTs, and his brother, aged 30, had a DVT following a herniorrhaphy.
An examination and investigations revealed a normal blood pressure and pulse. There was generalised upper abdominal tenderness, but no guarding or rebound. His cardiorespiratory examination was unremarkable. His blood tests revealed the following: bilirubin 21 μmol/L (normal range 5-17 μmol/L), aspartate aminotransferase (AST) 50 IU/L (normal range <40 IU/L), alkaline phosphatise (ALKP) 271 U/L (normal range <105 IU/L), gamma glutamyl transferase (GGT) 150 IU/L (normal range <35 IU/L), amylase 25 U/L, international normalised ratio (INR) 1.1, prothrombin time (PT) 27.4, C-reactive protein (CRP) 114 mg/L (normal range <4 mg/L), erythrocyte sedimentation rate (ESR) 53 mm/hr, normal full blood count (platelets 190 × 109/L) and normal renal function.
There was no growth in the blood culture. Serology for Epstein-Barr virus, hepatitis A virus and hepatitis C virus was negative. An autoimmune screen was negative (rheumatoid arthritis, antinuclear antibody, anti-mitochondrial antibody, anti-liver kidney microsomes, anti-smooth muscle antibody). An ultrasound scan of the patient's abdomen showed mild splenomegaly with a trace of ascites.
During a follow-up in clinic two months later, he complained of increased lethargy with reduced appetite. A unilateral leg oedema was noticed. A gastroscopy was normal and a computed tomography (CT) scan confirmed splenomegaly (13.5 cm), though he had a normal liver and had no ascites. An ultrasound Doppler examination showed a chronic DVT with incomplete recanalisation. Repeat blood tests resulted in the following: ALT 38 IU/L, ALKP 77 IU/L, bilirubin 22 μmol/L, AST 27 IU/L, GGT 58 IU/L, thrombocytopenia (78 × 106/mm3) and neutropenia (1.65 × 106/mm3), ESR 5 mm/hr.
Six months later, the patient experienced persisting vague abdominal pain, thrombocytopenia and a mild abnormality of the liver function tests. A repeat liver ultrasound showed a new 3 cm echo-poor area in the periphery of segment VIII, consistent with an infarct.
A repeat CT scan six months later showed multiple infarcts in the liver, numerous dilated veins on the greater and lesser curves of his stomach, splenic hilum, and surrounding the portal vein, consistent with portal hypertension.
A thrombophilia screen for anticardiolipin antibodies, lupus anticoagulant, protein C and protein S deficiency, factor V Leiden mutation and paroxysmal nocturnal haemoglobinuria were all negative. He was found to be homozygous for the prothrombin G20210A mutation with mild deficiency for antithrombin III (AT III 73%, normal range 80%-120%). His father and brother were subsequently tested and found to be heterozygous for the prothrombin gene variant. He was started on life-long warfarin.