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A 52 year old previously healthy Afro-Caribbean woman was admitted as an emergency with a 12 hour history of epigastric pain. She was a non-smoker, denied alcohol use, and had no significant comorbidity. Heart rate, respiratory rate, and temperature were normal at presentation. Abdominal examination revealed mild epigastric tenderness with guarding. Baseline investigations (full blood count, clotting, urea and electrolytes, and liver function tests) were within normal limits, except for a raised white cell count (12.1 (normal range 4–11)×109/l (neutrophilia)) and a raised amylase level (2409 (normal <220) U/l). Abdominal and chest x rays were also normal. She was diagnosed with acute pancreatitis and treated supportively with intravenous fluids, analgesia, and thromboprophylaxis.
Twelve hours after admission the patient deteriorated significantly, with signs of abdominal peritonitis and a marked metabolic acidosis. She underwent an emergency laparotomy where she was found to have a perforated necrotic gall bladder with biliary peritonitis. The common bile duct was dilated but no gall stones were identified. In addition, two segments of her liver were noted to be dusky. Her spleen was normal. The abdomen was washed out and a cholecystectomy performed. Histology confirmed that the gall bladder was necrotic. Several of the arteries were occluded by thrombus but there was no evidence of atheroma or vasculitis.
Following surgery she ran a prolonged septic course requiring ventilatory and renal support, and on day 13 had a large upper gastrointestinal bleed secondary to intestinal ischaemia. Serial computed tomography scans to identify the source of sepsis were normal until day 21 when a large right subphrenic collection was identified. In addition, an area of low attenuation at the site of the spleen and a cystic mass in the pancreatic tail, consistent with a pseudocyst, were noted. Radiological drainage of the abscess was performed and over the next week the patient was successfully weaned and withdrawn from circulatory and renal support. At this stage her blood film demonstrated the presence of Howell-Jolly bodies, which were consistent with the splenic changes identified on computed tomography.
Recurrent intrabdominal sepsis at day 42, not amenable to radiological drainage, necessitated a further laparotomy. The collection was drained and the remnants of her autolysed spleen and pancreatic tail removed. At this point the possibility of a thrombotic disorder was raised. Histology showed no evidence of vasculitis and she was antineutrophilic cytoplasmic antibody and autoantibody negative. Her thrombophillia screen revealed low levels of protein C (functional: 45 (65–250) u/dl; antigen: 52 (65–130) u/dl) and antithrombin III. (functional: 59 (80–120) IU/l, antigen: 70 (80–120) u/dl). Free protein S levels were normal (73 (55–120) iu/dl). She was negative for lupus anticoagulant, APC resistance ratio was normal 2.05 (1.8–4), and neither factor V Leiden nor prothrombin gene 20210 allele was detected. Her antithrombin level was not suggestive of an inherited defect and levels in first degree family members were within normal limits. A presumptive diagnosis of acquired antithrombin deficiency was made, her low molecular weight heparin was increased to therapeutic doses, and she was commenced on warfarin.
Two months after discharge her antithrombin levels had returned to normal and her warfarin was stopped. She had developed no further problems on follow up at 12 months.
This case illustrates how the systemic inflammatory response can be complicated by a series of thrombotic events. Antithrombin is a natural anticoagulant that plays a pivotal role in coagulation and haemostasis. In addition, it has potent anti-inflammatory properties, and is protective in animal models of sepsis.1–5 Acquired antithrombin III deficiency is commonly present in severe sepsis and levels can be predictive of outcome.6–8 It should therefore be considered in patients with severe sepsis when the clinical course is complicated by arterial or venous thrombosis.
Conflict of interest: None declared.
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