Portal Vein Thrombosis : Missed cause of Acute Cholecystitis or co-incidence

A Agrawal, ID Crate

KEY WORDS

Mesenteric vein thrombosis, antithrombin 3 deficiency, cholecystitis

ABSTRACT

Mesenteric vein thrombosis (MVT) is commonly forgotten as a possible cause of abdominal pain. Our case illustrates hereditary thrombophilia as an important predisposing factor along with the possibility of acute acalculus cholecystitis if thrombus extends to the portal vein.

REPORT

A 33 year old man was admitted with intermittent epigastric pain of 10 days duration radiating to his back and associated with nausea. He had been seen in the A&E Department twice during this period and discharged with proton pump inhibitors. His LFTs were ALP=507U/L, GGT=211U/L. Ultrasound of abdomen revealed an oedematous gall bladder without stones, a spleen size increased at 13.5 cm and other organs were normal. Upper GI endoscopy also was normal.

He suffered from hereditary Anti-thrombin 3(AT3) deficiency with his mother being deficient in AT3 as well. He had a past history of benign intracranial hypertension probably secondary to cerebral vein thrombosis about 12 years earlier.

Repeat USS 5 days post admission revealed a gall bladder still oedematous with small amount of free fluid between liver and gall bladder. Open cholecystectomy was performed and an inflamed gall bladder was found with no gall stones. He was prescribed pre-operative IV heparin and post-operative low molecular weight heparin (enoxaparin) followed by warfarin.

He was re-admitted 10 days later. A period of about 7 days free of clinical symptoms had elapsed between the cholecystectomy and the onset of pain similar to his first admission. Based on clinical grounds, USS was done to rule out a biliary collection He was discharged after having pain relief over the next 4 days and enoxaparin as prophylactic dose of 40mg.

He was re-admitted yet again 2 days later with the same pain. Repeated LFTs showed ALP=513U/L, GGT=240U/L, AST=81; the surgical team in consultation with a radiologist endeavoured to rule out Mesenteric Vein Thrombosis (MVT). He had a CT scan which revealed a filling defect in the superior mesenteric vein suggestive of thrombus. He was prescribed therapeutic enoxaparin 150mg daily in consultation with a consultant haematologist, where upon he improved and was discharged 3 days later. He was followed up in anti-coagulation clinic later and put on warfarin. He was well 6 months later.

DISCUSSION

Acute abdominal pain can be due to a variety of pathophysiological processes and, among the many possible causes, ischaemic intestinal disorders can present a difficult diagnostic dilemma. Thrombotic or embolic diseases within the arterial or venous systems may result in ischaemia of the intestine.

About 80% of cases of acute mesenteric ischaemia is due to occlusive disease and 20% due to low perfusion states. 15% of the occlusions are in the venous circulation. Most venous thromboses occur in the superior mesenteric vein and may be primary where the cause is unknown or secondary to a variety of abnormalities such as haematopoietic disorders, intra-abdominal inflammatory conditions e.g., pancreatitis and traumatic causes. Anti-thrombin 3 (AT 3) deficiency is one of the most common haematopoietic disorders underlying MVT. Of the 2 hereditary types of AT 3 deficiency, Type 1 is fatal antenatally while Type 2 predisposes to severe arterial and venous thrombosis.

Symptoms are most common in the 3rd decade though individuals between the ages of 15 to 35 years are commonly affected. Abdominal pain, typically, is out of proportion to clinical findings and associated with nausea, vomiting, and diarrhoea/constipation. Signs are mostly non-specific including abdominal tenderness, distension, decreased bowel sounds, fever and shock.

In a cross-sectional study, approximately 50% of patients with MVT had abdominal pain from 5 to 30 days before seeking medical attention [1]. Pooled prevalence of venous thrombosis in AT 3 deficiency subjects was 51% but objective testing was done in only 17% of these subjects [2]. Therefore, past medical history or family history of thrombosis in combination with abdominal symptoms should increase the index of suspicion for MVT. A hypercoagulable state is more commonly found in patients with MVT than in patients with DVT [3, 4]. AT3 deficiency has been found to account for about 2 % of all venous thrombosis and in autopsy studies, MVT is found in 0.2-2% of the population [5, 6]. MVT triggered by surgical procedure, drug administration and anticoagulation withdrawal has been reported. In young patients who do not have known risk factors for thrombosis, a thorough workup for a primary hypercoagulable state is warranted. CT scan is diagnostic in 90% of these patients and remains the initial investigation of choice though angiogram is the gold standard. Plain abdominal radiology shows in a typical case 'thumb printing'. Diagnostic laparoscopy helps to diagnose possible bowel infarction [7] though it should be kept in mind that 80% of ischaemia manifests in mucosa only.

Treatment ranges from observation with anticoagulation and bowel rest to surgical resection of bowel. Thrombectomy has been described [3] and also intra-arterial or intramesenteric venous lytic therapy, though long-term results of these modalities is unknown [8, 9]. The prevalent operative standard can be reserved for patients with complications (bowel infarction with peritonitis) or for those patients with absolute contra-indication to thrombolytic therapy.

Anticoagulation with heparin, warfarin, and LMW heparin are pharmacological prophylactic modalities. In multiple thrombotic episodes and high risk patients, long term wafarinisation should be considered. If this is not possible, anti-thrombin concentrates is an option.

Patients with congenital AT3 deficiency who have had unprovoked thrombotic events are much more likely to have recurrence. These should usually be treated with indefinite anti-coagulation particularly with clots in the mesenteric circulation even after a single episode.

Thrombosis of portal or splenic veins can be associated with MVT though isolated MVT are more likely to have hypercoagulable disorders [4]. The majority of portal vein thromboses (PVT) have an acquired causation but this can only be confirmed by careful examination of family members preferably including both parents for hereditary predisposition [10]. PVT is considered to be recent when there was abdominal pain of recent onset, there being no sign of chronic portal hypertension and no evidence of portal cavernoma [10, 11]. PVT usually presents as unexpected variceal haemorrhage or splenomegaly with peripheral blood cytopenias. However, diagnosis of hereditary natural anti-coagulation protein deficiency is difficult if there is impaired liver function. Abnormal liver function is defined by persistently abnormal serum albumin or AST concentration [10]. In addition, vascular dilatation of the gall bladder wall has been reported on high resolution duplex ultrasound in PVT [12].

CONCLUSION

Our patient had abdominal pain out of proportion to clinical findings. Repeated LFTs did reveal abnormal GGT, ALP and AST. Repeated USS abdomen revealed persistent oedematous gall bladder along with mild splenomegaly. Subsequent CT scan had shown MVT. On retrospective reflection, did this patient have PVT with MVT leading to a clinical picture of acute cholecystitis?

This case does make us re-iterate the well known but often forgotten fact that occlusive disorders of the intestine vasculature can be a cause of abdominal pain and that they should be appropriately investigated and treated at an early stage to prevent being lost in a diagnostic conundrum.

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