Mesenteric venous thrombosis in a patient with pancreatitis and protein C deficiency.

Abstract: Mesenteric vein thrombosis is an uncommon manifestation of hypercoagulable states. A case is reported of superior mesenteric vein (SMV) thrombosis in a patient with pancreatitis and protein C deficiency. A discussion of SMV thrombosis identification, management, and outcomes is included. The patient presented with a significant history of alcohol abuse and constant, midepigastric abdominal pain associated with nausea and vomiting. Amylase and lipase were elevated, and the patient was treated for pancreatitis. His symptoms initially responded to intravenous fluid hydration, but soon his clinical picture worsened, with increased nausea and vomiting, abdominal pain, and distension. Contrasted computed tomography of the abdomen revealed SMV thrombosis. A hypercoagulable workup revealed protein C deficiency. After a 3-month course of oral anticoagulant therapy, the SMV thrombosis resolved.

Key Words: abdominal pain, mesenteric vein thrombosis, pancreatitis, protein C deficiency

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Mesenteric vein thrombosis is an uncommon manifestation of hypercoagulable states. There have only been rare reports of pancreatitis and protein C deficiency individually associated with superior mesenteric vein (SMV) thrombosis. (1-3) To our knowledge, our case utilizes a previously unreported collective association of these two clinical entities with SMV thrombosis. Furthermore, this case highlights the importance of early detection of SMV thrombosis, permitting medical management with anticoagulation as a viable treatment option. A brief discussion of SMV thrombosis risk factors, prognosis, diagnostic modalities, and treatment options is included.

Case Report

A 51-year-old male with a history significant for severe alcohol abuse and no significant previous medical care presented with complaints of 2 days of constant, midepigastric and umbilical abdominal pain, associated with nausea, vomiting, and anorexia. No history of melena, hematochezia, hematemesis, diarrhea, or fevers/chills was given. The patient had no history of intravenous drug abuse, toxic ingestions, or prolonged nonsteroidal antiinflammatory medication use. The patient's family history was significant only for a brother who had multiple strokes during his late thirties. The patient reported that he was not taking any medications currently.

On physical examination, the patient was afebrile, mildly tachycardic and hypertensive, and appeared to be in mild distress. The rest of his physical examination was significant for dry mucus membranes, a diffusely tender and soft abdomen without peritoneal signs, hypoactive bowel sounds, and tympany to percussion of his midumbilical region.

Laboratory work revealed elevated amylase (201 IU/L) and lipase (67 IU/L) levels, transaminases within normal limits, and mildly elevated bilirubin (2.4 mg/dL) and alkaline phosphatase (118 IU/L) levels. Also of note, the patient had a white blood cell count of 14.0 K/[mm.sup.3], serum glucose of 186 mg/dL, and serum lactate dehydrogenase of 248 IU/L. Radiographic abdominal series-revealed an ileus. The patient was diagnosed with acutepancreatitis and admitted for intravenous hydration with bowel rest.

After an initial mild improvement in symptoms, the patient's clinical status worsened, with increased nausea and vomiting, abdominal pain, abdominal distension, and fever. A nasogastric tube was placed, an abdominal ultrasound showed no biliary duct obstruction with a poorly visualized pancreas, and abdominal radiography revealed worsening ileus versus small bowel obstruction.

Computed tomography (CT) with contrast of the abdomen (Figure) was performed on the fifth hospital day. This revealed superior mesenteric vein thrombosis as well as a mildly atrophic pancreas with loculated fluid collection, representing early pseudocyst formation. The findings on CT scan combined with the patient's family history of stroke at a young age prompted a search for a hypercoagulable syndrome. This revealed a protein C deficiency with a functional level of 27%. Prothrombin time, protein S level, and Factor V levels were all within normal limits. The patient was started on anticoagulation with heparin, which was continued until the patient became therapeutic on oral warfarin. Three-month clinic follow-up found the patient feeling well and asymptomatic. A repeat CT of the abdomen at that time showed resolution of the SMV thrombosis after 3 months of therapeutic warfarin use.

Discussion

Mesenteric vein thrombosis has been a recognized clinical entity since 1935, when it was first formally described by Warren and Eberhardt. (3) At that time, they reported a mortality rate of 34%, with only a 5% survival rate of patients who did not undergo surgical treatment. (4) Now, with the aid of new imaging techniques such as CT, diagnosis can be made at an earlier stage in the disease, allowing for more conservative management. The overall mortality rate, though still high, has decreased to approximately 20% by some reports. (5)

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Mesenteric vein thrombosis is often a difficult diagnosis to make, given its rarity and lack of specific symptoms on presentation. The most common presenting complaint is abdominal pain, usually vague in character. Contrast-enhanced abdominal CT scanning currently holds a sensitivity of greater than 90% (3) and is most commonly the diagnostic test of choice; however, magnetic resonance imaging and ultrasound have also been used in making the diagnosis. (6) Classification of mesenteric vein thrombosis falls into three sets, based on the time course of the patient's abdominal pain: acute, subacute, or chronic. The acute form is associated with the highest risk of bowel infarction and peritonitis. (7) Therefore, early recognition and treatment is critical in these patients. Historically, patients were treated surgically for this diagnosis. More recently, anticoagulation alone and close follow-up have become acceptable means of treatment when bowel ischemia has not led to transmural necrosis and bowel perforation. (8) Thrombolytic therapy has also been used successfully in a few case reports (6); however, long delays in the diagnosis of this condition often make thrombolytic therapy obsolete.

Multiple risk factors are associated with mesenteric vein thrombosis, including protein C deficiency, pancreatitis, oral contraceptive use, portal hypertension, and abdominal trauma. Protein C-deficient patients have a significant risk of a thrombotic event over the general population, up to a 7-fold increased risk. (9) Up to 63% of affected individuals will have recurrent venous thrombosis in need of lifelong anticoagulation. (9) However, some evidence suggests that thrombosis, in patients with a genetic hypercoagulable dysfunction, is more properly thought of as a multicausal disease, requiring an acquired risk factor for expression. (10) These acquired risk factors can include pregnancy, oral contraception, immobilization, and inflammatory conditions such as pancreatitis.

As mentioned, pancreatitis itself is a risk factor for thrombosis through a local inflammatory process and hypercoagulability syndrome. (11) The two most common risk factors for pancreatitis in the United States are gallstones and alcohol. Yet many years of alcohol abuse are required before the development of acute alcoholic pancreatitis presents, (12) representing a likely acute-on-chronic-type picture. Basic treatment consists of intravenous hydration, bowel rest, and analgesia. Further specific treatment may be warranted in the face of other complications, such as pseudocyst formation.

Conclusion

Our patient had a multifactorial thrombotic event. Given the patient's family history of thrombotic events in a first-degree relative at a young age, coupled with low protein C level, our patient probably had a genetic defect that predisposed him to this SMV thrombosis. The patient's history of alcohol abuse caused him to have pancreatitis, probably an acute-on-chronic pancreatitic picture. This pancreatitis was the acquired risk factor needed for expression of the patient's thrombosis, in the setting of protein C deficiency. The prompt initiation of anticoagulation with therapeutic heparin and a subsequent 3-month course of warfarin proved successful in this patient. Although the patient had a slow recovery period secondary to bowel obstruction from a pseudocyst, bowel infarct was not observed secondary to the mesenteric vein thrombosis. SMV thrombosis should always be considered in the setting of vague abdominal pain in a patient with hypercoagulable risk factors.

Men and nations behave wisely once they have exhausted all the other
alternatives.
--Abba Eban

Accepted June 4, 2004.

References

1. Cornu-Labat G, Kasirajan K, Simon R, et al. Acute mesenteric vein thrombosis and pancreatitis: a rare association. I J Pancreatol 1997;21:249-251.

2. Crowe PM, Sagar G. Reversible superior mesenteric vein thrombosis in acute pancreatitis: the CT appearances. Clin Radiol 1995;50:628-633.

3. Harward TR, Green D, Bergan JJ, et al. Mesenteric vein thrombosis. J Vasc Surg 1989;9:328-332.

4. Morasch M, Ebaugh J, Chiou A, et al. Mesenteric venous thrombosis: a changing clinical entity. J Vasc Surg 2001;34:680-684.

5. Divino C, Park I, Angel L, et al. A retrospective study of diagnosis and management of mesenteric vein thrombosis. Am J Surg 2001;181:20-23.

6. Karawi M, Quaiz M, Clark D, et al. Mesenteric vein thrombosis, noninvasive diagnosis and follow-up (US + MRI), and non-invasive therapy by streptokinase and anticoagulants. Hepatogastroenterol 1990;37:507-509.

7. Kumar S, Sarr M, Kamath P. Mesenteric venous thrombosis. N Engl J Med 2001;345:1683-1688.

8. Brunaud L, Antunes L, Collinet-Adler S, et al. Acute mesenteric venous thrombosis: case for nonoperative management. J Vasc Surg 2001;34:673-679.

9. Bauer KA. Protein C deficiency, in Hoffman R. Benz E Jr. Shattil S, et al (eds): Hematology: Basic Principles and Practice. 3rd edition. New York, Churchill Livingstone, 2000, pp 2017-2019.

10. Rosenthal FR. Venous thrombosis: a multicausal disease. Lancet 1999;353:1167-1173.

11. Fernandez-Cruz L, Navarro S, Castells A, et al. Late outcome after acute pancreatitis: functional impairment and gastrointestinal tract complications. World J Surg 1997;21:169-172.

12. Steinberg W, Tenner S. Acute pancreatitis. N Engl J Med 1994;330:1198-1207.

RELATED ARTICLE: Key Points

* A high index of suspicion must be maintained for superior mesenteric vein thrombosis in a patient with vague abdominal pain and appropriate risk factors.

* The key to successful treatment and best prognosis is early recognition of disease and initiation of anticoagulation.

* Therapeutic anticoagulation for at least 3 months is required for resolution of superior mesenteric vein thrombosis.

Andrew Rackoff, MD, Nathan Shores, MD, and Ira Willner, MD

From the Department of Medicine and Digestive Disease Center, Medical University of South Carolina, Charleston, SC.

Reprint requests to Dr. Andrew Rackoff, Department of Medicine, Medical University of South Carolina, 96 Jonathan Lucas Street, 916 Clinical Sciences Building, Charleston, SC 29425. E-mail: [e-mail]