Heyde Syndrome

The association between aortic valve stenosis and acute gastrointestinal bleeding was described by Heyde in 1958.[1] It has now been reported that enhanced proteolysis of the von Willebrand factor (vWF) by the elevated shear stress originating from passage of blood through the stenosed valve is responsible for this syndrome.[2] This is compatible with the observation that aortic valve replacement can eliminate recurrent blood loss and normalize von Willebrand multimers profiles in these patients.[3] We report a patient of Heyde syndrome in whom angiodysplasia of colon was confirmed as the source of bleeding and immunoblotting analysis revealed a decrease in high molecular weight vWF multimers.

Case Report

A 82 yrs old female was admitted with recurrent episodes of lower gastrointestinal bleed. She had received seven units of blood prior to admission. She had no history of chest pain, breathlessness or other symptoms of heart disease. She was evaluated elsewhere with upper gastrointestinal (GI) endoscopy, colonoscopy and contrast enhanced CT scan of abdomen, which were normal. A repeat colonoscopy in our hospital revealed multiple, discrete, vascular, flat lesions with bleed involving 10 cm of ascending colon, suggestive of angiodysplasia. On clinical examination she had a murmur suggestive of aortic stenosis. A 2-D Echo done revealed severe aortic stenosis. To clarify the association between the colonic hemorrhage and cardiac disorder we analyzed the vWF multimers by electrophoresis. The plasma level of the high molecular weight vWF multimers was significantly decreased. Considering her age and cardiac status, significant risk involved in surgery and anaesthesia and as she had stopped bleeding she has been managed conservatively. She is currently in good health in outpatient care for last six months without any further episodes of bleed.

Discussion

Colonic angiodysplasia is a degenerative ageing disease and accounts for up to 30% of patients presenting with lower- GI bleeding.[4] Most of these lesions are located proximal to the hepatic flexure. Many therapeutic strategies are described to treat angiodysplasia of the colon which include endoscopic methods that require direct contact by using monopolar/ bipolar probes or heat probe, and noncontact methods, eg, argon plasma coagulation. Injection sclerotherapy also appears to be effective.[5] Superselective embolization of the feeding artery at the bleeding site has also been proven to be effective for colonic hemorrhage. However, this procedure is technically difficult, and the risk of bowel infarction associated with embolisation proximal to the mesenteric border of the colon has been reported to exceed 10%.[6] Surgical resection is preferred for acute management of severe hemorrhage orfor recurrent hemorrhage over a relatively short period accompanied by a large transfusion requirement.

Heyde syndrome is named after E. C. Heyde who in 1958 described ten cases of aortic stenosis and massive gastrointestinal bleeding for which he could discover no cause.[1] The pathogenesis of this abnormality has now been studied. A possible mechanism for the bleeding in Heyde syndrome is an acquired form of von Willebrand disease (type II a) due to aortic stenosis. High shear stress rates across the stenotic valve leads to increased consumption of high molecular weight multimers of vWF. The subsequent functional deficit of vWF predisposes to bleeding. Vincentelli et al[7] confirmed that the high molecular weight vWF multimers were reduced in proportion to the severity of aortic stenosis, and a valve replacement could restore the impaired distribution of the multimers. Veyradier et al[8] reported that most patients with bleeding angiodysplasia had deficiency of high molecular weight vWF multimers in contrast to non bleeding patients. A survey on von Willebrand disease indicated that bleeding angiodysplasia was only observed in patients with either type 2 or type 3 von Willebrand disease, who lack the high molecular weight vWF multimers.[9] Several reports have suggested that von Willebrand disease complicates angiodysplasias, however, angiodysplasias can appear as an aging process in any patients, irrespective of von Willebrand disease. A reduction in the high molecular weight vWF multimers, for example, in von Willebrand disease type 2, type 3, or in Heyde syndrome, causes abnormal hemostasis under high shear stress conditions. As a result, the bleeding from latent angiodysplasia cannot be controlled. Therefore, diagnosis is easier in patients with bleeding angiodysplasia as compared to patients without angiodysplasia.

Surgical options are bowel resection or aortic valve replacement. There have been several reports of cessation of bleeding following aortic valve replacement.[7] In a retrospective study of 91 patients with aortic stenosis and unexplained gastrointestinal bleeding King et al found that bleeding ceased in 93% of patients treated by valve replacement compared with 5% of those managed by laparotomy with or without bowel resection.[10]

References

1. Heyde EC. Gastrointestinal bleeding in aortic stenosis. N Engl J Med. 1958;259:196.

2. Sadler JE. Aortic stenosis, von Willebrand Factor, and bleeding. N Engl J Med. 2003;349:323–5.

3. Cappell MS, Lebwohl O. Cessation of recurrent bleeding from gastrointestinal angiodysplasias after aortic valve replacement. Ann Intern Med. 1986;105:54–7.

4. Browder W, Cerise EJ, Litwin MS. Impact of emergency angiography in massive lower gastrointestinal bleeding. Ann Surg. 1986;204:530–6.

5. Suzuki N, Arebi N, Saunders BP. A novel method of treating colonic angiodysplasia Gastrointest Endosc. 2006;64:424–7.

6. Rosenkrantz H, Bookstein JJ, Rosen RJ, Goff WB 2nd, Healy JF. Postembolic colonic infarction. Radiology. 1982;142:47–51.

7. Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, Juthier F, et al. Acquired von Willebrand syndrome in aortic stenosis. N Engl J Med. 2003;349:343–9.

8. Veyradier A, Balian A, Wolf M, Giraud V, Montembault S, Obert B, et al. Abnormal von Willebrand factor in bleeding angiodysplasias of the digestive tract. Gastroenterology. 2001;120:346–53.

9. Fressinaud E, Meyer D. International survey of patients with von Willebrand disease and angiodysplasia. Thromb Haemost. 1993;70:546.

10. King RM, Pluth JR, Giuliani ER. The association of unexplained gastrointestinal bleeding with calcific aortic stenosis. Ann Thorac Surg. 1987;44:514–6.