Correspondence

Gastrointestinal Angiodysplasia and Aortic Stenosis

N Engl J Med 2002; 347:858-859September 12, 2002

Article

To the Editor:

For unknown reasons, bleeding from gastrointestinal angiodysplasia in patients with severe aortic stenosis (Heyde's syndrome1) usually ceases after aortic-valve replacement.2 We have proposed that this bleeding disorder may be explained by acquired type IIA von Willebrand's syndrome,3 which is a deficiency of high-molecular-weight multimers of von Willebrand factor associated with aortic stenosis. We now report two cases of Heyde's syndrome in which abnormal von Willebrand factor–multimer profiles normalized after aortic-valve replacement.

Two women, one 65 years old and one 70 years old, underwent aortic-valve replacement for severe aortic stenosis (estimated valve area, 0.67 and 0.50 cm², respectively); each received a 21-mm bioprosthesis. Preoperatively, both patients had bleeding from endoscopically proven angiodysplasia involving the jejunum (in one) or the colon (in the other), and both required blood transfusions and iron-replacement therapy. The preoperative platelet count, activated partial-thromboplastin time, and factor VIII coagulant level were normal in both patients. The level of von Willebrand factor antigen (0.82 and 0.73 U per milliliter) and the activity of von Willebrand factor ristocetin cofactor (0.50 and 0.72 U per milliliter) were also normal (normal range for both variables, 0.5 to 1.5 U per milliliter). The bleeding time was prolonged (14 minutes) in only the second patient. However, both patients had a severe deficiency of high-molecular-weight multimers of von Willebrand factor (less than 2 percent of the total multimers; normal range, 17 to 27 percent). Postoperatively, the bleeding time normalized in the patient whose bleeding time had been prolonged, and in both patients all the other hemostasis values remained normal. In both patients, the von Willebrand factor–multimer profiles also normalized after surgery, and they have remained normal during 10 years of follow-up (Figure 1Figure 1Analysis of von Willebrand Factor Multimers in Two Patients with Aortic Stenosis and Cessation of Bleeding Gastrointestinal Angiodysplasia after Aortic-Valve Replacement.). In neither patient has recurrent bleeding or anemia developed, and neither patient has needed iron supplements.

These data support the hypothesis3 that acquired type IIA von Willebrand's syndrome may explain the hemorrhagic diathesis underlying Heyde's syndrome — including its potential for surgical cure — even in patients with normal results on screening tests for von Willebrand factor deficiency. Recently, Veyradier and colleagues4 reported selective loss of high-molecular-weight multimers of von Willebrand factor (despite normal levels of von Willebrand factor) in eight of nine patients with bleeding angiodysplasia; seven of these eight patients had aortic stenosis. In contrast, control patients with nonbleeding angiodysplasia or diverticular hemorrhage had normal multimer profiles.

The activity of the von Willebrand factor–cleaving metalloproteinase is increased and von Willebrand factor–platelet interactions are enhanced when there is increased shear stress.5 High shear associated with aortic stenosis could thus predispose patients to selective loss of the largest von Willebrand factor multimers. After aortic-valve replacement, cessation of gastrointestinal bleeding in our patients was accompanied by lasting recovery of high-molecular-weight multimers of von Willebrand factor. Because bleeding angiodysplasia is a common feature of type IIA von Willebrand's syndrome of diverse causes,3 large von Willebrand factor multimers may play an important part in maintaining hemostasis in patients with gastrointestinal angiodysplasia.

Theodore E. Warkentin, M.D.
Jane C. Moore, B.Sc.
David G. Morgan, M.D.
McMaster University, Hamilton, ON L8L 2X2, Canada
twarken@mcmaster.ca

5 References

1. 1

   Heyde EC. Gastrointestinal bleeding in aortic stenosis. N Engl J Med 1958;259:196-196
   Web of Science

2. 2

   Love JW, Jahnke EJ, Zacharias D, Davidson WA, Kidder WR, Luan LL. Calcific aortic stenosis and gastrointestinal bleeding. N Engl J Med 1980;302:968-968
   Full Text | Web of Science | Medline

3. 3

   Warkentin TE, Moore JC, Morgan DG. Aortic stenosis and bleeding gastrointestinal angiodysplasia: is acquired von Willebrand's disease the link? Lancet 1992;340:35-37
   CrossRef | Web of Science | Medline

4. 4

   Veyradier A, Balian A, Wolf M, et al. Abnormal von Willebrand factor in bleeding angiodysplasias of the digestive tract. Gastroenterology 2001;120:346-353
   CrossRef | Web of Science | Medline

5. 5

   Pareti FI, Lattuada A, Bressi C, et al. Proteolysis of von Willebrand factor and shear stress-induced platelet aggregation in patients with aortic valve stenosis. Circulation 2000;102:1290-1295
   Web of Science | Medline

Citing Articles (17)

Citing Articles

1. 1

   Jean-Marie Michot, Xavier Treton, Charles Brink, Jean-Noël Fabiani, Yoram Bouhnik. (2011) Severe gastro-intestinal angiodysplasia in context of Heyde's syndrome durably cured after aortic valve replacement. La Presse Médicale
   CrossRef

2. 2

   Pernilla M. DʼSouza, Mark D. Blostein. (2011) Diagnosis of Heydeʼs syndrome by abnormal closure times despite normal von Willebrandʼs activity. Blood Coagulation & Fibrinolysis 22:7, 622-623
   CrossRef

3. 3

   Jess L. Thompson, Hartzell V. Schaff, Joseph A. Dearani, Soon J. Park, Thoralf M. Sundt, Rakesh M. Suri, Joseph L. Blackshear, Richard C. Daly. (2011) Risk of recurrent gastrointestinal bleeding after aortic valve replacement in patients with Heyde syndrome. The Journal of Thoracic and Cardiovascular Surgery
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4. 4

   Mahesh P. Sardesai, Joseph Sabik, Colleen G. Koch. (2011) Perioperative Management of Acquired von Willebrand Disease in Cardiac Surgery: Type 2B or Not 2B?. Journal of Cardiothoracic and Vascular Anesthesia 25:1, 131-133
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5. 5

   A. Casonato, S. Sponga, E. Pontara, M. G. Cattini, C. Basso, G. Thiene, G. Cella, V. Daidone, G. Gerosa, A. Pagnan. (2011) von Willebrand factor abnormalities in aortic valve stenosis: Pathophysiology and impact on bleeding. Thrombosis and Haemostasis 106:1, 58-66
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6. 6

   Helen M. Hayes, Lawrence G. Dembo, Robert Larbalestier, Gerry O'Driscoll. (2010) Management Options to Treat Gastrointestinal Bleeding in Patients Supported on Rotary Left Ventricular Assist Devices: A Single-Center Experience. Artificial Organs 34:9, 703-706
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7. 7

   Sakiko Ohta, Tomohiro Watanabe, Shuko Morita, Satoru Ueno, Yoshihisa Tsuji, Hiroshi Nakase, Tsutomu Chiba. (2009) Massive jejunal bleeding due to Heyde syndrome successfully treated with double balloon endoscopy. Clinical Journal of Gastroenterology 2:3, 187-189
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8. 8

   M. W. Massyn, S. A. Khan. (2008) Heyde syndrome: a common diagnosis in older patients with severe aortic stenosis. Age and Ageing 38:3, 267-270
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9. 9

   Armin J. Reininger. (2008) VWF attributes – impact on thrombus formation. Thrombosis Research 122, S9-S13
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10. 10

    Masatoshi Shimizu, Hiroyuki Masai, Yoichi Miwa. (2007) Occult Gastrointestinal Bleeding due to Acquired von Willebrand Syndrome in a Patient with Hypertrophic Obstructive Cardiomyopathy. Internal Medicine 46:8, 481-486
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11. 11

    Nenad Perisic, Radoje Doder, Radoje Ilic, Jasna Jovic, Ljiljana Tukic, Dragan Tavciovski. (2006) Heyde's syndrome. Vojnosanitetski pregled 63:7, 673-676
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12. 12

    Lidia Martí, Rosario Antón, Pedro Almela, Adolfo Benages. (2005) Angiodisplasia intestinal asociada a estenosis subaórtica hipertrófica: ¿una variante del síndrome de Heyde?. Medicina Clínica 125:16, 635-636
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13. 13

    R WHITLOCK, M CROWTHER, H NG. (2005) Bleeding in Cardiac Surgery: Its Prevention and Treatment—an Evidence-Based Review. Critical Care Clinics 21:3, 589-610
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14. 14

    Mohammed A Karajeh, Mark E McAlindon, Michael Makris, Wazir Baig, David S Sanders. (2004) Bleeding Small Bowel Angiodysplasia in Association With Aortic Stenosis: A Role for Combined Wireless Capsule Endoscopy and Push Enteroscopy?. Journal of Clinical Gastroenterology 38:9, 836-837
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15. 15

    Shahbudin H. Rahimtoola. (2004) The year in valvular heart disease. Journal of the American College of Cardiology 43:3, 491-504
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16. 16

    Theodore E Warkentin, Jane C Moore, Sonia S Anand, Eva M Lonn, David G Morgan. (2003) Gastrointestinal bleeding, angiodysplasia, cardiovascular disease, and acquired von Willebrand syndrome. Transfusion Medicine Reviews 17:4, 272-286
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17. 17

    Vincentelli, André, Susen, Sophie, Le Tourneau, Thierry, Six, Isabelle, Fabre, Olivier, Juthier, FrancisBauters, AnneDecoene, Christophe, Goudemand, Jenny, Prat, Alain, Jude, Brigitte, . (2003) Acquired von Willebrand Syndrome in Aortic Stenosis. New England Journal of Medicine 349:4, 343-349
    Full Text