CASE
REPORT
Arterial Thrombosis in Ulcerative Colitis D. B R A V E R M A N , MD, and A. B O G O C H , MD
Thrombosis o f the left brachial, ulnar, and radial arteries occurred during treatment of a patient with idiopathic ulcerative colitis. Arterial thrombosis is a rare and poorly understood complication. In 1936 Bargen and Barker (1) emphasized the occurrence of t h r o m b o e m b o l i s m as a significiant complication of ulcerative colitis. Since then venous thromboembolism has been well recognized (2-8), but arterial thrombosis has been reported only occasionally (9-12). The occurrence of arterial thrombosis in the left upper extremity of a patient while receiving Salazopyrin and A C T H for acute idiopathic ulcerative colitis is described in this report. CASE R E P O R T A 47-year-old man was admitted to Shaughnessy Hospital because of severe diarrhea, rectal bleeding, and weight loss. In his childhood he had meningitis. He was well-developed, well-nourished but looked pale. His weight was 62 kg, BP 130/70 mm Hg, and the temperature was normal. The carotid, radial, femoral, tibialis posterior, and dorsalis pedis pulses were normal. Funduscopic examination showed post meningitic optic atrophy and normal blood vessels. The abdomen was soft; there was tenderness over the sigmoid colon, the liver was not palpable, and the spleen was not enlarged. Rectal examination revealed no abnormality. At sigmoidoscopy the rectal and sigmoid mucosae were diffusely edematous, hyperemic, and friable; there were small ulcers covered with exudate, and subepithelial petechiae. A biopsy revealed acute and chronic inflammation and many crypt abscesses. The hemoglobin was 6.7 g/dl, hematocrit 21%, WBC 8300/mma (40% staff cells), platelet count 600,000 mm3 and fibrinogen 612 mg/dl (normal range 150-500 mg/ dl). The prothrombin time and PTT were normal. The serum iron was 12/~g/dl, and TIBC 282 pg/dl. Serum proFrom the Department of Medicine, ShaughnessyHospital, and the University of British Columbia, Vancouver, B.C., Canada. Address for reprint requests: Dr. A. Bogoch, Suite 601, 805 West Broadway, Vancouver, B.C. V5Z 1K1. Canada. 1148
tein electrophoresis revealed an albumin of 2.7 g/dl, but was otherwise normal. Urinalysis and the serum electrolytes, creatinine, and BUN were within normal range. The stools showed no parasites. A barium enema (Figure 1) revealed deep ulcers involving the distal transverse, descending, and sigmoid colon. A barium study of the esophagus, stomach, and small bowel was normal. Blood transfusions, Salazopyrin 1 g qid, and later intravenous ACTH (80 IU/24 hr, given as a constant infusion in 5% glucose and water to which potassium was added) were given. The diarrhea and rectal bleeding subsided gradually, the hemoglobin increased to 12 g/dl, and he was well hydrated. ACTH therapy was administered for 17 days in decreasing dosage; on the 8th day he developed numbness, and later pain in the left hand, which showed a mottled cyanosis. The radial and ulnar pulses were not palpable, but the brachial pulse was good. A selective left brachial arteriogram (Figure 2) showed a normal brachial artery, complete occlusion of the ulnar artery at its origin and of the radial artery about 4 cm below its origin. An arteriotomy of the distal portion of the brachial artery revealed thrombotic occlusion. A Fogarty catheter was passed distally and on withdrawing the catheter a thrombus was removed. Catherization of the radial artery was unsuccessful. The catheter was then passed up the brachial artery and a moderately large amount of thrombus was withdrawn followed by a gush of blood. The brachial, ulnar, and radial arteries were occluded. The patient received heparin for 14 days without further complication. Following arteriotomy, the brachial and ulnar artery pulses were good but there was no pulse in the radial artery at the time of discharge from hospital, 22 days after the occurrence of the thrombosis. However, the hand was warm, painless, and normal in color. Hematological tests done three days after discontinuing ACTH therapy revealed normal euglobulin lysis time, platelet aggregation, antithrombin III levels, and cryoglobulins. DISCUSSION Venous thrombosis is a well-recognized complication of idiopathic ulcerative colitis. H y p e r coagulability associated with increased levels o f the blood coagulation factors V, VI I, or fibrinogen, and Digestive Diseases, Vol. 23, No. 12 (December 1978)
0002-9211/78/1200-I148505.00/1 9 1978 Digestive Dtsease Systems, Inc.
ARTERIAL THROMBOSIS AND COLITIS
:~!:~
L
9
9? :
~, .:-, ~.,.-
...~.;~~ "
1
2",,, 'J.~l
Fig 1. Barium enemia showing deep ulcers and irregular mucosa in a portion of the sigmoid colon.
with decreased antithrombin III (13, 14), thrombocytosis (15), intravascular coagulation induced by bacterial endotoxin (16), and vasculitis and dehydration are among the causative mechanisms suggested. The question as to whether steroids play a role has also been raised and rejected (17). Acceleration of the early stages of coagulation reflected by increased factor V or VII activity appear to be related to the activity and extent of the disease and tend to return to normal when the disease is inactive (13). The patient reported had slight hyperfibrinogenemia and an elevated platelet count. Thrombocytosis is known to occur frequently in both ulcerative colitis and Crohn's disease (18); it Digestive Diseases, Vol. 23, No. 12 (December 1978)
may also occur in association with iron-deficiency anemia of diverse cause (19) and is probably of little importance in the development of venous thrombosis. Arterial thrombosis is a rare, serious, and poorly understood complication of inflammatory bowel disease. It has been described in the carotid, retinal, glans penis, femoral, subclavian, and brachial arteries. Thrombosis of the left brachial, radial, and ulnar arteries occurred in the patient of this report. Why certain patients develop arterial thrombosis while others develop venous thrombosis is unclear; local vascular factors may be of importance in determining the site of occurrence.
1149
BRAVERMAN
AND
BOGOCH
REFERENCES
l
ij,
,+
.
l '~ ~i.
. ~. ___
~.
~,, ! . . ,~.~.~
,,,~+$,-.
~,h,
'7
,~
~.
o
f 2. Left brachial arteriogram showing normal brachial artery and complete occlusion of the ulnar artery at its origin and of the radial artery a short distance below its origin.
Fig
1 150
1. Bargen JA, Barker NW: Extensive arterial and venous thrombosis complicating chronic ulcerative colitis. Arch Intern Med 58:17-31, 1936 2. Warren S, Sommers SC: Pathogenesis of ulcerative colitis. Am J Pathol 25:657-674, 1949 3. Sloan WP, Jr, Bargen JA, Gage RP: Life histories of patients with chronic ulcerative colitis; a review of 2000 cases. Gastroenterology 16:25-38, 1950 4. Ricketts WE, Palmer WL: Complications of chronic non specific ulcerative colitis. Gastroenterology 7:55-56, 1946 5. Dennis C, Karlson KE: Surgical measures as supplements to the management of idiopathic ulcerative colitis: Cancer, cirrhosis and a r t h r i t i s as f r e q u e n t c o m p l i c a t i o n s . Surgery 32:892-912, 1952 6. Edwards FC, Truelove SC: The course and prognosis of ulcerative colitis. Part III. Complications. Gut 5:1-15, 1964 7. Graef V, Baggenstoss AH, Sauer WG: Venous thrombosis occurring in non specific ulcerative colitis. A necropsy study. Arch Intern Med 117:377-382, 1966 8. Harrison MJG, Truelove SC: Cerebral venous thrombosis as a complication of ulcerative colitis. Am J Dig Dis 12:10251028, 1967 9. Bockus HL: Gastroenterology, Vol II. Philadelphia, WB Saunders, 1976, p 711 10. Sleisenger MH, Fordtran JS: Gastrointestinal Disease. Philadelphia, WB Saunders, 1973, p. 1337 11. Solheim K, Birkeland S: Arterial thrombosis in ulcerative colitis. Tiddskr Nor Laegforen 95:1721, 1975 12. Silverstein A, Present DH: Cerebrovascular occlusions in relatively young patients with regional enteritis. JAMA 215:976-977, 1971 13. Lee JCL, Spittel JA, Jr, Sauer WG, Owen CA, Thompson JH: Hypercoagulability associated with chronic ulcerative colitis: changes in blood coagulation factors. Gastroenterology 54:76-85, 1968 14. Lam A, Borda IT, Inwood MJ, Thomson S: Coagulation studies in ulcerative colitis and Crohn's disease. Gastroenterology 68:245-251, 1975 15. Morowitz DA, Allen LW, Kirsner JB: Thrombocytosis in chronic inflammatory bowel disease. Ann Intern Med 68:1013-1021, 1968 16. McKay DG, Shapiro SS: Alterations in the blood coagulation system induced by bacterial endotoxin I. In vivo (generalized Shwartzman reaction). J Exp Med 107:353-367, 1958 17. Truelove SC, Witts LJ: Cortisone in ulcerative colitis; Final report on a therapeutic trial. Br Med J 2:1041-1048, 1955 18. Talstad I, Rootwelt, Gjone E: Thrombocytosis in ulcerative colitis and Crohn's disease. Scand J Gastroenterol 8:135138, 1973 19. Schloesser LL, Kipp MA, Wenzel FJ: Thrombocytosis in iron deficiency anemia. J Lab Clin Med 66:107-114, 1965
Digestive Diseases, Vol. 23. No. 12 (December 1978)
REPORT
Arterial Thrombosis in Ulcerative Colitis D. B R A V E R M A N , MD, and A. B O G O C H , MD
Thrombosis o f the left brachial, ulnar, and radial arteries occurred during treatment of a patient with idiopathic ulcerative colitis. Arterial thrombosis is a rare and poorly understood complication. In 1936 Bargen and Barker (1) emphasized the occurrence of t h r o m b o e m b o l i s m as a significiant complication of ulcerative colitis. Since then venous thromboembolism has been well recognized (2-8), but arterial thrombosis has been reported only occasionally (9-12). The occurrence of arterial thrombosis in the left upper extremity of a patient while receiving Salazopyrin and A C T H for acute idiopathic ulcerative colitis is described in this report. CASE R E P O R T A 47-year-old man was admitted to Shaughnessy Hospital because of severe diarrhea, rectal bleeding, and weight loss. In his childhood he had meningitis. He was well-developed, well-nourished but looked pale. His weight was 62 kg, BP 130/70 mm Hg, and the temperature was normal. The carotid, radial, femoral, tibialis posterior, and dorsalis pedis pulses were normal. Funduscopic examination showed post meningitic optic atrophy and normal blood vessels. The abdomen was soft; there was tenderness over the sigmoid colon, the liver was not palpable, and the spleen was not enlarged. Rectal examination revealed no abnormality. At sigmoidoscopy the rectal and sigmoid mucosae were diffusely edematous, hyperemic, and friable; there were small ulcers covered with exudate, and subepithelial petechiae. A biopsy revealed acute and chronic inflammation and many crypt abscesses. The hemoglobin was 6.7 g/dl, hematocrit 21%, WBC 8300/mma (40% staff cells), platelet count 600,000 mm3 and fibrinogen 612 mg/dl (normal range 150-500 mg/ dl). The prothrombin time and PTT were normal. The serum iron was 12/~g/dl, and TIBC 282 pg/dl. Serum proFrom the Department of Medicine, ShaughnessyHospital, and the University of British Columbia, Vancouver, B.C., Canada. Address for reprint requests: Dr. A. Bogoch, Suite 601, 805 West Broadway, Vancouver, B.C. V5Z 1K1. Canada. 1148
tein electrophoresis revealed an albumin of 2.7 g/dl, but was otherwise normal. Urinalysis and the serum electrolytes, creatinine, and BUN were within normal range. The stools showed no parasites. A barium enema (Figure 1) revealed deep ulcers involving the distal transverse, descending, and sigmoid colon. A barium study of the esophagus, stomach, and small bowel was normal. Blood transfusions, Salazopyrin 1 g qid, and later intravenous ACTH (80 IU/24 hr, given as a constant infusion in 5% glucose and water to which potassium was added) were given. The diarrhea and rectal bleeding subsided gradually, the hemoglobin increased to 12 g/dl, and he was well hydrated. ACTH therapy was administered for 17 days in decreasing dosage; on the 8th day he developed numbness, and later pain in the left hand, which showed a mottled cyanosis. The radial and ulnar pulses were not palpable, but the brachial pulse was good. A selective left brachial arteriogram (Figure 2) showed a normal brachial artery, complete occlusion of the ulnar artery at its origin and of the radial artery about 4 cm below its origin. An arteriotomy of the distal portion of the brachial artery revealed thrombotic occlusion. A Fogarty catheter was passed distally and on withdrawing the catheter a thrombus was removed. Catherization of the radial artery was unsuccessful. The catheter was then passed up the brachial artery and a moderately large amount of thrombus was withdrawn followed by a gush of blood. The brachial, ulnar, and radial arteries were occluded. The patient received heparin for 14 days without further complication. Following arteriotomy, the brachial and ulnar artery pulses were good but there was no pulse in the radial artery at the time of discharge from hospital, 22 days after the occurrence of the thrombosis. However, the hand was warm, painless, and normal in color. Hematological tests done three days after discontinuing ACTH therapy revealed normal euglobulin lysis time, platelet aggregation, antithrombin III levels, and cryoglobulins. DISCUSSION Venous thrombosis is a well-recognized complication of idiopathic ulcerative colitis. H y p e r coagulability associated with increased levels o f the blood coagulation factors V, VI I, or fibrinogen, and Digestive Diseases, Vol. 23, No. 12 (December 1978)
0002-9211/78/1200-I148505.00/1 9 1978 Digestive Dtsease Systems, Inc.
ARTERIAL THROMBOSIS AND COLITIS
:~!:~
L
9
9? :
~, .:-, ~.,.-
...~.;~~ "
1
2",,, 'J.~l
Fig 1. Barium enemia showing deep ulcers and irregular mucosa in a portion of the sigmoid colon.
with decreased antithrombin III (13, 14), thrombocytosis (15), intravascular coagulation induced by bacterial endotoxin (16), and vasculitis and dehydration are among the causative mechanisms suggested. The question as to whether steroids play a role has also been raised and rejected (17). Acceleration of the early stages of coagulation reflected by increased factor V or VII activity appear to be related to the activity and extent of the disease and tend to return to normal when the disease is inactive (13). The patient reported had slight hyperfibrinogenemia and an elevated platelet count. Thrombocytosis is known to occur frequently in both ulcerative colitis and Crohn's disease (18); it Digestive Diseases, Vol. 23, No. 12 (December 1978)
may also occur in association with iron-deficiency anemia of diverse cause (19) and is probably of little importance in the development of venous thrombosis. Arterial thrombosis is a rare, serious, and poorly understood complication of inflammatory bowel disease. It has been described in the carotid, retinal, glans penis, femoral, subclavian, and brachial arteries. Thrombosis of the left brachial, radial, and ulnar arteries occurred in the patient of this report. Why certain patients develop arterial thrombosis while others develop venous thrombosis is unclear; local vascular factors may be of importance in determining the site of occurrence.
1149
BRAVERMAN
AND
BOGOCH
REFERENCES
l
ij,
,+
.
l '~ ~i.
. ~. ___
~.
~,, ! . . ,~.~.~
,,,~+$,-.
~,h,
'7
,~
~.
o
f 2. Left brachial arteriogram showing normal brachial artery and complete occlusion of the ulnar artery at its origin and of the radial artery a short distance below its origin.
Fig
1 150
1. Bargen JA, Barker NW: Extensive arterial and venous thrombosis complicating chronic ulcerative colitis. Arch Intern Med 58:17-31, 1936 2. Warren S, Sommers SC: Pathogenesis of ulcerative colitis. Am J Pathol 25:657-674, 1949 3. Sloan WP, Jr, Bargen JA, Gage RP: Life histories of patients with chronic ulcerative colitis; a review of 2000 cases. Gastroenterology 16:25-38, 1950 4. Ricketts WE, Palmer WL: Complications of chronic non specific ulcerative colitis. Gastroenterology 7:55-56, 1946 5. Dennis C, Karlson KE: Surgical measures as supplements to the management of idiopathic ulcerative colitis: Cancer, cirrhosis and a r t h r i t i s as f r e q u e n t c o m p l i c a t i o n s . Surgery 32:892-912, 1952 6. Edwards FC, Truelove SC: The course and prognosis of ulcerative colitis. Part III. Complications. Gut 5:1-15, 1964 7. Graef V, Baggenstoss AH, Sauer WG: Venous thrombosis occurring in non specific ulcerative colitis. A necropsy study. Arch Intern Med 117:377-382, 1966 8. Harrison MJG, Truelove SC: Cerebral venous thrombosis as a complication of ulcerative colitis. Am J Dig Dis 12:10251028, 1967 9. Bockus HL: Gastroenterology, Vol II. Philadelphia, WB Saunders, 1976, p 711 10. Sleisenger MH, Fordtran JS: Gastrointestinal Disease. Philadelphia, WB Saunders, 1973, p. 1337 11. Solheim K, Birkeland S: Arterial thrombosis in ulcerative colitis. Tiddskr Nor Laegforen 95:1721, 1975 12. Silverstein A, Present DH: Cerebrovascular occlusions in relatively young patients with regional enteritis. JAMA 215:976-977, 1971 13. Lee JCL, Spittel JA, Jr, Sauer WG, Owen CA, Thompson JH: Hypercoagulability associated with chronic ulcerative colitis: changes in blood coagulation factors. Gastroenterology 54:76-85, 1968 14. Lam A, Borda IT, Inwood MJ, Thomson S: Coagulation studies in ulcerative colitis and Crohn's disease. Gastroenterology 68:245-251, 1975 15. Morowitz DA, Allen LW, Kirsner JB: Thrombocytosis in chronic inflammatory bowel disease. Ann Intern Med 68:1013-1021, 1968 16. McKay DG, Shapiro SS: Alterations in the blood coagulation system induced by bacterial endotoxin I. In vivo (generalized Shwartzman reaction). J Exp Med 107:353-367, 1958 17. Truelove SC, Witts LJ: Cortisone in ulcerative colitis; Final report on a therapeutic trial. Br Med J 2:1041-1048, 1955 18. Talstad I, Rootwelt, Gjone E: Thrombocytosis in ulcerative colitis and Crohn's disease. Scand J Gastroenterol 8:135138, 1973 19. Schloesser LL, Kipp MA, Wenzel FJ: Thrombocytosis in iron deficiency anemia. J Lab Clin Med 66:107-114, 1965
Digestive Diseases, Vol. 23. No. 12 (December 1978)
