Saudi Journal of Gastroenterology
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CASE REPORT Table of Contents   
Year : 1998  |  Volume : 4  |  Issue : 1  |  Page : 34-37
Cerebral venous thrombosis as a complication of ulcerative colitis associated with protein-s deficiency: Case report and review of literature

1 Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
2 Department of Gastroenterology, Dallah Hospital, Riyadh, Saudi Arabia
3 Department of Radiology, King Fahd National Guard Hospital, Riyadh, Saudi Arabia

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Date of Submission21-Jun-1997
Date of Acceptance01-Dec-1997

How to cite this article:
Al Tahan A, Mageed SA, Al Momen A, Zaidan R, Daif A, Al Tahan F. Cerebral venous thrombosis as a complication of ulcerative colitis associated with protein-s deficiency: Case report and review of literature. Saudi J Gastroenterol 1998;4:34-7

How to cite this URL:
Al Tahan A, Mageed SA, Al Momen A, Zaidan R, Daif A, Al Tahan F. Cerebral venous thrombosis as a complication of ulcerative colitis associated with protein-s deficiency: Case report and review of literature. Saudi J Gastroenterol [serial online] 1998 [cited 2022 Oct 5];4:34-7. Available from:

Cerebral venous thrombosis (CVT) is one of many thromboembolic complications already recognized in association with ulcerative colitis [1],[2],[3],[4],[5],[6],[7],[8],[9] . The underlying mechanisms of thrombogenesis in inflammatory bowel disease are not well understood but different abnormalities have been described to explain the presence of a hypercoagulable state including increased coagulation factors, decreased clotting activation inhibitors, diminished fibrinolytic activity and the presence of antiphospholipid antibodies [10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22] .

In this article, we present a patient with ulcerative colitis (UC) who developed cerebral venous thrombosis in association with severe protein-S deficiency

   Case Report Top

A 14-year-old girld presented with recurrent episode of abdominal pain, frequent bloody motions and headache. Five months earlier she was admitted to a local hospital with weight loss, frequent episodes of abdominal pain and losse bloody motions. Diagnosis of UC was confirmed by colonic biopsies. She made excellent recovery on the combination of prednisolone 40 mg od and salazopyrine 1 mg bid. She maintained on salazopyrine which was used only for three months. The patient looked pale and ill, with pulse rate of 110/min, blood pressure 100/70mmHg and temperature 37.4°C. Apart from her tender abdomen, the rest of her physical examination was normal. Her white blood cell count was 12 x 10 9 /L, hemoglobin 5.6 g/L, reticulocytes 2 %, ESR 80 mm/hr, prothrombin time (PT) 11 seconds (control=11.5), activated partial thromboplastin time (APTT) 32 sec. (control 26-38). She was given three units of packed red cells and was started on prednisolone 40 mg od and salazopyrine continued. Two days later, she sustained a generalized tonic­clonic seizure preceded by right facial twitching. A computerized tomographic (CT) scan of the brain revealed small hyperdense lesion in the left frontal lobe [Figure - 1]. Magnetic resonance imaging (MRI) confirmed the presence of two hemorragic infarctions in the left frontal and parietal lobes [Figure - 2], and showed widespread thrombosis in the superior sagittal sinus [Figure - 3]. Blood samples were taken to investigate possible causes of thrombosis and heparin was started with warfarin which was maintained as 4 mg od. Results included free protein -S activity <15% (normal 70-140%), protein-C 135% (70-140), Fibrinogen 4.6 g/L (2-4), antithrombin III 90% (70-150) and factor XII 120% (70-150). Tests for both anticardiolipin and lupus anticoagulant were negative. The patient improved gradually on warfarin and reached a complete recovery within five weeks. Warfarin was stopped after three months and she was maintained on low dose of aspirin 100 mg od and salazopyrine 1 mg bid with regular follow-up in the clinic. She has been stable clinically for the past year.

   Discussion Top

Thromboembolic complications in UC were described as early as 1936 by Barker [23] . Since then thrombosis has been described mainly in the veins and also arteries of many organs including cerebral, retinal, portal, renal, gonadal and deep veins of the upper and lower Iimbs [1],[2],[23],[24],[25],[26],[27],[28].

Several thrombogenic factors have already been detected in what is considered now as a hypercoagulable state associated with inflammatory bowel disease and may have a role in the pathogenesis of the intestinal manifestations [10],[11] . These factors include those responsible for increased coagulation such as fibrinogen, thrombocytes, factors V and factor VIII [10],[11],[12],[13] , decrease of inhibitors of blood clotting activation including anti thrombin III, protein S and C [10],[14],[15],[16],[17] , decreased fibrinolytic activity [18],[19] and antiphospholipid antibodies [10],[20]. Also, a recently described abnormality of increased resistance to activated protein C due to factor V Leiden which may turn out to be the commonest defect associated with hypercoagulability [21],[22].

In our patient, presented with CVT six months after the onset of UC, severe protein-S deficiency was detected while a long list of CVT causes were either excluded or considered unlikely within the clinical picture. These causes include intracranial infections, systemic lupus erythematosus, Behcet disease, vasculitis and entities associated with a hypercoagulable state such as pregnancy, postpartum, contraceptive pills, postoperative state, cancer, cyanotic cogenital heart disease, blood dyscrasias and paroxysmal nocturnal hemaglobinuria [29],[30]. On this account, we concluded that protein S deficiency was the most likely cause in this instance and that it was probably an acquired and transient abnormality since it returned to normal later on, and was associated with a negative family history for thromboembolic disease.

The clinical manifestations of CVT are diverse, however, the picture described in our patient represent the commonest manifestation of CVT related to superior saggital sinus thrombosis which include increased intracranial pressure and papilledema; frequently simulating that of pseudotumour cerebri; seizures and focal neurological deficits related to associated cortical veins thrombosis [29],[30] .

Because CVT is a serious complication with occasional poor outcome [7] ,anticoagulation which have shown a significant benefit should be instituted at once, even in the presence of associated intracranial hemorrhage [31] . Moreover, improvement in refractory UC was reported after the use of subcutaneous Heparin, which highlights the yet not well defined role of coagulation disturbances in this disease [22] .

It is expected that increased awareness of this and other thrombotic complications in association with UC will promote early diagnosis and consequently the early institution of appropriate treatment[32].

   References Top

1.Kehoe EL, Newcomer KL. Thromboembolic phenomenon in ulcerative colitis. Arch Intern Med 1964;113:711-5.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Koenigs KP, McPhedran P, Spiro HM. Thrombosis in inflammatory bowel disease. J Clin Gastroenterol 1987;9:627-31.  Back to cited text no. 2  [PUBMED]  
3.Graef V, Baggenstoss AH, Sauer WG, Spittell JA. Venous thrombosis occuring in non specific ulcerative colitis. A necropsy study. Arch Intern Med 1966;1117:337-82.  Back to cited text no. 3    
4.Harrison MJG, Truelove SC. Cerebral venous thrombosis as a complication of ulcerative colitis. Am J Dig Dis 1967;12:1025-8.  Back to cited text no. 4    
5.Borda IT, Southern RF, Brown WF: Cerebral venous thrombosis in ulcerative colitis. Gastroenterology 1973;64:116-9.  Back to cited text no. 5    
6.Schederman JH, Sharpe JA, Sutton DMC. Cerebral and retinal vascular complications of inflammatory bowel disease. Ann Neurol 1979;5:331-7.  Back to cited text no. 6    
7.Kiff RS, Denton GW. Fatal cerebral venous thrombosis complicating acute ulcerative colitis. Am J Gastroenterol 1988;74:577-8.  Back to cited text no. 7    
8.Markowitz RL, Merit LR, Gryboski JD: Cerebral thromboembolic disease in pediatrics and adult inflammatory bowel disease: case report and review of the literature. J Paedia Gastroenterol Nutrition 1989;8:413-420.  Back to cited text no. 8    
9.Calderon A, Wong JW, Backer LE. Multiple cerebral venous thrombosis in a child with ulcerative colitis. Clin Ped 1993; 169-7 1.  Back to cited text no. 9    
10.Chiarantini E, Valanzano R, Alessandrello L, et al. Hemostatic abnormalities in inflammatory bowel disease. Thrombosis Research 1996;82:137-46.  Back to cited text no. 10    
11.Hudson M, Chitolie A, Hutton RA, Smith MSH, Pounder RE, Wakefield AJ. Thrombotic vascular risk factors in inflammatory bowel disease. GUT 1996;38:733-7.  Back to cited text no. 11    
12.Lee JCL, Spittle JA, Sauer WG, Owen CA, Thrompson JH. Hypercoagulability associated with chronic ulcerative colitis changes in blood coagulation parameters. Gastroenterology 1968;54:76-85.  Back to cited text no. 12    
13.Lam A, Borda IT, Inwood MJ, Thomson S. Coagulation studies in ulcerative colitis and Crohn's disease. Gastroenterol 1975;68:245-51.  Back to cited text no. 13    
14.Vaezi MF, Rustag PK, Elson CO. Transient protein S deficiency associated with cerebral venous thrombosis in active ulcerative colitis. Am J Gastroenterol 1995;90:313-5.  Back to cited text no. 14    
15.Ghosh S, Mackie MJ, McVerry Ba, Galloway M, Ellis A, McKay J. Chronic inflammatory bowel disease, deep-venous thrombosis and antithrombin activity. Acta Haematol (basel) 1983;70:50-3.  Back to cited text no. 15    
16.Jorens PG, Hermans CR, Halich I, et al. Acquired protein-C and -S deficiency, inflammatory bowel disease, and cerebral arterial thrombosis. Blood 1990;61:307-10.  Back to cited text no. 16    
17.Aadland E, Odegaard OR, Roseth A, Try K. Free protein-S deficiency in patients with chronic inflammatory bowel disease. Scand J Gastroenterol 1992;27:957-60.  Back to cited text no. 17    
18.De Jong E, Porte RJ, Knot EAR, Verheijen JH, Dees J. Disturbed fibrinolysis in patients with inflammatory bowel disease. A study in blood plasma, colon muscosa, and feces. Gut 1989;30:188-94.  Back to cited text no. 18    
19.Conlan MG, Haire WD, Burnett DA. Prothrombic abnormalities in inflammatory bowel diseases. Dig Dis Sci 1989;34:1089-93.  Back to cited text no. 19  [PUBMED]  
20.Papi C, Ciaco A, Aciemo G, Battista GD, Talamanca LF, Russo FL, Natali G, Capurso L. Severe ulcerative colitis, dural sinus thrombosis, and the lupus anticoagulant. Am J Gastroentero 1995;90:1514-7.  Back to cited text no. 20    
21.Jackson LM, O'Gorman PJ, O'connell J, Cronin CC, Cotter KP. Shanahan F. Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden. Q J Med 1997;90:183-8.  Back to cited text no. 21    
22.Svesson PJ, Dalhback B. Resistance to activated protein C as basis for venous thrombosis. N Engl J Med 1994;330:517-22.  Back to cited text no. 22    
23.Bargen JA, Barker NW. Extensive arterial and venous thrombosis complicating chronic ulcerative colitis. Arch Inter Med 1936;58:17-31.  Back to cited text no. 23    
24.Aronson AR, Steinheber FU. Portal vein thrombosis in ulcerative colitis. NY State J Med 1971;71:2310-1.  Back to cited text no. 24    
25.Miyazaki Y, Shinomora Y. Kitamura S, et al. Portal vein thrombosis associated with active ulcerative colitis: Percutaneous transhepatic recanalization. Am J Gastroenterol 1995;90:1533-4.  Back to cited text no. 25    
26.Kiran AJ, Brooke J Jr. Gonadal vein thrombosis in patients with acute gastrointestinal inflammation: Diagnosis with CT. Radiology 1991;180:111-3.  Back to cited text no. 26    
27.Wyshock E, Caldwell M, Crowley JP. Deep venous thrombosis, inflammatory bowel disease, and protein-S deficiency. Am J Clin Pathol 1988;90:633-5.  Back to cited text no. 27  [PUBMED]  
28.Vanwoert JE, Thompson RC, Cangemi JR, Metzger PP, Blackshear JL, Fleming CR. Streptokinase therapy for extensive venous thrombosis in a patient with severe ulcerative colitis. Mayo Clin Proc 1990;65:1144-9.  Back to cited text no. 28    
29.Bousser MG, Chiras J, Boris J, Castaigne P. Cerebral Venous Thrombosis-A review of 38 cases. Stroke 1985;16:199-213.  Back to cited text no. 29    
30.Daif AK, Awada A, Al Rajeh S, et al. Cerebral venous thrombosis in adults. A study of 40 cases Saudi Arabia. Stroke 1995;26:1193-5.  Back to cited text no. 30    
31.Einhaupl KM, Villringer A, Meister W, et al. Heparin treatment in sinus venous thrombosis. Lancet 1991;338:597­-600.  Back to cited text no. 31    
32.Gaffney PR, Doyle CT, Gaffney A, Hogan J, Hayes DP, Annis P. Paradoxical response to Heparin in 10 patients with ulcerative colitis. Am J Gastroenterol 1995;90:220-3.  Back to cited text no. 32  [PUBMED]  

Correspondence Address:
Radwan Zaidan
Neurologist, King Khalid University Hospital, P.O. Box 7805 (38), Riyadh-11472
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

PMID: 19864785

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