Alimentary tract and pancreas
ARCH
GASTROENTEROHEPATOL 2002; 21 ( No 3 – 4 ):
Massive
hepatic, splenic and superior mesenteric arteries thrombosis in a patients with
Crohn's disease
Masivna
tromboza hepatične,
splenične i gornje mezenterične arterije u pacijenta sa Crohnovom bolešću
( accepted December 29th, 2002 )
Aysel Ulker, Bilge Tunc, Mehmet Asil,
Levent Filik
Gastroenterology Clinic, Turkiye Yuksek
Ihtisas Hospital, Istambul.
Address correspondence to: Dr Levent Filik
Ziya Gokalp Cad. Isik Apt.,No 72/7
Kizilay, Ankara
06520 Turkiye
E-mail:[email protected]
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Massive visceral thrombosis in Crohn,s
disease Gastroenterološka sekcija
SLD-
01740,2002.
Abstract
Thromboembolic
events are serious complications of inflammatory bowel disease. Crohn's disease
(CD) is associated with hypercoagulability state of undefined aetiology (1-4).
Herein, we present 39-year-old male patient with CD. He was diagnosed of CD
with typical presentation of intestinal involvement and histopathologic
confirmation. One year later, he was admitted to the hospital because of acute
abdomen. Surgical exploration revealed complete hepatic, splenic and superior
mesenteric arterial occlusion.
Key Words: Crohn's disease, thrombophilia.
Ključne reči:Kronova bolest, trombofilija.
Patients with inflammatory bowel
diseases (IBD) are predisposed to thromboembolic complications because it seems
that IBD are accompanied with hypercoagulable state which contributes
significantly to their pathogenesis (1-12). Thrombophilia in IBD is probably
due to inappropriate hemostasis with a hypercoagulable state, thrombocytosis,
hyperfibrinogenemia, hyperhomocysteinemia and increased levels of lipoproteins.
Herein, we
present a case with a past medical history of Crohn's Disease (CD) who was
subsequently complicated with massive splenic, hepatic and superior mesenteric
arteries occlusion.
Case Report
A 39-yr-old man was admitted to the
hospital because of severe abdominal pain. His abdominal pain was present for
about 6 months and worsened day before admisison. He had diabetes mellitus
regulated with oral antidiabetic drugs. Beside that his past medical history
was unremarcable except nephrolithiasis. He was heavy smoker, around
100-package-year. In his family, there was no IBD and thromboembolism.
At admission he had borborygmi, but
no diarrhea, nausea, vomiting. Laboratory studies revealed elevated
sedimantation rate, mild anemia, normal white blood cell count. AST, ALT,
alkaline phosphatase, BUN, creatinine levels were all normal. Abdominal
ultrasonography sonography showed dilated jejunal loops and prominently
thickened ileal loops. Abdominal CT disclosed thickened walls of ileum loops,
caecum and proximal ascending colon. He underwent emergency laparotomy.
Intraoperatively, it was seen that the terminal ileum and caecum were
thickened, inflamed with adhesions between terminal ileum and surrounding
structures. Caecum and terminal ileum were resected with end-to-end
anastomosis. Pathological examination was consistent with CD. The patient was
started on azathiopyrin 50 mg bid. Even though close follow-up as scheduled, he
did not attend the outpetient clinic for regular controls for about one year.
Meanwhile, he felt relatively well with mild occasional abdominal pain and
normal stools. Laboratory studies revealed normal blood cell counts, liver and
renal function tests, erythrocyte sedimentation rates, fibrinogen and
C-reactive protein levels. Abdominal ultrasonography sonography showed mild
hepatic steatosis. Jejunoscopy and colonoscopy were normal except hyperemia and
mucosal oedema at ileocolostomy line from which biopsy was taken. Pathological
examination showed only nonspecific inflammatory changes.
After
nearly two months from the last check-up, he was brought to the emergency
department with severe abdominal pain started one day in advance. Nausea,
vomiting, fever and absence of flatulance accompanied the abdominal pain. Flat
and upright abdominal film disclosed air-fluid levels. Hematocrit, leukocyte, thrombocyte
counts were 42.5%, 12.440/mm3, 181.000/mm3 respectively. ALT, AST, GGT, LDH,alkaline
phosphatase, amylase, lipase, were 1.67 mg/dl, 58 mg/dl, 65 U/L, 90 U/L, 295
U/L, 140 U/L, 116 U/L respectively. Fibrinogen, serum electrolytes levels,
PT,PTT were norl. Emergency laparotomy was done. The whole intestinal tract
from pylorus to rectum was necrotic. Wedge
liver biopsy showed severe ischaemic changes. Palpation of
hepatoduodenal ligament disclosed absence of hepatic artery flow. Spleen seemed
to be totaly infarcted. The lumen of superior mesenteric artery was occluded
totally with thrombus. This was to sugest a massive thromboembolic event in
hepatic, splenic and superior mesenteric arteries. Intestinal resection was
done. Unfortunately, the patient died within a couple of hours after operation
in spite of all life support measures.
Discussion
It is well known
that patients with IBD are under the risk of thromboembolic disease. CD is
associated with hypercoagulability state which aetiology was not clearly
defined yet. Thrombophilia in IBD is probably due to inappropriate hemostasis
with hypercoagulable state, thrombocytosis, hyperfibrinogenemia,
hyperhomocysteinemia and increased levels of lipoproteins (1). In patients with
IBD anemia and thrombocytosis are commonly seen and are parameters of the clinical severity of the
IBD (2). It is likely that increased platelet function, abnormal fibrinolysis,
and hypercoagulation in IBD patients may cause thromboembolism, what probably
play a role in local microcirculatory alterations leading to IBD itself. In a
prospective study, specimens of resected small and large intestine from fifteen
patients with CD were examined and a pathogenetic sequence of events, vascular
injury, focal arteritis, fibrin deposition, arterial occlusion mainly at the
level of the muscularis propria, followed by tissue infarction or
neovascularisation were disclosed. These features were within borders of
affected intestinal segments and did not occur in normal bowel. This findings suggest
that multifocal gastrointestinal infarction might be one of the pathophysiologic mechanisms of CD (3).
The impairment of
the protein S, protein C and thrombomodulin system in patients with CD favours
coagulation and might be of importance for both the development of CD and its
thromboembolic complications (4,5).
Activated protein
C resistance (APCR) has been identified as inherited disorders of coagulation
which predisposes individuals to thromboembolism. The results of studies which
explored the link between Leiden mutation and thrombophilia in IBD are still
controversial. It was found out that there may be a weak association between
Factor V Leiden and UC with the emphasis that this association was not strong
enough to imply a causal relationship, but may be responsible for some of the
thromboembolic complications . Neverteless, in another study it was reported
that the factor V Leiden and the G20210A prothrombin-gene mutation in patients
with CD and ulcerative colitis did not seem to play a major pathogenic role or
be associated with an increased incidence of thrombotic complications.
Similarly, according to another report, it is suggested that the presence of
inherited thrombophilic defects of fibrinogen, antithrombin III, protein C,
protein S and APCR, are uncommon in patients with IBD and does not merit
routine screening. According to some authors,
these is no evidence that APC resistance is associated with IBD but,
when present, increases the risk of thromboembolism (6-11).
Elevated plasma homocysteine
concentration is associated with an increase risk of thrombosis. Terminal ileum
resection contributes to elevated plasma homocysteine levels in CD. It is
recommended that homocysteine screening in patients with CD, especially in
those with prior history of terminal ileum resection, and the initiation of
vitamin supplementation is mandatory (12). It has already known that smoking
and oral contraceptive pill use may take a role in thrombophilia.
In conclusion, we
were unable to identify in the litarature any previous case of total massive
occlusion of hepatic, splenic and superior mesenteric arteries in a patient
with CD. There were some reports presenting cases with ischemic bowel diseases
thus mimicking IBD (13-15). Further studies are neccessary to eludicate
haemostatic abnormalities in IBD, esspecialy CD and to explore vascular basis
of its pathophysiology.
References:
1. Van Bodegraven AA, Meuwissen
SG. Lipoprotein (a), thrombophilia and inflammatory bowel disease. Eur J
Gastroenterol Hepatol 2001;13:1407-9.
2. Udvardy M, Altorjay I,
Palatka K. Hematologic aspects of inflammatory bowel diseases. Orv Hetil
2001;142:883-6.
3. Wakefield AJ, Sawyerr AM,
Dhillon AP, et al. Pathogenesis of Crohn's disease: multifocal gastrointestinal
infarction. Lancet 1989;2:1057-62.
4. Aadland E, Odegaard OR,
Roseth A, et al. Free protein S deficiency in patients with Crohn's disease.
Scand J Gastroenterol 1994;29:333-5.
5. Aadland E, Odegaard OR,
Roseth A, et al. K. Free protein S deficiency in patients with chronic inflammatory
bowel disease: Scand J Gastroenterol 1992;27:957-60.
6. Haslam N, Standen GR, Probert
CS. An investigation of the association of the factor V Leiden mutation and
inflammatory bowel disease. Eur J Gastroenterol Hepatol 1999;11:1289-91.
7. Papa A, De Stefano V,
Gasbarrini A, et al. Prevalence of factor V Leiden and the G20210A
prothrombin-gene mutation in inflammatory bowel disease. Blood Coagul
Fibrinolysis 2000;11:499-503.
8. Heneghan MA, Cleary B, Murray
M, et al. Activated protein C resistance, thrombophilia, and inflammatory bowel
disease. Dig Dis Sci 1998;43:1356-61.
9. Zauber NP, Sabbath-Solitare
M, Rajoria G, et al. Factor V Leiden mutation is not increased in patients with
inflammatory bowel disease. J Clin Gastroenterol 1998;27:215-6.
10. Koutroubakis IE, Sfiridaki A,
Mouzas IA, et al. Resistance to activated protein C and low levels of free
protein S in Greek patients with inflammatory bowel disease. Am J Gastroenterol
2000;95:190-4.
11. Novacek G, Miehsler W,
Kapiotis S, et al. Thromboembolism and resistance to activated protein C in
patients with inflammatory bowel disease. Am J Gastroenterol 1999;94:685-90.
12. Vasilopoulos S, Saiean K,
Emmons J, et al. Terminal ileum resection is associated with higher plasma
homocysteine levels in Crohn's disease. J Clin Gastroenterol 2001;33:132-6.
13. Anthony A, Dhillon AP,
Pounder RE, et al. Ulceration of the ileum in Crohn's disease: correlation with
vascular anatomy. J Clin Pathol 1997;50:1013-7.
14. Johanns W, Jakobeit C, Louis
W, et al. Chronic mesenteric ischemia-a rare differential diagnosis of Crohn
disease. Z Gastroenterol 1994;32:444-6.
15. Crespo I, Murphy J, Wong RK.
Superior mesenteric venous thrombosis masquerading as Crohn's disease. Am J
Gastroenterol 1994;89:116-8.