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Case Report
Revised

Case Report: Large ileal intramural hematoma presenting as an intestinal obstruction in a patient on Warfarin with incidental breast cancer

[version 2; peer review: 2 approved]
PUBLISHED 30 Dec 2019
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Abstract

Intramural hematoma of the gastrointestinal (GI) tract, which can present as abdominal pain or obstruction, can be a rare complication of oral anticoagulants, in particular Warfarin. In this case report, we describe an 81-year-old female patient presenting with abdominal pain, nausea, and vomiting with a previous history of rectorrhagia. The patient was receiving Warfarin therapy due to cardiac valve replacement for the past 8 years. Laboratory workup revealed elevated INR and anemia. Diagnosis of ileal intramural hematoma was based on ultrasound and CT scan findings. The patient was treated by conservative approaches including administration of fresh frozen plasma, cessation of oral intake, and fluid resuscitation. In CT images, a mass on the left breast and lymphadenopathy on the left axilla were also noticed. Given that most GI intramural hematomas caused by over-anticoagulation are treated non-surgically, considering a patient's drug history, especially in older patients with abdominal pain and obstruction symptoms, is of particular importance.

Keywords

Gastrointestinal Tract, hematoma, anticoagulant therapy, warfarin.

Revised Amendments from Version 1

in this version of the manuscript, the discussion section was revised with more focus on hematomas in other GI sites. also, radiologic manifestation and therapeutic strategies were included.

See the authors' detailed response to the review by Kevin W. Olden
See the authors' detailed response to the review by Everton Cazzo

Introduction

Abdominal pain is a common complaint in patients referred to hospital emergency departments and varies from mild and self-limiting to severe and life-threatening conditions1,2. Depending on the location of the pain, symptoms, physical examination and medical history, a differential diagnosis is provided1. Since mortality and the rate of surgery secondary to abdominal pain is higher in elderly patients, prompt diagnosis of the causative agent is of particular importance3. Non-specific causes, gastroenteritis, irritable bowel syndrome, urologic disorders, and gastroenteritis are among the common etiologies for abdominal pain4. An uncommon reason for abdominal pain and bowel obstruction is intestinal intramural hematoma following anticoagulation therapy5,6. Warfarin, a vitamin K antagonist, is widely used to prevent thrombosis formation due to mechanical heart valves, atrial fibrillation, pulmonary embolism and deep venous thrombosis7. The occurrence of intestinal intramural hematoma secondary to anticoagulant therapy is an uncommon condition, which affects 1/2500 patients receiving Warfarin8. The small intestine is the common site affected by spontaneous intramural hematoma, and intramural hematoma of the colon and rectum are rare9. This complication is mostly treated by non-surgical approaches.

This article reports a case of a relatively large ileal intramural hematoma developed following Warfarin use and accidental detection of breast malignancy during a CT scan.

Case presentation

An 81-year-old woman was admitted to the Mazandaran Heart Center, Sari, Iran in February, 2018 with a 4-day history of nausea, vomiting, and abdominal pain. She had been taking Warfarin (5 mg orally once a day) and aspirin (80 mg/day) for 8 years after aortic valve replacement without close monitoring and had a history of hematochezia caused by Warfarin toxicity one year ago. Colicky pain, an increase in bowel sounds and periumbilical tenderness without distension was determined by physical examination. The primary laboratory findings revealed anemia (Hb: 9.8 g/dl; normal value: 11.5–13.5 g/dl) and elevated INR (6; therapeutic range: 2–3.5), liver function and biochemistry tests were within normal values. Normal left ventricular systolic function, LVEF of 55–60%, septal hypertrophy, normal functioning prosthetic valve, and dilatation of the ascending aorta were reported by echocardiography.

During an abdominal and pelvic ultrasound, long mucosal thickening possibly through the ascending and sigmoid colon was observed, suggestive of intramural hematoma. The patient was placed on nil per os, received supportive care and two units of fresh frozen plasma. Due to normal cardiac evaluation and partial relief of symptoms on the second day of admission, the patient was referred to surgical consultation with the possible diagnosis of descending colon and sigmoid intramural hematoma. For re-administration of anticoagulants, heparin infusion (1000 units/hour) began with precise monitoring of prothrombin time.

On the fourth day, CT scan was performed with intravenous and oral contrast (Figure 1) and intramural hematoma of ileum was diagnosed. During the CT, a radiologist noticed a mass on the left breast and a lymph node with a malignant feature on the left axilla. With the improvement of abdominal pain and vomiting (on the fourth day), oral feeding was resumed. After mammography and breast biopsy, pathological examination revealed invasive ductal cell carcinoma with lymphatic and perineural invasion. According to the immunohistochemistry staining, tumor cells were strongly ER positive, PR negative, 15% Ki67 positive and equivocal for HER2. The patient was referred to the oncology-hematology department to receive appropriate treatment.

b99f6628-62fc-4d7e-9d7f-0201b2320288_figure1.gif

Figure 1. Contrast-enhanced abdominal and pelvic CT.

(A) Circumferential thickening of an ileal loop with adjacent fat stranding in Sagittal (1) and Coronal (2) view. (B) LAP on left axilla with malignant feature measuring 18×16mm (3) and 32×26 mm mass in left breast (4).

The patient was discharged 10 days after admission and Warfarin therapy (5 mg/d) was resumed. The patient was visited 2 weeks later with good general health assessment. Letrozole (2.5 mg/day) was started because the patient refused chemotherapy and radiotherapy.

Discussion

The most significant reason for the intestinal intramural hematoma is trauma, while non-traumatic or spontaneous causes include anticoagulation therapy, malignancies, and blood disorders, which are considered to be rare10,11. The intestinal sites involved in the intramural hematoma in order of frequency include jejunum, duodenum, and ileum12. The intramural hematoma can affect the esophagus, gastric and colon, but these cases are less prevalent. This complication is mostly associated with Warfarin and is more common in male subjects10,13,14; patient's chief complaints are abdominal pain, nausea, vomiting, and absence of bowel movements or flatulence6,15. Melena and jaundice are rare presentation too16. Hyperechoic bowel wall thickening or free fluid may be noted in ultrasound findings, nevertheless, as a non-unspecific test, normal ultrasound results cannot rule out the possible diagnosis of gastrointestinal intramural hematoma. The diagnostic key test is a CT scan, but there is no agreement in the literature concerning the use of contrast materials, as it may obscure intramural hyper-density and hemorrhage, and also increase the risk of exposure17,18. Bowel wall thickening, luminal narrowing, obstruction caused by edema, picket fence sign can be demonstrated in CT-scan19,20. Products related to hemoglobin breakdown in hematoma site will lead to a high density signal as “ring sign” in MRI which is unique to confirm diagnosis21. In the review of fourteen patients by Yoldaş et al, nine patients were treated non-surgically, with eight of them were on Warfarin therapy for heart disorders. Increased INR was also observed in anticoagulant receiving patients10. In addition to impaired coagulation tests, increased WBC count and anemia may also present15,19. For early diagnosis of this complication, taking a detailed medical history of anticoagulation use, especially in older patients with abdominal pain, is required. Treatment usually is conservative and includes cessation of oral anticoagulation, serum therapy, and correction of coagulation indices by vitamin K and blood products8,19,22. As this condition is rare, there is no treatment as the best option in the literature but unlike the past, there is a tendency for conservative management of cases today. The patient's condition is the most important consideration in choosing the treatment. Referral to surgery is usually preferred when the patient has peritonitis, obstruction, ischemia or necrosis16. Accurate recognition of this complication leads to prevention of unnecessary surgical procedures and the risk of bleeding progression. There are also evidence that Warfarin may act as an anticancer agent; Warfarin was shown to lower the incidence of organ specific cancers including lung, prostate, and breast23,24. Therefore, the development of invasive breast cancer in the present case, despite the long-term use of Warfarin, is interesting.

Finally, the question arises of which anticoagulant can be used as an alternative to Warfarin in patients with frequent life threatening hemorrhagic events, which requires no regular monitoring but has an acceptable efficacy.

Consent

Written informed consent was obtained from patient during admission and follow up for the publication of the patient’s clinical information and accompanying images.

Data availability

All data underlying the results are available as part of the article and no additional source data are required.

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Version 2
VERSION 2 PUBLISHED 11 Jun 2018
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Alizadeh Forutan M, Mojarad FA and Rahmani N. Case Report: Large ileal intramural hematoma presenting as an intestinal obstruction in a patient on Warfarin with incidental breast cancer [version 2; peer review: 2 approved]. F1000Research 2019, 7:724 (https://doi.org/10.12688/f1000research.14848.2)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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Key to Reviewer Statuses VIEW
ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
Version 2
VERSION 2
PUBLISHED 30 Dec 2019
Revised
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5
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Reviewer Report 02 Mar 2020
Everton Cazzo, Department of Surgery, Faculdade de Ciências Médicas da Universidade Estadual de Campinas (FCM/UNICAMP), Campinas, Brazil 
Approved
VIEWS 5
All the comments and ... Continue reading
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CITE
HOW TO CITE THIS REPORT
Cazzo E. Reviewer Report For: Case Report: Large ileal intramural hematoma presenting as an intestinal obstruction in a patient on Warfarin with incidental breast cancer [version 2; peer review: 2 approved]. F1000Research 2019, 7:724 (https://doi.org/10.5256/f1000research.23800.r58052)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
Version 1
VERSION 1
PUBLISHED 11 Jun 2018
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Reviewer Report 21 Oct 2019
Everton Cazzo, Department of Surgery, Faculdade de Ciências Médicas da Universidade Estadual de Campinas (FCM/UNICAMP), Campinas, Brazil 
Approved with Reservations
VIEWS 16
This is an interesting and well-written case report of a disease which poses a significant difficulty in relation to its diagnosis and management.

The main comments which I think may improve and enrich this study are the ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Cazzo E. Reviewer Report For: Case Report: Large ileal intramural hematoma presenting as an intestinal obstruction in a patient on Warfarin with incidental breast cancer [version 2; peer review: 2 approved]. F1000Research 2019, 7:724 (https://doi.org/10.5256/f1000research.16162.r55318)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 06 Nov 2019
    Maryam Alizadeh Forutan, Gastrointestinal Cancer Research Center, Mazandaran University of Medical Science, Sari, Iran
    06 Nov 2019
    Author Response
    Hello and thanks for your attention.
    I will definitely consider and correct the things you have mentioned.
    Competing Interests: No competing interests were disclosed.
  • Author Response 30 Dec 2019
    Maryam Alizadeh Forutan, Gastrointestinal Cancer Research Center, Mazandaran University of Medical Science, Sari, Iran
    30 Dec 2019
    Author Response
    Dear reviewer,

    Many thanks for your attention and points.
    We have revised the manuscript according to your suggestions and highlighted them.
    Competing Interests: No competing interests were disclosed.
COMMENTS ON THIS REPORT
  • Author Response 06 Nov 2019
    Maryam Alizadeh Forutan, Gastrointestinal Cancer Research Center, Mazandaran University of Medical Science, Sari, Iran
    06 Nov 2019
    Author Response
    Hello and thanks for your attention.
    I will definitely consider and correct the things you have mentioned.
    Competing Interests: No competing interests were disclosed.
  • Author Response 30 Dec 2019
    Maryam Alizadeh Forutan, Gastrointestinal Cancer Research Center, Mazandaran University of Medical Science, Sari, Iran
    30 Dec 2019
    Author Response
    Dear reviewer,

    Many thanks for your attention and points.
    We have revised the manuscript according to your suggestions and highlighted them.
    Competing Interests: No competing interests were disclosed.
Views
28
Cite
Reviewer Report 12 Sep 2019
Kevin W. Olden, Division of Gastroenterology, Regional One Medical Center, University of Tennessee, School of Medicine, Memphis, TN, USA 
Approved
VIEWS 28
  • The case is well presented, and the clinical details are well written and meticulously enumerated. The case is relevant for practice and will benefit clinicians. 
     
  • The only comment I would have is to
... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Olden KW. Reviewer Report For: Case Report: Large ileal intramural hematoma presenting as an intestinal obstruction in a patient on Warfarin with incidental breast cancer [version 2; peer review: 2 approved]. F1000Research 2019, 7:724 (https://doi.org/10.5256/f1000research.16162.r35009)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
  • Author Response 16 Sep 2019
    Maryam Alizadeh Forutan, Gastrointestinal Cancer Research Center, Mazandaran University of Medical Science, Sari, Iran
    16 Sep 2019
    Author Response
    Greetings and regards.
    Thanks for bothering to read this case report and for taking the time to review the article.
    I will consider the issues raised.
    Competing Interests: There isn't any competing interest.
COMMENTS ON THIS REPORT
  • Author Response 16 Sep 2019
    Maryam Alizadeh Forutan, Gastrointestinal Cancer Research Center, Mazandaran University of Medical Science, Sari, Iran
    16 Sep 2019
    Author Response
    Greetings and regards.
    Thanks for bothering to read this case report and for taking the time to review the article.
    I will consider the issues raised.
    Competing Interests: There isn't any competing interest.

Comments on this article Comments (0)

Version 2
VERSION 2 PUBLISHED 11 Jun 2018
Comment
Alongside their report, reviewers assign a status to the article:
Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
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