These authors contributed equally to this study.
Spontaneous intramural small bowel hematoma (SISBH) is an extremely rare complication of anticoagulant or antiplatelet therapy. We assessed the clinical characteristics and outcomes of patients with SISBH according to the anatomical location of the hematoma.
From January 2003 to February 2016, medical records for all patients hospitalized for SISBH at 2 tertiary referral hospitals were retrospectively reviewed. The primary outcome was requirement for surgery.
A total of 37 patients were enrolled. The mean age was 74.1 years. Among them, 33 patients (89.2%) were taking anticoagulant and/or antiplatelet agents. Duodenal intramural hematoma was detected in 4 patients (10.8%), jejunal in 16 (43.2%), and ileal in 17 (45.9%). Compared to jejunal and ileal involvement, duodenal intramural hematoma was significantly associated with high Charlson comorbidity index and low levels of white blood cells, hemoglobin, and platelets in the blood. SISBH in the duodenum was related to thrombocytopenia in 3 patients following systemic chemotherapy for malignancy. All patients with SISBH showed clinical improvement with conservative therapy. Mean length of hospital stay was 9.35 days. Independent predictors of a hospital stay of more than 7 days were body weight less than 60 kg (odds ratio [OR], 12.213; 95% confidence interval [CI], 1.755–84.998;
Compared to jejunal and ileal involvement, thrombocytopenia may result in spontaneous duodenal intramural hematoma among patients who are treated with systemic chemotherapy for malignancies. Patients with SISBH have excellent clinical outcomes with conservative therapy regardless of the anatomical location of the hematoma.
Spontaneous intramural small bowel hematoma (SISBH) was initially described in 1838 [
Anticoagulant or antiplatelet therapy is a risk factor for SISBH. Warfarin use was associated with most cases of SISBH [
From January 2003 to February 2016, the medical records of all consecutive patients who were hospitalized for SISBH at 2 tertiary referral hospitals in Korea (Seoul National University Hospital and Seoul National University Bundang Hospital) were retrospectively reviewed. All patients in whom intramural small intestinal hematoma was detected on the CT scan of the abdomen and pelvis were included in this study. Intramural small bowel hematoma was characterized as circumferential bowel wall thickening, luminal narrowing, and intestinal tract obstruction on the CT scan [
Data such as age, sex, body weight, and medical history including diabetes mellitus, hypertension, cardiac arrhythmia, congestive heart failure, coronary heart disease, pulmonary thromboembolism, deep vein thrombosis, peripheral arterial disease, history of heart valve replacement, history of cerebrovascular accidents, and malignancy were collected. The Charlson comorbidity index was calculated to evaluate the severity of comorbidities in the study population. With each elevated level of the Charlson comorbidity index, there are stepwise increases in the cumulative mortality attributable to comorbid diseases [
Baseline characteristics and clinical outcomes according to the location of the hematoma in the small intestine were compared. Continuous variables were compared among the groups using one-way ANOVA with Bonferroni correction. Pearson chi-square test or Fisher exact test was used to calculate the statistical significance of the categorical variables. Continuous variables between prolonged (more than 7 days) and short (7 days or less) hospital stays were also compared using Student
From January 2003 to February 2016, a total of 110,698 patients were treated with anticoagulant and/or antiplatelet therapy at the participating medical centers. Among them, a total of 37 consecutive patients with SISBH were enrolled in this study. The annual incidence of SISBH was estimated at 0.003% per year. The study population comprised 19 males (51.4%), and the mean age at presentation with SISBH was 74.1 years (range, 51–89 years). Among these patients, 35 (94.6%) had cardiovascular comorbidities including 22 with hypertension (59.5%), 20 with cardiac arrhythmia (54.1%), 13 with a history of cerebrovascular accidents (35.1%), 10 with congestive heart failure (27.0%), 7 with coronary heart diseases (18.9%), 4 with pulmonary embolism and/or deep vein thrombosis (10.8%), 3 with a history of heart valve replacement (8.1%), and 2 with peripheral arterial diseases (5.4%). Three patients (8.1%) had malignant tumors at the time that SISBH presented, all of whom were being treated with systemic chemotherapy. In total, 29 patients (78.4%) had 2 or more comorbidities, and the mean Charlson comorbidity score was 4.6 points (range, 2–10 points). Warfarin, aspirin, clopidogrel, and LMWH was taken by 30 (81.1%), 5 (13.5%), 1 (2.7%), and 1 (2.7%) patient, respectively. None of the study participants received novel oral anticoagulants. Only 1 patient without any underlying illness, who did not use any anticoagulant or antiplatelet therapies, showed prolongation of PT and aPTT during use of an herbal medication at the time of SISBH presentation. Abdominal pain was the most common complaint at the time of presentation (24 of 37 patients; 64.9%). Nausea and/or vomiting were present in 13 patients (35.1%) and GI bleeding developed in 14 (37.8%). Mean WBC count was 12.9×103/μL (range, 0.2–31.1×103/μL), mean hemoglobin level was 11.6 g/dL (range, 4.3–18.3 g/dL), and mean platelet count was 235×103/μL (range, 19–458×103/μL). Mean PT was 9.9 INR (range, 0.9–18.2 INR) and mean aPTT was 103 seconds (range, 22.7–180 seconds) (
Duodenal intramural hematoma was detected in 4 patients (10.8%), jejunal intramural hematoma in 16 (43.2%), and ileal intramural hematoma in 17 (45.9%). Cardiac arrhythmia occurred significantly more frequently in patients with jejunal intramural hematoma (81.3%) than in those with ileal (35.3%) and duodenal intramural (25.0%) hematomas (
The clinical characteristics and treatment outcomes of the 4 patients with SISBH with duodenal involvement are shown in
All patients were treated successfully with conservative therapy including fasting, blood component transfusion, and/or vitamin K injections. None of the patients underwent surgical therapy for SISBH-related complications. Overt GI bleeding was detected in 14 (37.8%) patients with SISBH. Among them, GI bleeding in all patients improved spontaneously by conservative therapy, except 1 patient who underwent angiographic embolization for ileal angiodysplasias although there was no evidence of active bleeding at the time of angiography. Multi-segmental hematoma in proximal to mid-jejunum was detected only in 1 patient (2.7%) with SISBH, an 80-year-old woman who had been taking warfarin for a cerebral infarction and cardiovascular disease. She complained of abdominal pain and nausea, and the initial laboratory findings showed prolonged PT (9.99 INR). She also improved without any complication by conservative therapy including fasting, parenteral nutrition, a transfusion of fresh frozen plasma and a vitamin K injection within 7 days of hospitalization. Moreover, there was no disease-related mortality in the study population. The mean length of fasting and the hospital stay were 3.38 days (range, 0–22 days) and 9.35 days (range, 1–70 days), respectively. Fourteen patients (37.8%) were hospitalized for more than 7 days (
Among the 30 patients who were treated with warfarin, 26 (86.7%) continued warfarin after clinical improvement of the SISBH. Warfarin was switched to dual antiplatelet therapy with aspirin and clopidogrel in 2 patients, and to a novel oral anticoagulant (rivaroxaban and dabigatran) in 2 other patients. During the mean follow-up duration of 49.9 months (range, 5–153 months), recurrent SISBH developed in only 1 patient (2.7%) who was on warfarin therapy for a prosthetic heart valve 12 years after the presentation of the first SISBH.
Prolonged hospital stay of more than 7 days was significantly associated with female gender (
In this retrospective cohort study of 37 patients from 2 tertiary referral hospitals over 13 years, the clinical features and prognosis of SISBH were evaluated. To the best of our knowledge, this is the largest study done to determine the clinical characteristics of SISBH, especially according to the anatomical location of the hematoma.
A literature review of the MEDLINE database identified 40 published articles within the previous 30 years, with a total of 103 cases with SISBH that were analyzed [
In the literature review, jejunal, ileal, and duodenal intramural hematoma was confirmed in 39 (37.9%), 25 (24.3%), and 18 (17.5%) patients, respectively. Three cases (2.9%) with SISBH involved diffuse segments of the small intestine and the involved segments of SISBH in the remaining 18 cases were unspecified. The predominance of jejunoileal involvement in SISBH was consistent with the results in our study. The reason why the duodenum is rarely involved in SISBH remains unclear. Because the duodenum is the shortest part of the small intestine, and is fixed and compressed by surrounding extraluminal organs, a duodenal intramural hematoma may be more easily compressed by the tissues and absorbed compared to those in the jejunum or ileum.
In this study, 2 patients with acute myeloid leukemia and thrombocytopenia experienced duodenal intramural hematomas. The other patient was diagnosed with duodenal intramural hematoma associated with newly detected thrombocytopenia while being treated with systemic chemotherapy for pancreatic cancer. The platelet counts in patients with duodenal intramural hematoma were significantly lower than those who had jejunoileal involvement. In addition, patients with SISBH with duodenal involvement had significantly more severe comorbidities as estimated by the Charlson comorbidity index compared to jejunoileal involvement. In the literature review, the proportion of cases where warfarin contributed to duodenal intramural hematoma was relatively small compared to the proportion with jejunoileal involvement. Also, case reports described that pancreatic diseases, including acute pancreatitis or pancreatic cancer, were related to duodenal intramural hematoma (
In the 103 patients with SISBH identified in the literature review, 18 (17.5%) required surgical treatment for peritonitis, intestinal obstruction, or necrotizing pancreatitis. There were 6 deaths (5.8%) and the causes of death were sepsis or multi-organ failure. In this study, however, all patients who presented with SISBH recovered after conservative management, without surgery. Recently, some reports showed that GI obstructive symptoms of SISBH could be treated conservatively without any sequelae, even in cases of extensively long segmental involvement of the hematoma [
In our study population, a prolonged hospital length of stay more than 7 days was significantly associated with low body weight of less than 60 kg and a history of cerebrovascular accident, respectively. Underweight is considered a risk for malnutrition [
In conclusion, compared to jejunal and ileal involvement, thrombocytopenia may result in spontaneous duodenal intramural hematoma among patients who are treated with systemic chemotherapy for malignancies. Patients with SISBH have excellent clinical outcomes with conservative therapy regardless of the anatomical location of the hematoma.
The authors received no financial support for the research, authorship, and/or publication of this article.
No potential conflict of interest relevant to this article was reported.
Conceptualization: Kang EA and Han SJ. Methodology: Han SJ and Chun J. Data collecting and Formal analysis: Chun J, Lee HJ, Chung HS, and Yoon H. Project administration: Im JP, Kim SG, Kim N, and Lee DH. Visualization: Shin CM and Park YS. Writing-original draft: Han SJ and Chun J. Writingreview and editing: Kang EA, Chun J, Kim JS, and Jung HC. Approval of final manuscript: all authors.
Clinical Characteristics and Outcomes of 4 Patients with Duodenal Involvement
Comparison of Characteristics and Outcomes Regarding Duration of Hospital Stay
Baseline Characteristics of Study Population According to Location of Hematoma
Variable | Duodenum | Jejunum | Ileum | |
---|---|---|---|---|
No. of patient | 4 (10.8) | 16 (43.2) | 17 (45.9) | - |
Age (yr) | 73.8±4.3 | 76.3±6.8 | 72.1±9.2 | 0.331 |
Male sex | 3 (75.0) | 9 (56.3) | 7 (41.2) | 0.416 |
Body weight (kg) | 64.8±5.7 | 60.6±13.9 | 55.1±10.1 | 0.220 |
BMI (kg/m2) | 25.0±2.8 | 23.8±4.0 | 22.3±3.0 | 0.288 |
Underlying illness | ||||
Hypertension | 2 (50.0) | 12 (75.0) | 8 (47.1) | 0.242 |
Arrhythmia | 1 (25.0) | 13 (81.3) | 6 (35.3) | 0.012 |
Cerebrovascular accident | 2 (50.0) | 6 (37.5) | 5 (29.4) | 0.715 |
Congestive heart failure | 0 | 5 (31.3) | 5 (29.4) | 0.258 |
Coronary heart disease | 0 | 5 (31.3) | 2 (11.8) | 0.214 |
Diabetes mellitus | 1 (25.0) | 5 (31.3) | 2 (11.8) | 0.391 |
Pulmonary or deep vein thromboembolism | 1 (25.0) | 0 | 3 (17.6) | 0.189 |
Heart valve replacement | 0 | 0 | 3 (17.6) | 0.147 |
Peripheral arterial disease | 0 | 1 (6.3) | 1 (5.9) | 0.879 |
Malignancy | 3 (75.0) | 0 | 0 | 0.001 |
Charlson comorbidity index | 6.8±2.5 | 4.7±1.5 | 3.9±1.9 | 0.147 |
Medications | 0.057 | |||
Warfarin | 1 (25.0) | 13 (81.3) | 12 (70.6) | |
Warfarin and aspirin | 0 | 1 (6.3) | 2 (11.8) | |
Aspirin | 0 | 0 | 2 (11.8) | |
Warfarin and clopidogrel | 0 | 1 (6.3) | 0 | |
Low molecular weight heparin | 1 (25.0) | 0 | 0 | |
Complaint at the time of presentation | ||||
Nausea and/or vomiting | 0 | 7 (43.8) | 6 (35.3) | 0.261 |
GI bleeding | 3 (75.0) | 4 (25.0) | 7 (41.2) | 0.169 |
Abdominal pain | 1 (25.0) | 11 (68.8) | 12 (70.6) | 0.208 |
Initial laboratory findings | ||||
White blood cell count (×103/μL) | 4.9±7.5 | 14.2±4.6 | 13.6±6.0 | 0.016 |
Hemoglobin level (g/dL) | 7.9±1.2 | 12.3±2.8 | 11.8±3.2 | 0.032 |
Platelet count (×103/μL) | 83.5±93.9 | 234.6±64.8 | 271.5±89.3 | 0.005 |
BUN level (mg/dL) | 48.5±14.3 | 28.4±14.5 | 30.1±14.4 | 0.052 |
Creatinine level (mg/dL) | 1.5±0.6 | 1.3±0.8 | 1.2±0.5 | 0.746 |
Albumin level (g/dL) | 3.3±0.3 | 3.7±0.4 | 3.7±0.5 | 0.196 |
hs-CRP level (mg/dL) | 6.9±5.0 | 5.2±3.9 | 5.9±6.7 | 0.853 |
PT, INR | 5.3±8.3 | 10.3±4.9 | 10.6±5.5 | 0.227 |
aPTT (sec) | 58.0±42.6 | 100.1±49.2 | 116.5±46.7 | 0.096 |
Values are presented as number (%) or mean±SD.
P-value between duodenum and jejunum group.
P-value between duodenum and ileum group.
hs-CRP, high-sensitivity CRP.
Clinical Outcomes in Study Population According to Location of Hematoma
Variable | Duodenum | Jejunum | Ileum | |
---|---|---|---|---|
Requirement for surgery | 0 | 0 | 0 | - |
Disease-related mortality | 0 | 0 | 0 | - |
Length of fasting (day) | 4.50 (3–7) | 3.44 (0–22) | 3.06 (0–11) | 0.807 |
Length of hospital stay (day) | 15.00 (5–27) | 10.13 (1–70) | 7.29 (1–19) | 0.501 |
Stay in hospital for >7 day | 3 (75.0) | 5 (31.3) | 6 (35.3) | 0.353 |
Values are presented as number (%) or mean (range).
Predictive Factors of Hospital Stay for More Than 7 days
Variable | Length of hospital stay |
Univariate analysis |
Multivariate analysis |
|||
---|---|---|---|---|---|---|
≤7 day | >7 day | OR (95% CI) | OR (95% CI) | |||
Female sex | 8 (34.8) | 10 (71.4) | 4.687 (1.108–19.834) | 0.036 | - | - |
Body weight <60 kg | 9 (39.1) | 12 (85.7) | 9.333 (1.679–51.875) | 0.011 | 12.213 (1.755–84.998) | 0.011 |
History of cerebrovascular accidents | 5 (21.7) | 8 (57.1) | 4.800 (1.126–20.460) | 0.034 | 6.667 (1.121–39.650) | 0.037 |
White blood cell count <104/μL | 4 (17.4) | 7 (50.0) | 4.750 (1.056–21.360) | 0.042 | - | - |
Hemoglobin level <10 g/dL | 4 (17.4) | 7 (50.0) | 4.750 (1.056–21.360) | 0.042 | - | - |
Albumin level ≤3.5 g/dL | 4 (17.4) | 7 (50.0) | 8.550 (1.841–39.702) | 0.006 | - | - |
Length of fasting >3 day | 4 (17.4) | 7 (50.0) | 4.750 (1.056-21.360) | 0.042 | - | - |
Etiology of the Location Specified 82 Cases from the Literature Review
Variable | Duodenum | Jejunum | Ileum | |
---|---|---|---|---|
Warfarin | 6 (33.3) | 27 (69.2) | 17 (68.0) | 0.028 |
Low molecular weight heparin | 0 | 1 (2.6) | 2 (8.0) | |
Aspirin | 1 (5.6) | 0 | 0 | |
Hemophilia | 1 (5.6) | 2 (5.1) | 1 (4.0) | |
Pancreatic disease | 4 (22.2) | 0 | 0 | 0.002 |
Von Willebrand disease | 1 (5.6) | 0 | 0 | |
Glanzmann’s thrombasthenia | 1 (5.6) | 0 | 0 | |
Total |
18 | 39 | 25 |
Values are presented as number (%).
Total number including cases with unspecified etiology.