Keywords
colonoscopy - polypectomy - anticoagulation - periprocedural management
Introduction
Colonoscopy with polypectomy is an integral part of colorectal cancer (CRC) screening
both as a primary screening test and to follow-up an abnormal noninvasive screening
test, such as the fecal immunochemical test (FIT).[1] Bleeding is the most common complication after colonoscopy occurring in 0.3% of
patients.[2]
[3] Individuals on anticoagulants are at increased risk of bleeding and additional risk
factors including bridging anticoagulation with low molecular weight heparin (LMWH),
hot snare polypectomy, and large polyp removed further exacerbate this risk.[4] Periprocedural anticoagulation management is controversial due to the limited data
on the bleeding risk associated with uninterrupted anticoagulation and on the thromboembolic
risk associated with anticoagulation interruption. This has led to several published
clinical practice guidelines that endorse different management strategies.[4]
[5]
[6]
[7]
Management of anticoagulation in patients undergoing colonoscopy and polypectomy will
become more prevalent as the use of anticoagulation therapy increases with the aging
population.[8] Direct oral anticoagulants (DOACs) have become the most prescribed class of oral
anticoagulants because it is a more effective, safe, and convenient therapeutic alternative
to vitamin K antagonists (VKA) in many clinical settings.[9] Although robust data on the bleeding risk of anticoagulated patients undergoing
colonoscopy and polypectomy is not available, pooled data from cohort studies estimated
that the risk of bleeding after elective endoscopic gastrointestinal procedures in
patients on a DOAC is 3.1% when the DOAC was interrupted and 3.6% when the DOAC was
continued without interruption.[4] Similarly, data from the Periprocedural Anticoagulation Use for Surgery Evaluation
(PAUSE) trial, a prospective cohort study with a standardized protocol for DOAC interruption,
reported a bleeding rate of 2.5% among the subgroup of patients undergoing endoscopic
gastrointestinal procedures.[10]
[11]
The recently published American College of Gastroenterology–Canadian Association of
Gastroenterology Clinical Practice Guideline recommended continuation of VKA and temporary
interruption of DOACs for patients undergoing colonoscopy and cold snare polypectomy
of small polyps.[4] Due to insufficient evidence, the committee was unable to reach a recommendation
on the timing of DOAC resumption; however, the accompanying dissemination tool indicated
that the DOAC could be restarted the day after the colonoscopy in most patients.[12] This was a change from previous guidelines that recommended temporary interruption
of VKAs for any polypectomy, with bridging anticoagulation for patients at high risk
of thromboembolism; however, these published recommendations are based on low quality
of evidence.[4]
[6]
[7]
[13] Organized CRC screening programs provide an opportunity to standardize and evaluate
anticoagulation management in patients undergoing colonoscopy.
Given the high prevalence of patients on anticoagulation therapy and the low quality
of evidence informing current guidelines, the British Columbia Colon Screening Program
(BCCSP) in collaboration with the St. Paul's Hospital (SPH) Thrombosis Clinic created
a multidisciplinary patient care pathway to standardize periprocedural anticoagulation
management. A pilot project with a small group of selected patients was well-received
by health care providers and patients. This was subsequently adopted as the standard
of care in March 2022 for all anticoagulated patients referred for colonoscopy in
the Vancouver region of the BCCSP. This novel patient care pathway provided an opportunity
to conduct a real-world study to determine the incidence of adverse events after colonoscopy
with polypectomy in the setting of highly standardized periprocedural anticoagulation
management.
Objective
The primary objective of this study is to determine the incidence of bleeding and
thromboembolic complications among colon screening participants undergoing colonoscopy
following a novel patient care pathway for standardized periprocedural anticoagulation
management.
Methods
A retrospective cohort study was conducted using available medical records and relevant
imaging studies from the SPH Thrombosis Clinic and the BCCSP. Data were collected
anonymously and recorded in the REDCap database by study team members. The first draft
of the manuscript was written by the first, second, and last authors. All authors
approved the final version of the manuscript.
Participants
All BCCSP participants living in the Vancouver region referred for colonoscopy from
March 1, 2022 to August 31, 2022 who were prescribed an oral anticoagulant were included.
In the BCCSP, individuals 50 to 74 years of age undergo biennial FIT (OC-SENSOR, Eiken
Chemical Limited, Tokyo, Japan; cutoff 10 µg globin/gram feces) are referred for colonoscopy
to follow-up abnormal results. Precolonoscopy assessment is performed by a trained
nurse (patient coordinator). The use of oral anticoagulants, including VKAs (warfarin)
and DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban), prompts a referral to
the SPH Thrombosis Clinic. Prescription data were confirmed on PharmaNet, a centralized
platform recording all prescriptions dispensed in pharmacies in British Columbia.
Colonoscopies were performed by local gastroenterologists and general surgeons. At
the time of colonoscopy, the physician completes a standardized colonoscopy report
form, which documents cecal intubation, the quality of the bowel preparation, any
adverse events occurring during the colonoscopy, the polyp site and size, and method
and completeness of polypectomy for each polyp detected. Fourteen days following colonoscopy,
the patients are contacted by the patient coordinator and asked whether an unplanned
medical event had occurred. If an unplanned event occurred, details regarding the
event and any medical interventions are collected by the patient coordinator and submitted
to the BCCSP. This process has been described previously.[3]
Standardized Periprocedural Anticoagulation Patient Care Pathway
The periprocedural anticoagulation patient care pathway was implemented on March 1,
2022 and all patients on an oral anticoagulant were consecutively referred to the
SPH Thrombosis Clinic for evaluation and management before the colonoscopy ([Fig. 1]). Patients received comprehensive periprocedural anticoagulation assessment by a
thrombosis medicine physician. Instructions on when to stop and when to resume the
oral anticoagulant was provided to the patients before the colonoscopy. The timing
of anticoagulation interruption and the need for bridging with LMWH were guided by
clinical guideline recommendations,[14]
[15] but the final decisions were dependent on the thrombosis medicine physician's clinical
judgement. DOAC perioperative assessments were performed virtually to minimize the
time burden on the patients, but VKA perioperative assessments were conducted with
in-person appointment due to the complexity in communicating multistep instructions
and the need for international normalized ratio (INR) testing. Point of care INR testing
was performed during the in-person appointment to avoid additional patient visits
to the laboratory. During the same in-person appointment, the patients received an
education session on VKA management by the thrombosis nurse. The thrombosis nurse
managed the VKA dosing in the periprocedural period and then transferred the care
back to the primary care provider once the colonoscopy was completed and the INR was
stabilized. If the thrombosis medicine physician recommended bridging with LMWH, the
thrombosis nurse provided patient education on subcutaneous self-injection. The prescription
for LMWH was provided by the thrombosis medicine physician. During the 14-day telephone
follow-up, the BCCSP patient coordinator confirmed the resumption of oral anticoagulant.
Fig. 1 Interdisciplinary management pathway. PharmaNet is a province-wide database of all
prescription medication dispensed by a licensed pharmacy in British Columbia. BCCSP,
British Columbia Colon Screening Program; DOAC, direct oral anticoagulant; INR, international
normalized ratio; VKA, vitamin K antagonist.
Outcomes
The primary outcomes of interest were bleeding events and thromboembolic events from
the time of oral anticoagulant interruption until 14 days after the colonoscopy. The
outcome was ascertained by the BCCSP patient coordinator and documented using standardized
forms. All unplanned medical events were reviewed and adjudicated by two thrombosis
medicine physicians on the study team. Bleeding events were defined by the International
Society on Thrombosis and Hemostasis (ISTH) definition of major bleeding (fatal bleeding,
symptomatic bleeding in a critical area or organ, bleeding resulting in a decrease
in hemoglobin of ≥ 20 g/L, or leading to transfusion of ≥ 2 units of blood).[16]
Thromboembolic events included arterial thromboembolic events (ischemic stroke, transient
ischemic attack, and systemic arterial embolism) and venous thromboembolism. The secondary
clinical outcomes were clinically relevant nonmajor bleeding (ISTH definition), minor
bleeding (ISTH definition), acute coronary syndrome, emergency room visit, hospital
admission, and death due to any cause.
Statistical Analysis
Demographic characteristics of patients and colonoscopy findings were summarized with
descriptive statistics. The incidence rates for all major bleeding and thromboembolism
were reported in subgroups of patients on different oral anticoagulants.
Results
Over the 6-month study period (March 1, 2022 to August 31, 2022), 190 BCCSP patients
referred for colonoscopy were prescribed an oral anticoagulant. Twenty patients were
excluded, and eight patients were lost to follow-up ([Fig. 2]). The patients had a mean (standard deviation [SD]) age of 67 (6.3) years and 73.3%
were male. Of the included patients, 79 (46.5%) were on rivaroxaban, 61 (35.9%) were
on apixaban, 10 (5.9%) were on dabigatran, 1 (0.6%) were on edoxaban, and 19 (11.2%)
were on warfarin. A total of 7.6% of the patients had concomitant use of antiplatelet
therapy. The indications for anticoagulation include atrial fibrillation in 135 patients,
venous thromboembolism in 31 patients, and mechanical heart valve in 5 patients ([Table 1]). Some patients had more than one indication for anticoagulation. The atrial fibrillation
patients had a mean (SD) CHADS65 score of 2.2 (1.1).
Fig. 2 Participant flow diagram. BCCSP, British Columbia Colon Screening Program.
Table 1
Baseline patient characteristics
|
Variable
|
n = 170
|
|
Age, mean (SD) in years
|
66.9
|
(6.3)
|
|
Male (%)
|
124
|
(72.9)
|
|
Weight, mean (SD), kg
|
88.9
|
(22.6)
|
|
Comorbidities, n (%)
|
|
|
|
Heart failure
|
18
|
(10.6)
|
|
Hypertension
|
98
|
(57.6)
|
|
Diabetes
|
41
|
(24.1)
|
|
Cerebral arterial disease
|
29
|
(17.1)
|
|
Bioprosthetic heart valve
|
5
|
(2.9)
|
|
Severe mitral stenosis
|
4
|
(2.4)
|
|
Coronary artery disease
|
32
|
(18.8)
|
|
Chronic kidney disease
|
33
|
(19.4)
|
|
Mild (CrCl 50–70 mL/min)
|
23
|
|
|
Moderate (CrCl 30–49 mL/min)
|
10
|
|
|
Severe (CrCl < 30 mL/min)
|
0
|
|
|
Inherited thrombophilia
|
5
|
(2.9)
|
|
Antiphospholipid syndrome
|
1
|
(0.6)
|
|
Active cancer
|
3
|
(1.8)
|
|
Gastrointestinal bleed history
|
11
|
(6.5)
|
|
Lab value, mean (SD)
|
|
|
|
Hemoglobin
|
140.8
|
(18.4)
|
|
Platelet
|
233.7
|
(69.2)
|
|
Creatinine
|
88.7
|
(21.7)
|
|
Indication for anticoagulation, n
|
|
|
|
Atrial fibrillation
|
135
|
|
|
Mean CHADS65 score
|
2.2
|
|
|
Venous thromboembolism
|
31
|
|
|
Mechanical mitral valve
|
2
|
|
|
Mechanical aortic valve
|
3
|
|
|
Anticoagulant use, n (%)
|
|
|
|
Rivaroxaban
|
79
|
(46.5)
|
|
Apixaban
|
61
|
(35.9)
|
|
Dabigatran
|
10
|
(5.9)
|
|
Edoxaban
|
1
|
(0.6)
|
|
Warfarin
|
19
|
(11.2)
|
|
Concurrent antiplatelet use, n (%)
|
|
|
|
Aspirin
|
11
|
(6.5)
|
|
P2Y12 inhibitor
|
2
|
(1.2)
|
|
Other medication use, n (%)
|
|
|
|
Selective serotonin reuptake inhibitor
|
9
|
(5.3)
|
|
CYP 3A4 inhibitor
|
13
|
(7.6)
|
|
CYP 3A4 inducer
|
1
|
(0.6)
|
Abbreviations: CrCl, creatinine clearance; SD, standard deviation.
Periprocedural Anticoagulation Management
DOAC interruption intervals are reported in [Table 2]. A total of 63.2% of patients on VKA required bridging with LMWH. In the preprocedural
period, 91.7% of bridging used therapeutic dose LMWH. In the postprocedural period,
75.0% of bridging used therapeutic dose LMWH ([Table 3]).
Table 2
Perioperative direct oral anticoagulant management
|
Preprocedural DOAC management, n (%)
|
|
Last dose day −3
|
146
|
(96.7)
|
|
Last dose day −2
|
5
|
(3.3)
|
|
Postprocedural DOAC management, n (%)
|
|
Resumed day +1
|
70
|
(46.4)
|
|
Resumed day +2
|
80
|
(53.0)
|
|
Resumed day > 2
|
1
|
(0.7)
|
Abbreviation: DOAC, direct oral anticoagulant.
Table 3
Perioperative vitamin K antagonist management
|
Bridging vs. no bridging
|
n = 19
|
|
Uninterrupted VKA
|
1
|
|
Interrupted VKA with no bridging
|
6
|
|
Interrupted VKA with bridging
|
12
|
|
Preprocedural bridging
|
|
|
Preop bridge with therapeutic low molecular weight heparin
|
11
|
|
Preop bridge with nontherapeutic low molecular weight heparin
|
0
|
|
No preop bridging
|
1
|
|
Postprocedural bridging
|
|
|
Postop bridge with therapeutic low molecular weight heparin
|
9
|
|
Postop bridge with nontherapeutic low molecular weight heparin
|
3
|
Abbreviations: Postop, postoperative; preop, preoperative; VKA, vitamin K antagonist.
Colonoscopy and Polypectomy Characteristics
A total of 170 colonoscopies were performed. Two colonoscopy reports were missing.
In the remaining 168 colonoscopy reports, a few reports had missing information on
the location, size, mode of removal, and morphology of the polyps. The bowel preparation
was adequate in 158 (94%). A total of 133 (79%) patients underwent at least one polypectomy
with a mean number of polypectomies per colonoscopy of 2.6. A total of 338 polyps
were removed and the polyp characteristics are shown in [Table 4].
Table 4
Polyp characteristics
|
Polyp characteristics
|
Number (%)
|
|
Location
|
|
Ileum
|
1
|
(0.3)
|
|
Cecum
|
30
|
(8.9)
|
|
Ascending colon
|
80
|
(23.7)
|
|
Transverse colon
|
76
|
(22.5)
|
|
Descending colon
|
42
|
(12.4)
|
|
Sigmoid colon
|
73
|
(21.6)
|
|
Rectum
|
36
|
(10.7)
|
|
Size
|
|
≤5 mm
|
196
|
(58.0)
|
|
6–9 mm
|
110
|
(32.5)
|
|
10–19 mm
|
28
|
(8.3)
|
|
≥20 mm
|
2
|
(0.6)
|
|
Unknown
|
2
|
(0.6)
|
|
Morphology
|
|
Sessile
|
275
|
(81.4)
|
|
Pedunculated
|
31
|
(9.2)
|
|
Flat
|
15
|
(4.4)
|
|
Other
|
9
|
(2.7)
|
|
Unknown
|
8
|
(2.4)
|
|
Mode of removal
|
|
Cold snare
|
274
|
(81.1)
|
|
Hot snare
|
34
|
(10.1)
|
|
Biopsy forceps
|
28
|
(8.3)
|
|
Unknown
|
2
|
(0.6)
|
Study Outcomes
With regard to the primary outcomes, one (0.6%) patient had a major bleeding event
occurring 6 days after colonoscopy and one (0.6%) patient had an arterial thromboembolic
event postcolonoscopy.
In terms of secondary outcomes, there were no reported clinically relevant nonmajor
bleeding or minor bleeding. One patient had acute coronary syndrome 8 days after colonoscopy.
Five patients had an unplanned event requiring emergency department treatment. Among
these emergency department visits, two resulted in hospital admissions. There were
no reported deaths.
Discussion
The rates of major bleeding, arterial thromboembolism, and venous thromboembolism
after colonoscopy with polypectomy were low (0.6, 0.6, and 0%, respectively) in our
real-world cohort of patients who were on an oral anticoagulant and received periprocedural
anticoagulation management in a standardized patient care pathway by a multidisciplinary
team. The pathway offered patients with high-value, comprehensive care by multiple
expert providers in fewer in-person medical visits.
The major bleeding rate in the present study was similar to the 0.9% major bleeding
rate reported from the PAUSE trial data.[11] Other cohorts where postprocedure bleeding ranged from 2.5 to 3.6%.[4] Over 90% of the patients in our cohort had small polyps (less than 10 mm in diameter),
and over 80% underwent cold snare polypectomy. Two previously published randomized
trials support the use of cold snare polypectomy in anticoagulated patients. Takeuchi
et al compared uninterrupted oral anticoagulants and cold snare polypectomy to interrupted
oral anticoagulants and hot snare polypectomy in patients undergoing colonoscopy and
removal of polyps up to 10 mm in diameter.[17] The cold snare polypectomy strategy was noninferior with 4.7% (95% confidence interval
[CI]: 0.2–9.2%) of patients sustaining postpolypectomy bleeding, whereas 12% (95%
CI: 5.0–19.1%) of patients who underwent hot snare polypectomy experienced bleeding.
Second, Horiuchi et al randomized patients on continuous VKA to cold or hot snare
polypectomy of small polyps. The cold snare polypectomy arm had a significantly lower
rate of immediate and delayed bleeding.[18]
In the current study, of the 338 polyps resected, only one patient had a major bleeding
event, following removal of a large lesion. This patient had held rivaroxaban 2 days
prior to colonoscopy and resumed 2 days following the procedure. A 3-cm lateral spreading
tumor of the ascending colon was removed in multiple pieces by endoscopic mucosal
resection using a combination of hot and cold snare polypectomy. Intraprocedural bleeding
was treated with cauterization with satisfactory hemostasis. No clipping was used.
The patient was managed conservatively with blood transfusion in the emergency department
and interrupted rivaroxaban therapy for an additional 7 days. The patient did not
require hospital admission or repeat endoscopic procedure. This case illustrated that
endoscopic mucosal resection of large polyps may be associated with postpolypectomy
bleeding and delayed resumption of DOACs should be considered. In the PAUSE trial
protocol, patients undergoing high risk bleeding procedures resumed the DOAC 48 to
72 hours after the procedure. This is consistent with findings from other studies.[11]
[19] The patients with a low thromboembolic risk, including patients with atrial fibrillation
with a CHADS65 score < 4 and patients with venous thromboembolism treated for more
than 3-6 months, will particularly benefit from delayed resumption of oral anticoagulant
after resection of large lesions.
The thromboembolic event rate of 0.6% observed in the current study was similar to
the arterial thromboembolic event rate of 0.7% among patients in the PAUSE trial undergoing
endoscopic gastrointestinal procedures.[11] For this patient in our study, the indication for anticoagulation was atrial fibrillation
with a CHADS65 score of 1. In addition, the patient had a history of type 1 aortic
dissection 8 months prior to the colonoscopy, which was managed with ascending aorta
and aortic arch replacement and bioprosthetic aortic valve replacement. Rivaroxaban
was held 2 days prior to colonoscopy and resumed 2 days following colonoscopy. Two
polyps were removed: a 6-mm pedunculated polyp in the descending colon was resected
with hot snare polypectomy and a prophylactic hemoclip was placed on the base and
in the transverse colon, a 3-mm polyp was resected with cold snare polypectomy. Three
days following colonoscopy, the patient was diagnosed with a transient ischemic attack
in the emergency department and ultimately did not require hospital admission. This
event may have been potentially preventable if the DOAC was not interrupted. However,
it is clinically challenging to identify patients who will most likely benefit from
polypectomy with uninterrupted anticoagulation until we have more data and experience
with this strategy, particularly with patients on a DOAC. Importantly, the patient's
preference is another important factor in deciding on the strategy.
Nevertheless, we demonstrated that a standardized patient care pathway with collaboration
between different specialists involved in the patient's CRC screening journey can
minimize adverse events related to anticoagulant use in the real world. As there is
variability in guideline recommendations and clinical adherence to institutional guidelines
regarding periprocedural anticoagulation management during colonoscopy,[20] our standardized, multidisciplinary pathway with appropriate follow-up allows consistency
in evaluating safety outcomes and determining the most optimal anticoagulation management
for each individual patient. A standardized pathway is especially important given
that the BCCSP covers many different sites across a large geographic area, and therefore,
inconsistency in local adherence and policies can be a large issue. Clear communication
between the different health care providers and the patients is essential as the timing
of anticoagulation resumption depends on the findings on the colonoscopy. Another
strength to this standardized pathway is the early identification of postprocedure
thrombotic and bleeding complications, which allows appropriate specialists (gastroenterologists,
thrombosis specialists, etc.) to see the patient in a timely manner as the team is
already involved in the patient's care prior to the procedure. Our findings suggested
that most patients with atrial fibrillation and venous thromboembolism can safely
interrupt oral anticoagulant for polypectomy because the rate of arterial and venous
thromboembolism is low. However, a small group of patients with a very high thromboembolic
risk, such as those with mechanical heart valves or acute venous thromboembolism within
the prior 3 months, may benefit from polypectomy with uninterrupted oral anticoagulant.
It is reassuring that a recent randomized control trial demonstrated that the rate
of major bleeding after cold snare polypectomy with uninterrupted VKA is low.[21] To our knowledge, there are limited data on the bleeding risk after polypectomy
with uninterrupted DOAC.
Further studies will evaluate this standardized, multidisciplinary pathway over a
longer time period, with a larger cohort through expanding this pathway to more health
authorities and institutions. These future analyses will allow for cost–benefit analyses;
we hypothesize that this standardized pathway among multiple disciplines (e.g., colon
screening program nurses, thrombosis physicians, gastroenterologists) will reduce
the number of delayed and canceled procedures and address postprocedure complications
adequately, overall reducing system costs due to loss to follow-up, and lack of standardized
anticoagulation management.
This study has important limitations. First, this was a retrospective study, so some
relevant clinical information may be missing. Second, the sample size of 162 was modest,
with patients on VKAs underrepresented. We decided on the 6-month study period to
identify potential areas for improvement in the standardized patient care pathway
early and implement adjustments as needed sooner than later. Third, the event rates
were low preventing further investigation of putative variables associated with bleeding
or thromboembolism. Fourth, the follow-up period of 14-day postcolonoscopy may miss
a minority of delayed postpolypectomy bleeding or thromboembolic events.[22] The PAUSE trial followed participants for 30 days and the thromboembolic events
occurred at a mean of 24 days.[10] Since this is a retrospective study, the data depend on the existing documentation
and the 14-day follow-up has been the local practice of the BCCSP for years.
The strength of this study is the real-world environment enabling the results to be
generalized to other screening programs. Our standardized periprocedural patient care
pathway ensured consistency in anticoagulation management, and it minimized the number
of patients who were lost to follow-up.
Conclusion
This study showed that a standardized patient care pathway for periprocedural anticoagulation
management with multidisciplinary collaboration was associated with low rates of major
bleeding and thromboembolism after colonoscopy with polypectomy. Future studies assessing
a strategy of uninterrupted VKA or DOAC with cold snare polypectomy are needed.
