CLINICAL RESEARCH STUDY

Anticoagulation-Associated Adverse Drug Events

in Hospitalized Patients Across Two Time Periods
John Fanikos, BS, MBA, Yahya Tawfik, PharmD, Danya Almheiri, PharmD, Katelyn Sylvester, PharmD,
Leo F. Buckley, PharmD, Chris Dew, BA, Heather Dell’Orfano, PharmD, Andre Armero, BS, Antoine Bejjani, MD,
Behnood Bikdeli, MD, MS, Umberto Campia, MD, Julia Davies, BA, Karen Fiumara, PharmD, Heather Hogan, BSN,
Candrika Dini Khairani, MD, Darsiya Krishnathasan, BS, Junyang Lou, MD, PhD, Alaa Makawi, PharmD,
Ruth H. Morrison, RN, Nicole Porio, BA, Anthony Tristani, BS, Jean M. Connors, MD, Samuel Z. Goldhaber, MD,
Gregory Piazza, MD, MS
Thrombosis Research Group, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

ABSTRACT

PURPOSE: Anticoagulants often cause adverse drug events (ADEs), comprised of medication errors and
adverse drug reactions, in patients. Our study objective was to determine the clinical characteristics, types,
severity, cause, and outcomes of anticoagulation-associated ADEs from 2015-2020 (a contemporary
period following implementation of an electronic health record, infusion device technology, and anticoag-
ulant dosing nomograms) and to compare them with those of a historical period (2004-2009).
METHODS: We reviewed all anticoagulant-associated ADEs reported as part of our hospital-wide safety
system. Reviewers classified type, severity, root cause, and outcomes for each ADE according to standard
definitions. Reviewers also assessed events for patient harm. Patients were followed up to 30 days after
the event.
RESULTS: Despite implementation of enhanced patient safety technology and procedure, ADEs increased
in the contemporary period. In the contemporary period, we found 925 patients who had 984 anticoagula-
tion-associated ADEs, including 811 isolated medication errors (82.4%); 13 isolated adverse drug
reactions (1.4%); and 160 combined medication errors, adverse drug reactions, or both (16.2%). Unfractio-
nated heparin was the most frequent ADE-related anticoagulant (77.7%, contemporary period vs 58.3%,
historical period). The most frequent anticoagulation-associated medication error in the contemporary
period was wrong rate or frequency of administration (26.1%, n = 253), with the most frequent root cause
being prescribing errors (21.3%, n = 207). The type, root cause, and harm from ADEs were similar
between periods.
CONCLUSIONS: We found that anticoagulation-associated ADEs occurred despite advances in patient
safety technologies and practices. Events were common, suggesting marginal improvements in anticoagu-
lant safety over time and ample opportunities for improvement.
Ó 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
The American Journal of Medicine (2023)
136:927−936

KEYWORDS: Adverse drug events; Adverse drug reactions; Anticoagulants; Direct oral anticoagulants; Medication
errors; Unfractionated heparin; Warfarin

Funding: None. INTRODUCTION

Conflict of Interest: None.
Authorship: All authors had access to the data and a role in writing
this manuscript.
Requests for reprints should be addressed to John Fanikos, BS, MBA,
Pharmacy Department, Brigham and Women’s Hospital, 75 Francis Street,
Boston, MA 02115.
E-mail address: jfanikos@partners.org
Anticoagulants often cause adverse drug events (ADEs),
comprised of medication errors and adverse drug reactions,
in hospitalized patients, long-term care residents, and
elderly outpatients (Figure 1). These complications arise
from the complexity of anticoagulant dosing, inadequate
laboratory monitoring, inconsistencies in patient adherence,

0002-9343/© 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/)
https://doi.org/10.1016/j.amjmed.2023.05.013
928 The American Journal of Medicine, Vol 136, No 9, September 2023

and underlying patient comorbidities.1−3 Complications of a 5-year period (2015-2020; “contemporary period”) at
anticoagulant therapy generate a disproportionate number Brigham and Women’s Hospital, an 826-bed academic
of emergency department visits, hospitalizations, and pre- medical center. We reviewed all anticoagulant-associated
ventable injuries.4−6 In the United States, hospitalization ADEs reported at Brigham and Women’s Hospital as part
costs associated with anticoagulant-associated ADEs have of our hospital-wide safety reporting system. We compared
been estimated at more than $2.5 billion.1,7 the ADEs during this period with a historical comparator
Since 2008, decreasing patient harm related to anticoag- (2004-2009).1
ulant use has been a Joint Commission National Patient Our clinicians voluntarily report ADEs through a soft-
Safety Goal (NPSG.03.05.01) and a ware application RL6 systemÓ
component of their current survey (RL Solutions, Columbia, South
process.8 Anticoagulant safety is a CLINICAL SIGNIFICANCE Carolina). RL6 is a desktop appli-
major focus of the National Action
Anticoagulation-associated adverse cation that captures safety incident
Plan for Adverse Drug Event Preven- details including date, time,
drug events occurred despite advances
tion, released in 2014 by the Office patient identifiers, location, medi-
of Disease Prevention and Health in the hospital’s patient safety efforts, cation, event type, severity, and a
Promotion of the US Department of such as the implementation of a brief event description. Our medi-
Health and Human Services. In 9 sophisticated electronic health record, cation safety officer reviews every
addition, anticoagulation safety was installation of new infusion device report daily, captures further
a key component of the Centers for technology (“smart” pumps with drug details and outcomes of the events,
Medicare and Medicaid Services’ libraries), and adoption of anticoagu- and inputs the final information
Quality Innovation Network and lant dosing nomograms. into the report to close the inci-
Hospital Improvement Innovation
Unfractionated heparin was the most dent.
Network within efforts to improve common anticoagulant associated with We collected patient demo-
medication safety.10 Local solutions adverse drug events. graphics from the electronic health
and systematic efforts on improving
While record (DA, CD, HD, JF, AM, YT)
anticoagulation-associated
quality of anticoagulant administra- and adjudicated the event type, root
adverse drug events were commonly
tion have been limited.11−13 causes, and outcomes (HD, JF, KF),
In 2011, we reported that most reported, patient harm was infrequent. according to standardized defini-
anticoagulant-associated ADEs were tions as previously reported.1,17
1
potentially preventable medication errors. Since that his- Instances of anticoagulant-related ADEs and their causes were
torical period, our institution has implemented several analyzed by our team of physicians (AB, BB, UC, SG, CK,
patient safety-first practices. The hospital system imple- GP, JL), pharmacists (DA, LB, HD, JF, AM, YT), and a hos-
mented a new, more sophisticated electronic health record pital patient safety officer (KF). For all ADEs, we determined
(Epic, Verona, WI) with enhanced provider order entry fea- the ADEs’ type of error (see Supplemental Appendix A, avail-
tures and prescribing safeguards and placed new infusion able online), root cause (see Supplemental Appendix B, avail-
device technology (“smart” pumps with drug libraries) into able online), and outcomes.18−20 We also included additional
service, in 2015 and 2019, respectively. All physicians, types of errors (documentation error, medication discontinued
nurses, and pharmacists underwent “Just Culture” training without an order, and system error) and root causes (prescrib-
to implement a system of shared accountability for health ing error and system error) when categorizing ADEs. In cases
care delivery and provider behavior.14,15 Two new unfrac- where disagreement existed, resolution was decided by the
tionated heparin dosing nomograms were developed, senior pharmacist (JF).
approved, and implemented. Finally, we launched a hemo- ADEs were categorized into either the medication error
static and antithrombotic stewardship program to provide and adverse drug reaction categories, or both. All ADEs
real-time clinical surveillance and management of hemo- that resulted from medication errors were considered poten-
static and antithrombotic agents to optimize appropriate tially preventable. An adverse drug reaction was defined as
use, decrease serious adverse events, and minimize costs.16 a patient’s bodily response to a drug normally used for pro-
Whether these safety infrastructure improvements were phylaxis or therapy of disease and that was potentially nox-
associated with a change in the number, type, and down- ious and unintended. A subset of adverse drug reactions
stream consequences of anticoagulant-related ADEs has may lead to patient harm. A medication error was defined
been unclear. The objective of this study was to determine as an event that caused or led to inappropriate medication
the clinical characteristics, types, severity, root cause, and use or patient harm. A medication error that was discovered
outcomes of anticoagulant-associated ADEs. and corrected before reaching the patient was classified as a
near hit.
We evaluated bleeding complications by applying the
METHODS GUSTO (Global Use of Streptokinase and t-PA for
We performed a retrospective review of anticoagulation- Occluded Coronary Arteries) bleeding criteria, and we fol-
associated ADEs that originated during hospitalization over lowed patients for 30 days after an event.21 We included all
Fanikos et al Anticoagulation-Associated Adverse Drug Events in Hospitalized Patients
Figure 1 Anticoagulation-associated adverse drug
events: medication process and outcomes.
anticoagulants intended for the prevention and treatment of
thrombosis, including parenteral (unfractionated heparin,
low-molecular-weight heparin, fondaparinux, argatroban,
and bivalirudin) and oral (apixaban, dabigatran, edoxaban,
rivaroxaban, and warfarin) agents.
The proportions of categorical variables were compared
between the historical and contemporary periods using the
x2 test. Continuous variables were compared between the 2
periods using the Student t-test for normally distributed
data and the Mann-Whitney U test for non-normally distrib-
uted data. The statistical significance threshold was set at
P < .05. For other comparisons, we did not adjust for multi-
plicity of the tests and potential error rate inflation and
therefore, other analyses should be considered exploratory.
Statistical comparisons were performed using Stata
929
(StataCorp. 2021. Stata Statistical Software: Release 17.
College Station, TX: StataCorp LLC.).
RESULTS
ADE Characteristics
The total number of hospital admissions was 250,725 in the
historical period and 287,136 in the contemporary period.
In the contemporary period, we found 925 voluntary reports
of patients who had an anticoagulation-associated ADE
(Table 1). Patients had a median age of 64 years, 53.6%
were male, and the median body mass index was 27 kg/m2.
More patients had a history of hypertension, atrial fibrilla-
tion, renal disease, venous thromboembolism, stroke, other
thromboembolism, heart failure, diabetes, and cancer dur-
ing the contemporary period compared with the historical
period. Fewer patients in the contemporary period had a
prior surgical procedure.
In the contemporary period, we found 984 ADEs, com-
prised of 811 isolated medication errors (82.4%), 13 iso-
lated adverse drug reactions (1.3%), and 160 combined
medication errors and adverse drug reactions (16.2%)
(Table 2, Figure 2). We found that 98.6% (n = 971) of
ADEs, defined as comprising both medication errors and
adverse drug reactions, were potentially preventable. There
was a higher reported ADE rate per admission (0.34 ADE
per 100 contemporary patient admissions vs 0.18 ADE per
100 historical patient admissions, respectively). There was
also a higher number of ADEs during the contemporary
period compared with the historical period (984 ADEs vs
463 ADEs, respectively).
Unfractionated heparin was the most frequent anticoagu-
lant associated with an ADE, accounting for 769 (77.7%) of
all ADEs in the contemporary period and 270 (58.3%) dur-
ing the historical period. There was a lower number of
ADEs attributed to warfarin in the contemporary period
compared with the historical period (6.6%, n = 66 vs
20.7%, n = 96, respectively). Low-molecular-weight hepa-
rin was associated with 5.5% (n = 55) of ADEs in the con-
temporary period and 9.5% (n = 44) in the historical period.
We found a small number of direct oral anticoagulants
(DOACs) associated with ADEs in the contemporary
period; apixaban (2.7%, n = 27), rivaroxaban (1.9%,
n = 19), and dabigatran (0.9%, n = 9). These agents were
not available or not in routine use during the historical
period.
ADE Types
In the contemporary period, the most frequent types of anti-
coagulation-associated medication errors were wrong rate
or frequency of administration (26.1%, n = 253) and missed
dose or late dose (20%, n = 195), which was similar to the
historical period (Table 3, see Appendix A, available
online, for definitions). Wrong dose (13.1%, n = 127 vs
7.1%, n = 23), inadequate monitoring (7.5%, n = 73 vs
0.3%, n = 1), and administration without an order (2.5%,
930 The American Journal of Medicine, Vol 136, No 9, September 2023

Table 1 Comparison of Baseline Characteristics and Medical Conditions in Patients with Anticoagulation-Associated Adverse Drug
Events Between 2004-2009 and 2015-2020 Studies
Baseline Characteristic 2004-2009 Study 2015-2020 Study P Value
(N = 463 patients) (N = 925 patients)
Number of hospital admissions 250,725 287,136 -
Median age on admission, years (interquartile range) 62 (49-72) 64 (52-72) .05
Age >75 years, n (%) 92 (19.9) 180 (19.4) .82
Male, n (%) 246 (53.1) 496 (53.6) .86
Median body mass index, kg/m2 (interquartile range) 27.4 (23.8-33.1) 27 (23.2 - 32.3) -
Median length of stay, d (interquartile range) 13 (7-32) 10 (5 − 22) -
Medical condition, n (%)
Hypertension 243 (52.5) 612 (66.1) <.0001
Surgery in past 2 months 213 (46) 167 (18) <.0001
Status post valve replacement 68 (14.7) 108 (11.6) .10
Coronary artery disease − ischemic heart disease NA 295 (31.9) -
Atrial fibrillation 126 (27.2) 313 (33.8) .01
Serum creatinine >1.5 mg/dL 125 (27) 266 (28.7) .51
End-stage kidney disease on renal replacement 30 (6.5) 98 (10.5) .01
therapy
Venous thromboembolism* 121 (26.1) 382(41.3) <.0001
History of stroke 45 (9.7) 144 (15.5) .003
History of MI NA 193 (20.8) -
Other thromboembolism 40 (8.6) 195 (21.0) <.0001
Heart failure 106 (22.9) 310 (33.5) <.0001
Diabetes 104 (22.5) 292 (31.5) .005
Active cancer without metastases 34 (7.3) 198 (21.4) <.0001
Active cancer with metastases 42 (9.1) 182 (19.6) <.0001
History of cancer 34 (7.3) 380 (41) <.0001
Pulmonary diseasey 66 (14.3) 132 (14.2) .96
Thrombophilia 16 (3.5) 39 (4.2) .53
MI = myocardial infarction; NA = not applicable, not available.
*Includes history or active venous thromboembolism (deep vein thrombosis or pulmonary embolism)
yIncludes chronic obstructive pulmonary disease, interstitial lung disease, cystic fibrosis, restrictive lung disease, pulmonary fibrosis

n = 25 vs 0.6%, n = 2) occurred more often in the contem-
porary period compared with the historical period. Incorrect
anticoagulation administration timing (2.9%, n = 29 vs
5.3%, n = 17), anticoagulant not discontinued (2.3%,
n = 23 vs 9.6%, n = 31), wrong patient (0.8%, n = 8. vs
2.2%, n = 7), expired medication (0.4%, n = 4 vs. 2.5%,
n = 8), and wrong route of administration (0.4%, n = 4 vs
3.1%, n = 10) occurred less frequently in the contemporary
period than in the historical period.
ADE Root Causes
The most common root causes of anticoagulation-associ-
ated medication errors reported in our contemporary period
were prescribing errors (21.3%, n = 207), rule violation
(18.1%, n = 176), and memory lapse (14.8%, n = 144)
(Table 3, see Appendix B, available online, for definitions).
When we compared the 2 periods, we found that rule viola-
tion, faulty dose checking, and faulty interaction or commu-
nication between services as root causes of medication
errors were more frequent in the contemporary period
(18.1% [n = 176] vs 5.9% [n = 19], 13.9% [n = 135] vs
0.3% [n = 1], and 7.7% [n = 75] vs 2.2% [n = 7], respec-
tively) compared with our historical period. However,
transcription errors, the leading cause of medication errors
in the historical period, decreased from 48% (n=155) to
4.7% (n=46) in the contemporary period.
In the contemporary period, we completed a secondary
contributing type of unfractionated heparin-associated med-
ication error and root cause for each patient that was not
reported in the original study (Figure 3). We found that the
most frequent types of anticoagulant-associated adverse
events resulted from incorrect use of the unfractionated
heparin nomograms (inappropriate patient selection, incor-
rect weight, failure to respond to coagulation study results,
and failure to deliver correct bolus or infusion dose).
ADE-Associated Outcomes
We reviewed the adverse drug reactions and found that
52.7% (n = 91) of anticoagulant adverse drug reactions
were associated with abnormal coagulation studies
(Table 4). Of these, 29.4% (n = 51) were associated with
excessive intensity of anticoagulation demonstrated by a
supratherapeutic activated partial thromboplastin time,
anti-Xa assay, or international normalized ratio and
occurred less frequently than our historical study. Any
bleeding event occurred in 14.4% (n = 25) of adverse drug
Fanikos et al Anticoagulation-Associated Adverse Drug Events in Hospitalized Patients 931

Table 2 Comparison of Characteristics of Adverse Drug Events in Patients Receiving Anticoagulation Between 2004-2009 and 2015-2020
Studies
Characteristics of Adverse Drug Event, n (%) 2004-2009 Study (n = 463 Events) 2015-2020 Study (n = 984 Events) P Value
Near miss 33 (7.1) 116 (11.7) .007
Potentially preventable ADE 322 (69.5) 971 (98.6) <.0001
Number of hospital admissions 250,725 287,136 -
Crude event rate (ADE per 100 patient-admissions) 0.18 0.34 -
Total ADEs 5,585 10,047
% of anticoagulant contributing events 8.3 9.8
Anticoagulant perpetrator, n (%)
Unfractionated heparin 270 (58.3) 769 (77.7) <.0001
Warfarin 96 (20.7) 66 (6.6) <.0001
Low-molecular-weight heparin (enoxaparin) 44 (9.5) 55 (5.5) .005
Bivalirudin 18 (3.9) 31 (3.1) .43
Apixaban NA 27 (2.7) -
Rivaroxaban NA 19 (1.9) -
Dabigatran NA 9 (0.9) -
Fondaparinux 3 (0.67) 4 (0.4) .49
Edoxaban NA 2 (0.2) -
Argatroban 29 (6.3) 2 (0.2) <.0001
Lepirudin 3 (0.7) NA -
ADEs = adverse drug events; = not applicable, not available.

reactions, and thromboembolic events were infrequent,
occurring in 3.4% (n = 6), in the contemporary period. We
further reviewed the 25 bleeding events. We found that 14
were related to medication errors. Eleven events were
linked to wrong application of an unfractionated heparin
nomogram, 2 events employed incorrect patient weights,
and in 1 event, the infusion device was programmed incor-
rectly. The remaining 11 events were unanticipated bleed-
ing without errors in care delivery. Of the 6 thrombotic
events documented, none were a consequence of medica-
tion errors.
When we compared our contemporary period with the
historical period, there was a lower frequency of abnormal
coagulation studies (52.7%, n = 91 vs 72.3%, n = 172),
excessive anticoagulation (29.4%, n = 51 vs 71.9%,
n = 171), any bleeding event (14.4%, n = 25 vs 24.8%,
n = 59), and thrombocytopenia (0.5%, n = 1 vs 18.1%,
n = 43). We found medication error and undetected
predisposing condition were the most frequent root causes
associated with characteristics of anticoagulant-associated
adverse drug reactions for both the original and current
studies. When we compared the contemporary period with
the original study, we found that the contribution of medi-
cation error increased by 2-fold from the original study
(40% vs 85%, respectively), and undetected predisposing
conditions declined in the contemporary period compared
with the original study (14.4%, n = 25 vs 58%, n = 138,
respectively). In the management of bleeding, we found
fewer patients required blood transfusions for bleeding
management (9.3% vs 16.8%), and a less frequent use of
fresh frozen plasma (1.2% vs 4.6%) and vitamin K (1.2%
vs 4.2%) in the contemporary period compared with the his-
torical period.
Although we observed 82 (8.3%) in-hospital deaths in
our contemporary period compared with 26 (5.6%) deaths
in the original study, in only 1 patient in each study period
did an ADE contribute to this outcome (Table 5). In our
contemporary period cohort, 1 patient in whom anticoagu-
lation was unintentionally discontinued in the hospital suf-
fered an ischemic stroke and expired.

DISCUSSION
In this study of anticoagulant-associated ADEs in hospital-
ized patients, we found unfractionated heparin to be the
most frequently implicated drug. The most common type of
anticoagulant medication errors included wrong rate, wrong
frequency, wrong dose, or missed dose (accounting for half
of our reports). Prescribing errors emerged as a common
Figure 2 Types of anticoagulants-associated adverse root cause in 1 of 5 patients. Although the most common
events. adverse outcomes of an adverse drug reaction were abnor-
mal coagulation studies and excessive anticoagulation,
932 The American Journal of Medicine, Vol 136, No 9, September 2023

Table 3 Comparison of Types and Root Causes of Anticoagulant-Associated Medication Errors Between 2004-2009 and 2015-2020
Studies*
Type of Medication Error 1, n (%) 2004-2009 Study (n = 323) 2015-2020 Study (n = 971) P Value
Wrong rate or frequency 75 (23.2) 253 (26.1) .30
Missed dose, late dose 79 (24.5) 195 (20.0) .09
Wrong dose 23 (7.1) 127 (13.1) .004
Inadequate monitoring 1 (0.3) 73 (7.5) <.0001
Extra dose 26 (8.1) 62 (6.3) .26
Failure to act on laboratory result 17 (5.3) 41 (4.2) .41
Wrong drug 7 (2.2) 34 (3.5) .25
Wrong time of administration 17 (5.3) 29 (2.9) .04
Documentation error NA 29 (2.9) -
Medication administered without order 2 (0.6) 25 (2.5) .04
Medication not discontinued when ordered 31 (9.6) 23 (2.3) <.0001
Preparation error 6 (1.9) 22 (2.2) .75
Wrong technique of administration 3 (0.9) 21 (2.1) .16
Wrong patient 7 (2.2) 8 (0.8) .04
Medication discontinued without order NA 8 (0.8) -
Known allergy or contraindication 1 (0.3) 7 (0.7) .42
System error NA 6 (0.6) -
Medication expired 8 (2.5) 4 (0.4) .0006
Wrong route 10 (3.1) 4 (0.4) <.0001
Root cause of medication errors, n (%)
Prescribing error NA 207 (21.3) -
Rule violation 19 (5.9) 176 (18.1) <.0001
Memory lapse 52 (16.1) 144 (14.8) .57
Faulty dose checking 1 (0.3) 135 (13.9) <.0001
Faulty interaction between services 7 (2.2) 75 (7.7) .0004
Infusion or parenteral administration problem 28 (8.7) 68 (7.0) .31
Transcription error 155 (48) 46 (4.7) <.0001
Drug stocking or delivery problem 9 (2.8) 33 (3.4) .60
Lack of knowledge about drug 18 (5.6) 26 (2.6) .01
System error NA 21 (2.1) -
Drug preparation error 12 (3.7) 15 (1.5) .02
Lack of information about the patient 4 (1.2) 11 (1.1) .88
Faulty drug identity checking 17 (5.3) 10 (1) <.0001
Known allergy or contraindication 1 (0.3) 4 (0.4) .80
NA=Not applicable, not available.
*Includes medications errors alone (n = 811) and combined medications errors and adverse drug reactions (n = 160).

hemorrhagic and thrombotic events were infrequent, and
most patients suffered no harm. When comparing our study
periods, unfractionated heparin remained the primary cause
in both periods, ADEs with warfarin declined, and DOAC
events appeared in the contemporary period. We found
abnormal anticoagulant studies, excessive anticoagulation,
and any bleeding events were less common in the contem-
porary period compared with our historical period.
There are several differences in our hospital operations
when comparing the contemporary period to our historical
period. We recognize that in our contemporary period the
hospitalized patient population had a higher proportion of
hypertension, stroke, other thromboembolism, heart failure,
diabetes, and cancer. This increased complexity could have
contributed to a higher number of reported ADEs. We cap-
tured anticoagulant-associated ADEs during the implemen-
tation period of the new electronic health record. Some of
the reported ADEs were the result of learning a new
computer application. Our hemostatic and antithrombotic
stewardship program, an interdisciplinary program created
to monitor and manage hemostatic and antithrombotic
agent usage, lower costs, and decrease the frequency of
ADEs, led to several improvements in patient outcomes
and costs.16, 22−24 Thus, we believe that the higher number
of anticoagulation-related ADEs in the contemporary
period compared with the historical period (9.8% vs 8.3%
of reported ADEs) reflected changes in the hospital safety
culture and infrastructure and use of dosing nomograms
that increased clinician reporting of ADEs. Furthermore,
the introduction of unfractionated heparin nomograms cou-
pled with the inability to interpret and complete the tasks
associated with them was a frequent contributing cause of
reported events. Finally, we urge caution in interpreting the
increase in reported events as compromising care. The
operational changes, while increasing care complexity,
were intended to improve anticoagulation management by
Fanikos et al Anticoagulation-Associated Adverse Drug Events in Hospitalized Patients 933

Figure 3 Unfractionated heparin adverse drug events, secondary review.

broadening clinician responsibilities including greater par-
ticipation in the culture of safety and providing more timely
surveillance and response. These changes also encouraged
the identification of pitfalls in anticoagulation care that had
not been recognized and reported in the past.
Recent national reporting of ADEs in hospitalized
patients has been conflicting. Comparing event rates across
hospitals or time periods is difficult. Some have shown a
reduction in ADEs across a series of disease populations,
all of whom would require anticoagulation for prevention
or treatment of thrombosis.25 Others have reported no
change in ADE rates in hospitalized Medicare patients over
the past 10 years.26 However, a common type of medica-
tion-related harm identified was excessive bleeding, which
was most often related to anticoagulant use. In addition, a
study across 11 hospitals found that 1 in 4 patients admitted
had an ADE, of these 33% were drug related. These find-
ings support the need for routine, reliable reporting coupled
with continuous safety improvements.27
Since their introduction, DOACs have accounted for a
growing proportion of total anticoagulant use.28 The greater
number of warfarin-associated ADEs in the historical
period compared with the contemporary period likely
reflects the contemporary period decrease in warfarin use
and the increase in DOAC prescription during these study
periods. Unfractionated heparin remains a pervasive antico-
agulant tool in the hospital because of its pharmacokinetic
characteristics (rapid onset, short half-life, low cost, dose
adjustment in renal dysfunction, and drug interactions) in
medically and surgically managed patients. Administration
of unfractionated heparin requires frequent monitoring and
titration using hospital specific nomograms. Successful

Table 4 Comparison of Characteristics, Root Causes, and Management of Adverse Drug Reactions Between 2004-2009 and 2015-2020
Studies*
Characteristic of Adverse Drug Reaction n, (%) 2004-2009 Study (n = 238) 2015-2020 Study (n = 173) P Value
Abnormal coagulation studies 172 (72.3) 91 (52.7) <.0001
Occurrence of excessive anticoagulation during hospitalization 171 (71.9) 51 (29.4) <.0001
Any bleeding event 59 (24.8) 25 (14.4) .01
Any thromboembolic event 16 (6.7) 6 (3.4) .14
Other arterial thromboembolic event 1 (0.4) 4 (2.3) .08
Stroke 2 (0.8) 2 (1.1) .75
Thrombocytopenia 43 (18.1) 1 (0.5) <.0001
Root cause of adverse drug reaction n, (%)
Medication error 94 (39.5) 147 (84.9) <.0001
Undetected predisposing condition 138 (58) 25 (14.4) <.0001
Patient medication non-adherence 2 (0.8) 1 (0.5) .71
Management of bleeding n, (%)
Packed red blood cells 40 (16.8) 13 (9.3) .03
4-factor prothrombin complex concentrate (Kcentra) Not reported 1 (0.58) -
Fresh frozen plasma 11 (4.6) 2 (1.2) .05
Platelets Not reported 2 (1.2) -
Vitamin K 10 (4.2) 2 (1.2) .07
*Includes adverse drug reactions alone (n = 13) and combined medication errors and adverse drug reactions (n = 160)
934 The American Journal of Medicine, Vol 136, No 9, September 2023
Table 5 Comparison of Outcomes of Adverse Drug Reactions Between 2004-2009 and 2015-2020 Studies
Outcome, n (%) 2004-2009 Study (n = 463)
In-hospital death 26 (5.6)
Death after discharge but within 30 days of ADEs 23 (5.0)
Death due to thromboembolism 4 (0.86)
Death due to bleeding event 1 (0.22)
Discharge status, n (%)
Home 236 (51.0)
Rehabilitation center 186 (40.2)
Hospice 13 (2.8)
Other acute care facility 2 (0.4)
Deceased 26 (5.6)
ADEs = adverse drug events.
unfractionated heparin delivery requires nomogram famil-
iarity, timely coagulation study ordering, result interpreta-
tion, and adjustments in dosing, all of which create more
workload on physicians, physician-assistants, nurses, nurse
practitioners, and pharmacists. Nurse to patient ratio, nurse
shift changes, night shift staffing, and parenteral medica-
tions are risk factors that increase the odds of medication
errors.29,30 The use of systemic guidance by hospital care
pathways or computer alerts that aid clinicians in recom-
mending less heparin use or switching patients to low
molecular weight heparin would be helpful and potentially
reduce instances of anticoagulant-related ADEs. For
instance, expert opinion suggests the use of low-molecular-
weight heparin, rather than unfractionated heparin, as the
preferred immediate anticoagulant for patients with inter-
mediate risk for pulmonary embolism.31 This practice is in
fact frequent in many European hospitals.32
Some have advocated for specialized, dedicated consulta-
tion services or stewardship programs that rigorously follow
evidence-based, professional, or societal guidelines.33,34
Others have promoted the electronic health record as a tool
for safety. Although a consensus list of features has been
established to optimize anticoagulant management, we have
not identified which strategies provide the most benefit.35
Studies of clinical decision support systems and anticoagulant
monitoring systems have not demonstrated consistent
improvements in safety and outcomes.33,36−39 Other studies
have focused on human and organizational factors to identify
problems associated with human-machine interfaces and
mimic routine work sequences. However, few initiatives have
focused on anticoagulant use.40,41
Our study has several strengths. We have dedicated hospi-
tal resources to address and evaluate the medication safety
quality in our hospital in a multidisciplinary approach that
involves all hospital personnel including, physicians, physi-
cian assistants, nurses, nurse practitioners, and pharmacists.
We used the Epic electronic medical record system (Epic
Systems Corporation, Verona, Wis) to collect our data and to
gather more information and details regarding the events and
patient characteristics. Each patient included in the study also
had consistent and thorough follow up within 30 days.
2015-2020 Study (n = 984) P Value
82 (8.3) .11
0 (0.0) <.0001
1 (0.1) .04
0 (0.0) .32
625 (63.5) <.0001
235 (23.8) <.0001
26 (2.6) .86
16 (1.6) .07
82 (8.3) .11
We also note limitations to our analysis. It was con-
ducted at a single center. All event reporting was volun-
tary, which could lead to under-reporting.42 We
recognize that the there is substantial variability in ADE
reporting, which limits the ability to analyze data across
time periods and institutions. We also acknowledge that
voluntary incident reporting results in a much lower rate
specifically in reporting of adverse drug events.43 More
efforts to standardize as well as increase rates of report-
ing in cases of ADEs would improve quality of data for
future studies. We captured anticoagulant-associated
ADEs during the implementation period of the new elec-
tronic health record. Some of the reported ADEs were
likely the result of learning a new computer application.
Finally, the RL6 application (RLDatix, London, England,
the United Kingdom) may have restricted reporting
details of the events, and it may lack interoperability and
adaptability to newer technologies and services at other
health care systems.
CONCLUSION
In conclusion, we found that reported anticoagulation-asso-
ciated ADEs increased when comparing a contemporary
period to a historical period. Unfractionated heparin was
the most common anticoagulant associated with ADEs. The
fostering of “Just Culture” training and anticoagulation
stewardship, the implementation of a new electronic health
record, “smart” infusion devices, and dosing nomograms
likely contributed to the additional reported events.
Although ADEs were commonly reported, patient harm
was infrequent. These data suggest that clinicians should be
mindful of dosing errors when prescribing unfractionated
heparin and consider alternatives, such as low-molecular-
weight heparin, when appropriate to ensure the safe and
effective care of patients. Advances with electronic health
safety applications and human factor engineering require
more attentiveness during the process of delivering care to
patients on anticoagulants. Healthcare team members
should proactively take measures to analyze and mitigate
anticoagulation-associated adverse drug events.
Fanikos et al Anticoagulation-Associated Adverse Drug Events in Hospitalized Patients
DECLARATION OF COMPETING INTEREST
None.
References
1.. Piazza G, Nguyen TN, Cios D, Labreche M, Hohlfelder B, Fanikos J,
Fiumara K, Goldhaber SZ. Anticoagulation-associated adverse drug
events. Am J Med. 2011;124(12):1136–42.
2. Fanikos J, Stapinski C, Koo S, Kucher N, Tsilimingras K, Goldhaber
SZ. Medication errors associated with anticoagulant therapy in the
hospital. Am J Cardiol. 2004;94:532–5.
3. Fanikos J, Cina JL, Baroletti S, Fiumara K, Matta L, Goldhaber SZ.
Adverse drug events in hospitalized cardiac patients. Am J Cardiol.
2007;100:1465–9.
4. Shehab N, Greenwald JL, Budnitz DS. Anticoagulation across care
transitions: identifying minimum data to maximize drug safety. Jt
Comm J Qual Patient Saf. 2017;44(11):627–9.
5. Medication Safety Program. Centers for Disease Control and Prevention.
Adverse drug events in adults. Available at: https://www.cdc.gov/medi-
cationsafety/adult_adversedrugevents.html. Accessed June 1, 2022.
6. Agency for Healthcare Research and Quality. US Department of
Health and Human Services. Blood thinner pills: your guide to using
them safely. Available at: https://www.ahrq.gov/sites/default/files/
wysiwyg/patients-consumers/diagnosis-treatment/treatments/btpills/
btpills.pdf. Accessed June 1, 2022.
7. Spector WD, Limcangco R, Furukawa MF, Encinosa WE. The mar-
ginal costs of adverse drug events associated with exposures to antico-
agulants and hypoglycemic agents during hospitalization. Med Care.
2017;55(9):856–63.
8. The Joint Commission. National Patient Safety Goals effective January
2022 for the hospital program. Available at: https://www.jointcommis-
sion.org/-/media/tjc/documents/standards/national-patient-safety-goals/
2022/npsg_chapter_hap_jan2022.pdf. Accessed June 2, 2022.
9. U.S. Department of Health and Human Services. National action plan
for ADE prevention. Available at: https://health.gov/sites/default/files/
2019-09/ADE-Action-Plan-508c.pdf. Accessed June 2, 2022.
10. Agency for Healthcare Research and Quality. AHRQ national score-
card on hospital-acquired conditions updated baseline rates and pre-
liminary results 2014-2017. Available at: https://www.ahrq.gov/sites/
default/files/wysiwyg/professionals/quality-patient-safety/pfp/
Updated-hacreportFInal2017data.pdf. Accessed March 1,2023.
11. Dawson T, DeCamillo D, Kong X, et al. Correcting inappropriate pre-
scribing of direct oral anticoagulants: a population health approach. J
Am Heart Assoc 2020;9:e016949.
12. Graves CM, Haywart B, Kline-Rogers E, et al. Root cause analysis of
adverse events in an outpatient anticoagulation management consor-
tium. Jt Comm J Qual Patient Saf. 2017;43:299–307.
13. Andreica I, Grissinger M. Oral anticoagulants: a review of common errors
and risk reduction strategies. PA Patient Saf Advis. 2015;12(2):54–61.
14. Volkar JK, Phrampus P, English D, et al. Institution of just culture
physician peer review in an academic medical center. J Patient Saf.
2021;17(7):e689–93.
15. Wasserman JA, Redinger M, Gibb T. Responding to unprofessional
behavior by trainees-a “Just Culture” framework. N Engl J Med.
2020;382(8):773–7.
16. Reardon DP, Atay JK, Ashley SW, Churchill WW, Berliner N, Con-
nors JM. Implementation of a hemostatic and antithrombotic steward-
ship program. J Thromb Thrombolysis 2015;40(3):379–82.
17. Bates DW, Cullen DJ, Laird N, et al. Incidence of adverse drug events
and potential adverse drug events. Implications for prevention. ADE
Prevention Study Group. JAMA 1995;274(1):29–34.
18. National Coordinating Council for Medication Error Reporting and
Prevention. NCC MERP taxonomy of medication errors.1998. https://
www.nccmerp.org/sites/default/files/taxonomy2001-07-31.pdf.
19. Lacher B. American Society of Health-System Pharmacists. Pharmacy
technician certification review and practice exam. Bethesda, MD:
American Society of Health-System Pharmacists; 2016.
935
20. Leape LL, Bates DW, Cullen DJ, et al. Systems analysis of adverse drug
events. ADE Prevention Study Group. JAMA 1995;274(1):35–43.
21. GUSTO Investigators. An international randomized trial comparing
four thrombolytic strategies for acute myocardial infarction. N Engl J
Med. 1993;329(10):673–82.
22. Ritchie BM, Sylvester KW, Reardon DP, Churchill WW, Berliner N,
Connors JM. Treatment of heparin-induced thrombocytopenia before
and after the implementation of a hemostatic and antithrombotic stew-
ardship program. J Thromb Thrombolysis 2016;42(4):616–22.
23. Gilmore JF, Adams CD, Blum RM, Fanikos J, Hirning B, Matta L.
Evaluation of a multi-target direct thrombin inhibitor dosing and titra-
tion guideline for patients with suspected heparin-induced thrombocy-
topenia. Am J Hematol 2015;90(8):E143–5.
24. Baroletti S, Piovella C, Fanikos J, Labreche M, Lin J, Goldhaber SZ.
Heparin-induced thrombocytopenia (HIT): clinical and economic out-
comes. Thrombosis Haemost. 2008;100(6):1130–5.
25. Eldridge N, Wang Y, Metersky M, et al. Trends in adverse event rates
in hospitalized patients, 2010-2019. JAMA. 2022;328(2):173–83.
26. US Department of Health and Human Services; Office of Inspector
General. Adverse events in hospitals: a quarter of Medicare patients
experienced harm in October 2018 (OEI-06-18-00400). Available at:
https://oig.hhs.gov/oei/reports/OEI-06-18-00400.asp. Accessed Janu-
ary 12,2023.
27. Bates DW, Levine DM, Salmasian H, et al. The safety of inpatient
health care. N Engl J Med 2023;388(2):142–53.
28. Ting C, Fanikos C, Fatani N, Buckley LF, Fanikos J. Use of direct oral
anticoagulants among patients with limited income and resources. J
Am Coll Cardiol. 2019;72(4):526–8.
29. Valentin A, Capuzzo M, Guidet B, et al. Errors in administration of
parenteral drugs in intensive care units: multinational prospective
study. BMJ 2009;338:b814.
30. Di Muzio M, Dionisi S, Di Simone E, et al. Can nurses’ shift work
jeopardize the patient safety? A systematic review. Eur Rev Med
Pharmacol Sci 2019;23(10):4507–19.
31. Kahn SR, de Wit K. Pulmonary embolism. N Engl J Med 2022;387
(1):45–57.
32. Bikdeli B, Jimenez D, Hawkins M, et al. Rationale, design and meth-
odology of the computerized registry of patients with venous thrombo-
embolism (RIETE). Thromb Haemost 2018;118(1):214–24.
33. Frazer A, Rowland J, Mudge A, Barras M, Martin J, Donovan P. Sys-
tematic review of interventions to improve patient safety and quality
of anticoagulant prescribing for therapeutic indications for hospital
patients. Eu J Clin Pharmacol. 2019;75(12):1645–57.
34. El-Bosily HM, Abd El Meguid KR, Sabri NA, Ahmed MA. Phys-
icians’ adherence to evidence-based guidelines as a major predictor of
anticoagulant-related medication error incidence and severity. Br J
Clin Pharmacol. 2022;88(8):3730–40.
35. Spyropoulos AC, Viscusi A, Singhal N, et al. Features of electronic
health records necessary for the delivery of optimized anticoagu-
lant therapy: consensus of the EHR Task Force of the New York
State Anticoagulation Coalition. Ann Pharmacother. 2015;49
(1):113–24.
36. Oyen LJ, Nishimura RA, Ou NN, Armon JJ, Zhou M. Effectiveness of
a computerized system for intravenous heparin administration: using
information technology to improve patient care and patient safety. Am
Heart Hosp J . 2005;3(2):75–81.
37. Nieuwlaat R, Connolly SJ, Mackay JA, et al. Computerized clinical
decision support systems for therapeutic drug monitoring and dosing:
a decision-maker-researcher partnership systematic review. Implement
Sci 2011;6:90.
38. Becker RC, Ball SP, Eisenberg P, et al. A randomized, multicenter
trial of weight-adjusted intravenous heparin dose titration and point-
of-care coagulation monitoring in hospitalized patients with active
thromboembolic disease. Antithrombotic Therapy Consortium Investi-
gators. Am Heart J 1999;137(1):59–71.
39. Daniel JW, Kramer J, Burgess LH. Assessment of oral anticoagulant
adverse drug events before and after implementation of a real-time
clinical surveillance tool. J Patient Saf. 2021;17(4):e350–4.
936 The American Journal of Medicine, Vol 136, No 9, September 2023

40. Xiao Y, Smith A, Abebe E, Hannum SM, Wessell AM, Gurses AP. 43. Desikan R, Krauss M, Dunagan WC, Christensen Rachmiel E, Bailey
Understanding hazards for adverse drug events among older adults T, Fraser V. Advances in Patient Safety: From Research to Implemen-
after hospital discharge: insights from frontline care professionals. J tation, Vol 1. Rockville, MD: Agency for Healthcare Research and
Patient Saf 2022. Quality (US); 2005.
41. Carayon P, Wetterneck TB, Cartmill R, et al. Characterizing the com-
plexity of medication safety using a human factors approach: an obser-
vational study in two intensive care units. BMJ Qual Saf. 2014;23
(1):56–65. SUPPLEMENTARY DATA
42. Milch CE, Salem DN, Pauker SG, Lundquist TG, Kumar S, Chen J.
Voluntary electronic reporting of medical errors and adverse events.
Supplementary data to this article can be found online at
An analysis of 92,547 reports from 26 acute care hospitals. J Gen https://doi.org/10.1016/j.amjmed.2023.05.013.
Intern Med 2006;21(2):165–70.
Fanikos et al Anticoagulation-Associated Adverse Drug Events in Hospitalized Patients
Supplementary Appendix A Types of Anticoagulant-Associated Medication Errors: Definition and Example
Type of Medication Error Definition
Wrong rate or frequency Anticoagulant is prescribed with an infu-
sion rate or frequency, but the anticoag-
ulant is being administered at a different
rate or frequency.
Missed dose, late dose Administration outside a predefined time
interval from the anticoagulant’s
scheduled administration time.
Wrong dose Anticoagulant dose resulting in overdosage
or underdosage.
Inadequate monitoring Inadequate therapy assessment of antico-
agulant response.
Extra dose Patient given an additional dose of antico-
agulant he or she was not supposed to
receive.
Failure to act on coagulation study or labo- Coagulation study completed and result
ratory result reported but anticoagulant dose not
adjusted.
Wrong drug Patient is given a medication other than
the prescribed medication.
Wrong time of administration Anticoagulant administration at the wrong
time.
Documentation error Documentation error or omission in medi-
cal record chronicling anticoagulant
dose, route, time, or duration.
Medication administered without order Anticoagulant administration to a patient
without the prescriber’s proper
authorization.
Medication not discontinued Drug continued to be given despite order
when ordered for administration to stop.
Preparation error Anticoagulant is not properly prepared
prior to dispensing or administration
such as improper reconstitution.
Wrong technique of administration Anticoagulant administered using an
inappropriate procedure or incorrect
technique.
Wrong patient Medication intended for one patient was
given to another.
Medication discontinued without order Anticoagulant stopped despite no order
given to do so.
Known allergy or contraindication Patient administered anticoagulant
despite recognized allergy or indication
not to give said drug.
936.e1
Example
Unfractionated heparin infusion prescribed
with a rate of 15 units/kg/hour but
incorrectly administered with a rate of
18 units/kg/hour.
Enoxaparin ordered to start at 9 AM but the
dose is incorrectly administered at 9 PM.
Fondaparinux ordered and administered as
2.5 mg daily when indicated dose was
10 mg daily.
Unfractionated heparin infusion initiated
but, no corresponding coagulation study
was performed.
Edoxaban prescribed 30 mg once daily but
incorrectly administered as 2 doses at 2
different times.
Activated partial thromboplastin time
result reported at 30 seconds and target
range activated partial thromboplastin
time is 60-80 seconds. The infusion rate
was not adjusted according to the hospi-
tal’s unfractionated heparin dosing
nomogram.
Patient ordered for enoxaparin subcutane-
ously but incorrectly administered fil-
grastim subcutaneously.
Warfarin prescribed to be administered
evening before surgery but incorrectly
administered day of surgery.
Enoxaparin documented as being adminis-
tered to the patient in the medication
administration record, but dose was
never administered.
Intravenous unfractionated heparin initi-
ated in the Emergency Department but
never prescribed by a clinician.
Intravenous unfractionated heparin
ordered to be discontinued at 10 AM but
was still infusing at 3 PM.
Argatroban prepared as 0.5 mg per mL but
correct concentration was 1 mg per mL.
Dabigatran administered via gastrostomy
tube.
Unfractionated heparin 5000 unit intrave-
nous bolus prescribed for a patient but
incorrectly given to another patient
who was not prescribed unfractionated
heparin.
Unfractionated heparin administered intra-
procedure with intent to continue but
incorrectly stopped during recovery.
A patient with a history of heparin-induced
thrombocytopenia and administered
unfractionated heparin to “flush” the
intravenous line.
936.e2 The American Journal of Medicine, Vol 136, No 9, September 2023

Supplementary Appendix A (Continued)

Type of Medication Error Definition Example
System error Error occurring in the electronic medical Unfractionated heparin ordered for a future
record. encounter (procedure) date but this
order is displaying in the current encoun-
ter and medication administration
record.
Medication expired Medications that are dispensed or adminis- Bivalirudin infusing with a beyond use date
tered beyond their expiration date or of the prior day.
beyond use date.
Wrong route Ordered as one route of administration and Patient prescribed morphine intravenously
given through different route. and heparin subcutaneously but incor-
rectly administered morphine subcutane-
ously and heparin intravenously.
Fanikos et al Anticoagulation-Associated Adverse Drug Events in Hospitalized Patients
Supplementary Appendix B Root Causes of Anticoagulant-Associated Medication Errors: Definition and Example
Root Cause Definition
Faulty interaction or communication Incomplete, omitted, or misinterpreted
between services communication between disciplines or
services.
Faulty dose checking Clinician failed to complete a proper proc-
essing step to ensure the correct antico-
agulant or dose was dispensed or
administered.
Rule violation Failure to follow accepted and well-estab-
lished procedures.
System error Error occurring in the electronic medical
record.
Lack of information about the patient Nurse, physician, or pharmacist was
unaware of an important aspect of the
patient’s condition or treatment plan.
Transcription error Error associated with the prescribed anti-
coagulant order being transcribed and
verification for medication administra-
tion steps.
Memory lapse Error occurring when a clinician forgets to
perform a function that he or she would
ordinarily do or performs a task for which
he or she does not recall the reason.
Lack of knowledge about drug Inadequate knowledge of the anticoagu-
lant, indications for use, available forms,
appropriate doses, routes, and incompat-
ibilities.
Prescribing error Clinician error in prescribing of anticoagu-
lants resulting in too high or low a dose.
Infusion or parenteral administration Errors in setting pumps; accidental tubing
problem disconnections; confusion between cen-
tral and peripheral lines, or suspected
device malfunction.
Drug preparation error Anticoagulant is not properly prepared
prior to dispensing or administration
such as improper reconstitution.
Known allergy or contraindication Patient administered anticoagulant
despite recognized allergy or indication
not to give said drug.
936.e3
Example
Nurse communicates elevated activated
partial thromboplastin time lab result to
physician. Nurse assumes physician will
prescribe new dose. Physician assumes
nurse would adjust dose based on nomo-
gram. Anticoagulant doses unchanged
6 hours later.
Argatroban prescribed based on a body
weight of 60 kg, but dose entered on
infusion device was for 65 kg.
Nurse administered incorrect dose of enox-
aparin first then bar code scanned the
drug and patient wristband identifier
rather than scanning the drug and iden-
tifier first.
Unfractionated heparin ordered for a future
encounter (procedure) date but display-
ing in the current encounter and medica-
tion administration record.
Medical patient administered unfractio-
nated heparin 5000 unit dose for throm-
boprophylaxis because the patient was
incorrectly thought to be a thoracic sur-
gery patient where this prescription is
routinely employed.
Apixaban prescribed with specific instruc-
tions to be discontinued in the peri-
operative period, but these instructions
were not forwarded to the medication
administration record and hence therapy
not stopped.
Patient prescribed unfractionated heparin
by nomogram. Nurse administered
40 unit/kg bolus, forgot giving this ini-
tial dose, and erroneously administered a
second bolus dose.
Argatroban dispensed in 1 mg/mL “ready-
to-use” formulation. Nurse incorrectly
thought that additional mixing/diluting
preparation was necessary prior to
administering.
Physician prescribes enoxaparin 1.5 mg per
kg but as a twice daily dose rather than
the correct once daily dose.
Nurse programs intravenous unfractionated
heparin to infuse at 12 units/kg/hour.
Returns to room 2 hours later and pump
is off despite being plugged into electri-
cal outlet.
Argatroban prepared as 0.5 mg per mL, but
correct concentration was 1 mg per mL.
A patient with a history of heparin-induced
thrombocytopenia is erroneously admin-
istered unfractionated heparin to “flush”
the intravenous line.