SCIENTIFIC ARTICLE

Upper-Extremity Venous Thromboembolism

Following Operative Treatment of Distal Radius
Fractures: An Uncommon but Dangerous Complication
Nicholas A. Calotta, MD,* Jaimie T. Shores, MD,* Devin Coon, MD, MSE*

Purpose Distal radius fractures are the most common long bone fracture in the United States, with
an estimated incidence of 640,000 cases per year. Operative fixation presents a theoretical risk
factor for the development of upper-extremity venous thromboembolism (UE-VTE). Addition-
ally, patients presenting with distal radius fracture commonly have preexisting comorbidities that
further increase the risk of UE-VTE. Finally, UE-VTE is considered the highest risk for eventual
development of pulmonary embolism. Despite this, scant attention has been paid to studying UE-
VTE in this population. The purpose of this study was to measure the incidence of this compli-
cation and to identify possible medical factors that increased the risk of developing UE-VTE.
Methods We queried the Truven MarketScan Commercial Claims and Encounters Database
for all patients who experienced a distal radius fracture and were subsequently treated with
open reduction and internal fixation between 2012 and 2016. Patients were identified using
relevant Common Procedural Terminology codes. Demographic and medical variables were
tabulated. Our primary outcome was the development of ipsilateral UE-VTE or pulmonary
embolism in the first 60 days after surgery.
Results The study included 24,494 patients. The mean age was 50.7 years (range, 18e91), and
58% were women. There were 79 cases (0.3%) of UE-VTE and 19 cases of pulmonary embolism
in the study population (24.1% of all UE-VTE cases; 0.08% of total sample). Multivariable logistic
regression showed that coexisting heart failure and estrogen use were associated with increased
risk of UE-VTE.
Conclusions Although uncommon, the development of UE-VTE after open reduction and internal
fixation for distal radius fractures is a concerning complication. Coexisting heart failure and es-
trogen use are associated with increased risk of UE-VTE. (J Hand Surg Am. 2021;46(12):1123.e1-
e7. Copyright Ó 2021 by the American Society for Surgery of the Hand. All rights reserved.)
Type of study/level of evidence Prognostic II.
Key words Distal radius fracture, deep vein thrombosis, upper-extremity venous thromboembolism.

From the *Department of Plastic and Reconstructive Surgery, Johns Hopkins University School
of Medicine, Baltimore, MD.
Received for publication March 4, 2020; accepted in revised form March 18, 2021.
No benefits in any form have been received or will be received related directly or indirectly
to the subject of this article.
Corresponding author: Nicholas A. Calotta, MD, Johns Hopkins Outpatient Center, 601 N.
Caroline Street, Room 8152C, Baltimore, MD 21287; e-mail: Ncalott1@jhmi.edu.
0363-5023/21/4612-0018$36.00/0
https://doi.org/10.1016/j.jhsa.2021.03.011

Ó 2021 ASSH r Published by Elsevier, Inc. All rights reserved. r 1123.e1

1123.e2 VENOUS THROMBOEMBOLISM DISTAL RADIUS SURGERY
D
ISTAL RADIUS FRACTURES are the most common
long bone fractures incurred by adults in the
United States, with approximately 640,000
cases per year.1 Of patients who sustain a distal
radius fracture, there is a bimodal age distribution,
with younger patients accounting for approximately
36% of fractures and elderly adults for approximately
30% of cases.2 Treatment options can be broadly
categorized as nonsurgical (eg, immobilization) and
surgical (eg, open reduction and internal fixation
[ORIF]). Compared with patients older than 75 years,
younger patients are more likely to have surgical
intervention offered as the first-line treatment,
depending on the nature of the fracture.3
The treatment approach for older adults is often
more nuanced. One major contributor to this differ-
ence from the younger population is the increased
prevalence of comorbid conditions such as diabetes,
osteoporosis, coronary artery disease, and chronic
pulmonary disease.4 In the context of these condi-
tions, the risk-benefit ratio of surgical intervention,
especially ORIF, is unclear. Complications of ORIF
are relatively infrequent but include complex regional
pain syndrome, malunion, infection, and tendon
complications; these are more common in older pa-
tients than in younger patients. Increasing age as well
as the presence of comorbid conditions are both
associated with an increased probability of devel-
oping a complication.5,6
Despite the large body of evidence surrounding the
complications of ORIF for distal radius facture, there
is little attention paid to the epidemiology or out-
comes of upper-extremity venous thromboembolism
(UE-VTE). ORIF poses several potential risks for the
development of UE-VTE that include the operation
itself, possible need for intravenous central lines
during surgery (and possibly during admission, if
required), and relative immobility of the extremity
compared with baseline. Furthermore, extrapolating
from the data pertaining to tourniquet use in the lower
extremity, the use of a tourniquet during distal radius
ORIF could be another risk factor.7,8 Although the
venous anatomy of the upper extremity is not iden-
tical to that of the lower extremity, the most plausible
hypothesis for this stems from the Virchow triad,
namely venous stasis from tourniquet use. Moreover,
UE-VTE poses a substantial risk of pulmonary em-
bolism (PE) if unrecognized, with studies reporting as
many as 36% of UE-VTEs progressing to PE in the
absence of timely treatment.9
The purpose of this study was to quantify the
incidence of UE-VTE following ORIF for distal
radius fractures and to identify the factors that may be
J Hand Surg Am.
associated with additional risk of developing UE-
VTE. We hypothesized that older patients with an
increased number of medical morbidities would be at
a greater risk of developing UE-VTE. Our specific
aims included the following: (1) to measure the
prevalence of UE-VTE in an age-diverse cohort of
patients undergoing ORIF for distal radius fractures,
(2) to elucidate the prevalence of PE following UE-
VTE in this context, and (3) to identify the relevant
risk factors for the development of UE-VTE, espe-
cially those that may be modifiable.
MATERIALS AND METHODS
Data source
Retrospective analyses were conducted using the
Truven Health Analytics MarketScan Commercial
Claims and Encounters database.10 The Commercial
Claims and Encounters database is a publicly avail-
able database comprising longitudinal commercial
claims and associated encounter data from over 70
million health plan enrollees. All health care and
enrollment data were deidentified prior to the study;
thus, this research was deemed exempt from institu-
tional review board review.
Sample selection
The study population was initially selected on the
basis of having at least 1 service claim indicating
ORIF for distal radius fracture between January 1,
2010 and December 31, 2017. This population was
identified using the following Common Procedural
Terminology (CPT) codes: 25607, 25608, and 25609.
To ensure the completeness of our data, participants
were examined for continuous enrollment in a health
plan with medical and prescription drug benefits
during the study period.
The inclusion criteria for the study were as fol-
lows: (1) continuous enrollment in a health plan for at
least 60 days following the date of the index pro-
cedure, (2) presence of a CPT code for ORIF distal
radius (25607, 25608, and/or 25609), (3) isolated
unilateral distal radius fracture, and (4) at least 60
days of follow-up. The exclusion criteria for the study
were as follows: (1) encounters for unexpected
reoperation within 60 days, (2) the presence of a CPT
code for the insertion of a central venous catheter
(36555e36569), (3) the presence of preexisting
thrombophilic condition (eg, inherited thrombophilia,
blood cell dyscrasia, current oncologic diagnosis, etc)
or the administration of anticoagulation within 60
days preceding surgery, (4) the evidence of
r Vol. 46, December 2021
 VENOUS THROMBOEMBOLISM DISTAL RADIUS SURGERY 1123.e3

multisystem trauma or other long bone fractures, and that condition.14e16 Because there were so few cases
(5) incomplete records. (<1%) with CCI scores above 3, we elected to
combine all patients with a score greater than 3 into
Variables one group of “3þ.” Finally, estrogen use was only
A comprehensive analytic file was assembled considered for female participants in the study.
describing the study sample’s parameters of interest.
Relevant demographic variables included age at the RESULTS
time of operation, sex, and surgical setting. Medical
The study considered 134,938 people who underwent
variables of interest included those variables shown
ORIF for distal radius fractures between January 1,
to be associated with the development of VTE in
2010, and December 31, 2017. Ultimately, 24,494
surgical patients, namely heart failure exacerbation,
were included in the study after the application of all
estrogen use, neurological disease with paresis, and
inclusion and exclusion criteria (Fig. 1). Mean age of
obesity (body mass index of >35 kg/m2).11,12 We
the sample was 50.7 years, median age 53 years, and
also assessed for any association between Charlson
the range was 18e91 years. With regard to sex,
Comorbidity Index (CCI) scores and the development
57.9% of the population were females. Other relevant
of UE-VTE.
demographic and baseline medical characteristics are
The primary outcome variable was the develop-
presented in Table 1.
ment of an ipsilateral UE-VTE within 60 days of the
Approximately 0.3% (n ¼ 79 cases) of the study
index operation, determined by querying for the
sample developed UE-VTE following ORIF for distal
appropriate International Statistical Classification of
radius fracture. Of these 79 cases, 19 (24.1% of UE-
Diseases and Related Health Problems versions 9 and
VTE cases; 0.08% of the total sample) were diag-
10 code (I82.6X) and CPT codes 93970 or 93971
nosed with PE, and 6 patients (31.6% of cases of PE;
(extremity venous Duplex studies). The secondary
7.6% of UE-VTE cases; 0.03% of the total sample)
outcome variable of interest was the development of
with PE subsequently died. Univariable regression
PE following UE-VTE within 60 days of operation
showed that both heart failure and estrogen use
(International Statistical Classification of Diseases
demonstrated a significant association with the
and Related Health Problems code I26X).
development of UE-VTE (P < .05 for both). Obesity
Statistical analysis had no association, and the presence of poststroke
paralysis was similarly not significantly associated
Categorical demographic and clinical characteristics
(P ¼ .07). The CCI score was not associated with the
were described with frequency and proportion and
development of UE-VTE for those participants with a
compared using a chi-square test. The Freeman-
score of 0 (P ¼ .61), 1 (P ¼ .55) or 2 (P ¼ .05);
Halton extension of the Fisher exact test was used
however, a CCI score of 3 was significant
to assess significance of relationships between the
(P < .05). We also considered procedural detail with
primary outcome and multileveled variables such as
the stratified CPT codes 25607, 25608, and 25609;
CCI and the 3 CPT codes.13 A multivariable logistic
however, the procedure code had no significant
regression model was constructed to calculate odds
association with the development of UE-VTE
ratios of factors associated with the development of
(P ¼ .40).
UE-VTE. Two-sided tests were used, and a P value
The multivariable regression model included all
of <.05 was considered significant.
covariates with a bivariate P value of <.10; estrogen
Individual comorbidities that were factored into
use, heart failure, stroke, and CCI score of  2 were
the CCI were not included in the regression analysis
included (Table 2). This analysis showed significant
to avoid redundancy. Exceptions were made for heart
results for heart failure, estrogen use, and CCI score
failure and paresis because these were the known risk
of 3. The odds ratios and 95% confidence intervals
factors for the development of VTE. The CCI was
for the covariates included in the multivariable
used in lieu of individual comorbidities for 2 reasons.
regression are shown in Table 3
First, it was a validated measure of an individual’s
overall health status that captured a disease-specific
malady. Second, the CCI is well regarded as a use- DISCUSSION
ful tool in research concerning administrative data. Our study demonstrated that 0.3% of patients devel-
The measure comprised 19 chronic conditions, each oped UE-VTE following distal radius fixation.
of which was weighted with an additive “score” of 1, However, approximately 25% of those patients sub-
2, 3, or 6, denoting the risk of death associated with sequently developed PE. We identified modifiable

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1123.e4 VENOUS THROMBOEMBOLISM DISTAL RADIUS SURGERY
FIGURE 1: Inclusion and exclusion criteria.
risk factors, including heart failure (odds ratio 18.6)
and current estrogen use (odds ratio 4.7). A CCI score
of 3 was also statistically significant in the multi-
variable model (odds ratio 4.9), which could be
modifiable in some patients. This information may be
useful to surgeons contemplating surgical versus
nonsurgical management, because UE-VTE, though
uncommon, poses a serious morbidity and mortality
risk.
Considerable time and energy have been invested
in the past 3 decades to understand all aspects of
VTE.17 Most attention has been paid to the lower
extremities, with a consequential reduction in the
incidence of lower extremity VTE in virtually all
patient populations.18 The upper extremity, however,
has received comparatively sparse attention. There is
a body of literature concerned with the effect of
“upper-extremity surgery” on the development of
UE-VTE, though there is no clear stratification of the
types of operations considered.19e23 Specifically
considering UE-VTE risk in the setting of ORIF for
upper-extremity fractures, only 1 small case series
was identified.24 Other studies have considered the
J Hand Surg Am.
risk of UE-VTE as secondary outcome measures,
such as the group led by Wilson et al25,26 who first
reported only 3 cases out of nearly 10,000 distal
radius ORIF cases and who later identified 3 “he-
matologic complications” in nearly 6,500 distal
radius ORIF cases. Another group attempted to pro-
vide guidelines for VTE prophylaxis after upper-
extremity surgery but considered only 4 articles, all
of which were of low quality and none of which
considered hand or wrist surgery.27 This lack of
attention is somewhat surprising given that the distal
radius fractures are extremely common and operative
interventions create conditions ripe for VTE: venous
stasis, endothelial injury, supranormal platelet acti-
vation and relative hypercoagulability, extremity
immobilization, and long bone fracture. Surgeons
belonging to the Orthopaedic Trauma Association
self-reported a 38% rate of prescribing some form of
pharmacoprophylaxis against VTE for patients with
isolated upper-extremity fractures.28 It is noteworthy
to consider that, despite the low incidence of UE-
VTE identified (0.3%), the typical hand surgeon is
likely to encounter this problem during a career. A
r Vol. 46, December 2021
 VENOUS THROMBOEMBOLISM DISTAL RADIUS SURGERY 1123.e5

concerning aspect of UE-VTE is the high likelihood

TABLE 1. Medical and Demographic Variables
of progression to PE compared with lower extremity
Variable Value VTE.9 In our study, we observed that nearly 25% of
Demographic variables patients with UE-VTE subsequently experienced PE,
Mean age (median; range) 50.7 y (53; 18e91) with 6 fatalities (31.6% of PE cases; 7.6% of UE-
Female (%) 14,184 (57.9%)
VTE cases; 0.03% of study population).
Our data suggest avenues by which UE-VTE risk
Mean follow-up 8 mo
can be mitigated. Heart failure and current estrogen
Surgical setting
use are practically modifiable risk factors. A patient
Inpatient or outpatient hospital 12,173 (49.7%)
can be admitted and heart failure medically optimized
Ambulatory center 12,321 (50.3%) prior to surgery, if necessary. Estrogen therapy for
Surgical Procedure Code (CPT) osteoporosis prevention can be temporarily sus-
25607 14,076 (57.5%) pended without measurable effect on bone mineral
25608 5,408 (22.1%) density or, indirectly, the risk of osteoporotic frac-
25609 5,010 (20.4%) ture.32 In instances in which estrogen therapy is being
Medical variables used for postmenopausal sexual considerations, there
Heart failure 1,502 (6.1%) is no physiologic risk to suspending estrogen therapy
Obesity 2,669 (10.9%) but compassionate counseling as to the possibility of
Estrogen use* 544 (3.8%) the temporary return of undesirable pelvic symptoms
Stroke (with paralysis) 765 (3.1%)
may be advisable. No clear evidence-based guide-
lines exist for when to resume hormonal therapy, but
CCI score
expert opinion is that medication should be resumed
0 7,257 (30%)
when the acutely increased risk of VTE has subsided,
1 8,473 (35%)
though specific indications for estrogen use (such as
2 7,039 (29%) in patients with breast cancer) may require more
3 1,725 (7%) prompt resumption.33 Finally, patients with CCI
*Estrogen calculations using only the total female participants in the
scores of 3 or greater have chronic medical conditions
study (N ¼ 14,184). that pose a considerable risk of mortality. Given that
the CCI score is composed of 19 distinct conditions,
innumerable clinical scenarios could possibly lead to
50% probability of having a patient with UE-VTE patients with this score. The involvement of medical
exists by the time a surgeon has repaired 167 distal specialists is paramount to ensuring a safe operation
radius fractures, and there is a 99% probability by in this population. From a surgeon’s perspective, UE-
334 distal radius fractures. Although these numbers VTE is a rare event in an absolute sense, which
overall are small compared with those risks in the makes the administration of pharmacoprophylaxis to
treatment of lower extremity fractures, we do not feel all patients strictly for this indication a practice
they are so small as to be negligible. without strong supporting evidence. We recommend
Although the incidence of UE-VTE is low (0.3%), careful consideration of the various individual risk
the morbidity associated with the condition is known factors for UE-VTE that may be present in a single
to be substantial.29 UE-VTE can progress to post- patient, with emphasis placed on the estimated sum-
thrombotic syndrome. This condition can manifest med effect of these factors. Although our study is not
with permanent pain, swelling, extremity disability, designed to validate specific treatment, we feel
and recalcitrant venous ulcers. Mild variants of the confident that patients who present with both
syndrome can be seen in as many as 50% of patients numerous individual risk factors and who the surgeon
who develop VTE, and severe forms are estimated to feels would benefit from ORIF are good candidates
affect 5% of patients following VTE.30 The treatment for some form of prophylaxis against UE-VTE. This
of UE-VTE is similar to that of lower extremity VTE, is reflected in our practice.
often consisting of 3e6 months of systemic anti- Our study design is well-suited to addressing the
coagulation therapy.31 There is a multitude of con- specific aims and hypothesis of this study. Adminis-
sequences of VTE treatment, ranging from the need trative databases contain a large number of patients,
for injections to medication toxicities and, of course, which are essential for identifying an adequate
bleeding events. The latter 2 are of particular concern number with this relatively rare outcome. This large
in the population of older adults. Perhaps the most sample size also enabled us to formulate strict

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1123.e6 VENOUS THROMBOEMBOLISM DISTAL RADIUS SURGERY

TABLE 2. Covariates Considered in Univariate Regression Models for 79 Cases of UE-VTE

UE-VTE No UE-VTE
Covariate With Covariate Without Covariate With Covariate Without Covariate P Value

Heart failure, N (%) 45 (53.0%) 34 (43.0%) 1,457 (6.0%) 22,958 (93.7%) <.05
Obesity, N (%) 6 (7.6%) 73 (92.4%) 2,663 (10.9%) 21,752 (88.8%) .47
Estrogen use,* N (%) 70 (88.6%) 9 (11.4%) 474 (3.3%) 13,631 (96.7%) <.05
Stroke, N (%) 41 (51.9%) 38 (48.1%) 724 (3.3%) 23,691 (96.7%) .07

*Estrogen calculations using only the total female participants in the study (N ¼ 14,184).

TABLE 3. Multivariable Regression Statistics

Covariate Odds ratio 95% Confidence Interval P Value

Heart failure 18.6 11.8e29.4 <.05

Estrogen use 4.7 2.2e9.7 <.05
CCI score of 3 4.9 2.4e9.8 <.05
Stroke 1.9 0.88e3.4 .45
CCI score of 2 2.4 0.95e5.0 .13

inclusion and exclusion criteria without sacrificing
statistical power. For example, exclusion of patients
with confounding factors, such as multisystem injury
or central venous lines (both independent risk factors
for VTE) enhances the validity of our findings.
Moreover, because this data source relies on billing
records, the instances of UE-VTE are virtually
guaranteed to have been diagnosed via ultrasound,
the reference standard methodology. The identifica-
tion of DVT by means of diagnosis codes in the
presence of procedural codes for the ultrasound
diagnostic test has been shown to be appropriately
sensitive and specific.34 The entity responsible for
medical billing would only enter a reimbursement
claim for UE-VTE (which is a complication of
treatment) with the risk of nonpayment from the
payer hedged by the presence of incontrovertible
evidence of the disease process. Similarly, with PE,
administrative data sources have been shown to
exhibit a high true positive rate when the code for PE
is entered.35
This study has important limitations. First, we
were not able to completely control for perioperative
mechanical prophylaxis methods or postoperative
drug administration. Although patients with preop-
erative anticoagulation medications were excluded,
it is possible that some patients received prophylactic
doses of antiplatelet medications or anticoagulants in
the perioperative period, over-the-counter medications
after surgery, or prescriptions not paid for through an
insurance plan, all of which were not recorded in the
MarketScan files. Second, administrative data did not
provide granular clinical information (eg, length of
surgery, anesthetic type, use of tourniquet, post-
operative dressing or orthosis type, weight bearing and
range of motion restrictions, hand therapy frequency,
laterality of clot, etc), all of which are important for
this analysis of UE-VTE. Third, the MarketScan data
source primarily compiles commercial claims, which
limits our ability to comment on uninsured patients
and those adults over 65 years old who are exclusively
covered by Medicare. This point is particularly notable
as a limitation on our ability to estimate the magnitude
of risk of UE-VTE associated with advancing age in
this surgical population. Finally, as with all adminis-
trative studies, our data may be adversely affected by
clinical conditions that were not properly documented
and, thus, improperly coded or not coded at all.
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