Article

Vascular and Endovascular Surgery

2015, Vol. 49(5-6) 100-109
Arterial Embolisms and Thrombosis ª The Author(s) 2015
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in Upper Extremity Ischemia DOI: 10.1177/1538574415596740
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Nedaa Skeik, MD1, Sarah S. Soo-Hoo, BA3, Brandon R. Porten, BA3,

John Graber, MD2, Peter Alden, MD2, Andrew Cragg, MD2,4,
Jason Q. Alexander, MD2, Adnan Rizvi, MD2,
Jesse M. Manunga Jr, MD2, Ross F. Garberich, MS3,
and Timothy Sullivan, MD2

Abstract
Objective: Upper extremity ischemia (UEI) is an uncommon condition that can lead to permanent disability. There is a limited
understanding of the etiology, management, and outcomes of the disease. Methods: We retrospectively reviewed the charts of
all patients who were diagnosed with ‘‘embolism and/or thrombosis of arteries of upper extremity’’ at our institution from January
2005 to December 2013. Results: Patients diagnosed with embolisms were older (P < .001), more likely to undergo throm-
boembolectomy (P < .001), had higher rates of hypertension (P ¼ .001), and had longer lengths of hospital stay (P ¼ .002). There
were no significant differences in complications or mortality at 30 days and up to 1 year. Conclusion: At our center, embolism
was found to be the most common etiology for UEI followed by thrombosis and stenosis. Patients presented with embolism were
older, were more likely to undergo thromboembolectomy, and had higher rates of hypertension and longer hospital stays.

Keywords
upper extremity ischemia, arterial embolism, arterial thrombosis

Introduction at Abbott Northwestern Hospital (Minneapolis, Minnesota)

Although critical upper extremity ischemia (UEI) is less
common than lower limb ischemia, delayed or unsuccessful
treatment can jeopardize limb viability and lead to serious con-
sequences such as amputation.1-3 While the 6-month amputa-
tion rate can reach up to 40% in patients with critical limb
ischemia, there has been no consistent data addressing the
amputation rate for critical UEI per se.4 Patients typically pres-
ent with multiple comorbidities, complicating the disease man-
agement. Thromboembolectomy has long been the primary
treatment option for critical UEI, but endovascular approaches
including catheter-based thrombolysis have been used more
frequently in the recent years.5-7 The current understanding
of the etiology, management, and outcomes of UEI is limited
as existing literature is primarily comprised of small case
series.8-10 To address current gaps in this knowledge, we
assessed patients who presented with UEI at our institution and
compared our center’s experience to the existing literature.
Methods
This retrospective single-center study was approved by our
center’s institutional review board. We reviewed the elec-
tronic charts of 100 patients diagnosed with UEI including
‘‘embolism and/or thrombosis of arteries of upper extremity’’
between January 1, 2005, and December 31, 2013. Patient data
including age, gender, underlying comorbidities (eg, hyperten-
sion [HTN], hyperlipidemia, diabetes mellitus [DM], and
tobacco abuse), and presentation of symptoms (eg, numbness,
pain, and discoloration) were obtained by a single investigator
from patient charts using our electronic medical record system.
Operative notes were reviewed to identify intervention modal-
ity. Patient charts were further reviewed to identify outcomes
and subsequent complications, including amputation, hema-
toma, reocclusion, weakness, and nerve damage, 30 days and
up to 1 year after treatment. If there was no record of such
information in the electronic medical record, patients were
interviewed by telephone. Minnesota Department of Health
Death Certificates and hospital records were used to determine
1
Vascular Medicine, Minneapolis Heart Institute, Minneapolis, MN, USA
2
Vascular Surgery Department, Abbott Northwestern Hospital, Minneapolis,
MN, USA
3
Minneapolis Heart Institute Research Foundation
4
Interventional Radiology, Minneapolis Heart Institute
Corresponding Author:
Nedaa Skeik, Vascular Medicine, Minneapolis Heart Institute, 800 East 28th
Street, H2100, Minneapolis, MN 55407, USA.
Email: Nedaa.skeik@allina.com

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Skeik et al
100 Patients diagnosed with “Embolism and Thrombosis of Arteries of Upper
Extremity” at Abbott Northwestern Hospital from January 2005-December 2013
64 patients included in final analysis
28 Thrombosis
Figure 1. Selection of study population with exclusion criteria.
date and cause of death. Thirty-six patients were excluded from
this study because (1) there was no diagnosis of UEI; (2) site of
disease was undetected on diagnostic imaging; (3) etiology was
unknown and there was insufficient thrombophilia workup;
and/or (4) follow-up data were not available (Figure 1).
Definitions
Pathophysiology of upper extremity was categorized as embo-
lism, thrombosis, or severe stenosis. Embolic ischemia was
diagnosed if there was sudden clinical presentation, absence
of peripheral arterial disease, presence of an embolic source,
and the patient had no history of ischemic symptoms of the
upper extremity prior to evaluation at our center. Thromboem-
bolus, or a thrombus that embolizes distally, was classified as
an embolism. A thrombosis was diagnosed if there was athero-
sclerotic plaque at the occlusion site, risk of thrombosis (eg,
atherosclerosis [ASO]), or if the patient experienced previous
ischemic symptoms in an upper extremity. Severe stenosis was
defined as peak systolic velocity of 300 cm/s at the stenotic
segment or peak systolic velocity ratio of 4:1 between the
stenotic and normal adjacent arterial segments. Upper extremity
ischemia was further categorized as either acute or chronic.
Acute UEI was diagnosed if the patient presented to our center
within 2 weeks of onset of ischemic symptoms, while chronic
UEI was classified as presentation beyond this time frame.
Underlying etiologies examined included ASO, Buerger
disease, cancer, cardiac, thrombophilia, hormonal stimulation
therapy (HST), thoracic outlet syndrome (TOS), trauma, and
vasculitis. Buerger disease was considered to be the cause of
disease if the patient was less than 45 years of age, had signif-
icant tobacco history, and had no indications of autoimmune
disease, thrombophilia, or proximal embolic sources.11,12 Car-
diac abnormalities, such as intracardiac thrombus and atrial
fibrillation (AF), were identified using transthoracic or esopha-
geal echocardiogram imaging. The TOS was diagnosed in
patients who had symptoms consistent with TOS and imaging
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101
36 patients excluded
26: did not have UEI
4: area of disease undetected
3: unknown etiology AND
insufficient thrombophilia testing
3: lost to follow-up
2 Severe Stenosis 34 Embolism
studies confirming compression over the subclavian artery with
provocative maneuvers.
Patients believed to be at high risk of thrombophilia had
workup including antithrombin III, protein C, protein S, homo-
cysteine levels, antiphospholipid syndrome (APLS), and pro-
thrombin and factor V Leiden genetic mutations. Laboratory
results were considered abnormal if values did not fall within
prespecified normal ranges of the assays used at our institution:
antithrombin III, 79% to 131%; protein C, 68% to 140%; pro-
tein S, 60% to 120%; and homocysteine, 5.0 to 15.4 mmol/L.
Patients were diagnosed with APLS if they experienced a
thromboembolic event and satisfied at least 1 of the following
criteria: (1) lupus anticoagulant (LAC) was detected according
to given guidelines, (2) abnormal anticardiolipin (immunoglo-
bulin [Ig] M or IgG) levels in moderate or high titer (>40 GPL
or MPL units or >99th percentile for the testing laboratory), or
(3) abnormal B2 glycoprotein levels at a titer >99th percentile
for the testing laboratory.13,14 Additional laboratory analyses
were conducted on patients who tested positive for LAC at least
once. If the patient was administered anticoagulation therapy
less than 2 weeks prior to time of LAC testing, it was assumed
anticoagulation interfered with proper testing, and positive
LAC results were considered false unless further workup indi-
cated otherwise. However, patients receiving anticoagulation
who tested positively a second time for LAC were considered
to have APLS due to physician discomfort in halting anticoagu-
lation solely for the purpose of APLS testing.
Diagnostics
Diagnosis was determined retrospectively based on patient
history and symptomology (paresthesia, pain, pallor, pulseless-
ness, poikilothermia, and paralysis). Continuous wave Doppler
and Allen tests were performed to evaluate blood flow to the
upper extremities. Diagnostic imaging modalities such as com-
puterized tomography angiography (CTA), magnetic resonance
angiography (MRA), ultrasound (US), and catheter-based digital
102 Vascular and Endovascular Surgery 49(5-6)

subtraction angiography were performed to establish the loca- Table 1. Baseline Demographic and Clinical Characteristics, Manage-
tion of disease. Transthoracic or transesophageal echocardio- ment, Length of Stay, and Outcomes of Thrombosis Versus Embolism.
graphy was performed in patients with known or suspected Thrombus Embolism
cardiac history to identify cardiac abnormalities that might (n ¼ 28) (n ¼ 34) P Value
have contributed to the disease.
Age, years, mean (SD) 56.4 + 12.6 80.9 + 15.0 <.001
Male (%) 13 (46.4) 13 (38.2) .52
Management Hormonal therapya (%) 1 (6.7) 1 (4.8) .81
Treatment modalities used in this study included bypass of the Tobacco use (%) 16 (57.1) 13 (38.2) .14
Diabetes (%) 6 (21.4) 11 (32.4) .34
occluded vessel, open thromboembolectomy, or endovascular
Hypertension (%) 11 (39.3) 27 (79.4) .001
approach including catheter-based thrombolysis, angioplasty, Hyperlipidemia (%) 10 (35.7) 16 (47.1) .37
or stenting. Anticoagulation and aspirin were administered Presentation
immediately upon admission for all eligible patients and con- Chronic (%) 8 (28.6) 3 (8.8) .043
tinued after treatment at the discretion of the physician. Antic- Acute (%) 20 (71.4) 31 (91.2)
oagulation was omitted or discontinued from treatment if it APLSb (%) 2 (10.0) 1 (6.7) .092
posed a high risk to patients or resulted in complications such TEE or TTE (%) 20 (71.4) 21 (61.8) .42
CT imaging (%) 12 (42.9) 18 (52.9) .43
as bleeding and/or heparin-induced thrombocytopenia.
MR imaging (%) 6 (21.4) 2 (5.9) .069
US imaging (%) 19 (67.9) 22 (64.7) .79
Statistical Methods CB imaging (%) 10 (35.7) 3 (8.8) .010
Discoloration (%) 13 (46.4) 8 (23.5) .058
Descriptive statistics are displayed as means and standard Gangrene (%) 2 (7.1) 0 (0) .20
deviations for continuous variables, and the number and per- Pain (%) 21 (75.0) 26 (76.5) .89
centage with characteristic are given for categorical variables. Cold (%) 10 (35.7) 20 (58.8) .068
When continuous variables had skewed distributions (survival Numbness (%) 13 (46.4) 25 (73.5) .029
time), data are summarized with medians and 25th and 75th Swelling (%) 4 (14.3) 1 (2.9) .17
Ischemic side .76
percentiles. Categorical variables were analyzed using Pearson
Right (%) 13 (46.4) 19 (55.9)
chi-square or Fisher exact tests, and continuous variables were Left (%) 14 (50.0) 14 (41.2)
analyzed using Student t test. Kaplan-Meier survival analysis Both (%) 1 (3.6) 1 (2.9)
was used to evaluate overall survival and complication-free LOS, days, median (25th, 2 (0, 4) 4 (2, 8) .002
survival at 30 days and up to 1-year follow-up. A value of 75th percentile)
P < .05 was considered significant, and P values are 2-sided Heparin (%) 19 (67.9) 32 (94.1) .007
where possible. All statistical calculations and plots were done Thrombo/embolectomy (%) 8 (28.6) 25 (73.5) <.001
Angiogram (%) 8 (28.6) 5 (5.9) .016
with Stata 11.2 (Statacorp, College Station, Texas).
Bypass (%) 3 (10.7) 0 (0) .087
Antiplatelets (%) 18 (64.3) 20 (58.8) .66
tPA/thrombolysis (%) 1 (3.6) 2 (5.9) .67
Results Complications at 30 days (%) 2 (7.3) 5 (14.7) .35
Complications at 1 year (%) 3 (11.1) 7 (22.2) .29
Over the span of 8 years, 100 patients were diagnosed with UEI Death at 30 days (%) 1 (3.6) 0 (0) .27
with underlying arterial embolus or thrombosis at our center. Death at 1 year (%) 2 (7.1) 8 (20.9) .13
Sixty-four (64.0%) patients met the inclusion criteria and were
included in this study. For the overall group, the mean age of Abbreviations: SD, standard deviation; APLS, antiphospholipid syndrome; TEE,
transesophageal echocardiography; TTE, transthoracic echocardiography; CT,
patients at initial presentation was 69.8 + 18.3 years, and computerized tomography; MR, magnetic resonance; US, ultrasound; CB,
59.4% were female. History of HTN (62.5%), hyperlipidemia catheter based; LOS, length of stay; tPA, tissue plasminogen activator.
a
(42.2%), past or current tobacco use (51.6%), and DM b
Percentage based on female patients only.
(26.6%) were prevalent. In addition, 2 women reported receiv- Percentage based only on those with known outcomes (n ¼ 35).
ing HST. Upon evaluation, patients commonly reported symp-
toms of pain (76.6%), numbness (59.4%), coldness (46.9%), patients underwent catheter-based angiogram to further deter-
and discoloration (34.4%). Only 1 patient was asymptomatic mine the extent of disease. Forty-one (64.1%) patients with
but had significant (>10 mm Hg) blood pressure difference known or suspected cardiac history underwent echocardiogram
between both arms. Patients presented with symptoms in the to diagnose a cardiac origin. Median length of hospital stay for
right and left upper extremities in similar frequencies (52% all patients was 3 days [1, 5].
vs 45%). Two patients presented with symptoms bilaterally. Embolism was diagnosed in 34 (53%) patients, 28 (45%)
Fifty-one (79.7%) patients presented with acute ischemia. The patients were diagnosed with thrombosis, and 2 (3%) patients
brachial (61%), ulnar (34%), and the radial (28%) arteries were were diagnosed with severe stenosis. Baseline demographic
the most common sites of involvement. Both CTA and US ima- and clinical characteristics, management, length of stay, and
ging were performed in 65.6% and 46.9% patients, respec- outcomes are shown in Table 1 for the embolism and thrombo-
tively, to establish the location of occlusion. Fifteen (33.4%) sis groups. Due to small sample size, the 2 patients with severe

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Skeik et al 103

Table 2. Etiology of Upper Extremity Ischemia. Table 3. Summary of Thrombophilia Workup.

Etiology Frequency (%) Tested Tested Total Pts Total Pts

Thrombophilia Positive Negative Untested Tested, %
ASO 11 (17.2)
Buerger disease 3 (4.7) APLS 3 32 29 54.7
Cancer metastasis 3 (4.7) Protein S 0 11 52 17.2
Cardiac 30 (46.9) Protein C 5 9 50 21.9
AF 26 (86.7) Factor V Leiden 3 19 42 34.4
AV vegetation 1 (3.3) gene mutation
Aortic thrombus 1 (3.3) Prothrombin gene 1 19 44 31.3
PFO/DVT 2 (6.7) mutation
Hormonal stimulation therapy 1 (1.6) Antithrombin III 4 10 50 21.9
Thrombophilia 1 (1.6) Homocysteine 2 8 54 15.6
Trauma 12 (18.8)
General 4 (33.3) Abbreviations: APLS, antiphospholipid syndrome; pts, patients.
Hypothenar hammer syndrome 5 (41.7)
Iatrogenic 3 (25.0)
Vasculitis 1 (1.6) and/or factor II and factor V Leiden genetic mutations. In total,
Unknown 1 (1.6) at least 1 form of thrombophilia was detected in 11 patients.
Eight patients on anticoagulation had positive test results for
Abbreviations: ASO, atherosclerosis; AF, atrial fibrillation; AV, aortic valve; LAC and underwent further testing. In addition to otherwise
PFO, patent foreman ovale; DVT, deep vein thrombosis.
unremarkable laboratory test results, 5 (63%) of these patients
tested negatively for LAC the second time and were deter-
stenosis were omitted from comparative analysis. Patients mined not to have APLS. Three patients with positive LAC
diagnosed with embolisms were older, had higher rates of results for the second time were diagnosed with APLS. Throm-
HTN, and were more likely to present with numbness than bophilia results are summarized in Table 3.
patients diagnosed with thrombosis (P < .05 for all). In addi- Eleven (17%) patients experienced a total of 12 periopera-
tion, patients with emboli had longer lengths of hospital stay tive complications, most commonly hematoma at the incision
(4 [2, 8] days vs 2 [0, 4] days; P ¼ .002) and were more likely site following thromboembolectomy (n ¼ 4). Two (3%)
to be treated with heparin (94.1% vs 68.0%; P ¼ .007) and patients continued to exhibit limited perfusion after treatment
thromboembolectomy (73.5% vs 28.6%; P < .001) than and required additional intervention. Furthermore, 2 (3%)
patients diagnosed with thrombosis. Patients with thrombosis patients underwent amputation for either persistent ischemic
had greater use of catheter-based imaging (35.7% vs 8.8%; or necrotic tissue. Complications at 30 days and up to 1 year
P ¼ .01). There was no difference in gender, history of were 11.0% and 16.6%, respectively. Complications are sum-
DM, tobacco use, presentation with pain, discoloration, cold, marized in Figure 2. There was a limb salvage rate of 96.3%
affected extremity, treatment with bypass or antiplatelet ther- for all patients. With a median follow-up of 521 [305, 1156]
apy, and complications as well as mortality at 30 days and up days, mortality at 30 days and up to 1 year were 1.6%
to 1 year between the thrombosis and embolism groups. and 14.6%, respectively, and there was a mean survival of
Etiology of UEI is shown in Table 2. Embolism of cardiac 672 + 681 days. At time of last follow-up, 21 (32.8%) patients
origin, specifically AF, was the most prevalent etiology, occur- died from causes unrelated to UEI, including congestive heart
ring in 46.9% of cases. Two patients with patent foreman ovale failure (CHF; n ¼ 9), cancer (n ¼ 7), respiratory failure (n ¼ 3),
had paradoxical embolisms with underlying deep vein throm- renal failure (n ¼ 1), and liver failure (n ¼ 1).
bosis. All patients with underlying ASO etiology presented
with either a thrombus or severe stenosis.
Patients underwent various combination of treatments for Discussion
UEI, and therapies were often coupled (eg, thromboembolect- Upper limb ischemia is a rare condition resulting from var-
omy and anticoagulation) to optimize treatment efficacy. ious disorders associated with compromised blood supply.1,2
Patients were administered anticoagulation (81.3%) and Despite the severity of UEI, the exact incidence remains
antiplatelet therapy (60.9%) during the perioperative period. unknown as most of the current statistics are derived from
Eleven (17.2%) patients solely received anticoagulation for surgical case series.5,15 History of DM, thrombophilia, hyper-
treatment. More than half (51.6%) of the patients underwent tension, hyperlipidemia, tobacco use, and vasospasm are
thromboembolectomy, while 10 (15.6%) patients underwent known risk factors for UEI.16-18
catheter-based angiogram. Less common treatment modalities The UEI can be classified as either acute or chronic, and it is
used included angioplasty and stenting (4.7%), arterial bypass most commonly caused by embolism, thrombosis, and or ste-
(4.7%), catheter-based thrombolysis (4.7%), and vasodilators nosis of upper extremity arteries.19,20 Thromboembolic events
(3.1%). may occur in patients with AF, ASO, trauma, and TOS.16,20,21
Thirty-five (55%) patients were tested for abnormalities in Depending on the etiology, patients present with various
antithrombin III, protein C, protein S, homocysteine, APLS, symptoms referred to as the 6 P’s: paresthesia, pain, pallor,

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104
Complications of Upper Extremity Ischemia
50%
40% 36.4%
Percent of Cases 30%
18.2%
20%
10%
0%
Hematoma Amputations
Figure 2:. Complication events of upper extremity thrombosis.
pulselessness, poikilothermia, and paralysis.20,22,23 It is essen-
tial for patients with critical UEI to undergo limb-salvage treat-
ment within 6 hours from the onset of symptoms, as any delay
jeopardizes limb viability.24 Duration and site of occlusion,
collateral blood flow, and underlying comorbidities determine
the acuity of symptoms and extent of disease.16,24,25
The UEI can be diagnosed based on patient history, physical
examination, and imaging. Imaging modalities such as US,
CTA, and MRA are used frequently due to the ease of estab-
lishing disease and the low risk of complications.10 However,
catheter-based angiography is considered the gold standard in
identifying the extent of arterial obstruction and may improve
outcomes when combined with thromboembolectomy.20
Thromboembolectomy is the most prevalent treatment, and
evidence suggests timely surgical approaches are beneficial
for treating UEI.6,26,27 Catheter-based treatments, such as
angioplasty, stenting, and more recently thrombolysis, are
playing an increased role in UEI treatment. These strategies
have been associated with reductions in mortality, complica-
tion events, and length of hospitalization.7,28 Although throm-
bolysis is a common treatment for lower limb ischemia, it has
been cautiously used for patients with UEI due to the risk of
inducing stroke.5,29,30 However, studies have demonstrated
promising results with thrombolysis in the management of
UEI.3,7,19
Despite its frequent use, conservative therapy has rarely
been evaluated as a primary treatment for UEI.5 Conservative
management, which includes anticoagulation, rehydration, and
treatment of comorbidities, is reserved for patients who do not
qualify for intervention due to mild disease or significant
comorbidities.5,23,31,32 Around 54% of our patients were
treated medically. Amputation is performed as a last resort in
patients when all treatment options are exhausted or in patients
presenting with significant tissue necrosis, unsalvageable limbs,
or high risk of reperfusion injury.33,34
The UEI is frequently accompanied with significant comor-
bidities, such as AF and cardiovascular disease. Patients with
these comorbidities tend to have poor prognoses and a mor-
tality rate of up to 12%. Prophylactic measures, including
management of HTN, smoking cessation, and antithrombotic
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Vascular and Endovascular Surgery 49(5-6)
Up to One Year (n=12)
18.2% 18.2%
9.1% 9.1%
Persistent HIT Embolus in Weakness
Occlusion Contralaterial
Extremity
therapy, may decrease the risk future of cardiovascular events
following detection of UEI.3,5,20,35
The current literature evaluating the demographics, etiol-
ogy, and management of UEI is limited and is primarily com-
prised of small case studies.8 To the best of our knowledge, this
is one of the largest North American studies to date and is the
only study that distinguishes and compares embolisms and
thrombosis in the arteries of the upper extremities.
Epidemiology
Fifty-one (79.7%) of our patients had acute presentation of
UEI. The mean age of our overall study population was
69.8 + 18.3 years (Table 1). Several studies have reported sim-
ilar mean ages at presentation.2,8 In a review of 182 patients
with UEI, Deguara et al reported a mean age of presentation
of 72.4 years.15 Stonebridge and colleagues, in a 5-year review
of 61 patients with acute UEI, reported a mean age of onset of
74 years.36 However, we found patients diagnosed with embo-
lism were significantly older than patients diagnosed with
thrombosis. The 23.8-year difference in the mean age of the
2 diagnostic groups may be due to a higher prevalence of
AF, a disease that increases in prevalence with age and is also
the leading cause of embolisms in the upper extremity.16,37
There is a lack of consensus regarding gender distribution of
UEI. In our study, 59% of patients were female. Multiple stud-
ies have corroborated our findings.30,36 However, studies by
Magishi and Baird reported that 59% and 66% of patients,
respectively, were male, while other studies have reported
equal gender distribution.9,25,38,39 Despite this ambiguity, gen-
der may influence the risk of stroke during or following throm-
boembolectomy, and females and males are 5 times and
3 times, respectively, more likely to develop a stroke than those
who do not undergo the procedure.22
Pathophysiology
The pathophysiology of UEI in our study was embolism (53%),
thrombosis (44%), and severe stenosis (3%). Although the
authors of one previous study found it clinically impossible
Skeik et al
to distinguish between embolism and thrombosis in 10% to
15% of cases, we were able to distinguish etiology of UEI in
most of our patients.16 Our findings regarding the distribution
of UEI etiology are similar with the results reported in 2 earlier
studies. One smaller, retrospective analysis of 36 patients
reported the most common causes of acute UEI to be embolism
(47%), thrombosis (28%), and trauma (25%).20 A separate,
single-center study reported that thromboembolism (35%),
trauma (31%), and ASO (17%) were the most common reasons
for patients to undergo upper limb revascularization.15
Risk Factors and Comorbidities
Hormonal stimulation therapy resulted in the formation of a
thrombus in 1 (1.6%) patient with no other significant comor-
bidities or risk factors for UEI. Postmenopausal patients on
hormonal replacement therapy (HRT) are known to be at a
greater risk of stroke and venous thromboembolisms, but arter-
ial thromboembolisms are relatively rare with an estimated
incidence of 1.7 to 3.4 per 100 000 women-years.40-42 In a
series of 769 institutions, Adachi and Sakamoto found only
1% of females receiving HRT experienced arterial thromboem-
bolisms.42 Despite the relatively low incidence, HRT should
not be overlooked as a cause of UEI in women.
In our study, patients with embolisms were significantly
more likely to have a history of HTN (P ¼ .001). Hypertension
contributes to cardiac changes, which favor the development of
AF, thereby increasing the risk of embolic events.43 The large
percentage of patients with UEI having a history of HTN sug-
gest a possible association between HTN and UEI.44 To the
best of our knowledge, no other studies have reported compa-
rable data.
Presentation
Presentation with coldness, pain, cyanosis, pallor, and par-
esthesia have been previously reported in patients with UEI.3,19
Most patients at our center reported symptoms of pain, numb-
ness, and coldness. However, presentation with numbness was
significantly more frequent in patients diagnosed with embo-
lism (73.5% vs 46.4%, P ¼ .029). We believe the dramatic
development of ischemic injury with embolism may have con-
tributed to this finding.
In situ thrombosis secondary to progressive ASO may cause
patients to manifest milder symptoms due to the development
of collateral blood vessels over time.24 One patient with a his-
tory of ASO was asymptomatic upon presentation. He had a
significantly lower blood pressure in his right arm during a rou-
tine examination. Chronic asymptomatic UEI can be detected
by comparing contralateral blood pressures (>10 mm Hg
difference).45
In our study, 51.6% of patients presented with UEI in the
right arm. Numerous studies have reported the most commonly
affected extremity to be the right arm, which evidence suggests
is due to anatomical conditions.5,8,25,26 Furthermore, the bra-
chial artery was the most common location of occlusion,
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105
occurring in 61% of our patients. Similar to our findings,
Haimovici found that most arterial occlusions occurred in the
brachial artery (61%), followed by the axillary artery (23%),
and radial artery (23%).46 Numerous other studies corroborated
our results, reporting the brachial artery to be the most fre-
quently involved vessel.2,6,15,25 Studies have proposed patients
with either radial artery or ulnar artery involvement present
with less serious symptoms because either of these vessels may
compensate for the other.5
Diagnosis
In our study, preliminary tests such as continuous wave Dop-
pler and Allen’s tests were routinely performed on patients to
diagnose the disease. Imaging modalities such as US, CTA,
MRA, and catheter-based angiogram were conducted on all
patients prior to the intervention. Patients with a known or sus-
pected cardioembolic event (64.1%) underwent echocardiogra-
phy. Patients with thrombosis were significantly more likely to
have undergone catheter-based angiogram (P ¼ .005). This
may reflect our institution’s multidisciplinary approach rather
than general trends in UEI management. Catheter-based angio-
graphy may have been reserved for patients with thrombosis as
this modality allows operating physicians to incorporate thera-
pies such as thrombolysis and angioplasty simultaneously. In
the study by Zaraca et al, all 100 patients treated for arterial
occlusions were diagnosed based on clinical assessment and
Doppler test.47 There was heterogeneity in the use of diagnostic
modalities among different practices. In a retrospective study
of 35 patients, Islam et al reported angiography was the most
common diagnostic modality.48 Another study reported that
after physical examination, 62% of patients underwent diag-
nostic angiogram, while the remaining 38% underwent diag-
nostic CT and US.9
Etiology
At our center, the most common underlying etiologies were AF
(40.6%), ASO (17.2%), and hypothenar hammer syndrome
(7.8%). Atrial fibrillation is the most common cardiac arrhyth-
mia and is a significant risk factor for developing UEI.35
Numerous studies have reported AF to be the primary etiology
for acute UEI. A national cohort study including 1377 patients
found 62.7% of patients presented with AF prior to or at the
time of admission.15,22 Andersen and colleagues described the
incidence of patients with AF who underwent thromboembo-
lectomy of the upper limb to be 58.9 per 100 000 person-years
for men and 139.1 per 100 000 person-years for women.44
Given the high risk of thromboembolic events, AF should
be investigated routinely in patients presenting with UEI.37
In our study, the most common cause of trauma was
hypothenar hammer syndrome (42%). These patients under-
went a variety of treatments, including anticoagulation, throm-
boembolectomy, and antiplatelet therapy. Given the rarity of
hypothenar hammer syndrome, very few studies have been
conducted to analyze the disease within the scope of UEI.49
106
However, case studies have shown the goals of hypothenar
hammer syndrome management are similar to those of patients
with UEI.50
One patient excluded from this study presented with clinical
and imaging evidence of arterial TOS. Arterial TOS can lead to
both chronic and acute UEI by causing local thrombosis or
distal embolism.24 Patients who do not respond to physical
therapy or patients who present with acute arterial or venous
thrombosis would benefit from catheter-based lytic therapy fol-
lowed by compression release surgeries.51-53
In this study, all patients diagnosed with APLS were treated
with anticoagulation and/or thromboembolectomy. It is recom-
mended to manage patients with APLS carefully, as improper
treatment can lead to amputation.54-56 Patients with a history
of thromboembolic events of unknown etiology should be
tested for APLS as confirmation of the disease and proper man-
agement will reduce the likelihood of future recurrence.
Management
Common treatment modalities include surgical thromboembo-
lectomy and endovascular procedures, such as thrombolysis,
angioplasty, and/or stenting. Patients not treated with surgical
intervention typically were older, were at higher risk of compli-
cations, had significant comorbidities, or had insignificant
disease.
Twenty-five (73.5%) patients with embolisms underwent
thromboembolectomy, while only 8 (28.6%) patients with
thrombosis underwent this procedure (P < .001). We believe
embolectomy may have been utilized more frequently to treat
embolisms because these emergency procedures are reserved
for patients who experience a sudden onset of symptoms
and require immediate limb-salvaging therapy. Patients with
thrombosis may present with chronic disease, collateral ves-
sels, and milder symptoms, allowing noninterventional treat-
ments such as anticoagulation to be explored. However, Rapp
et al suggested that patients with thrombosis in situ have worse
prognosis and outcomes than those with embolisms due to the
underlying ASO requiring more extensive revascularization.57
Thromboembolectomy is the most popular treatment because
of its clinical success.19 Savelyev et al reported the best success
rate of 91% with thromboembolectomy in 256 patients.58 Other
authors have also reported relatively high success rates of
86%, 87%, and 91.7% in smaller patient groups.5,34 Although
surgical intervention is the preferred treatment for UEI, there
are significant risks associated with it. Andersen et al reported
patients undergoing thromboembolectomy were up to 5 times
more likely to develop a stroke than the general population.35
There is growing data to support the use of endovascular
approaches for treatment of UEI, especially in patients with
other comorbidities who are at high risk of surgical complica-
tions.3,10,19,58-60 Cejna et al reported surgery and thrombolysis
in small patient groups have equal effectiveness, except in
patients with distal occlusions where surgery proved to be
the superior treatment.59 In patients without tissue loss or
gangrene, Islam et al reported thrombolysis had a superior
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Vascular and Endovascular Surgery 49(5-6)
amputation-free survival compared to those treated with other
modalities, suggesting thrombolysis may be most beneficial for
these patients.48
Anticoagulation, if not contraindicated, is an important
treatment modality for all patients with acute UEI to prevent
further thromboembolic events. Anticoagulation was adminis-
tered to most of our patients (81.3%) during the perioperative
period or upon discharge. According to a systematic review,
operative management was more commonly used than anticoa-
gulation for acute UEI.5 Variations in patient selection may
have led to this difference in results. It is also hypothesized
that many patients undergoing solely conservative manage-
ment are unreported and omitted from surgical studies.5
Stonebridge et al found when anticoagulation was omitted
from treatment, there was a 22% increase in the incidence
of reocclusion, a known indicator of poor prognosis and high
mortality rates 16,36,61
Anticoagulation is used regularly to treat UEI, but few stud-
ies have evaluated its efficacy as a sole treatment.5 Turner et al
reported clinical success in 14 of 16 patients who received
anticoagulation as a primary therapy, demonstrating results
comparable to those of thromboembolectomy.62 In contrast,
Galbraith and colleagues showed 50% of patients treated solely
with conservative management including anticoagulation expe-
rienced residual symptoms.25 Despite the controversy surround-
ing anticoagulation as a primary treatment modality, studies
have supported anticoagulation use for patients to minimize the
risk of reocclusion and to prolong survival.8,16,36 Based on this
evidence, we recommend that anticoagulation with intravenous
heparin should be administered immediately to reduce symp-
toms and minimize progression of disease, as demonstrated in
earlier studies.5,62
Hospital Stay
To our knowledge, our study is the first to assess hospital
length of stay in patients with UEI. The median length of hos-
pital stay was 4 days for the embolism group and 2 days for the
thrombosis group (P ¼ .002). Patients with embolisms had
more comorbidities such as HTN, hyperlipidemia, and DM
than patients with thrombosis, which may have contributed to
this difference.
Complications and Survival
At 30 days and up to 1 year of treatment, 11.0% and 16.6%
of our patients, respectively, experienced complications. The
most common complication was hematoma at the incision site
following thromboembolectomy (36.4%). Two patients under-
went subsequent amputation, while 2 other patients experi-
enced reocclusion. Hernandez et al reported comparable
results and found thromboembolectomy was associated with
a notably high complication rate of 20.3%, including reocclu-
sion of the artery (8.8%) and amputation (1.8%).26 Other stud-
ies have also demonstrated similar amputation rates of 0% to
Skeik et al
6.6%.35 In contrast, patients with lower limb ischemia have a
higher 1-year amputation rate, ranging from 23% to 26.1%.63,64
At the most recent follow-up (July 2014), 21 (32.8%)
patients were no longer alive. Mortality at 30 days and up to
1 year was 1.6% and 14.6%, respectively. Higher mortality
rates have been reported. Deguara et al showed the 30-day and
1-year mortality rate for patients undergoing thromboembo-
lectomy to be 18.2% and 38.2%, respectively.15 Another study
with 148 patients treated with embolectomy had a 30-day mor-
tality rate of 8% and a 5-year mortality rate of 63%.27 In our
study, all causes of death were directly linked to patients’
underlying comorbidities, such as CHF and cancer and not to
UEI disease or related treatment. Our results support the sug-
gestion that UEI is usually not a cause of death but rather an
indicator of overall poor outcome.22,25
Limitations
This is a retrospective study with a small sample size. How-
ever, we do not believe this is a significant limitation, given the
presentation and rarity of the disease. Second, not all patients
underwent thrombophilia testing. However, to adjust for this,
patients with incomplete thrombophilia workup and otherwise
unidentifiable etiologies were excluded. Finally, patients with
an unidentified site of occlusion or disease were excluded, but
the number of these patients was negligible.
Conclusion
The current literature examining the etiology, management,
and outcomes of UEI has been limited. This was one of the first
studies to distinguish between and analyze the significance of
embolisms and thrombosis in UEI. We found that embolism
was the most common etiology for UEI, and these patients were
found to be older, more likely to undergo thromboembolect-
omy, had higher rates of hypertension, and had longer lengths
of hospital stay than patients diagnosed with thrombosis. There
were no significant differences in complications and 30-day
and up to 1-year mortality between these groups.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
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