Angiology

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Intracoronary Macrothrombus Formation During Percutaneous Coronary Intervention Despite Optimal

Activated Clotting Time Using Bivalirudin: A Case Report
George M. Tadros, Kevin Broder and Fouad Bachour
ANGIOLOGY 2005 56: 761
DOI: 10.1177/000331970505600614
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Angiology

Volume 56, Number 6, 2005

761

Intracoronary Macrothrombus Formation

During Percutaneous Coronary Intervention
Despite Optimal Activated Clotting Time
Using Bivalirudin
A Case Report
George M. Tadros, MD,* Kevin Broder, and Fouad Bachour, MD FACC,
Minneapolis, MN

The occurrence of intracoronary thrombus during percutaneous coronary intervention (PCI) is

a well-known complication. It has been estimated that it complicates approximately 6% of all
coronary procedures. Patients at highest risk for this complication include those with acute
ischemic syndromes or with angiographically apparent thrombus. Since the development of
PCI, intravenous unfractionated heparin (UFH) has remained the primary antithrombotic
therapy for the prevention of periprocedural ischemic complications. The availability of a rapid
point of care test for dose individualization (the activated clotting time [ACT]) has facilitated
this process. Other forms of antithrombotic therapies such as direct thrombin inhibitors or
low-molecular-weight heparin have been proposed as more effective anticoagulants during
PCI. Bivalirudin is a direct thrombin inhibitor proven to decrease post-PCI ischemic complication
rate compared with UFH and have a lower vascular complication rate compared with glycoprotein IIb/IIIa receptor antagonists. We herein report a case of acute macrothrombus
formation during PCI despite adequate ACT achieved with bivalirudin.

Introduction

Angiology 56:761765, 2005

From the *Division of Cardiology, University of Minnesota;
University of Minnesota Medical School; and Division of
Cardiology, Department of Internal Medicine, Hennepin County
Medical Center, Minneapolis, MN
Correspondence: Fouad Bachour, MD, FACC, Cardiac
Catheterization Laboratory, Hennepin County Medical Center,
701 Park Ave, Minneapolis, MN 55415
E-mail: bacho0003@umn.edu
2005 Westminster Publications, Inc, 708 Glen Cove Avenue,
Glen Head, NY 11545, USA

The occurrence of intracoronary thrombus during

percutaneous coronary intervention (PCI) is a
well-known complication. It has been estimated
that it complicates approximately 6% of all coronary procedures. Patients at highest risk for this
complication include those with acute ischemic
syndromes or with angiographically apparent
thrombus.1 Since the development of PCI, intravenous unfractionated heparin (UFH) has remained the primary antithrombotic therapy for
the prevention of periprocedural ischemic complications. The availability of a rapid point of
care test for dose individualization (the activated

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Angiology

Volume 56, Number 6, 2005

clotting time [ACT]) has facilitated this process.

Other forms of antithrombotic therapies such as
direct thrombin inhibitors or low-molecularweight heparin (LMWH) have been proposed as
more effective anticoagulants during PCI.
Bivalirudin is a direct thrombin inhibitor proven
to decrease post-PCI ischemic complication rate
compared with UFH and have a lower vascular
complication rate compared with glycoprotein
IIb/IIIa receptor antagonists.2
Despite compliance with the current recommendations of an optimum ACT level of 300350
seconds and use of newer forms of anticoagulation, thrombotic complications still occur. We
herein report a case of acute macrothrombus formation during PCI. The thrombus formation site
was not at the angioplasty site, as the patient was
adequately pretreated with clopidogrel and aspirin and anticoagulated using bivalirudin with
an ACT of 370 s at the time of PCI.

Case Report
A 48-year-old man with a history of coronary
artery disease, type 2 diabetes mellitus, hypertension, and hyperlipidemia, presented to the
Emergency Department with significant worsening of shortness of breath. He had presented almost a year before this admission with ST elevation myocardial infarction, which was treated
with primary angioplasty and stenting of his left
anterior descending (LAD) artery. He was noted
to have moderate disease in his right coronary
and left circumflex arteries. The patient was discharged then on adequate medical therapy, including a beta-blocker, angiotensin-converting
enzyme inhibitor, HMG-CoA reductase inhibitor,
aspirin, and clopidogrel, along with strict control
of his diabetes mellitus.
In the interim year, the patient presented
with symptoms of congestive heart failure. He
was treated medically with better control of his
hypertension and diabetes mellitus. However, his
symptoms progressed until he presented for this
admission with worsening symptoms of fluid retention and resting dyspnea. He was treated in
the Emergency Department with intravenous diuretics, nitrates, and oxygen supplementation. He
was transferred to the coronary care unit for further treatment for congestive heart failure.
Physical examination on presentation to the
CCU revealed a hemodynamically stable middleaged male in mild respiratory distress with a reg-

ular heart rate of 100 and blood pressure of

130/60, and oxygen saturation of 98%. He had
evidence of jugular venous distension with positive hepatojugular reflux. Heart sounds were distant but regular with an S3 gallop. His chest examination revealed inspiratory crackles appreciated over all lung fields, extending up to the clavicles bilaterally. Extremities were warm to palpation with significant bilateral, painless, symmetrical grade 3 pitting pedal edema.
An initial electrocardiogram (EKG) demonstrated Q waves in inferior leads and poor progression of R waves in the anterior leads. There
was no evidence of acute ischemic changes. A
chest radiograph was suggestive of cardiomegaly
and pulmonary edema. Initial serum cardiac enzymes documented a negative troponin I and creatine kinase (CK-MB). A 2-D echocardiogram revealed left ventricular (LV) systolic dysfunction
with an estimated ejection fraction of 30%. When
compared to the prior echocardiogram, an assessment of his regional wall function demonstrated a
new large inferior wall motion abnormality, with
akinesis of the basal inferior segment.
With his acute decompensation and the new
inferior wall motion abnormality, the patient was
taken to the cardiac catheterization laboratory to
evaluate his coronary artery disease and possible
revascularization. A diagnostic coronary angiogram revealed a normal left main, patent LAD
stents with mild in-stent restenosis, and moderate
diffuse disease in the left circumflex artery. A
dominant right coronary artery (RCA) gave rise to
a large posterolateral (PLA) branch and a subtotally occluded posterior descending artery (PDA)
at the ostium with TIMI flow grade I (Figure 1),
which was filling via poor left-to-right collateral
flow. Given his presentation, the decision was
made to attempt to open the PDA occlusion.

Procedure
A 6 French Judkins right 4 cm Launcher guide
catheter (Medtronic, Santa Rosa, CA) without
sideholes engaged the RCA with adequate support. Bivalirudin was given as the anticoagulant
for the PCI, and the activated clotting time (ACT)
was 370 seconds before engagement. Using kissing wire technique to protect the PLA, a 182 cm
0.014" Luge wire (Boston Scientific, Maple
Grove, MN) was introduced in the PLA successfully. A 300 cm Luge wire failed to cross the
PDA subtotal occlusion with the support of an

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Tadros

Figure 1.

RCA in Lao/Cranial 100% PDA.

Figure 2. Kissing wire (RPAV and RPDA)

PTCA to RPDA.

OTW 1.5 mm x 20 mm Maverick balloon

(Boston Scientific, Maple Grove, MN). The Luge
wire was changed to a 300 cm 0.014" PT2 moderate support (Boston Scientific, Maple Grove,
MN) with successful canalization of the PDA. The
1.5 mm x 20 mm Maverick balloon inflated at

Intracoronary Macrothrombus Formation

763

Figure 3. RCA intracoronary thrombus

formation and slow flow.

12 atm (Figure 2). A second dilation with a 2.0

x 20 Maverick was done and the balloon was
pulled out with a total time of 9 minutes from
guide engagement to successful dilation.
The patient started to complain of chest pain
and bilateral shoulder pain and the monitored
lead II revealed mild ST elevation. Angiographic
pictures showed a filling defect in the mid RCA
proximal to the acute marginal branch. This clot
propagated distally to involve the distal RCA
with slow flow in the whole vessel (Figure 3). A
repeat ACT was 350 seconds. With the presence
of the acute thrombus with a high ACT with use
of bivalirudin, we decided to use abciximab as a
bailout. A 0.25 mg/kg bolus of abciximab was
given half intracoronary in the RCA and half
given intravenously, and an intravenous drip was
started at 0.125 mcg/kg/minute. Using the
Export aspiration catheter (Medtronic, Santa
Rosa, CA), 3 runs of suction were performed and
resulted in suctioning of a clot and debris from
the artery (Figure 4). With successful restoration
of TIMI grade III flow in the RCA, further work on
the PLA and RCA was done, including stenting of
the PLA using a 2.5 mm x 16 mm Express stent
(Boston Scientific, Maple Grove, MN). At the end
of the procedure, the patient was asymptomatic
and EKG changes had resolved (Figure 5).
The patient was then transferred to the coronary care unit and abciximab infusion was continued at 0.125 mg/kg/min for a total of 12

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Discussion

Figure 4.

Thrombus aspirated from RCA.

Figure 5.

RCA final result.

hours. Post-PCI CK-MB peaked at 54.5 mg/dL.

The patients recovery was not complicated, and
he was subsequently discharged on aspirin, clopidogrel, HMG-CoA reductase inhibitor, beta-blocker, angiotensin-converting enzyme inhibitor, and
diuretics.

Despite advances in periprocedural safety and

subsequent improved morbidity and mortality
rates after percutaneous coronary interventions,
the incidence of acute thrombotic complications
remains a major concern. Postprocedural CK-MB
elevation is associated with increased long-term
risk of cardiac events.3-10 While many complications are attributed to suboptimal periprocedural
anticoagulation,11 other possibilities include direct vessel injury and risk of clotting associated
with contact between blood and devices such as
intracoronary wires, balloons, and guide catheters. This was challenged by a study by Moreyra
et al,12 in which the deposition of cellular and
amorphous material on the surface and grooves
of the Teflon-coated guidewires was not significantly different at 3, 5, and 10 minutes of bloodwire contact in the presence of low-dose heparinization.
The use of heparin has been associated with
an optimal level of anticoagulation, most commonly tested by ACT in most patients undergoing PCI. Defining the optimal level of ACT has
been hampered by the lack of large-scale, randomized data. Current recommendations of ACT
levels of 300 to 350 s are empiric and based on
relatively small studies.13-17 In a recent metaanalysis of 6 randomized, controlled trials by
Chew et al,18 the optimal level of ACT for the suppression of periprocedural ischemic events after
PCI was defined as the range of 350 to 375 s.
Specifically, in subgroups at greater risk of thrombotic events, a steeper gradient of benefit between lower and higher levels of ACT is evident
by a reduction in the composite ischemic end
point from 11.1% at an ACT of 275 to 300 s to a
nadir of 6.6% with an ACT of 350 to 375 s.
Prospective use of glycoprotein IIb/IIIa receptor antagonist (eptifibatide) during PCI was
studied in the ESPRIT trial,19 which revealed a
statistically significant reduction in CK-MB elevation of 4% compared with 7% in placebo (p
= 0.003) in patients without angiographic complications. However there was no statistically significant reduction in the incidence of angiographic complications.19 When used prospectively
in the EPISTENT trial,20 abciximab reduced angiographic complications during coronary stenting
and decreased the incidence of significant CK-MB
elevations in patients with and without angiographic complications. Bailout use of GP IIb/IIIa
receptor antagonists is not proven to reduce the
rate of ischemic complications.

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Tadros

Data suggest that other anticoagulants (eg,

low-molecular-weight heparin, hirudin, bivalirudin, argatroban) may have more predictable
dose-response characteristics than heparin and
are potentially more efficacious than clot-bound
thrombin. The REPLACE-2 trial2 demonstrated
noninferiority of bivalirudin compared with heparin and glycoprotein IIb/IIIa receptor antagonist (eptifibatide) in terms of periprocedural complication rate in nonurgent PCI and superiority of
bivalirudin compared with heparin alone.
In conclusion we report a case of acute
macrothrombus formation leading to vessel closure despite minimal wire time and optimal anticoagulation with bivalirudin as indicated by an
ACT of 370 s. This case report underscores the
importance of aggressive periprocedural anticoagulation, the successful use of the aspiration
catheter in resolving this complication, and the
need for diligent monitoring and anticipation of
complications despite perceived adequate thrombin inhibition. Further studies are required to define the optimal ACT and define the role of
newer agents in the cardiac catheterization laboratory and more accurate methods of monitoring
their effect.

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765

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