Open Journal of Thoracic Surgery, 2012, 2, 10-12
http://dx.doi.org/10.4236/ojts.2012.21003 Published Online March 2012 (http://www.SciRP.org/journal/ojts)
Surgeries for the Heart and Abdominal Aorta in a Patient
with Heparin-Induced Thrombocytopenia: Manifestations
Following Initial Heart Surgery
Shoh Tatebe1, Makoto Taoka2, Imun Tei2, Shuko Nakamura2, Ei-ichi Tei2
1Department of Thoracic and Cardiovascular Surgery, Mito Saiseikai General Hospital, Mito City, Japan; 2Department of Cardio-
vascular Surgery, Ayase Heart Hospital, Tokyo, Japan.
Email: statebe@yahoo.com
Received December 4th, 2011; revised January 24th, 2012; accepted February 6th, 2012
ABSTRACT
A 72-year-old man with abdominal aortic aneurysm and angina pectoris underwent coronary artery bypass grafting
(CABG) prior to abdominal aortic surgery. Perioperatively, he developed thrombocytopenia (29,000 mm3), which was
suggested as heparin-induced thrombocytopenia. Cardiac status was also aggravated at the same time, suggestive of
bypass graft thrombosis. The results of platelet factor 4 (pf4) antibody test were negative, but platelet aggregation test
was positive for heparin. Heparin was immediately discontinued, and replaced by argatroban; the patient’s cardiac
status improved. One month later, he underwent abdominal aortic surgery using argatroban without issues related to
anticoagulation and hemostasis. Autologous donated fresh blood prepared by the “switch-back method” was also used
in this case, and its value was confirmed.
Keywords: Heparin-Induced Thrombocytopenia
1. Introduction
Heparin-induced thrombocytopenia (HIT) is an immune-
mediated clotting disorder caused by frequent and exten-
sive heparin exposure. The clinical manifestations of HIT
are thrombocytopenia and thrombosis, usually with dev-
astating consequences, such as limb ischemia, stroke,
pulmonary embolism, or death [1]. The clinical picture of
HIT after cardiac surgery is complicated, and may result
in fetal thrombotic events, such as myocardial infarction.
Here, we report a case of HIT revealed after cardiac sur-
gery, which was treated successfully without sequelae,
and the patient subsequently underwent abdominal aortic
surgery without HIT-re lated adverse events.
2. Case Presentation
A 72-year-old man was referred by a local general hos-
pital for surgical treatment of an abdominal aortic aneu-
rysm (AAA). His medical history included myocardial
infarction on posterior and lateral walls over 20 years
previously, for which conservative treatment was per-
formed because catheter intervention for the coronary
artery was not available. He was diagnosed as diabetic 1
month prior to presentation at a local general hospital,
where he had been hospitalized. Treatment for diabetes
was initiated and systemic workup was performed. An
AAA 5 cm in diameter was found during systemic
workup, but he was asymptomatic. However, coronary
angiography (CAG) revealed multiple stenoses on the
coronary arteries, including 75% stenosis of the left main
trunk. Due to concerns regarding life-threatening pe-
rioperative complications, he was scheduled for coronary
artery bypass grafting (CABG) prior to surgery for AAA.
The patient underwent CABG (three vessels) with car-
diopulmonary bypass (CPB). An intraaortic balloon pump-
ing (IABP) catheter was introduced after induction of
general anesthesia to avoid critical intraoperative myo-
cardial infarction. The initial postoperative course was
uneventful, and IABP was discontinued on postoperative
day 1 (POD1). However, platelet count decreased sud-
denly to 29,000/mm3 on POD2 and 30,000/mm3 on PO D3.
Although platelet factor 4 (pf4) antibody test was nega-
tive, heparin was discontinued immediately and replaced
with argatroban due to suspected heparin-induced thro-
mbocytopenia (HIT). Cardiac status became aggravated,
and intravenous argatroban was started at 20 mg/day due
to concerns regarding graft occlusion. Platelet counts
normalized and heart failure improved. Postoperative
CAG indicated that all grafts were tolerated and patent.
Platelet aggregation test (PAT) was positive at 10 mi-
cromol heparin, confirming diagnosis of HIT type I.
The patient underwent abdominal aortic surgery one
Copyright © 2012 SciRes. OJTS
Surgeries for the Heart and Abdominal Aorta in a Patient with Heparin-Induced Thrombocytopenia:
Manifestations Following Initial Heart Surgery 11
month after CABG. Preoperatively, 6 units of autologous
blood were obtained using erythropoietin. In the operat-
ing room, 6 units of autologous fresh blood were taken
by the “switch-back method”. All pressure lines and the
circuit of the autologous blood transfusion device were
replaced with saline containing argatroban or acid-cit-
rate-dextrose solution. Prior to clamping the arteries, 8.5
mg (0.1 mg/kg) of argatroban was administered as a bo-
lus, and maintained at 10 - 15 mg/h to achieve activated
coagulation time (ACT) >200 s. The AAA was success-
fully replaced by a vascular prosthesis. Argatroban was
discontinued after reperfusion, and autologous fresh blood
was given. No bleeding was noted, but as there is no an-
tidote to argatroban, it was necessary to wait for over 90
min until ACT had normalized. Postoperatively, argatro-
ban was resumed and then switched to oral warfarin. The
postoperative course was uneventful and the patient was
discharged on POD14. PAT were repeated and remained
positive with heparin for 3 years.
3. Discussion
In the present case with postoperative manifestations of
HIT after CABG, the patient underwent abdominal aortic
surgery using argatroban instead of heparin. This case
raised the issue of the time between onset of HIT and
treatment. Perioperatively, platelet count may be lower
than 100,000/mm3 after cardiac surgery. Therefore, it is
quite difficult to make a definite diagnosis in patients
with initial manifestations of HIT. IABP may have been
responsible for thrombocytopenia in this case. Therefore,
another day was required for suspicion of HIT, and the
initiation of treatment was delayed. Most patients under-
going cardiovascular surgery have been exposed to hepa-
rin during treatment or examination by the cardiology
service. Postoperative manifestations of HIT tend to oc-
cur in patients referred from institutes other than cardi-
ology services or requiring emergent surgery. In the 3
years since treating this patient, three other patients have
presented with HIT postoperatively in our department;
two of these patients underwent emergent surgery due to
acute mitral regurgitation and dissecting ao rtic aneurysm.
Based on these cases, we have implemented preoperative
PAT using heparin in patients without heparin exposure.
The pf4 antibody test is a simple means of identifying
HIT type II, but does not provide information to exclude
a diagnosis of HIT type I. Even by ELISA, the presence
of pf4 antibodies can be confirmed only with a delay of 2
days or more in approximately 50% of patients in whom
HIT develops [2]. At present, PAT using heparin is much
faster even in cases with HIT type I in our institution, but
no HIT patients have been encountered to date.
Another issue is the initial treatment for HIT. The cur-
rent recommendation is to discontinue heparin in cases of
suspected HIT and begin treatment with direct thrombin
inhibitors, such as hirudin/bivalrudin, danaparoid, and
argatroban [3]. Danaparoid and argatroban are available
in Japan. Argatroban is a derivative of l-arginine, which
binds reversibly to the active site of thrombin, and is ap-
proved for treating HIT by the FDA as well as recombi-
nant hirudin (lepirudin). We chose argatroban because it
has a number of advantages, includi ng speci fi c rapi d onset ,
and is safe in patients with renal impairment. Periopera-
tively, when HIT was suspected, hemodynamic status
was aggravated in this case. As coronary angiography
was not performed, there was no actual evidence of graft
occlusion. However, it was suspected that bypass would
have a risk of thrombotic occlusion. In this patient, car-
diac status settled down after initiation of argatroban
treatment, suggesting thrombolysis in the n ative coronary
arteries and/or bypass grafts. Argatroban would be effec-
tive for HIT not only in this case, but also in the three
HIT patients we encountered previously.
The other issue is the treatment strategy for the AAA.
Over the past decade methods for endovascular repair
(EVAR) of aortic aneurysms have been developed, and
the indications have been expanded from the descending
aorta to other branched aortae, such as the aortic arch,
thoracoabdominal aorta, and abdominal aorta. At the
time of surgery for AAA in the present case, approval for
EVAR in Japan was strictly limited to elderly patients or
those with difficulties in conventional surgical repair,
such as previous abdominal surgery. Therefore, this pa-
tient underwent conventional surgical repair of AAA
with argatroban treatment. There have been no previous
reports of EVA R in patients known to hav e HIT, but two
cases of HIT manifestations following EVAR by graft
occlusion were reported [4,5]. There have been a small
number of reports and reviews regarding EVAR in pa-
tients with preoperatively diagnosed HIT, but many re-
views regarding cardiovascular surgery the principles of
which can be summarized as: 1) wait until pf4 antibody
level subsides, then use heparin; 2) use alternative anti-
coagulation, such as danaproid or hirudin/bivalrudin to
replace heparin. Warkentin and Greinacher included use
of heparin with epoprostenol/tirofiban as an option [1].
As mentioned above, not all cases of HIT are diagnosed
by pf4 antibody, and therefore there are HIT type II pa-
tients negative for pf4 antibody. We encountered a pa-
tient on hemodialysis who underwent surgery to create
an internal shunt when he was found to have HIT. Al-
though pf4 antibody was negative, he developed severe
thrombosis with a trace amount of heparin. In this case,
although pf4 antibody was negative, PAT remained posi-
tive for heparin for at least 3 years. The PAT results
suggested high risk in this case, and we were hesitant to
use heparin. We again chose argatroban bolus and con-
Copyright © 2012 SciRes. OJTS
Surgeries for the Heart and Abdominal Aorta in a Patient with Heparin-Induced Thrombocytopenia:
Manifestations Following Initial Heart Surgery
Copyright © 2012 SciRes. OJTS
12
tinuous infu sion on abdominal ao rtic su rgery. Th ere w ere
no difficulties in monitoring clotting activ ities by ACT or
changing the dose accordingly. Questions have been
raised regarding whether argatroban is well tolerated in
CPB during cardiac surgery [1,3]. However, argatroban
was effective fo r vascular surg ery not only in our p atient
but also in many previously reported cases [6,7]. There is
no antidote for argatroban, such as protamine for heparin.
In this case, after reperfusion, it was necessary to wait
more than 90 min until ACT normalized. During this
time, autologous fresh blood was returned and no bleed-
ing issues occurred. The so-called “switch-back method”
involves transfusion of homologous/autologous blood
before injection of anticoagulant, storage of fresh blood,
and return after CPB or reperfusion. This method has
been recognized as effective in normalizing clotting ac-
tivities after CPB in cardiac surgery. We also use this
method in cases of vascular disease and it was beneficial
in HIT.
REFERENCES
[1] T. E. Warkentin and A. Greinacher, “Heparin-Induced
Thrombocytopenia and Cardiac Surgery,” Annals of Tho-
racic Surgery, Vol. 76, No. 6, 2003, pp. 2121-2131.
doi:10.1016/j.athoracsur.2003.09.034
[2] H. Gulbins, T. Chavez and J. Ennker, “Postoperative Ma-
nifestation of Heparin-Induced Thrombocytopenia with
Intracavitary Thrombosis: Diagnostic Pitfalls and Con-
servative Therapy,” Jounal of Thoracic and Cardiovas-
cular Surgery, Vol. 133, No. 3, 2007, pp. 809-810.
doi:10.1016/j.jtcvs.2006.11.004
[3] G. S. Murphy and J. H. Marymont, “Alternative Antico-
agulation Management Strategies for the Patient with
Heparin-Induced Thrombocytopenia Undergoing Cardiac
Surgery,” Journal of Cardiothoracic and Vascular Anes-
thesia, Vol. 21, No. 1, 2007, pp. 113-126.
doi:10.1053/j.jvca.2006.08.011
[4] T. A. M. Chuter, L. K. Pak, R. L. Gordon, L. M. Reilly
and L. M. Messina, “Heparin-Induced Thrombocytepenia
and Graft Thrombosis Following Endovascular Aneurysm
Repair,” Journal of Endovascular Therapy, Vol. 10, No.
6, 2003, pp. 1087-1090.
doi:10.1583/1545-1550(2003)010<1087:HTAGTF>2.0.C
O;2
[5] R. Kolluri, K. Rocha-Singh, T. Sarac and J. R. Bartholo-
mew, “Heparin-Induced Thrombocytopenia with Throm-
bosis after Endovascular Anerysm Repair,” Vascular and
Endovascular Surgery, Vol. 43, No. 1, 2009, pp. 89-92.
doi:10.1177/1538574408322660
[6] J. T. Edwards, J. K. Hamby and N. K. Worrall, “Success-
ful Use of Argatroban as a Heparin Substitute during Car-
diopulmonary Bypass: Heparin-Induced Thrombocyto-
penia in a High-Risk Cardiac Surgical Patient,” Annals of
Thoracic Surgery, Vol. 75, No. 5, 2003, pp. 1622-1624.
doi:10.1016/S0003-4975(02)04782-3
[7] S. E. Hallman, L. Hebbar, J. Robison and W. E. Uber,
“The Use of Argatoroban for Carotid Endarterectomy in
Heparin-Induced Thrombocytopenia,” Anesthesia and An-
algesia, Vol. 100, No. 4, 2005, pp. 946-948.
doi:10.1213/01.ANE.0000146940.47989.5F