Surgeries for the Heart and Abdominal Aorta in a Patient with Heparin-Induced Thrombocytopenia: Manifestations Following Initial Heart Surgery

doi:10.4236/ojts.2012.21003

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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: [email protected]

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

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-

Surgeries for the Heart and Abdominal Aorta in a Patient with Heparin-Induced Thrombocytopenia:

Manifestations Following Initial Heart Surgery

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.

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