Cardiovascular Drugs and Therapy 18 503–505 2004


C 2005 Springer Science + Business Media, Inc. Manufactured in The Netherlands
CASE REPORT
Repetitive Profound Thrombocytopenia After Treatment
with Tirofiban: A Case Report
Summary. The GPIIb/IIIa inhibitors are used in the acute
coronary syndromes and interventional cardiology as an-
tiplatelet agents. These drugs induce thrombocytopenia in
approximately 1–5% of patients. Thrombocytopenia is rapid
in onset and antibody mediated. Abciximab is associated
with higher incidence of thrombocytopenia than eptifibatide
and tirofiban. Profound thrombocytopenia has reportedly
been an issue with abciximab, but not with tirofiban. We re-
ported a case of acute profound thrombocytopenia due to
on tirofiban treatment in the same patient at two different
times.
Key Words. thrombocytopenia, tirofiban
Introduction
The GPIIb/IIIa inhibitors are used in acute coronary
syndromes and interventional cardiology [1,2]. These
drugs induce thrombocytopenia in approximately 1%
to 5% of patients [3]. Thrombocytopenia is rapid in on-
set and antibody mediated. Abciximab was associated
with higher incidence of thrombocytopenia than epti-
fibatide and tirofiban [4–6]. Also, profound thrombocy-
topenia has been reported to occur with abciximab, but
not with tirofiban. We report here a case of acute pro-
found thrombocytopenia due to tirofiban treatment in
same patient at two different times.
Case Summary
A 63 year old man underwent primary angioplasty be-
cause of an acute inferior myocardial infarction. His
history was normal except smoking. During coronary
angiography, the left coronary arteries appeared nor-
mal, but the proximal segment of the right coronary
artery was totally occluded. Balloon angioplasty and
stent implantation were successfully done. Before in-
tervention, patient was treated with aspirin (300 mg),
clopidogrel (300 mg), and 10,000 U bolus of unfrac-
tioned heparin. Just after the intervention, tirofiban
(0.15 µg/kg/min for 3 min followed by 0.1 µg/kg/min)
was added to beta blocker and statin treatment. Also,
heparin infusion was started as 1000 U/h. Before the
intervention, the platelet count was 240 × 109 /L (Table
1, Fig. 1). Twelve hours after the intervention, bleed-
ing was seen from femoral sheat insertion site. A con-
trol hemogram showed a platelet count of 4 × 109 /L.
Beyhan Eryonucu, Mustafa Tuncer and Reha Erkoc
Cardiology Department, Yüzüncü Yil University, Medical
Faculty, Van, Turkey
Thrombocytopenia was confirmed by careful review of
the blood film. Tirofiban, heparin, clopidogrel and as-
pirin were stopped and the patient was transfused with
platelets. The platelet count increased to 190 × 109 /L
three days later and to 331 × 109 /L after seven days. 10
days later, the patient was discharged with classic treat-
ment protocol including 100 mg aspirin, 75 mg clopido-
grel and 10 mg atorvastatin once daily.
In the follow up period, the platelet count was nor-
mal. Five months later, he was readmitted with typical
angina pectoris. Coronary angiography was repeated
and a critical instent restenosis was revealed. Balloon
angioplasty was successfully done. Unfractioned hep-
arin was not given at any time. Tirofiban was given
as a half dose (0.075 µg/kg/min for 3 min followed by
0.05 µg/kg/min). Platelet count was 173 × 109 /L before
intervention. Five hours later, the platelet count was
again severely reduced, now to 3 × 109 /L. Thrombo-
cytopenia was confirmed by review of the blood film.
Tirofiban was stopped, platelet suspension was given
and the sheat was removed. Bleeding was not seen. The
platelet count increased to 123 × 109 /L after three days.
The patient’s hospital course was uneventful and he was
discharged seven days later with a normal haematologic
status.
Discussion
We reported here two acute and profound thrombocy-
topenias after cardiac interventions in the same patient.
During the first intervention, because of limited labo-
ratory opportunity, thrombocytopenia could not deeply
investigated. Testing for disseminated intravascular
coagulation was negative. Platelet aggregation test and
ELISA for antibodies to platelet factor4/heparin are
used to detect antibodies associated with heparin in-
duced thrombocytopenia. Thus, the cause of thrombo-
cytopenia was not clarified during the first episode. Pa-
tient received clopidogrel and aspirin after the normal-
ization of platelet count. Thrombocytopenia was not
seen during a subsequent 5 months period. Thus, the
Address for correspondence: Dr. Beyhan Eryonucu, Yüzüncü Yil
Üniversitesi, Tip Fakültesi Kardiyoloji AD, 65200 Van-Türkiye,
Tel.: +90 532 3544996; Fax: +90 432 2121867; E-mail: drbeyhan@
yahoo.com
503
504 Eryonucu, Tuncer , and Erkoc
Table 1. Clinical and laboratory features of thrombocytopenia episodes platelet count (×109 )
Platelet count (×109 )
Minimum
Intervention Before level Third day Seventh day
First 240 4 190 331
Second 173 3 123 221
Fig. 1. Changes of platelet counts after tirofiban.
possibility of thrombocytopenia induced by these drugs
was tested and excluded.
During the second intervention, we could not eas-
ily decide on the proper anticoagulation regimen. The
patient was under treatment with aspirin and clopi-
dogrel. We suspected heparin- or tirofiban-induced
thrombocytopenia. At the end, the reason for the first
thrombocytopenia was mistakenly accepted as heparin-
induced thrombocytopenia, so heparin was not given.
Tirofiban (only tirofiban is available in our country as
a GPIIb/IIIa inhibitor) was started half dose. Unfor-
tunately, thrombocytopenia was seen again. Since hep-
arin was not used in this intervention, heparin induced
thrombocytopenia was definitely ruled out. Thus, the
reasons of both thrombocytopenias were clarified as
tirofiban treatment. Use of the Naranjo ADR Probabil-
ity Scale [7] indicated a possible relationship between
the adverse effect and therapy in this patient.
The mechanism of tirofiban induced thrombocytope-
nia in this case is not clear. Reports proposed that
thrombocytopenia could be of immunologic origin and
that ‘natural’ preexisting antibodies could explain the
early thrombocytopenia [8,9]. This mechanism may ex-
plain the first thrombocytopenia in our patient within
five hours of drug administration.
In conclusion, in contrast to previous reports [10],
acute, profound thrombocytopenia may develop after
tirofiban treatment. Platelet count should be monitor ed
closely especially within the early hours after the start
of the infusion. Furthermore, more extensive testing
for thrombocytopenia and related haematologic param-
Platelet Time elapsed between tirofiban and
transfusion observed thrombocytopenia (h) Bleeding
3 12 Minor
1 5 No
eters should be done after the first thrombocytopenia
episode.
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