Discussion:
Platelets play a major role in the formation and propagation of a
thrombus, which is the key mechanism in developing Acute coronary
syndromes(1). GP IIB/IIIA receptors are found on the surface of
platelets and play a crucial role in the aggregating platelets by
binding to fibrinogen and Von Willebrand factors(2).
Eptifibatide is an antiplatelet medication which reversibly binds and
inhibits glycoprotein IIb/IIIa receptor on the surface of platelets (1),
which means that it will prevent the binding of fibrinogen and Von
Willebrand factors to GP IIb/IIIA receptors, thus inhibiting platelet
aggregation and decreasing risk of thrombosis and thrombus propagation
(3).
Eptifibatide had been approved by FDA based on three large, randomized
trials, the PURSUIT, ESPIRIT, and IMPACT-II trials (5-7), the PURSUIT
trial showed benefits in the settings of acute coronary syndrome
(unstable angina and Non-ST elevation MI), while both ESPIRIT, and
IMPACT-II approved eptifibatide for patients undergoing percutaneous
coronary intervention only (PCI).
Profound thrombocytopenia is a rare side effect of GP IIB/IIIA in
general. It has been reported with large molecule GPIIB/IIIA inhibitors
such as Abciximab (8), but its incidence is quite rare with smaller
molecules, specifically with Eptifibatide, with a risk of
thrombocytopenia around (0.1 to –1%) (3,10). The data and evidence
that are available suggest that Eptifibatide induced thrombocytopenia
noticed to be profound within 24 hours of administration of the
medication (9).
One of the suggested mechanisms for Eptifibatide induced
thrombocytopenia is formation of antibodies
against a group of epitopes, called ligand-induced binding sites
(LIBSs), which are normally hidden,
but binding of the GP IIb/IIIa to the receptors will expose these (LIBs)
and allows the antibodies
to bind to them (LIBs) which facilitates the clearance of platelets by
the reticuloendothelial system (4)
Other causes of thrombocytopenia needs to be excluded like, Heparin
induced thrombocytopenia (HIT) , (HIT)-type 1 is less likely in our
case, as it usually develops in the first 2 days of heparin
administration and usually is mild, with platelets usually staying
within the normal range, and type II which usually develops 5-10 days if
no previous heparin exposure, and even within hours if there is a
history of heparin exposure (12) . It is usually diagnosed with
platelet-factor 4 immunoassays. In our case, the platelet-factor 4
immunoassay for HIT was negative and the drop was acute immediately
after starting eptifibatide and improved after stopping it, which makes
HIT unlikely.
Eptifibatide induced thrombocytopenia was reported in multiple case
reports (4,9-11) which was treated by withholding the eptifibatide, with
significant improvement of platelet count, as in our patient.
In summary, we have presented here a case of eptifibatide induced
thrombocytopenia in a patient with acute coronary syndrome who underwent
PCI. While eptifibatide is a rare cause of thrombocytopenia, it is a
serious side effect that warrants careful and close follow up of
platelet counts if it happens.