Discussion
The incidence of AITP is unknown due to the rarity of this complication
and paucity of documented cases. DITP has been associated with increased
risk of in-hospital mortality1. A distinctive feature
of one of the well-known examples of DITP such as quinine induced DITP
involves a platelet reactive antibody that bind tightly to platelets
only in the presence of quinidine leading to immune destruction of
platelets after 5-7 days of continuous drug administration. In addition
to the above, Aster and Bougie have summarized various mechanisms for
DITP, some of which include hapten-dependent antibody (e.g. penicillin),
autoantibodies which elicit immune response in the absence of drug (gold
salt, procainamide) and immune complex formation
(heparin)2. Weinberger et al was the first to
postulate delayed hypersensitivity as a mechanism for AITP by performing
a lymphocyte stimulation test6. Monitoring drop in
platelet counts two weeks after starting amiodarone was recommended.
Amiodarone-dependent antibodies causing platelet destruction cannot be
identified using traditional serological methods owing to water
insolubility of the drug. This issue was elucidated by Sahud et al who
described a case series of three patients with AITP and employed
elaborate laboratory techniques to demonstrate amiodarone-dependent
antibodies specific for platelet glycoproteins GPIa/IIa and/or
GPIIb/IIIa to explain thrombocytopenia in these
patients5.
Thrombocytopenia is one of the commonest reasons for inpatient
hematology consultation. The differential diagnosis is long and
sometimes multifactorial. Thrombocytopenia workup guidelines described
by Arnold and Lim were useful to approach our case. They have described
a handy 6 step approach to evaluate thrombocytopenia: exclude
thrombocytopenic emergencies, peripheral blood smear examination,
consider clinical context, degree timing and lastly assess for
bleeding/thrombosis12. In the case discussed here,
firstly a citrated platelet level ensured that severely low platelet
count was not a lab error. Fatal etiologies of severe (sometimes
referred as significant ) thrombocytopenia like disseminated
intravascular coagulation (no overt bleeding, normal hemolysis markers,
normal fibrinogen), and thrombotic thrombocytopenic purpura (no
schistocytes, no hemolysis), heparin-induced thrombocytopenia (negative
HIT ELISA screen, typical platelet nadir is 60 K/mm3in HIT) were ruled out. DITP as a possible cause of severe
thrombocytopenia was suspected given worsening thrombocytopenia to less
than 20 K/mm3 despite prompt resolution of sepsis with
appropriate antibiotic, timing of onset at day 5 after starting
amiodarone, and, presence of giant platelets on the blood smear, high
immature platelet fraction (20.1%) both indicating an immune mediated
phenomenon. Severe sepsis can sometimes cause severe thrombocytopenia
but that is usually associated with severe leukopenia as a marker of
severe bone marrow suppression. Amiodarone was listed as a possible
cause of DITP in a commonly referred expanded online list of drugs and
their level of association with thrombocytopenia athttps://www.ouhsc.edu/platelets/ditp.html13.
Later during the clinical course, recurrence of thrombocytopenia with
amiodarone introduction and improvement after drug discontinuation lent
more support to the diagnosis. It must be pointed that drug rechallenge
is not required to diagnose any DITP. Platelet reactive antibodies were
not tested since amiodarone-dependent platelet-responsive antibodies are
not detectable by conventional methods5. It was not
feasible to apply criteria laid out by George et al to establish causal
relation of amiodarone to immune thrombocytopenia since the patient died
prematurely before platelet count could return to
normal14. Regardless, the clinical picture pointed to
AITP and there was no alternate explanation. Although platelet recovery
may be relatively prompt after drug discontinuation, complete recovery
may take a few weeks owing to the long half-life of amiodarone from its
large volume of distribution3,7. Antibodies can
persist for years and hence re-exposure of the drug even months to years
later can elicit a similar immune destruction of
platelets15. Offending medication must be added to the
allergy list in order to maximize safety.