Discussion
This case highlights the importance of closely monitoring polypharmacy
and avoiding the assumption that over the counter (OTC) medications are
benign. This patient underwent HCT with a history of complex regional
pain disorder. Therefore, she was very aware of any discomfort she felt
and was intuitive and vocal about her desires for pain management. In an
effort to respect burgeoning autonomy in a young adolescent, she was
encouraged to help manage medication choices. She identified
phenazopyridine as the single agent that helped to alleviate her dysuria
and in fact asked for it to be removed last in an effort to facilitate
an oxycodone wean. Unfortunately, despite phenazopyridine being thought
of as a benign agent, she developed a rapid onset of hemolysis about 6
weeks into therapy.
Phenazopyridine is an azo dye analgesic used for symptomatic relief of
dysuria that exists in many OTC formulations.4 It
exerts its action via rapid metabolization, urinary excretion and
topical effect.5 It is intended for use for a short
duration due to a number of possible side effects including rash, renal
failure, and hemolytic anemia.6 Patients who remain on
the medication beyond 15 days should be cautioned of
risks.6 Phenazopyridine is also thought to mask signs
and symptoms of urinary tract infection however in our patient her
urinalysis and urine culture was negative prior to initiating the agent.
Phenazopyridine is thought to cause hemolysis by a toxic reaction on red
blood cells, producing methemoglobinemia and Heinz body
anemia.7 From a hematopathologic standpoint, all
causes of hemolytic anemia (except for paroxysmal nocturnal
hemoglobinuria) have a characteristic red cell morphology. For Heinz
body anemia, an accurate understanding of the clinical setting can lead
to a rapid diagnosis.
There have been few reports in the literature of hemolysis following the
use of phenazopyridine and most involve small children or elderly
individuals. The first published report dates from 1961 and describes a
3-year-old who developed methemoglobinemia and hemolysis following the
administration of phenazopyridine.8 Interesting, Shore
et al reported no incidence of hemolysis following the use of
phenazopyridine for greater than 14 days in a cohort of 90 males
utilizing the agent for radiation cystitis.9 Currently
there is no clinical data for phenazopyridine use for HC following HCT.
Although this patient remained on phenazopyridine longer than is
recommended, she benefitted from timely diagnosis of her Heinz body
anemia. This speaks to the importance of communication between the
pathologist and clinical physician and the need for closely monitoring
for medication induced hematologic side effects. During this phase of
post-HCT recover, medication induced complications may be overshadowed
by multiple complications such as TA-TMA, immune mediated cytopenias or
acute GVHD.