Appeal type: Experimental
Decision: Insurer Denial Overturned

Summary Reviewer 1 
 
A 58-year-old male enrollee has requested reimbursement for therapeutic phlebotomy from 
1/6/21 through 1/26/21. The Health Insurer has denied this request and reported that the service 
at issue was investigational for the treatment of the enrollees hereditary hemochromatosis. The 
physician  reviewer  found  that  in  this  case,  the  patient  meets  criteria  for  hereditary 
hemochromatosis. Kowdley and colleagues report that phlebotomy remains the mainstay of 
therapy  for  hereditary  hemochromatosis.  The  American  College  of  Gastroenterology  
recommends that phlebotomy be used as the first-line treatment in patients diagnosed with 
hereditary hemochromatosis, as determined by C282Y homozygosity or C282Y/H63D compound 
heterozygosity. The guidelines further recommend against chelation as the first-line therapy for 
hereditary hemochromatosis, given the effectiveness of phlebotomy, the associated side effects 
of chelation including hepatic and renal toxicity, and the relatively small sample size of clinical 
trials supporting chelation. However, the guidelines note that iron chelation may be used in the 
treatment of hereditary hemochromatosis for the patient who is intolerant or refractory to 
phlebotomy or when phlebotomy has the potential for harm, such as in patients with severe 
anemia or congestive heart failure. Phlebotomy in fit patients with biochemical or clinical 
evidence of iron overload is proven to improve overall survival and reduce end organ damage, 
such  as  by  cirrhosis  or  heart  failure,  due  to  iron  overload.  In  the  maintenance  of 
hemochromatosis, phlebotomy is also recommended as needed to keep serum ferritin below 50-
100  ug/L.  Intolerance  of  phlebotomy,  such  as  congestive  heart  failure  with  unstable 
hemodynamics, may be an indication for alternative therapies such as erythocytapheresis or iron 
chelation therapy. There are three chelating agents currently approved by the U.S. Food and Drug 
Administration (FDA) for the treatment of secondary iron overload, but none that are approved 
for primary iron overload and hereditary hemochromatosis. Deferoxamine has been approved 
for the treatment of secondary iron overload in thalassemia, with adverse effects including 
retinopathy and auditory toxicity. Deferiprone is an oral chelator which is approved for the 
treatment  in  transfusion-dependent  patients  with  thalassemia  when  chelation  with 
deferoxamine  is  inadequate,  with  significant  side  effects  including  neutropenia  and 
agranulocytosis. Deferasirox, the most recently approved oral chelator, has side effects including 
gastrointestinal upset, rash, aminotransferase elevation, and renal toxicity, which can occur in 
more than 10% of  all patients.  In this clinical setting, phlebotomy is considered standard 
treatment and is likely to be superior to other treatments such as erythocytapheresis or iron 
chelation therapy. Therefore, therapeutic phlebotomy from 1/6/21 through 1/26/21 was likely 
to have been more beneficial for treatment of the enrollee's condition than any available 
standard therapy.