Hearing Loss due to Sickle Cell Disease

Hearing Loss due to Sickle Cell Disease
A Promising Drug Treatment?
A Promising Drug Treatment?

By Jess Dancer, EdD

Page 1 DPOAEs: An Unexpected Finding
An unexpected finding regarding the amplitude of distortion product otoacoustic emissions (DPOAEs) by researchers at East Carolina University shows promise in the monitoring of a drug’s effectiveness in inhibiting or preventing cochlear pathology and hearing loss in individuals with sickle cell disease (SCD).1 What was this important finding? First, let’s take a look at SCD and the drug hydroxyurea.
Sickle Cell Disease
SCD is an inherited blood disorder, primarily in individuals of African, Indian, Middle Eastern, Mediterranean and Latino descent, which affects red blood cells. Normal red blood cells are soft and pliable and can squeeze through tiny blood vessels. Red blood cells affected by SCD are sickle- or crescent-shaped and become stiff and sticky. These changes lead to difficulty in the sickled cells passing through small blood vessels.
When sickle-shaped cells block small blood vessels, less oxygen reaches that part of the body, leading to widespread organ and tissue damage. Such damage causes the familiar complications of SCD, which include painful episodes in the arms, legs, chest and abdomen, recurrent acute chest syndrome, a pneumonia-like symptom due to lung tissue damage, severe anemia, stroke and painful, prolonged erections called priapism in males. Sickle cell conditions are inherited from parents in much the same way as blood type, hair color and texture, eye color and other physical traits.
The blood-rich end-organ of hearing, the cochlea, is often affected by SCD, and the percentage of patients with hearing loss, primarily sensorineural, is reported as high as 41 percent.2 Based on these data, researchers at Memphis State University recommended that…“routine audiologic assessment be incorporated into the regular medical examination for adults with sickle cell disease.”2
Treatment for SCD starts with early diagnosis and includes drugs, antibiotics, pain management, intravenous blood transfusion, and surgery, all backed by psychosocial support.
Page 2 Hydroxyurea
One promising drug treatment to prevent red blood cells from sickling is the chemical compound hydroxyurea, which is approved by the FDA for use in adult patients. The drug is a potent anti-tumor agent used to treat cancers of the blood, skin, ovary, head and neck.
Hydroxyurea, known more familiarly by brand names Droxia or Hydrea, is available in capsule form and can be taken by mouth. The drug is an essentially tasteless, white crystalline powder, which appears to increase the flexibility of sickled cells through increasing the production of fetal hemoglobin in red blood cells.
The American Sickle Cell Anemia Association indicates that… “fetal hemoglobin is a form of hemoglobin that all humans produce before birth, but most of us stop making it shortly after birth…However, some people with sickle cell anemia continue to produce large amounts of fetal hemoglobin after birth, and studies have shown that these people have less severe cases of the disease.”3
According to a review article in the Cochrane Database of Systematic Reviews, SCD causes crystals to form in the red blood cells, blocking blood flow and causing pain and organ damage. Raising the fetal hemoglobin level in affected individuals can reduce the effects of the disease, since fetal hemoglobin interferes with crystal formation in red blood cells. Reviewers concluded that … “the drug hydroxyurea is effective in raising hemoglobin in people with SCD without any adverse effects.”4
Hydroxyurea treatment is associated with a reduced frequency of vaso-occlusive crises, acute chest syndrome, transfusions and hospitalization. It improves survival by 40 percent in the most severely affected patients and may reduce the risk of childhood strokes.5
Unexpected DPOAE Finding in Sickle Cell Disease
In a 2000 publication, researchers at East Carolina University measured the amplitude of distortion product otoacoustic emissions (DPOAEs) in young normal-hearing children with and without SCD.6 DPOAEs measure the functional integrity of the outer hair cells through the simultaneous presentation of two tones at different frequencies. In general, even mild hearing loss diminishes or eliminates the amplitude of such emissions, thus serving as a valuable indicator of cochlear function. Contrary to researcher expectations, DPOAE amplitudes were significantly larger for children with SCD than for those without the disorder. Follow-up research in 2004 further confirmed the findings of increased DPOAE amplitudes in children with SCD and ruled out the status of the outer/middle ear as contributing factors.7
Page 3 Interestingly, such increased DPOAE amplitudes, even in the presence of normal hearing, may be an early warning sign of cochlear pathology. For example, in l998, researchers at the University of Toronto reported on changes in both transient otoacoustic emissions (TEOAES) and DPOAEs during and after ototoxic drug treatment in six adult chinchillas over a 6-week time course. As the measured damage in the cochlea progressed from base to apex, a temporary increase in OAE activity often occurred before the activity was ultimately reduced or lost. Researchers concluded that…“the increase in OAE amplitudes precedes the expression of detectable cochlear pathology.”8
In a 1998 companion publication, the University of Toronto researchers again concluded that localized damage to the apical or middle turns of the cochlea … “may be accompanied by an increase in OAE measured from adjacent apparently normal cochlea.”9
In 2006, researchers at East Carolina University again published findings on DPOAEs in normal-hearing children with SCD. Half the experimental subjects were on a regimen of hydroxyurea (HDU) while the other half were not. A normal control group without SCD was also included in the study for comparison purposes. Researchers found that … “increased DPOAE amplitudes, believed to be a precursor of eventual hearing loss, were evident in children with SCD who were not receiving HDU. Those taking HDU had DPOAE amplitudes similar to normal controls. These findings suggest that HDU, in addition to reducing symptoms of SCD, may play a role in inhibiting or preventing cochlear pathology and hearing loss in individuals with SCD.”1
As treatments for sickle cell disease become ever more prevalent, audiologists should remain vigilant and informed of their potential effects on hearing and hearing loss. The inclusion of OAEs to monitor drug treatment and check for incipient cochlear damage even in the face of normal hearing should be a part of the routine audiological assessment provided to all patients with SCD.

  1. Stuart A, Jones SM, Walker LJ. (2006). Insights into elevated distortion product otoaoustic emissions in sickle cell disease: comparisons of hydroxyurea-treated and non-treated young children. Hearing Research, 212(1-2): 83-9.
  2. Crawford MR, Gould HJ, Smith WR, Beckford N, Gibson WR, Bobo L. Prevalence of hearing loss in adults with sickle cell disease. (1991). Ear and Hearing, 12(5): 349-51.
  3. Amerian Sickle Cell Anemia Association. What is the future of sickle cell anemia treatment? Accessed online at www.ascaa.org/ftreat.htm
  4. Davies S, Olujohungbe A. (2001). Hydroxyurea for sickle cell disease. Cochrane Database of Systematic Reviews, (2): CD002202.
  5. University of Maryland Medical Center. What are treatments aimed at sickle-cell disease itself? Accessed online at www.umm.edu/patiented/articles/what_treatments_aimed_at_sickle-cell_disease_itself_000058_7.htm
  6. Downs CR, Stuart A, Holbert D. (2000). Distortion product otoacoustic emissions in normal-hearing children with homozygous sickle cell disease. Journal of Communication Disorders, 33(2): 111-27.
  7. Walker LJ, Stuart A, Green WB. (2004). Outer and middle ear status and distortin product otoacoustic emissions in children with sickle cell disease. American Journal of Audiology, 13(2): 164-72.
  8. Kakigi A, Hirakawa H, Harel N, Mount RJ, Harrison, RV. (l998). Basal cochlear lesions result in increased amplitude of otoacoustic emissions. Audiology & Neuro-otology, 3: 361-372.
  9. Raveh, E, Mount RJ, Harrison, RV. (1998). Increased otoacoustic-emission amplitude secondary to cochlear lesions. Journal of Otolaryngology, 27(6): 354-60.
    Jess Dancer is professor emeritus of audiology at the University of Arkansas at Little Rock. E-mail him at jedancer@ualr.eduof any experiences you have had with hearing loss due to sickle cell disease.