Detection of Hemoglobin D in a Patient with Hemolysis due to Dapsone Treatment
Authors: OKUYUCU Muhammed , ATAY Memiş Hilmi , BİLGİCİ Birşen 
Published: September 2019

Dear
Editor,Several mutations occur in the genes that encode
globin chains which are a part of hemoglobin (Hb) structure. Such mutations
give rise to formation of different hemoglobin variants.1 One of
these hemoglobin variants (Hb C, D, E, F and S) is Hb D [β 121 Glu→Gln (GAA→CAA)]. Hb D occurs in 0.2% in
Turkey.2 Molecular analysis has revealed many types of Hb D. Hb
D-Los Angeles or Hb D-Punjab is the most common type.3 Clinically,
heterozygous types of Hb D do not produce any hematological manifestations. However,
mild-to-moderate cases of hemolysis have been rarely reported in conjunction
with its homozygous forms.4 In this study, we present a case of
hemolysis due to
dapsone theraphy in coexistence with Hb D.
A 17-year-old female patient who had been on colchicin
treatment for Behçet’s disease for the last 3 years presented to the
rheumatology department with persistent painful sores in her mouth. Following
assessment of the patient, treatment with dapsone 50 mg tablets, three times
daily was started by the rheumatology department. Two months after initiation
of medical treatment, the patient presented to the hematology department with
complaints of pallor, chills and fatigue. Her diagnostic work-up showed the
following: Hb: 11.2 g/dL (11.9-14.6),
MCV: 92.8 fL (81.8-95.5), PLT: 307 x 10³/uL (173-390), reticulocyte
count: 264.5 x 103/uL (17-63.8),
reticulocyte%: 7.09%, LDH: 367 U/L (0-279), total bilirubin: 2.7 mg/dL
(0.1-1.5), indirect bilirubin: 1.5 mg/dL (0.08-1.1) and haptoglobulin&lt; 30
mg/dL (30-200). Peripheral smear showed the presence
of spherocytes and fragmented red blood cells. Direct and indirect Coombs tests
were negative. Papain antibody and glucose 6 phosphate dehydrogenase (G6PD)
tests were negative. Her laboratory values before dapsone therapy were as
follows: Hb: 14.2 g/dL, MCV: 85.2 fL, PLT: 309 x 10³/uL. Initially, hemolytic
anemia induced by dapsone was considered as possible diagnosis and dapsone
treatment was discontinued. Laboratory work-up after three weeks showed a
reticulocyte count of 125.6 x 10³/uL, % reticulocyte of 3.49%. These results
prompted a request for hemoglobin electrophoresis based on a preliminary
diagnosis of thalassemia. Hb D was found as 41.65% (Figure 1). Moleculer
genetic test (DNA analysis) was found to be Hb D-Los Angeles [c.3646&gt;C(p.E122Q)(p.Glu.122Gln)(Heterozygous)].
Hemoglobin electrophoresis was performed from the blood sample of her father
and revealed Hb D of 88.13% and HbA2 of 3.91%. Her father was diagnosed with beta-thalassemia
minor and Hb D. Drugs are a rare cause of hemolytic anemia. Dapsone
is known to cause oxidative hemolysis. This situation has been reported to
result from the direct toxic effect of a hydroxlamine derivative formed by
N-hydroxylation to erythrocytes.5 Hemoglobin electrophoresis was performed for the patient during
follow-up due to persistent
hemolysis and a rare Hb variant was detected. This was a surprising finding for
us, the physicians who were following the patient because her previous hemogram
and biochemical analyses were not suggestive of thalassemia. Thus, we were
facing two rare conditions at the same time: drug-induced hemolysis and Hb D.As a result;
coexistence of hemolysis due to dapsone and Hb D is a rare condition. Since Hb
D was found to be heterozygous in the patient, we think that this condition did
not have clinical effect on hemolysis. To the best of our knowledge, this is
the first case in which Hb D is detected in a patient with hemolysis due to
dapsone.