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Dapson Tedavisine Bağlı Hemoliz Görülen Bir Hastada Hemoglobin D Saptanması

Year 2019, Volume: 5 Issue: 3, 160 - 162, 06.09.2019
https://doi.org/10.30934/kusbed.585149

Abstract



Sayın Editör,

Hemoglobin
(Hb) yapısında bulunan globulinleri kodlayan genlerde birtakım mutasyonlar
oluşmaktadır. Gelişen bu mutasyonlar farklı hemoglobin varyantlarının oluşmasına
yol açar.1 Oluşan hemoglobin varyantlarından (Hb C, D, E, F ve S)
biri de Hb D [β 121 Glu→Gln
(GAA→CAA)]’dir. Hb D Türkiye’de %0,2 oranında görülür.2 Moleküler
analizde birçok Hb D tipi saptanmıştır. Hb D-Los Angeles veya Hb D-Punjab tipi
en sık gözlenendir.3 Klinik olarak Hb D’nin heterozigot tiplerinde
herhangi bir hematolojik belirti yoktur. Homozigot tiplerinde ise nadiren
hafif-orta derecede hemoliz bildirilen vakalar vardır.4 Bu çalışmada
Hb D ile birlikte olan, dapson tedavisi nedeniyle ortaya çıkan bir hemoliz
vakası sunuyoruz.

Behçet
hastalığı nedeniyle son 3 yıldır kolşisin tedavisi alan 17 yaşında bir kadın
hasta, ağzında geçmeyen ağrılı yaraları olması üzerine romatoloji bölümüne
başvurmuştur. Romatoloji
bölümü tarafından değerlendirilen hastaya dapson 50 mg 3x1 tablet başlanmıştır.
Hasta ilaç tedavisine başladıktan iki ay sonra solukluk, üşüme ve halsizlik
şikayetleri ile hematoloji bölümüne başvurmuştur. Yapılan tetkiklerde Hb: 11,2
g/dL, MCV: 92,8 fL, PLT: 307
x 10³/uL, retikülosit: 264,5 x 10³/uL, %retikulosit: %7,09, LDH: 367 U/L (0-279), total bilirubin: 2,7
mg/dL, indirekt bilirubin: 1,5 mg/dL ve haptoglobin< 30 mg/dL (30-200)
olarak geldi. Periferik yaymada sferositler ve fragmente eritrositler izlendi.
Direkt ve indirekt coombs testleri negatif olarak geldi. Papain antikoru ve
glukoz 6 fosfat dehidrogenaz (G6PD) testleri negatifti. Dapson tedavisi almadan
önce yapılan tetkiklerinde Hb: 14,2 g/dL, MCV: 85,2 fL, PLT: 309
x 10³/uL idi. Öncelikle
tanı olarak dapsona bağlı hemolitik anemi düşünüldü ve dapson tedavisi kesildi.
Üç hafta sonra yapılan tetkiklerde retikülosit: 125,6
x 10³/uL, %retikulosit: %3,49
olması üzerine talasemi ön tanısıyla hemoglobin elektroforezi istendi ve Hb D
değeri: %41,65 olarak bulundu (Şekil 1). Moleküler genetik testi (DNA analiz)
Hb D-Los Angeles
[c.3646>C(p.E122Q)(p.Glu.122Gln)(Heterozigot)]
olarak bulundu. Hastanın babasından istenen hemoglobin elektroforezinde Hb D: %88,13
ve HbA2: %3,91 olarak bulundu. Hastanın babasına Hb D ve beta talasemi minor
tanısı konuldu.

İlaçlar
hemolitik aneminin nadir görülen bir nedenidir. Dapsonun oksidatif hemolize
neden olduğu bilinmektedir. Bu olayın N-hidroksilasyon ile oluşan bir
hidroksilamin türevinin eritrositlere direkt toksik etkisi nedeniyle olduğu
bildirilmiştir.5Hastanın
takibinde hemolizi devam etmesi nedeniyle istenen hemoglobin elektroforezinde
nadir olarak görülen Hb varyantına rastlanmıştır. Bu vakayı takip eden biz
hekimler için şaşırtıcı bir durumdur. Hastanın önceki hemogram ve biyokimya
değerlerinde talasemiyi düşündürecek patolojik bir durum yoktu. Yani iki tane
nadir durum; ilaça bağlı hemoliz ve Hb D ile karşı karşıyaydık.

Sonuç olarak; dapsona
bağlı hemoliz ve Hb D birlikteliği nadir bir durumdur. Hastada Hb D heterozigot
olarak tespit edildiğinden, bu durumun hemolize klinik olarak etki etmediğini
düşünüyoruz. Bildiğimiz kadarıyla dapsona bağlı hemoliz gelişen bir hastada Hb
D’nin tespit edildiği ilk vakadır.




References

  • Kohne E. Hemoglobinopathies: clinical manifestations, diagnosis, and treatment. Dtsch Arztebl Int. 2011;108(31/32):532–40.
  • Itano HA. A third abnormal hemoglobin associated with hereditary hemolytic anemia. Proc Natl Acad Sci U S A. 1951;37(12):775–84.
  • Baglioni C. Abnormal human haemoglobins. VII. Chemical studies on haemoglobin D. Biochim Biophys Acta. 1962;59(2):437–49.
  • Taghavi Basmanj M, Karimipoor M, Amirian A, et al. Co-inheritance of hemoglobin D and thalassemia traits in three families: clinical relevance. Arch Iran Med. 2011;14(1):61–3.
  • Ward KE, McCarthy MW. Dapsone-induced methemoglobinemia. Ann Pharmacother 1998; 32:549.
  • Coleman MD. Dapsone toxicity: some current perspectives. Gen Pharmacol 1995; 26:1461.

Detection of Hemoglobin D in a Patient with Hemolysis due to Dapsone Treatment

Year 2019, Volume: 5 Issue: 3, 160 - 162, 06.09.2019
https://doi.org/10.30934/kusbed.585149

Abstract



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< 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>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.

References

  • Kohne E. Hemoglobinopathies: clinical manifestations, diagnosis, and treatment. Dtsch Arztebl Int. 2011;108(31/32):532–40.
  • Itano HA. A third abnormal hemoglobin associated with hereditary hemolytic anemia. Proc Natl Acad Sci U S A. 1951;37(12):775–84.
  • Baglioni C. Abnormal human haemoglobins. VII. Chemical studies on haemoglobin D. Biochim Biophys Acta. 1962;59(2):437–49.
  • Taghavi Basmanj M, Karimipoor M, Amirian A, et al. Co-inheritance of hemoglobin D and thalassemia traits in three families: clinical relevance. Arch Iran Med. 2011;14(1):61–3.
  • Ward KE, McCarthy MW. Dapsone-induced methemoglobinemia. Ann Pharmacother 1998; 32:549.
  • Coleman MD. Dapsone toxicity: some current perspectives. Gen Pharmacol 1995; 26:1461.
There are 6 citations in total.

Details

Primary Language English
Subjects Haematology
Journal Section Letter To The Editor
Authors

Muhammed Okuyucu 0000-0002-6026-2024

Memiş Hilmi Atay 0000-0001-9666-6955

Birşen Bilgici 0000-0001-7783-5039

Publication Date September 6, 2019
Submission Date July 1, 2019
Acceptance Date September 3, 2019
Published in Issue Year 2019 Volume: 5 Issue: 3

Cite

APA Okuyucu, M., Atay, M. H., & Bilgici, B. (2019). Detection of Hemoglobin D in a Patient with Hemolysis due to Dapsone Treatment. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi, 5(3), 160-162. https://doi.org/10.30934/kusbed.585149
AMA Okuyucu M, Atay MH, Bilgici B. Detection of Hemoglobin D in a Patient with Hemolysis due to Dapsone Treatment. KOU Sag Bil Derg. September 2019;5(3):160-162. doi:10.30934/kusbed.585149
Chicago Okuyucu, Muhammed, Memiş Hilmi Atay, and Birşen Bilgici. “Detection of Hemoglobin D in a Patient With Hemolysis Due to Dapsone Treatment”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 5, no. 3 (September 2019): 160-62. https://doi.org/10.30934/kusbed.585149.
EndNote Okuyucu M, Atay MH, Bilgici B (September 1, 2019) Detection of Hemoglobin D in a Patient with Hemolysis due to Dapsone Treatment. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 5 3 160–162.
IEEE M. Okuyucu, M. H. Atay, and B. Bilgici, “Detection of Hemoglobin D in a Patient with Hemolysis due to Dapsone Treatment”, KOU Sag Bil Derg, vol. 5, no. 3, pp. 160–162, 2019, doi: 10.30934/kusbed.585149.
ISNAD Okuyucu, Muhammed et al. “Detection of Hemoglobin D in a Patient With Hemolysis Due to Dapsone Treatment”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 5/3 (September 2019), 160-162. https://doi.org/10.30934/kusbed.585149.
JAMA Okuyucu M, Atay MH, Bilgici B. Detection of Hemoglobin D in a Patient with Hemolysis due to Dapsone Treatment. KOU Sag Bil Derg. 2019;5:160–162.
MLA Okuyucu, Muhammed et al. “Detection of Hemoglobin D in a Patient With Hemolysis Due to Dapsone Treatment”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi, vol. 5, no. 3, 2019, pp. 160-2, doi:10.30934/kusbed.585149.
Vancouver Okuyucu M, Atay MH, Bilgici B. Detection of Hemoglobin D in a Patient with Hemolysis due to Dapsone Treatment. KOU Sag Bil Derg. 2019;5(3):160-2.