Acute hemolysis in glucose-6-phosphate dehydrogenase deficiency after coronary angiography

Abstract

The contrast agents in current use are generally safe, however have some side reactions, can range from minor to severe, sometimes resulting in death. Nowadays, glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is known as one of the most common hereditary disorders of erythrocytes, causing intravascular hemolysis. Most of patients with G-6-PD deficient are usually asymptomatic, on the other hand can present by hemolytic anemia particularly after the administration of some drugs, exposure to fava beans, infections and during diabetic acidosis. We describe here a 44-year-old man with G-6-PD deficient, who developed acute severe hemolysis after diagnostic coronary angiography.

Full text

Vol. 174 - No. 1 GAZZETTA MEDICA ITALIANA - ARCHIVIO PER LE SCIENZE MEDICHE 1
The contrast media used for radio-
logic studies are markedly hyperosmolar
and hypo-osmolar, some of them being
up to eight times the physiologic level of
300mOsm/kg of water,2 and all types of
adverse reactions are more common with
these agents, are associated with nephrotic,
less serious cardiovascular and anaphy-
lactoid reactions. We report a patient with
G-6-PD deciency who developed severe
hemolysis following administration of radi-
ographic contrast material for coronary an-
giography; we draw attention to this poten-
tial complication of angiography in patients
with G-6-PD deciency.
Case report
A 44-year-old man was admitted to cardiology
service with persistent chest pain (CCS II) and
dyspnea (NYHA II) for one month. He had type-2
diabetes for one year and denied a history of aller-
gies and drug use. The initial examination showed
a moderately obese, who was afebrile, normoten-
sive, and anicteric. Cardiac examination disclosed
a grade 2/6 pansystolic murmur at the left sternal
border. An electrocardiogram (ECG) reportedly
showed a normal sinus rhythm, with a rate 90 beats
per minute. The cardiac markers were normal. No
hepatosplenomegaly was detected. At admission his
1Cardiologyclinic
AntalyaTrainingandResearchHospital
Antalya, Turkey
????
GAZZ MED ITAL - ARCH SCI MED 2015;174:1-2
S. KÜÇÜKSEYMEN 1, G. ÇAĞIRCI 1, E. KÖKLÜ 1
I. O. YÜKSEL 1, N. BAYAR 1, M. ESIN 1, Ş. ARSLAN 1
Acute hemolysis in glucose-6-phosphate
dehydrogenase deciency after coronary angiography
The contrast agents in current use are gener-
ally safe, however have some side reactions,
can range from minor to severe, sometimes
resulting in death. Nowadays, glucose-6-phos-
phate dehydrogenase (G-6-PD) deciency is
known as one of the most common heredi-
tary disorders of erythrocytes, causing in-
travascular hemolysis. Most of patients with
G-6-PD decient are usually asymptomatic,
on the other hand can present by hemolytic
anemia particularly after the administration
of some drugs, exposure to fava beans, in-
fections and during diabetic acidosis. We de-
scribe here a 44-year-old man with G-6-PD
decient, who developed acute severe hemo-
lysis after diagnostic coronary angiography.
Key words: Hemolysis - Coronary Angiography
- Glucosephosphate Dehydrogenase Deciency -
Contrast Media.
Glucose-6-phosphate dehydrogenase
(G-6-PD) is a critical enzyme in the re-
dox metabolism of all aerobic cells. Also,
G-6-PD deciency, is the most common
hereditary enzyme deciency worldwide,
but the people with G-6-PD deciency are
usually asymptomatic, on the other hand, it
may develop an acute hemolytic state after
exposure to drugs, infections and chemi-
cals, for example, streptomycin, paraami-
nosalicylic acid, suplhonamides, acetylsali-
cylic acid, isoniazid and acetaminophen.1
Corresponding author: S. Küçükseymen, Cardiology clin-
ic, Antalya Training and Research Hospital, Varlik mahallesi,
Kazim Karabekir caddesi, Soğuksu, 07100, Antalya, Turkey.
E-mail: skucukseymen@gmail.com
Anno: 2015
Mese: ??
Volume: 174
No: 1
Rivista: GAZZETTA MEDICA ITALIANA - ARCHIVIO PER LE SCIENZE MEDICHE
Cod Rivista: GAZZ MED ITAL - ARCH SCI MED
Lavoro: 3093-GMI
titolo breve: ACUTE HEMOLYSIS IN G-6-PD DEFICIENCY AFTER CORONARY
ANGIOGRAPHY
primo autore: KÜÇÜKSEYMEN
pagine: 1-2
3093-GMI
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KÜÇÜKSEYMEN ACUTE HEMOLYSIS IN G-6-PD DEFICIENCY AFTER CORONARY ANGIOGRAPHY
hemoglobin level was 13.6 g/dL (normal 13.5-17.3
g/dL); blood cell counts, serum bilirubin and lactate
dehyrogenase (LDH) levels were normal and fasting
blood glucose level of 128 mg/dL. Coronary angi-
ography was performed via the right femoral artery
with 6Fr Judkins catheter. Totaly thirty-eight millili-
ters of contrast material, IOPAMIRO 300 (Iopami-
dol, 61.2 g; Trometamol, 100 mg; calcium disodium
EDTA (6H2O), 39 mg; HCl pH 7.1) was injected for
total procedure. The coronary angiography revealed
normal coronary arteries (Figures 1, 2). In the two
days after the follow-up, the patient developed
generalized back pain without ant chills, rigors, or
shortness of breath. On examination, there are no
varying ndings, she was afebrile and normoten-
sive, no rash was noted and there was no bleeding
at the catheterization site, but the hemoglobin level
was found to be 10.2 g/dL; serum bilirubin and LDH
levels were slightly increased, total bilirubin 2.2 mg/
dL of which the direct component was 0.41 and
LDH was 279 U/L (normal 135-225 U/L). Abdomi-
nal and pelvic ultrasound examinations were per-
formed by radiologist and there was no evidence
of any bleeding. The following day the patient was
severely icteric, fasting blood glucose level of 108
mg/dL but otherwise felt well. Controlled laboratory
parameters and hemoglobin level was 7.0 g/d and
total bilirubin 13.1 mg/dL, serum indirect bilirubin
11.3 mg/dL, LDH 943 U/L. We headed to a hematol-
ogist for a consult to determine why these parame-
ters increased. Peripheral blood smear, haptoglobin
level and coombs tests were made. All coombs tests
were negative, but in peripheral blood smear heinz
bodies and spherocytosis were seen in red blood
cells (gure 3.) and haptoglobin level was 9.8 mg/
dL (normal 16-200 mg/dL), reticulocyte count 5.1%
and hemolytic anemia was diagnosed. G-6-PD de-
ciency test was performed and 2.16 U/g Hb values
were found (normal 4.60-13.50 U / g Hb). Treated
with 3 units of leukocyte reduced packed RBCs
with the diagnosis of G6PD deciency. Hemoglobin
level increased to 12.1 g/dL and total and indirect
bilirubin improved 3.14 mg/d Land 0.98 mg/dL, re-
spectively. No trace of hemolysis was found. Patient
found to be stable and discharged subsequently.
Discussion
Hemolytic anemia is a form of anemia due
to hemolysis in which the red blood cells
are destroyed faster than the bone marrow
can produce them. There are two types of
hemolytic anemia: intrinsic and extrinsic.3
Intrinsic (hereditary) hemolytic anemias
can be due to defective red cell metabo-
lism as in G-6-PD deciency and pyruvate
kinase deciency, defects in hemoglobin
production as in thalassemia, sickle-cell dis-
ease and congenital dyserythropoietic ane-
mia, defects of red blood cell membrane
production as in hereditary spherocytosis
and hereditary elliptocytosis, on the other
hand extrinsic hemolytic anemias may be
caused by immune-mediated causes, drugs
and other miscellaneous causes.4.
G-6-PD deciency is the most common
of all clinically signicant enzyme defects:
more than 200 million people are G-6-PD
decient around the world.5 The best char-
acterized exogenous triggers of hemoly-
sis in G-6-PD decient, several factors are
apart from infection, fava beans and drug
induced hemolytic attack in a G-6-PD de-
ciency.6 G-6-PD deciency is diagnosed by
a quantitative spectrophotometric analysis
or a rapid uorescent spot test detecting the
generation of NADPH from NADP. Howev-
er, G-6-PD deciency disease is generally
suspected from routine laboratory analysis
as complete blood count, liver enzymes and
lactate dehydrogenase and clinical features
of patients, and then is investigated.
Contrast materials, also called contrast
agents or contrast media, are used to im-
Figure 2.—Normal right coronary artery angiogram. Figure 1.—Normal left anterior descending artery (LAD),
and circumex artery (Cx) angiogram.
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Vol. 174 - No. 1 GAZZETTA MEDICA ITALIANA - ARCHIVIO PER LE SCIENZE MEDICHE 3
ACUTE HEMOLYSIS IN G-6-PD DEFICIENCY AFTER CORONARY ANGIOGRAPHY KÜÇÜKSEYMEN
contrast agent in our clinic.
In literature, there are many cases drug-
induced hemolytic anemia, additionally
these drugs are therapeutic or symptomatic
drugs. However contrast agent, which we
provide, is only for diagnostic and hemoltik
severe anemia associated with a substance
like this agent, such cases are very rare in
the literature. Previously, in the literature
in patients with sickle cell anemia, hemo-
lytic anemia have been reported depend-
ing on the contrast agent, but in that case,
hemolytic anemia may have arisen due to
infection.10 They have used MD-76 con-
trast agent in their case, so a hyperosmolar
agent, on the other hand, our case is the
rst in the literature, acute severe hemolysis
occurred after contrast agent in G-6-PD de-
cient patient.
In our case, we have used a hypo-osmo-
lar contrast agent, and after the procedure,
we encountered a acute severe hemolysis.
As a result, in the differential diagnosis of
hemolytic anemia, no matter what type of
contrast agents should be considered.
Conclusions
In such a complication after coronary an-
giography, if it is compatible with the nd-
ings of acute hemolysis, G-6-PD deciency
should always bring to mind and advise
prove pictures of the inside of the body
produced by x-rays, computed tomography
(CT), magnetic resonance (MR) imaging,
and ultrasound.7 Radiocontrast agents are
typically iodine or barium compounds. Bar-
ium sulfate is mainly used in the imaging of
the digestive system. Iodine contrast agents
are used for angiography (arterial investiga-
tions), venography (venous investigations),
VCUG (voiding cystourethrography), HSG
(hysterosalpingogram) and IVU (intrave-
nous urography). Modern iodinated contrast
agents are generally well tolerated; adverse
reactions ranging from mild to severe do
occur but severe reactions are very uncom-
mon, the major side effects of radiocontrast
are anaphylactoid reactions and contrast-
induced nephropathy.8 Hyperosmolar and
hypo-osmolar solutions are type of ionic
contrast agents. Many of the side effects are
due to the hyperosmolar solution being in-
jected. Hypoosmolar contrast agents are less
likely to induce side effects than hyper-os-
molar agents and these are Iopamidol, Ioxi-
lan, Iohexol, Iopromide and Iodixanol.9
In our case of patient had type 2 diabe-
tes, but did not use any drugs and there was
also no family history. Additionally he nev-
er before had not been sufcient to blood
transfusion. Events that occurred in our
case, jaundice and acute severe hemolysis
occurred two days after coronary angiog-
raphy. He did not receive any drug except
Figure 3.—Heinz bodies and spherocytosis were seen in peripheral blood smear.
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4 GAZZETTA MEDICA ITALIANA - ARCHIVIO PER LE SCIENZE MEDICHE ?? 2015
KÜÇÜKSEYMEN ACUTE HEMOLYSIS IN G-6-PD DEFICIENCY AFTER CORONARY ANGIOGRAPHY
6. Pamba A, Richardson ND, Carter N, Duparc S, Premji
Z, Tiono AB, et al. Clinical spectrum and severity of
hemolytic anemia in glucose 6-phosphate dehydro-
genase-decient children receiving dapsone. Blood
2012;120:4123-33.
7. Bettmann MA. Angiographic contrast agents: conven-
tional and new media compared. AJR Am J Roentge-
nol 1982;139:787-94.
8. Bottinor W, Polkampally P, Jovin I. Adverse Reactions
to Iodinated Contrast Media. Int J Angiol 2013;22:149-
54.
9. Wittbrodt ET1, Spinler SA. Prevention of anaphy-
lactoid reactions in high-risk patients receiving
radiographic contrast media. Ann Pharmacother
1994;28:236-41.
10. Rao AK, Thompson R, Durlacher L, James F. Angi-
ographic contrast agent-induced acute hemolysis in a
patient with hemoglobin SC disease. Arch Intern Med
1985;145:759-60.
Conicts of interest.—The authors certify that there is no
conict of interest with any nancial organization regarding
the material discussed in the manuscript.
Received on July 9, 2014.
Accepted for publication on January 8, 2015.
that newer contrast agents with hypo-osmo-
lar ones need to be carefully evaluated for
radiologic studies in patients with G-6-PD
decient disease.
References
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