Rev. Med. Chir. Soc. Med. Nat., Iaşi – 2012 – vol. 116, no. 4
INTERNAL MEDICINE - PEDIATRICS
CASE REPORTS
MACRO-CREATINE KINASE SYNDROME AS AN UNDERDIAGNOSED
CAUSE OF CK-MB INCREASE IN THE ABSENCE OF MYOCARDIAL
INFARCTION: TWO CASE REPORTS
C. I. Axinte 1, Teodora Alexa 2, Irina Cracana1 , Ioana Dana Alexa3
University of Medicine and Pharmacy ”Grigore T. Popa” - Iasi
Faculty of Medicine
1. Discipline of Internal Medicine
3. Discipline of Geriatrics
2. Regional Institute of Oncology, Iasi
MACRO-CREATINE KINASE SYNDROME AS AN UNDERDIAGNOSED CAUSE OF CKMB INCREASE IN THE ABSENCE OF MYOCARDIAL INFARCTION. CASE REPORTS
(Abstract): When assessing an acute coronary syndrome (ACS) by means of high serum levels
of creatine kinase (CK) and its MB fraction (CK-MB), one must keep in mind that there are
several other causes for an increase of these markers, such as myocarditis, pericarditis, heart
failure, severe aortic stenosis, stroke, renal failure, malignant hyperthermia, Reye syndrome,
polymyositis, and borreliosis (1). Also, there are cases when CK-MB is falsely increased due to
certain abnormalities that occur in the CK isoenzymes. One such example is the formation of
the so-called macro-creatine kinase complexes (macro-CK) that give a false increase of the
CK-MB fraction. We report two clinical cases where macro-CK was the cause of apparent increase in serum CK and CK-MB: in a 79-year old male with a history of coronary disease and a
82-year old female with permanent atrial fibrillation. Keywords: MACRO-CK SYNDROME,
CK-MB FRACTION, ACUTE CORONARY SYNDROME.
Acute coronary syndrome (ACS) includes unstable angina and myocardial
infarction. The only way to differentiate
between unstable angina and myocardial
infarction without ST segment elevation
(NSTEMI) reveal myocardial necrosis by
dosing biomarkers of myocardial cytolysis.
Introduction of cardiac enzymes in clinical
practice increased the rate of diagnosis of
myocardial infarction by 30%.Cardiac
markers are extremely important diagnostic
tools especially in the elderly because of
atypical clinical forms (insidious onset
painless forms, atypical pain) and poor
electrocardiographic changes through the
predominance of NSTEMI forms.
CK-MB may increase in other diseases
than acute myocardial infarction, such as
myocarditis, cardiomyopathy, pericarditis,
congestive heart failure, close aortic stenosis, stroke, renal failure, malignant hyperthermia, Reye's syndrome, strenuous efforts,
trauma muscle, polymyositis, dermatomyositis, Duchenne muscular dystrophy,
myoglobinaemia, borreliosis (1).
CK-MB is the most widely used marker
for evaluating patients with acute coronary
syndromes. Cardiac troponins (I and T)
have greater sensitivity and specificity
because they are contractile proteins that
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C. I. Axinte et al.
are found only in the cardiac myocytes (2).
Serial measurements of total CK and CKMB, associated with troponin measurements may better indicate temporal evolution and infarct size (3, 4).
Creatine kinase (CK) consists of 3 fractions (CK-MM, CK-MB, and CK-BB). A
report of total CK / CK-MB> 50% is suggestive for the presence of macro CK complexes (type 1 or 2), resulting in a reaction
type Ag-Ac. The occurrence of these immune complexes produces a false increase
in CK-MB which can 't be differentiated
except by electrophoresis (5).
CASE REPORT Ι
Patient 1 is known with significant coronary and hypertensive damage ; at the age
of 76 years he was performed angioplasty
with active pharmacologically on circumflex
artery and at the age of 78 years a coronary
angiography is carried out again because of
prolonged chest pain and occurrence of
electrocardiographic changes in dynamics.
The coronary angiography revealed the
following changes: left coronary artery LAD stenosis 80% II, 80% ostial stenosis,
stent re-stenosis minimum CX I, stenosis
80% GM I, GM II 90% ostial stenosis, right
coronary artery - 80% stenosis CD I CD III
80% stenosis, 80% stenosis IVP with surgical myocardial revascularization indication
that the patient has timed it.
In April 2012, he was admitted in Geri-
atric Hospital Clinic "Dr. C.I. Parhon " for
precordial pain having angina character and
worsening in the last 4 hours before addressing and which partially wakened after
Nitroglycerin administration.
Aim at internment: BP = 140/80 mm
Hg, FC = 76 b / min, rhythmic, without
signs of cardiac decompensation.
Electrocardiogram: sinus rhythm, FC =
70/min, AQRS = -30 °, concentric left
ventricular hypertrophy type, ISL = 40 mm
Holter ECG: sinus rhythm throughout
the recording
Echocardiography: significant left ventricular wall hypertrophy, SIV = 16 mm,
EF = 60%, without hypo-kinetic areas.
Of laboratory results note: total CK =
245 U / l, CK-MB = 226 U / L, troponin T
hs = 11 ng / ml (normal: 0-14 ng / ml),
SGPT = 30 U / L, SGOT = 31 U / l, LDH =
175 U / l, glucose = 98 mg%.
Because of increased CK-MB, troponin T
hs normal, ratio CK / CK-MB> 50%, without
significant electrocardiographic abnormalities
dynamic and echocardiographic appearance's
CK electrophoresis was performed (tab. I).
Suspected a false increase in CK-MB. Macro
CK Complex has been identified type 1 (1.56
micromol / SL), total CK = 2.5 (normal: 2.85
micromol / SL), CK-MB = 0 micromol / sL
(normal: <0.1 micromol / SL), CK-MM =
0.94 micromol / sL (normal: <2.85 micromol
/ SL), CK-BB = 0 micromol / sL (normal: 0)
(tab Ι, fig. 1, 2).
TABLE Ι
Results of CK izoenzyme electrophoresis in patient 1
Patient values
Normal values
CK
2,5 μmol/sl
< 2,85 μmol/sl
CK-MM
0,94 μmol/sl
< 2,5 μmol/sl
CK-BB
0 μmol/sl
0,00 μmol/sl
CK-MB
0 μmol/sl
< 0,1 μmol/sl
Macro CK
1,56 μmol/sl (62% of CK)
0 μmol/sl
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Macro-creatine kinase syndrome as an underdiagnosed cause of CK-MB increase
Fig. 1. CK and CK-MB values during previous hospital stay.
Values in 2009 are previously recorded PTCA
CASE REPORT ΙΙ
Patient 2, well known hypertensive
with permanent atrial fibrillation and heart
failure NYHA class II left side is admitted
for dyspnea at minor efforts occurred two
days ago due to psycho-emotional stress.
Associates prior atypical chest pain, with
emphasis on compression onset 24 hours
ago.
Aim at internment: BP = 150/90 mm
Hg, FC = 110 / min.
Electrocardiography: Atrial fibrillation,
FCM = 104/min, AQRS = 30°, negative T
waves in V1, V2.
Echocardiography: EF = 50%, SIV = 11
mm, without hypo-kinetic areas without
pericardial fluid, VCI completely inspiratory collapse.
From the laboratory results its is noted:
total CK = 248 U / l, CK-MB = 274 U / L,
troponin T hs = 17 ng / ml, SGPT = 36 U /
l, ALT = 28 U /l.
CK s electrophoresis was performed as in
the case of the first patient. It has been identified macro CK complex type 1 (4.33 micromol / sL) = 4.79 total CK, CK-MB = 0
micromol / SL, CK-MM = 0.46 micromol /
SL, CK-BB = 0 micromol / SL (tab ΙΙ, fig. 2).
TABLE ΙΙ
Results of CK izoenzyme electrophoresis in patient 2
Patient values
Normal values
4,79 μmol/sl
< 2,85 μmol/sl
CK
0,46 μmol/sl
< 2,5 μmol/sl
CK-MM
0 μmol/sl
0,00 μmol/sl
CK-BB
0 μmol/sl
< 0,1 μmol/sl
CK-MB
4,33 μmol/sl (90% of CK)
0 μmol/sl
Macro CK
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C. I. Axinte et al.
Fig. 2. CK and CK-MB values throughout hospital stay
DISCUSSION
In both cases one can notice a large increase in CK-MB values that could not be
explained by acute myocardial ischemia or
other common causes of this enzyme increase. Analyzing the previous documents
of patient 1 reveals a constant value increase of CK-MB. The only normal value
was recorded only in 2009 after stent angioplasty. On the internment in January 2011
and August 2011 the lowest CK-MB value
was 125 U / l despite vigorous treatment,
properly administered.
A report of total CK / CK-MB> 50% is
suggestive for the presence of macro CK
complexes. The occurrence of these immune complexes produces a false increase
in CK-MB can t be differentiated except
with electrophoresis. The presence of macro CK complex still doesn't have a precise
use being possible to increase in many
other diseases (6).
There are two types of macro CK: type
1 and type 2. Macro CK type 1 occurs via
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antigen-antibody reaction type between
CK-BB and IgG or, less commonly, between CK-MM and IgA (7, 8). Macro CK
type 1 (incidence = 0.45% - 1.2%) occurs
in hypothyroidism, autoimmune diseases,
cancer, myositis, cardiovascular disease
and even apparently healthy individuals. It
is more common in women and in people
over 70 years (9). Macro CK type 2 (incidence = 0.5 - 3.7%) is close to home and
migrate mitochondrial CK-MM band. In
more severe disease than type 1 appears:
malignancy (most commonly colon or prostate cancer) and severe liver disease with a
poor prognosis (10).
Macro CK complex appearance does
not determine great increase value of total
CK (<500 U /l). It should be suspected a
false increase in CK-MB in the presence of
atypical symptoms of acute ischemia, lack
of electrocardiographic changes, echocardiographic and persistent increases regardless of the therapeutic scheme administered
(11).
Macro-creatine kinase syndrome as an underdiagnosed cause of CK-MB increase
Growth of these enzymes, with a total
CK report /CK-MB under 5% is suggestive
for non cardiac muscle damage. Troponin
specificity and sensitivity is higher than
CK-MB determination. Troponin T hs
shows frequently increased values than
CK-MB in the absence of acute coronary
ischemia therefore it is important to determine its dynamics. Any significant increase
in intraventricular pressure can lead to
abnormal Troponin T hs without myocardial infarction. In patient 2, the slightest
increase of Troponin T hs at interment with
normalization in the next determination
was interpreted in the context of heart failure and atrial fibrillation with fast frequency.
There are few cases of this type reported in literature. Among these, some associate the presence of this syndrome with
digestive disorders such as Crohn's disease
or ulcerative colitis (12) or persistent diarrhea (13). In other reports it has been noticed associations with cancer (14) or myopathies (15). Rosa Jimenez & et al (16)
presents a series of 7 cases with macro-CK
type 1 syndrome, of which 3 cases had a
history of cardiovascular disease and the
rest were not known. Patients reported in
this article are the first reported in Romania
with macro-CK syndrome.
CONCLUSIONS
Highlighting cases of macro CK is useful
for avoiding invasive investigations and unnecessary treatments. The particularity of the
first patient case consists in a false increase
of CK-MB at a patient with three-vessel
lesions and indication for revascularization
surgery. The systolic function is maintained
within normal limits and poses no arrhythmia
at ECG Holter monitoring, in significant
myocardial ischemia. The particularity of the
second case is the combination of a significant increase in CK-MB in the presence of a
chest pain caused by musculoskeletal pain
(possible intricate pain) and without electrocardiographic changes in dynamics and without echocardiographic hypo-kinetic areas.
Electrophoresis Creatine is currently quite
expansive investigation and can be suspected
the presence of complex macro CK emergency when the total report CK / CK-MB> 50%.
Discrepancy between the values of CKMB and troponin must raise a question
mark for the diagnosis of acute myocardial
infarction and the values of these biomarkers must be correlated with clinical
examination, electrocardiographic and
echocardiographic aspect.
Guidelines for acute coronary syndrome
should mention this false increase in CKMB as a variant of differential diagnosis.
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