CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 1, February 2012
AFRICA
e7
2 4 July/August 2011
143
Case Report
Macro CK in patients with elevated troponin I levels
RUCHIKA KOHLI-KOCHHAR, EVELYNE MULWA, GEOFFREY OMUSE, PETER OJWANG
Abstract
CK-MB activity levels can be falsely elevated by the presence
of macro CK, especially if immuno-inhibition assays are used
in the measurement. In patients with macro CK and cardiac
pathology that could result in an elevated CK-MB activity,
the diagnostic challenge lies in determining the true cause of
the elevated CK-MB activity. We present two case reports of
patients with elevated CK-MB activity and troponin I levels,
but who subsequently had CK-MB activity higher than total
CK activity, raising the suspicion of the presence of macro
CK.
Keywords:
macro CK, CK-MB interference, elevated troponin I
Submitted 8/4/10, accepted 31/8/10
Cardiovasc J Afr
2011;
22
: 00–00
DOI: CVJ-21.051
Creatine kinase can exist as a macroenzyme, which is an enzyme
with a higher molecular mass than the corresponding enzyme
normally found in serum.
1-3
Macroenzymes except macro CK
type 2 consist of a normal enzyme complexed with an immuno-
globulin, most commonly IgG or IgA. The complexed enzyme
has reduced blood clearance, resulting in increased circulating
amounts of the higher-than-normal molecular weight form of
the relevant enzyme. When quantitative total CK enzymatic
assays are used, macro CK is indistinguishable from normal CK,
causing an elevation of the total CK. Macroenzymes should be
suspected when the enzyme levels are persistently raised to rela-
tively constant levels and there is no obvious clinical explanation
or other laboratory abnormality.
4
Macro CK has a molecular weight of over 200 kDa, which
results in different electrophoretic and chromatographic mobil-
ity.
1,5,6
Macro CK type 1 is an isoenzyme–Ig complex created via
an antigen–antibody reaction. The most common form of type 1
macro CK is a CKBB–IgG complex. When CK electrophoresis
is used, the diagnosis is confirmed through the different electro-
phoretic mobility of the macro CK compared with the other CK
isoenzymes.
4
Macro CK type 2 is a polymer of mitochondrial
CK and has been linked to malignant tumours and to the use of
tenofovir-containing regimens in the treatment of HIV.
7
Analytical interferences in laboratory assays are an occasion-
ally encountered problem and if not recognised, can lead to
misdiagnosis of patients and unnecessary investigations. Here
we report two cases of falsely elevated creatine kinase MB activ-
ity due to assay interference caused by the presence of macro
CK type 1.
Case report 1
A 74-year-old female patient had been admitted at the Aga
Khan University Hospital, Nairobi, Kenya on several occasions
since June 2009. She presented at the third admission with a
two-month history of bilateral lower-limb weakness and pain,
which was progressive. She also complained of urine and stool
incontinence but the duration of symptoms was unclear.
The patient underwent coronary angioplasty in 2006. In 2007
she was diagnosed with Guillian Barre syndrome (GBS); in 2008
she underwent bilateral knee replacement for osteoarthritis and
in 2009 she was admitted on several occasions for angina attacks.
She also had poorly controlled hypertension. On examination, the
major findings were bilateral weakness, power grade 4 in both
the upper and lower limbs.
A number of investigations were done and abnormalities
of serum CK, CK-MB and troponin levels were as shown in
Table 1. The assays of serum CK and CK-MB were done on an
Olympus AU600
®
analyser using an immuno-inhibition method
and troponin I was measured with an Abbott Axsym
®
analyser
using a microparticle enzyme immunoassay.
Based on the above-abnormal CK and CK-MB results,
further laboratory investigations done were: an electrocardio-
gram (ECG) which showed a sinus tachycardia, and a coronary
angiogram which showed cardiomyopathy. Investigations to rule
out a connective tissue disorder were also done, including a panel
of anti-nuclear antibody (ANA), anti-smooth muscle antibody
(ASMA) and anti-mitochondrial antibody (AMA) tests, which
were all negative. Aldolase level was also normal.
Radiological investigations included an MRI of the brain,
which showed a Dandy Walker variant, and an electromyogram
with nerve conduction studies. This showed features of peri-
Department of Pathology, Aga Khan University Hospital,
Nairobi, Kenya
RUCHIKA KOHLI-KOCHHAR, MD,
EVELYNE MULWA, MD
GEOFFREY OMUSE, MD
PETER OJWANG, MD
TABLE 1. TRENDS OF SERUM CK, CK-MBAND
TROPONIN I LEVELS FOR PATIENT ONE.
THE NORMAL REFERENCEVALUES OF THE
ANALYTESARE INDICATED IN BRACKETS
CK (U/l)
(34–145)
CK-MB
(U/l)
(0–24)
Troponin I
(ng/ml)
(
<
0.4)
%CK-MB
(
<
6%)
Index day
482
820
0.44
>
100
Day 2
422
721.1
0.5
>
100
Day 12
512
966.2
>
100
2
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e7 1
10.5830/CVJA-2010-082