ARTICLE
Green serum: should
the laboratory be worried?
The appearance of green serum following centrifugation
of a blood sample is very rare. There are, however, several
possible causes of this phenomenon, as Paul Randell explains.
A 68-year-old woman undergoing breast
cancer excision and sentinel node biopsy had
bloods taken for a hepatitis screen, as she had
a history of hepatitis B three years previously.
Following centrifugation of the blood sample,
the head biomedical scientist in microbiology
was asked if it was permissible and safe to
perform the test on bright green serum and if
it would interfere with any testing or cause
problems with the analyser. Green serum is
very rare so a quick literature search was
undertaken, and three possible causes for this
hue were identified:
r copper-containing compounds
r bilirubin or biliverdin
r an imaging dye.
COPPER ABNORMALITIES
In over 1000 blood transfusion bottles
checked at the Leeds Blood Transfusion
Laboratory in 1968, about 1% had green
plasma, and a link between the green
colouration and women taking combined oral
contraceptives was noticed (15/19 from a
random sample). The green colour was
thought to be due to caeruloplasmin, a blue,
copper-containing glycoprotein. Elevated
levels (3570 mg/100 mL) were found in
these blood samples and it was concluded that
Green plasma has long been known to occur in
pregnancy. As oestrogens are sometimes
effective in elevating caeruloplasmin in patients
with Wilsons disease, increased caeruloplasmin
in these pill users was probably due to the
oestrogen in the pill.1
BILE PIGMENTS
Green jaundice has been documented with
cases of green serum and green-black urine.
A review on green jaundice concluded that
a mixture of biliverdin, mesobiliverdin and
related pigments appeared to contribute to the
402 THE BIOMEDICAL SCIENTIST
green colour observed.2 More
recently, it has been concluded that
this green jaundice may be caused
by a genetic defect in the biliverdin
reductase-A (BVR-A) gene causing
reduced activity of the enzyme that
converts biliverdin to bilirubin, in
conjunction with decompensated
liver cirrhosis,3 findings that are revisited on
page 362 of this issue.4
IMAGING DYES
At least one report of green colouration of
serum has been reported with a fluorescent
dye used to evaluate mesenteric-vessel viability
by intraoperative angiography in a patient with
colon cancer.5 Imaging dyes could theoretically
interfere with test results, depending on the
detection system used in the test (ie
colorimetric, fluorescence or luminescence).
ANAPHYLAXIS, PULSE OXIMETRY
AND SENTINEL NODE BIOPSY
The 68-year-old womans liver function tests
had been normal, but the patient had
undergone breast surgery that day and a
radioisotope and coloured dye had been used
in the procedure to identify the sentinel node.
The dye used, patent blue V, is a well-known
dye used to visualise lymph nodes and identify
the sentinel lymph node for biopsy in breast
carcinoma, and it has been documented that
it can cause green colouration of the blood.
Literature reports concentrate on
anaphylaxis caused by blue dyes6,7 and that this
discolouration has been reported to make the
use of pulse oximetry useless by mimicking
true intraoperative hypoxia.7,8 However, no
reports were found to indicate whether or not
this discolouration interferes with pathology
tests (the requested microbiology tests use a
luminescent signal).
THE COLOUR GREEN
In conclusion, it was decided prudent
to add a comment to the final report that
stated: Green dye present in serum
sample which may affect the quality of
these results. r
REFERENCES
1 Tovey LA, Lathe GH. Caeruloplasmin
and green plasma in women taking
oral contraceptives, in pregnant
women, and in patients with
rheumatoid arthritis. Lancet 1968;
2(7568): 596600.
2 Greenberg AJ, Bossenmaier I,
Schwartz S. Green jaundice a study
of serum biliverdin, mesobiliverdin
and other green pigments. Am J Dig
Dis 1971; 16(10): 87380.
3 Gfvels M, Holmstrm P, Somell A et al.
A novel mutation in the biliverdin
reductase-A gene combined with liver
cirrhosis results in hyperbiliverdinaemia
(green jaundice). Liver Int 2009; 29:
111624.
4 Higgins C. A very unusual case of
jaundice. The Biomedical Scientist 2009;
53(10): 82830.
5 Bailey H, Wu AHB. Images in clinical
medicine. Bright green serum.
N Engl J Med 2007; 356(11): e10.
6 Scherer K, Studer W, Figueiredo V, Bircher
AJ. Anaphylaxis to isosulfan blue and
cross-reactivity to patent blue V: case
report and review of the nomenclature of
vital blue dyes. Ann Allergy Asthma
Immunol 2006; 96(3): 497500.
7 Sprung J, Tully MJ, Ziser A. Anaphylactic
reactions to isosulfan blue dye during
sentinel node lymphadenectomy for breast
cancer. Anesth Analg 2003; 96(4): 10513.
8 Motiani P, Ahuja S, Agrawal S. Prolonged
interference of patent blue dye on pulse
oximetry readings. J Anaesth Clin
Pharmacol 2006; 22(1): 879.
Paul Randell (paul.randell@wsht.nhs.uk) is
head biomedical scientist in microbiology
at Western Sussex Hospitals NHS Trust,
St Richards Hospital, Chichester PO19 6SE.
JUNE 2011