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How to Cite this article: Critical Limits of Laboratory Results for Urgent Clinician
Notification, eJIFCC vol 14 no 1: http://www.ifcc.org/ ejifcc/vol14no1/140103200303n.htm

Critical limits of laboratory The laboratory should not report a criti-

cal result to the treating physician until
results for urgent clinician it has been confirmed by a second deter-
notification mination in the same sample.

Professor Dr Lothar Thomas The laboratory test value should be

ascertained by a competent member of the
laboratory (laboratory doctor, clinical
chemist, senior medical laboratory tech-
nician) who should discuss the result with
the treating physician.
precision and accuracy, allow blood parameters to
Kirschbaumweg 8, 60489 Frankfurt
be determined in concentration ranges, which
E-mail: th-books@t-online.de indicate that the patient is in acute danger or even a
Critical limits of laboratory results need danger to others. The laboratory must report such
urgent notification to the clinician because results to the treating physi-cian immediately. For
they are an indicator of a critical or even life- this to happen, there must be an agreement
threatening condition of the patient. between the treating physician and the laboratory as
to what constitutes a critical result that needs to be
reported to him. The parameters chosen and the
The publications about this topic are
mainly from the 1970s. Since then, critical limits depend essentially on the disease
many laboratory methods have been prevalence expected in the clinic or practice.
improved, new parameters have been
added, and there have also been
changes in the evaluation and
treatment of diseases.

Against this background and at the request of

the Ameri-can Medical Association, J.G. Kost
[1] conducted a survey on critical pa-
rameters in the USA in 1990 and Howanitz et
al. [2] in 2002. The spectrum of critical pa-
rameters reported in these publications does
not meet the require-ments of laboratory
medicine in every respect.

I have therefore put together a new list

of qualitative and quantitative
parameters. If you think there are
parameters that should perhaps be
added or deleted, limits, which need
changing, or notes that need to be
amended, your suggestions would be
most welcome.

Quantitative laboratory test results for

the blood and extravascular body fluids
are indicators, for example, of organic
disease, metabolic disorders, diseases of
the haematopoietic system, disturbances
of haemostasis, abnormalities of the
endocrine system, activation or
insufficiency of the immune system,
inflammation, infections, and
autoimmune processes.

High detection sensitivity, a wide

measurement range, and good to acceptable
 [1]. The others are based on 25 years’
This is because influences and experience as a 1 doctor for laboratory
interfer-ence factors in the medicine working in a hospital.
preanalytical phase, e.g. sample
collection for glucose measurement References:
using a venous catheter that had
been used for glucose infusion, are Kost, GJ. Critical limits for urgent clinician
not infrequently the cause of notification at US medical centers. JAMA
seemingly critical values. Such cases 1990; 263: 704-7
are usually clarified by the testing of
another, properly collected sample.
Howanitz PJ, Steindel SJ, Heard NV.
Laboratory critical values, policies and
The specified parameters and limits are procedures. A College of Ameri-can
taken partly from Pathologists Q-probes study in 623
institutions. Arch Pathol Lab Med
2002; 126: 663-9.

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Table 1: Adult and paediatric limits of laboratory results which, after confirmation
through repeat measurement in the same sample, need urgent notification of the
physician

Parameter Value Note

Activated 75 sec Deficiency or inactivity of factor VIII, IX, XI, or

partial XII, with risk of haemorrhage. In persons
thromboplastin receiving heparin therapy there is a risk of
time (APTT) haemorrhage if the APTT is more than 2.5 times
higher than the upper reference limit.

Aminotrans- > 1000 U/l Notification depends on the patient population of

ferases the clinic or practice in question.

Ammonia > 100 mg/dl (59 Risk of hepatic encephalopathy. Comatose states
mmol/l) do not usually occur unless levels exceed 300
mg/dl (176 mmol/l).

Anion gap > 20 mmol/l Indicative of ketoacidosis or lactacidosis, uraemia, 2

alcohol consumption, salicylate intoxication,
poisoning from methanol or ethylene glycol.

Inorganic < 1.0 mg/dl Muscle weakness, muscle pain, central-nervous

phosphate (0.32mmol/l) symptoms such as disorientation, confusion,
convulsions, coma, respiratory insufficiency with
> 9.0 mg/dl (2.9 metabolic acidosis.
mmol/l)
Occurs in acute tumour lysis syndrome and in
terminal renal failure.

Antithrombin < 50% There is substantial inhibitor deficiency, which in

(AT) those with elevated procoagulant activity poses a
high risk of thromboembolic complications.

Ethanol > 3.5 g/l (76 Blood alcohol concentrations of 3-4 g/l can be
mmol/l) fatal, even in those who are not simultaneously
using medicinal products.
> 3.5 %

Bilirubin > 15 mg/dl (257 Hepatobiliary disease caused mainly by

mmol/l) hepatotropic viruses and thus of infectious origin
with risk of contagion.

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Parameter Value Note

Chloride < 75 mmol/l Indicative of considerable metabolic alkalosis.

>125 mmol/l Indicative of massive primary metabolic acidosis

or pseudohyperchloraemia in the case of bromide
intoxication.

Creatinine > 7.4 mg/dl (654 Acute renal failure, e.g. in multiple organ failure
mmol/l) or sepsis.

Creatine kinase > 1000 U/l Notification depends on the patient population of
the clinic or practice in question.

D-dimers Positive In disseminated intravascular coagulation (DIC),

detection of D-dimers is indicative of phase II
(decompensated activation of the haemostasis
system) or phase III (full-blown DIC).
3
Digoxin > 2.0 mg/l (2.56 Non-cardiac symptoms such as tiredness, muscle
nmol/l) weakness, nausea, vomiting, lethargy, and
Digitoxin headache and cardiac symptoms such as sinus
> 40 mg/l (52 arrhythmia, bradycardia, and various degrees of
nmol/l) AV block.

Fibrinogen < 0.8 g/l Risk of haemorrhage.

Fibrin Positive Indicative of consumption coagulopathy in

monomers disseminated intravascular coagulation, sepsis,
shock, multiple injury, acute pancreatitis, and
obstetric complications.

Glucose < 45 mg/dl (2.5 Neuroglycopenic symptoms, which can range

mmol/l) from impairment of cognitive functions to loss of
consciousness.
> 500mg/dl
Diabetic coma due to insulin deficiency.
(27.8 mmol/l) Development of osmotic diuresis with severe
exsiccosis and diabetic ketoacidosis (b-
hydroxybutyrate > 5 mmol/l, standard
bicarbonate < 10 mmol/l).

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Parameter Value Note

Haemoglobin < 6.6 g/dl Supply of oxygen to the myocardium inadequate.

> 19.9 g/dl Corresponds to haematocrit of 61% and leads to

hyperviscosity syndrome.

Lactate > 45 mg/dl (5.0 Indicator of type A hyperlactataemia, which is

mmol/l) caused by an inadequate supply of oxygen to the
tissue. Pyruvate is no longer metabolised
oxidatively, but reductively.

Lactate > 1000 U/l Notification depends on the patient population of

dehydrogenase the clinic or practice in question.
4
Leukocyte < 2000/ml High risk of infection if the granulocyte count is <
count 500/ml.
> 50,000/ml
Indicative of leukemoid reaction, e.g. in sepsis, or
of leukemia.

Lipase > 700 U/l Indicative of acute pancreatitis.

Magnesium < 1.0 mg/dl (0.41 Characteristic symptoms are paresthesias, cramp,
mmol/l) irritability, and athetoid tetany. The patient often
shows cardiac arrhythmia in conjunction with
> 4.9 mg/dl (5.0 hypokalemia; arrhythmia is intensified by
mmol/l) digitalis.

Reduction of neuromuscular impulse

transmission, resulting in sedation, hypo-
ventilation with respiratory acidosis, muscle
weakness, and reduced tendon reflexes.

Myoglobin > 110 mg/l Myocardial infarction should be suspected in

patients with angina pectoris.

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Parameter Value Note

Osmolality < 240 mOsm/kg Cellular oedema with an increase in cell volume
H2O and development of neurological-psychiatric
symptoms.
> 330 mOsm/kg
H2O Cellular water loss and intracellular increase in
osmotically active substances, which do not
permeate the cell membrane. Result: central
symptoms and coma.

Osmolar gap > 10 mOsm/kg Indicative of intoxication from non-electrolytes,

H2O which increase plasma osmolality, such as
ethanol, methanol, ethylene glycol, isopropanol,
and dichloromethane. 5

pCO2 < 19 mm Hg (2.5 Hyperventilation

kPa)
Hypoventilation
> 67 mm Hg (8.9
kPa)

pH < 7.2 Such pH values are characteristic of severely

decompensated acidosis or alkalosis. Values <
> 7.6 7.20 and > 7.60 are life-threatening.

pO2 < 43 mm Hg (5.7 Such values correspond to a haemoglobin oxygen

kPa) saturation of less than 80% and are to be regarded
as life-threatening.

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Parameter Value Note

T4, free > 35 ng/l (45 Indicative of thyrotoxicosis, a condition

pmol/l) detectable clinically and in laboratory tests; the
T3, total tissues are exposed to too high a thyroid
> 30 mg/l (46 hormone concentration and react to this. Possible
nmol/l) causes are: Graves’ disease, trophoblastic tumour,
hyperfunctional adenoma, toxic nodular goitre,
and, in rare instances, overproduction of TSH.

Thromboplastin > 27 sec (approx. Decrease in the vitamin K-dependent factors II,
time (TT) 50%) VII, and X or in factor V. Since all these factors
are synthesized in the liver, a decrease in the TT
to values below the specified level indicates a
considerable disturbance of synthesis. In persons
receiving coumarin therapy, there is a risk of
haemorrhage if the TT is < 15% – which
corresponds roughly to an INR of > 4.
6
Platelet count < 20,000/ml Risk of haemorrhage. Exclude EDTA-induced
thrombocytopenia.
> 1 million/ml
Risk of thrombosis.

Troponin > 0.1 mg/l Indicative of myocardial infarct or unstable

angina pectoris.

Uric acid > 13 mg/dl (773 Acute urate nephropathy with tubular blockade
mmol/l) and renal failure. The uric acid/creatinine ratio in
spontaneous urine in such cases is > 1.0 (mg/mg).

Urea > 214 mg/dl (35.6 Indicative of acute renal failure; unlike pre-renal
mmol/l) and post-renal kidney failure, no
BUN disproportionate increase in urea compared to
> 100 mg/dl (35.6 creatinine in serum.
mmol/l)

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Table 2: Critical limits of qualitative laboratory results which must be reported to the
treating physician immediately

Cerebrospinal fluid

• Increased cell count

• Leukocytosis, tumour cells
• Glucose lower than in serum
• Lactate > 20 mg/dl (2.2 mmol/l)
• Detection of pathogens in Gram stain or agglutination test
Urine · Strongly positive test strip reaction for glucose and acetone

• Red cell casts or > 50% dysmorphic erythrocytes

• Severe haemoglobinuria (no erythrocytes on microscopic examination)
• Detection of drugs
Differential blood count · Leukemoid reaction

• Suspected leukemia
7
• Suspected aplastic crisis
• Sickle cells
• Malarial parasites
Microbiology · Detection of pathogens in Gram staining of blood culture or of exudates and
transudates of body cavities

• Antigenic detection of pathogens with rapid tests such as latex agglutination,

immunofluorescence, or immunoassay, e.g. group B streptococci, legionella,
Pneumocystis carinii, Cryptococcus, hepatitis B
• Detection of acid-fast bacilli or detection of M. tuberculosis after amplification (PCR)
• Cultural detection of salmonellae, shigella, Campylobacter, C. difficile, C. perfringens, N.
gonorrhoeae, B. pertussis, N. menin-gitidis, C. diphtheriae, and pathogenic fungi such as
Aspergillus, Blastomyces, Coccidioides, Histoplasma, and Cryptococcus
• Detection of HIV antibodies

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Table 3: Neonatal quantitative limits of laboratory results which, after confirmation

through repeat measurement in the same sample, need urgent notification by the
physician.

Parameter Value Note

Bilirubin > 14 mg/dl (239 On first day of life, e.g. in hemolytic disease of the
mmol/l) newborn; risk of kernicterus.

C-reactive > 5mg/l Indicative of neonatal sepsis.

protein

Glucose < 30 mg/dl (1.7 Hypoglycemia, caused, for example, by a congenital

mmol/l) metabolic disorder or hyperinsulinism due to
maternal diabetes mellitus. Glucose concentrations <
25 mg/dl (1.3 mmol/l) should be treated by parenteral
administration of glucose.

Urgent clarification of pathogenicity required.

> 325 mg/dl (18

mmol/l)

Hematocrit < 33% (L/L) Indicative of marked anemia with an inadequate 8

supply of oxygen to tissue.

Hyperviscosity of the blood with increased

>71% (L/L) circulatory resistance.

Hemoglobin < 8.5 g/dl Risk of multiorgan failure, especially if the patient
has a combination of ischemia and hypoxia.

Abnormal flow kinetics (hyperviscosity) with

> 23 g/dl increased circulatory resistance and an increased
load on the heart.

Igm > 20 mg/dl A cord blood IgM concentration above the limit can
be linked to an intrauterine infection.

Potassium < 2.6 mmol/l Occurrence of neuromuscular symptoms with

hyporeflexia and paralysis of the respiratory muscles.

Clinical consequences are heart-rhythm disturbances,

³ 7.7 mmol/l weakness of the skeletal muscles, and respiratory
paralysis.

Leukocyte count < 5,000/ml Values below and above these limits can be
indicative of neonatal sepsis.
> 25,000/ml

pO2 < 37 mm Hg (4.9 Drop in hemoglobin oxygen saturation to below 85%.

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