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Effect of gender and age on the prothrombin time (PT), activated partial
thromboplastin time (aPTT) levels and international normalized ratio (INR)

Article · January 2013

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 International Journal of
Mevlana Medical Sciences
Advanced Technology and Science

ISSN:2147-8236 www.atscience.org/IJMMS Research Article

Effect of Gender and Age on the Prothrombin Time (PT), Activated

Partial Thromboplastin Time (aPTT) Levels and International
Normalized Ratio (INR)
Abdullah SIVRIKAYA1,*, Hatice BARAN1, Sedat ABUSOGLU1, Bahadır OZTURK1, Husametin
VATANSEV1, Ali UNLU1
Received 22th July 2013, Accepted 13th August 2013
DOI: 10.1039/b000000x

Abstract: Prothrombin time (PT), a test for analysis of coagulation extrinsic pathway, is used for disorders of coagulation, to assess the
risk of bleeding in patients undergoing operative procedures, to monitor the patients being treated with oral anticoagulant therapy, and
evaluate liver function. Activated partial thromboplastin time (aPTT) is used to determine the function of the intrinsic pathway and
common pathway factors. The objective of our study is to examine whether PT, International normalized ratio (INR) and aPTT levels
differ between the genders and ages in patients without any known liver disease or anticoagulant drug medication. In this retrospective
study, plasma PT, aPTT and PT levels of patients admitted to Selcuk University Faculty of Medicine hospital for various reasons, were
analyzed from the laboratory information system. 403 males and 403 females were included in the study. Cases were classified
according to age as 0-14, 15-50 and over 50 years. PT and INR levels of male patients were significantly higher from the female patients
(p = 0.019 and p =0.031, respectively). aPTT levels did not differ between genders when total participants evaluated. aPTT levels were
significantly lower in men in the age groups 15-50 (p= 0.039), while no significant difference was detected in the age groups 0-14. PT,
INR and aPTT levels demonstrated slight differences in certain age and gender groups. Thus, population-based reference intervals
should be determined in order to evaluate borderline patients.

Keywords: INR, PT, aPTT, gender, age.

reporting method used in many countries is the INR. Recently,

1. Introduction INR is recognized as the most current and acceptable method for
laboratory measurement of oral anticoagulant therapy in Canada,
Prothrombin time (PT) assay is a test extensively used in extrinsic Europe and USA [2]-[4]. Activated partial thromboplastin time
coagulation pathway evaluation [1]. The method principles of PT (aPTT) is a screening test for deficiency of factors II, V, VIII, IX,
for monitoring anticoagulant therapy was introduced by Quick et X, XI and XII of the intrinsic and common pathways [1].
al. in 1935 and is still in use in our laboratories. Briefly, in this
The International sensitivity index (ISI) allows of measuring
method, calcium and tissue thromboplastin are added to citrated
control and stability over the variability of different
plasma to activate the clotting cascade. PT is used for diagnosing
thromboplastin reagents. As a rule of thumb, high ISI values are
coagulation disorders, evaluating liver functions and determining found in less sensitive thromboplastin reagents and provide less
the risk of bleeding prior to surgical intervention. In addition, it is accurate PT values. Conversely, more sensitive results are
used for monitoring of deep vein thrombosis, heart valve produced by reagents with low ISI ratings [2].
replacement, pulmonary embolism, coronary thrombosis, other
Laboratory-specific reference intervals are essential for
thromboembolic diseases or at monitoring of high-risk patients
appropriate interpretation of test results, and can significantly
taking oral anticoagulant therapy (OAT). PT, a method for
impact clinical decision-making and the quality of patient care.
evaluating the coagulation factors of the “extrinsic pathway”, is Each clinical laboratory is responsible for assuring the validity of
the most commonly used coagulation test in routine laboratories. reference intervals related with their test results. Different
International normalized ratio (INR), which was introduced to analytical methods, diet, local population and various analytical
overcome the problem of marked variation in PT results among
procedure have effects on coagulation tests. However,
laboratories, has been used to standardize PT value. The INR
laboratories usually apply the manufacturer's reference range
level is used to measure the extrinsic pathway of the coagulation
rather than its own reference range [5].
cascade and influenced by coagulation factors I (fibrinogen), II The objective of our study is to examine whether PT, INR and
(prothrombin), V, VII, and X. Different methods have been used aPTT levels differ between the genders and ages in patients
for monitoring of anticoagulant therapy, however, the standard without any known liver disease or anticoagulant use.
_______________________________________________________________________________________________________________________________________________________________
1.,
Department of Biochemistry, Selcuk University Faculty of Medicine,
Konya, TURKEY
* Corresponding Author: Email: biyokaya@selcuk.edu.tr

This journal is © Advanced Technology & Science 2013 IJMMS, 2013, 1(2), 27–29 | 27
2. Materials and Methods Table 1. PT, INR and aPTT levels of male and female subjects

In this retrospective study, plasma PT, INR and aPTT levels of Male (n=403) Female (n=403) p value
patients without any history of bleeding admitted to the Selcuk PT 12.10 (9.90-16.50) 11.90 (9.80-15.60) 0.007
University Faculty of Medicine Hospital for minor surgical INR 1.01 (0.83-1.35) 0.99 (0.830-1.290) 0.007
interventions (such as the repair of inguinal hernia, umbilical
aPTT 26.20 (19.90-42.20) 26.30 (18.00-43.00) 0.910
hernia repair, excision of rectal polyps, diagnostic cystoscopy)
between the months of January-July 2012 were analyzed from the
laboratory information system records. The PT, INR and aPTT levels of the individuals in the first group
Blood samples were collected into the tubes containing of 3.2% (0-14 age group) were significantly higher than the patients in the
sodium citrate blue cap tubes (Vacuette, Italy). Whole blood second (15-50 age group) and third group (over 50 years of age),
samples were centrifuged at 3000 g for 5 minutes and then were aPTT levels of the individuals in the third group (over the age of
immediately separated from plasma and analyzed. 50) were significantly lower than the other groups (Table 2).
403 males and 403 females were included in the study. Cases Table 2. The PT, INR and aPTT levels. A group of 0-14 years of age, B
were classified into total, 0-14, 15-50 years, and over the age of group of 15-50 years of age and C group of above the age of 50 were
50. defined as groups considering the age parameter.
0-14 age group is consisted of 92 females, 133 males; 15 - 50 age
p value
group is consisted of 197 males and 248 females and there were
Age 0-14, 15-50, >50, A- B-C A-C
63 females, 73 males in the third group (over the age of 50 years). (n=226) (A) (n=446) (B) (n=134) (C) B
Plasma PT and aPTT levels were measured in SYSMEX CA-
1500 auto analyzer using Siemens commercial test kits. PT was PT 12.30 (9.90- 11.90 (9.80- 11.90(10.00- 0.000 0.141 0.000
15.40) 16.50) 14.20)
expressed as PT (sec) and INR. Calibration and control samples
were studied using standard methods of the manufacturer. These INR 1,02 (0.83- 0.99 (0.83- 0,99 (0.84- 0.000 0.148 0.000
tests were evaluated with normal and abnormal controls on a 1.26) 1.35) 1.17)
daily control basis and a monthly based Clinic Biochemistry aPTT 27.75 26,00 24.20(18.00- 0.000 0.000 0.000
Specialists Organization (KBUD, Turkey) external quality (19.40- (18.90- 37.10)
43.00) 42.20)
control program.
2.1. Statistical Analysis
Table 3. The PT, INR and aPTT levels according to age and sex of the
SPSS 16.0 statistical software package was used to evaluate the participants and the comparison between groups
data. Shapiro-Wilk test were used for determining the result
normality. Non-parametric distribution was observed for the PT, GENDER
INR and aPTT values. Kruskal-Wallis test was used to assess Age Groups Male Female
whether the difference in total age groups, the Mann-Whitney U 0-14 years (n=134) (n=92)
test was used for comparison of two groups. p value of <0.05 was
PT 12,30 (9.90-15.40)a 12.2 (15.2-10.6)a
considered statistically significant. Reference ranges of 95%
confidence interval were calculated by age and sex. INR 1.02 (0.89-1.25)a 1.02 (0.89-1.25)a
aPTT 27.90 (20.80-37.40)a 27.35 (19.40-43)a
3. RESULTS 15-50 years (n=197) (n=248)
b
The PT and INR levels of males were significantly higher PT 12.00* (10.40-16.5) 11.90 (9.80-15.60)b
compared to females (Table 1). INR 1.00* (0.87-1.35) b
0.99 (0.83-1.29)b
The PT, INR and aPTT levels of males and females aged between aPTT 25.30* (20.60-42.20)b 26.25 (18.90-38.30)b
0-14 years were found to be significantly higher compared to
>50 years (n=71) (n=63)
males and females aged between 15-50 years and above the age
b
of 50. The aPTT levels of male and female over the age of 50 PT 12.10* (10.00-14.20) 11.60 (10.20-14.20)c
b
were lowest. PT, INR and aPTT levels of women aged between INR 1.01* (0.84-1.17) 0.97 (0.86-1.17)c
15 and 50 were significantly higher than females over the age of aPTT 24.60 (19.90-35.10)c 23.40 (18.00-37.10)c
50. The PT, INR and aPTT levels of females aged between 0-14 *The significant difference between females and males in the
were significantly higher than the males in the 15 - 50 age group same age group (p <0.05). abcd: there was no difference
and over the age of 50; while there was no difference between compared with each other all age groups in the same sex groups,
males and females in age of 0-14 group. The PT, INR and aPTT including the groups with the same characteristics.
levels of females aged 15-50 were significantly lower than males PT, INR and aPTT reference ranges of male and female subjects,
aged 0-14, while the aPTT levels of females aged 15-50 were based on 95% confidence interval, in Table 4, according to
higher than males over the age of 50. The PT and INR levels of gender and age groups in Table 5, according to age groups are
females over the age of 50 were significantly lower than the displayed in Table 6.
males of all age groups, while the aPTT levels lower than males
aged of 0-14 years and 15-50 years (Table 3).

28 | IJMMS, 2013, 1(2), 27–29 This journal is © Advanced Technology & Science 2013
 Table 4. The PT, INR and aPTT reference values according to gender, Greenway and Monagle P et al. [8] suggested that many children
based on 95% confidence interval. may be misdiagnosed as Von Willebrand disease due to
prolonged aPTT values compared to adults. In our study, there
Male (n=403) Female (n=403)
were differences in the 0-14 age group compared to adults. The
PT 10.80-13.99 10.60-14.19 aPTT values of this study were quite different from our study.
INR 0.90-1.15 0.89-1.16 The reason for alteration may be related to the population and
aPTT 21.10-33.89 20.40-33.87 analyzer derived reference intervals.
Flanders et al [10]. found no significant difference between
Table 5. The PT, INR and aPTT reference values, based on 95%
children and adults for the levels of aPTT and reported that in
confidence interval.
children, PT levels prolonged about 1 second compared to adults.
Age 0-14, (n=226) 15-50, (n=446) >50, (n=134) In our study, the average PT levels of 0-14 age group were 0.4
PT 10.86-14.20 10.60-13.90 10.27-14.08 seconds longer than in adults.
Studies [11] provide evidences about the physiological
INR 0.91-1.17 0.89-1.15 0.86-1.16
differences of pediatric population from adults.
aPTT 21.84-36.89 20.80-32.40 19.26-32.05
In conclusion, it would be more accurate to take into account the
gender and age differences for determining reference ranges of
4. Discussion PT, INR and aPTT in clinical use.
Reference ranges are of great importance for evaluation of
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