Laboratory Variables That May Affect Test Results in Prothrombin ...

124 

science [coagulation and hematology] 

Laboratory Variables That May Affect 

Test Results in Prothrombin Times 

(PT)/International Normalized Ratios (INR) 

David L. McGlasson, MS, CLS/NCA, H, ASCP 

59th Clinical Research Squadron/MSRL, Lackland AFB, TX 

DOI: 10.1309/RT9D02JXCHY8V9HM 

Monitoring patients on oral 

anticoagulant therapy (OAT) requires 

constant monitoring by physicians 

using highly sophisticated coagulation 

testing. 

The World Health Organization (WHO) 

put forth the idea for prothrombin 

time standardization based on a 

mathematical formula known as the 

International Normalized Ratios (INR) 

Because manufacturers provide 

limited guidelines for instruments, the 

laboratory should validate its values 

by performing local on-site 

International Sensitivity Index (ISI) 

calibration. 

In a MMWR report dated August 

24, 2001 the following circumstances 

on “Adverse events and deaths associated 

with laboratory errors at a hospital-Pennsylvania, 

2001” were reported. 

On August 3, 2001, the Center for Disease 

Control (CDC) was contacted by 

the Pennsylvania Department of Health 

(PADOH) to assist with an investigation 

of laboratory errors that may have contributed 

to the deaths of at least 2 persons 

taking the anticoagulant drug 

warfarin (Coumadin, DuPont Pharmaceuticals 

M, Wilmington DE). The 

Food and Drug Administration (FDA) 

also was investigating this incident. The 

monitoring of warfarin’s anticoagulant 

effect is accomplished by performing 2 

laboratory assays: the prothrombin time 

(PT) and the INR. The INR is a 

numeric value calculated from the PT, a 

clotting assay result, and the ISI, which 

indicated the sensitivity of the reagent 

used to perform the assay. The WHO 

recommends that INR values be used by 

physicians to compare laboratory results 

between reagent/instrument combinations 

at different institutions. 

During June 4 through July 25, 

2001 the hospital laboratory in Pennsylvania 

reported 2,146 test with correct 

PT results but with incorrectly calculated 

INR results. The mathematical formula 

required for calculating the INR 

uses a reagent-specific number, the ISI, 

which is usually furnished by the manufacturer 

of the reagent. In June, the hospital 

laboratory did not verify the new 

reagent used in the coagulation analyzer 

for performing the PT assay. As a result, 

the ISI used to calculate the INR was 

incorrect for the reagent used. For approximately 

7 weeks, the reported INRs 

were falsely low. Several physicians 

who interpreted these results increased 

their patients’ doses of coumadin. In 

several cases, this led to the patient’s 

OAT regimen being compromised. 1 One 

subject previously had coronary bypass 

surgery and was having the INR 

followed on an outpatient basis. He 

started having bleeding from the gums 

and was bruising easily. At the original 

hospital laboratory the INR result was 

2.62, which is in the therapeutic range. 

He then went to another hospital to have 

the INR repeated. That result yielded an 

INR of 5.7, which was very high. His 

cardiologist directed the patient to discontinue 

the coumadin dosing for 4 

days. 2 Investigations are also under way 

by PADOH, Centers for Medicare and 

Medicaid Services (CMS), and CDC to 

identify other patient morbidity and 

mortality associated with the error, its 

possible causes, and the steps needed to 

laboratorymedicine> february 2003> number 2> volume 34 

© 

prevent its recurrence. The FDA is reviewing 

possible deficiencies in the 

manufacturer’s reagent package labeling. 

Discussion 

Monitoring patients on OAT requires 

constant monitoring by physicians using 

highly sophisticated coagulation testing. 

The most frequently used assay is the PT. 

Standardization of the PT test results has 

proven to be difficult because of the 

abundance of manufacturer thromboplastins 

and instrumentation available 

throughout the world. 

Physicians monitor patients on OAT 

by frequently performing repeat measurement 

of the PT assay. By doing this 

they can adequately monitor the subjects 

warfarin intake. They are then able to 

maintain each subject in a designated 

therapeutic range. There are many variables 

in the performance of the PT that 

may affect the test result. These include 

the specimen collection, processing of 

the sample, instrumentation used to perform 

the assay, and the sensitivity of the 

thromboplastin used to perform the PT 

assay. Each thromboplastin’s sensitivity 

is determined by the individual ISI. 

Manufacturers individual thromboplastin 

reagent sensitivity to the Vitamin K dependent 

coagulation factors affected by 

warfarin have a wide range of variability. 

This has created problems for physicians 

when trying to monitor patients in 

different institutions with different 

reagent/instrument combinations. A subject 

monitored with a low sensitivity 

reagent (high ISI) may give a low PT 

time of 14 seconds. While the same patient 

when using a high sensitivity 

reagent (low ISI) may give a time of 18

seconds. These results may drastically 

affect the interpretation of the PT assay 

and the warfarin dosage in the individual 

patients. 3 

The WHO in 1977 introduced a standardized 

thromboplastin that was touted 

as an international reference preparation 

(IRP). The hope was that each laboratory 

could develop a reference range for PT 

testing that was to be compared to the 

IRP range. Taking this initial step further 

the WHO in 1983 then put forth the idea 

for PT standardization based on a mathematical 

formula (INR) that uses the elements 

of the PT assay. 

The INR then would be the PT result 

that a laboratory would obtain if the test 

were performed using the standardized 

WHO reference thromboplastin reagent 

with an assigned ISI value of 1.0. Each 

assigned thromboplastin ISI could then 

compare the individual reagent sensitivity 

to an IRP that has been calibrated with a 

WHO reference plasma. The INR is calculated 

using the following formula 3 : 

INR = (patient PT) ISI 

Mean normal PT 

Each individual laboratory would 

supply the mean normal PT. The INR 

method would then allow the physician to 

compare the PT results with different laboratories 

reagent/instrument 

combinations. Manufacturers now produce 

a wide variety of thromboplastin 

with ISI values ranging from 0.9 to 3.0. 

This wide range of ISI will produce a 

huge difference of PT results. 3 The INR 

was designed to correct for this 

difference. Therefore, if a patient were 

traveling from one city to another the 

physician would have the advantage of 

expecting a standardized INR value to 

maintain a patient’s OAT range. 

As observed in the case report improper 

assignment of ISI values with different 

reagent/instrument combinations 

can result in clinically significant inaccurate 

values. This difference in ISI values 

resulted in improper management of a 

large group of patients on OAT with catastrophic 

consequences. Huge 

differences in INR values have been reported 

when there are significant differences 

between low versus high ISI 

sensitivities in thromboplastins. 4,5 

Preanalytic Variables of INR 

Testing 

Citrate Concentration 

Prothrombin time assays are 

performed on citrated platelet-poor 

plasma. The concentration of the sodium 

citrate anticoagulant can affect the PT time 

thus affecting the INR value. 6-8 In the 

United States, until recently, 

approximately 80% of the PT assays were 

performed in plasma that was collected 

using vacutainer tubes that contained 3.8% 

(129 mol/L) sodium citrate. In 1998, 

NCCLS Subcomittee on Coagulation 

started to recommend that a 3.2% (109 

mol/L) sodium citrate concentration be 

used for most coagulation studies. This 

concentration was selected because the 

WHO was calibrating thromboplastins 

using the 3.2% concentration. 9 Other international 

standardization organizations also 

recommend using the 3.2% citrated anticoagulant. 

The osmolality of the 3.2% concentration 

is apparently closer to plasma. 

Higher INR values have been found in 

some thromboplastin reagents in plasma 

collected with 3.8% citrated vacutainer 

tubes. In one direct comparison study between 

the 2 citrate concentrations using a 

low ISI thromboplastin, the INR difference 

in 18.0% of the specimens showed a INR 

difference of 0.7. In another study, the difference 

on all specimens gave an average 

difference of 19.0%. The lower the ISI 

value is the more difference the citrate 

concentration makes in the INR results. 9 In 

platelet studies and testing of blood bank 

products such as cryoprecipitate, the 3.8% 

citrate concentration is still recommended. 

Specimen Handling 

Improper specimen collection can 

also drastically affect the PT assay thus 

affecting the INR value. This area has 

become controversial due to a number of 

studies that discuss the length of time 

and how a specimen can be stored be 

performing a PT assay. One study 

showed that storage of specimens for up 

to 6 hours at room temperature did not 

affect the PT results. 10 In another study, 

it was found that specimens from patients 

who were on low dose warfarin could be 

shipped overnight at room temperature 

© 


without significantly changing the INR 

values. 11 Another study looked at specimens 

stored as whole blood. It found 

that after 3 days stored at room temperature 

that there was no significant change 

in the INR. 12 NCCLS guidelines from 

1998 stated that uncentrifuged 

specimens for the PT/INR test or centrifuged 

plasma left of top of the separated 

cells stored at various temperatures 

from 2 to 24°C should be run within 24 

hours from the time the sample was obtained 

from the test subject. 13 The PT 

results may vary from the time of collection 

of the specimen and storage of the 

sample if the subject was receiving heparin 

and was on OAT. The laboratory 

must be sure that the thromboplastin has 

a heparin neutralizer to counteract the 

effects of heparin. Evidence has also 

been presented that if specimens are 

stored at approximately 4°C that the 

PT/INR results may be shortened due to 

cold activation of FVII. 9 Our recommendation 

is that all specimens should be 

treated as if they were the last specimens 

that could be obtained from the test subject 

without having to recollect the sample. 

If another assay is required, such as 

an APTT or factor assay, the prolonged 

storage times of >4 hours would possibly 

render the specimen compromised 

and required the patient to have a second 

venipuncture. This increases time and 

expense for all concerned. 

More recently it has been discovered 

that the coagulation tube has been 

found to be a clinically significant 

source of variability in coagulation testing. 

There has been controversy in using 

“partial-draw tubes” which required less 

vacuum to manufacture which resulted 

in 1.8 mL or 2.7 mL blood draws versus 

the conventional 4.5 mL draw with the 

blood to anticoagulant ratio of 9:1. Since 

the partial-draw tubes filled more slowly 

than the so-called full-draw tubes to 

platelets may have been activated due to 

lengthy exposure to shear forces arising 

from exposure to shear forces arising 

from drawing blood into the increased 

headspace. The activated platelets then 

may release platelet-factor 4 or phospholipids 

which could compromise coagulation 

testing. 14 

125

126 

Instrumentation 

There are over 300 different methods 

of performing a PT assay in the United 

States alone. Because of this wide variety 

of testing it is almost impossible for manufacturers 

to provide accurate reagent/instrument 

specific ISI values for each 

reagent/instrument combination. The 

WHO protocol for assigning ISI values 

to thromboplastin reagents is determined 

by performing a manual tilt-tube method 

in quadruplicate. 15 Laboratories then 

have to depend on manufacturers to accurately 

assign the proper ISI of their 

reagents based on some adaptation of 

the WHO protocol. 16 Therefore, the instrumentation 

can vastly affect the PT 

test results. If a coagulation laboratory is 

using a reagent from one company and 

an instrument from another supplier they 

have to rely on the reagent companies 

generic assignment of mechanical or 

photo-optic ISI values. Laboratories may 

not be aware that different automated 

coagulation systems can directly affect 

the ISI and the INR result. There may be 

distinct differences between mechanical 

and photo-optical coagulation systems 

with different reagents. 16,17 In our institution, 

we performed a protocol with 7 

different reagent/instrument combinations 

on the same specimens. 16 In many specimens, 

we saw clinically significant differences 

of INR values between the 

different reagent/ combinations. T1 dis- 

plays some of these INR result 

differences. Observe that the specimen 

#1180 has an INR value of 3.95 with 

one reagent/instrument combination and 

7.16 with another system. This is an 

81.3% difference. The 3.95 value might 

be considered a high therapeutic range 

value that would probably require no 

intervention. The 7.16 INR might cause 

some institutions to consider this result a 

panic value. Many other variables can 

affect the coagulation instrument ISI sensitivity 

used in the PT analysis. These are 

temperatures of the system and reagents, 

accuracy of volume of the reagents being 

dispensed, and the citrate concentration of 

the specimen collected. 15,16 

Looking for a simpler method to locally 

calibrate ISI values we performed a 

protocol at our institution that was sponsored 

by Dade Behring M (Deerfield, IL) 

using a calibration system supplied by Precision-Biologic 

M (Dartmouth, NS, Canada). 

Precision Biologic has proposed a simplified 

method of locally calibrating the 

reagent ISI using a 5-day ISI calibration 

protocol. The method used a set of 5 OAT 

frozen plasmas and 1 normal frozen plasma 

that are assayed against a standard (WHO 

IRP) thromboplastin. The frozen OAT calibrators 

and the normal plasma encompassed 

the 4 therapeutic categories used in OAT 

(4.5). Two recent 

papers discussed in detail how any laboratory 

can use the frozen calibrator plasma 

Comparison of Selected INR Differences of Human Subject’s Plasma 


© 

method to locally calibrate their reagent/instrument 

combinations and how they would 

affect subject and manufacturers suggestions 

for ISI values with many different 

thromboplastins and instruments. 15,17 Laboratories 

that run PT/INR assays can then set 

up there own ISI calibration of the locally 

used thromboplastin. This method may be 

the most practical for improving inter-laboratory 

INR agreement. See the results in 

T2 and T3 on differences in local and 

manufacturer calibrations of ISIs that were 

used in our study. 14 

Heparin Effects on PT/INR 

Testing 

Unfractionated heparin contamination 

can adversely affect the results of a 

PT/INR assay. Many subjects starting on 

OAT are coming off heparin therapy, 

which could give physicians problems 

with falsely elevated INR values when 

trying to establish baseline INR ranges 

for patients. Each manufacturer’s thromboplastin 

has an individual sensitivity to 

the effect of heparin. Some reagents 

have a heparin neutralizer present such 

as polybrene or protamine sulfate that 

can counteract the effects of heparin in 

the therapeutic range so the PT/INR results 

are not compromised. However, 

reagents without a heparin neutralizer 

present have been found to have PT results 

prolonged in some subjects by as 

long as 10 seconds. This could lead to 

Human MLA 900C CI+ MLA 900C T-D MLA 900C T-R MLA 1600C T-D STA CI+ STA T-D STA T-R 

Sample 

1167 2.77 3.41 3.72 3.62 2.68 3.24 3.41 

1181 2.53 3.2 3.65 3.36 2.64 2.85 2.91 

1180 3.95 5.98 5.83 7.16 4.02 4.93 5.05 

1398 2.94 3.94 3.44 4.14 3.06 3.61 3.35 

1393 3.57 4.98 4.48 5.0 3.57 4.39 4.18 

1391 3.03 4.14 3.41 4.43 3.13 3.82 3.14 

1684 3.72 5.82 4.99 6.29 3.99 5.57 4.47 

1688 2.95 3.94 3.93 4.44 3.12 3.7 3.79 

1814 3.15 1.97 4.0 4.85 3.24 4.23 3.58 

1669 3.25 2.41 3.66 3.93 3.24 4.29 3.28 

T1 

Done on the STA and MLA 900 C with thromboplastins: Neoplastine CI+, Diagnostica Stago (CI+); Thromboplastin D, Pacific-Hemostasis (T-D); Recombiplastin, Hemolance (T-R) and 

the MLA 1600C with T-D only.

Summary of Mean INR Results on 25 Normal Patient Samples Before and After Local ISI Calibration 

Instrument Reagent Mean INR Using Mean INR Using Difference in 

Vendor-Assigned ISI Locally Calibrated ISI INR Means (%) 

Diagnostica Stago/STA Neoplastine CI+ 1.24 1.29 -3.9 

Thromborel S 1.12 1.13 -0.9 

Thromboplastin C+ 1.96 1.76 10.1 

Innovin 0.92 1.00 -8.5 

Sysmex CA 540 Neoplastine CI+ 1.24 1.09 11.9 

Thromborel S 1.06 1.02 3.4 


Innovin 1.02 0.92 10.3 

Dade-Behring BCS Neoplastine CI+ 1.24 1.16 6.9 

Thromborel S 1.06 1.02 3.5 


Innovin 0.90 1.07 -18.9 

Summary of Mean INR Results on 95 Patient OAT Samples Before and After Local ISI Calibration 

Instrument Reagent Mean INR Using Mean INR Using Difference in Results >10% 

Vendor-Assigned ISI Locally Calibrated ISI INR Means (%) Difference 

Diagnostica Stago/STA Neoplastine CI+ 2.58 2.69 4.1 0.0 

Thromborel S 2.56 2.58 0.8 0.0 

Thromboplastin C+ 2.39 2.15 10.0 37.1 

Innovin 2.45 2.67 7.9 22.1 

Sysmex CA 540 Neoplastine CI+ 3.46 2.90 16.1 63.9 

Thromborel S 2.69 2.58 4.1 0.0 



Dade-Behring BCS Neoplastine CI+ 2.81 2.60 7.5 20.6 

Thromborel S 2.67 2.57 3.7 0.0 



serious patient mismanagement during 

OAT. There is no current evidence that 

the heparin neutralizers may neutralize 

the presence of low molecular weight 

heparin. Each institution should check 

the effect of a therapeutic dose of unfractionated 

heparin against their 

reagent/instrument system. 

Possible Effect of a Lupus 

Anticoagulant (LA) on PT/INR 

The recommended therapeutic range 

of INR for OAT in patients with the presence 

of a LA is currently 2.5 to 3.5. This 

is still a controversial subject. It has 

been suggested that using the INR to 

monitor these patients may be inadequate 

due to interference by the presence of a 

LA on the clot-based PT assay. Some 

investigators have suggested using the 

prothrombin-proconvertin assay in lieu 

of the PT/INR for patients with this disorder 

since it doesn’t appear to be 

affected by a LAs inhibitory actions. 3 

Others have suggested measuring coagulation 

factors II and X by either chromogenic 

or 1-stage clotting assays based 

on at least 3 dilutions to lessen the LA 

inhibitory effect. 3 Other investigators 

found little effect of the presence of a LA 

on PT/INR results using different thromboplastins 

and instruments. One small exception 

was a subgroup of 6 patients in 

which a recombinant thromboplastin 

© 


T2 

T3 

(Innovin, Dade-Behring) was used. 3 One 

recent study performed a protocol to see if 

subjects who have the presence of anticardiolipin 

antibodies without the presence 

of an LA to see if the INR assay was affected 

using local specific ISIs with 11 

different thromboplastins. No effect on the 

INR results was observed. 18 In another 

study using 11 different LA positive, 11 

negative LA subjects, and 7 different 

thromboplastins, the presence of an LA 

did not disturb the laboratory tests for 

monitoring subjects on OAT. 19 Each institution 

should check their own reagent/instrument 

combination with positive LA 

plasmas to determine if the LA interference 

is an issue in their laboratory. 

127

128 

Reporting of PT/INR results 

There continues to be no consensus 

on the method of reporting INR values for 

conditions other than OAT. Many laboratories 

report only the INR for all PT measurements 

since the INR is simply a 

mathematical conversion of the PT using 

the ISI. 9 Many laboratories have been reluctant 

to convert to low ISI thromboplastins 

because the prolonged PTs are thought 

to be confusing to physicians used to 

shorter PTs with high ISI (less sensitive) 

reagents. This may be true when a PT is 

ordered for situations other than monitoring 

OAT. 9 A situation such as a preoperative 

coagulation screen or liver diseases 

can confuse the issue of INR reporting. It 

has been suggested by some clinicians to 

use 2 systems for reporting PT results. 

One result for patients on OAT and 

another for subjects not on OAT has been 

instituted at some facilities. There is data 

that suggests that the INR value is appropriate 

for use in patients beginning anticoagulation 

as well as in subjects with other 

coagulation disorders (eg, liver 

impairment). The range of PT prolongation 

appears to be greater for patients on 

OAT than for patients with liver disease or 

disseminated intravascular coagulation, but 

the PT and INR has been shown to correlate 

in a linear fashion when reagents of 

varying ISI were compared. Some experts 

have proposed reporting the INR in lieu of 

the PT for all patients, but suggested the 

best way to accomplish this would be to 

have an international consensus conference. 

This has still not been accomplished 

as recently as the 2001 International Society 

of Thrombosis and Hemostasis Conference 

in Paris, France. In the subcommittee 

conference that dealt with this issue, there 

was still no consensus on how to use the 

INR for other than those subjects on OAT. 

Some notable clinicians and 

researchers have publicly stated that the 

INR is recommended as the most appropriate 

means for reporting PT results in 

patients who are stable, orally anticoagulated. 

They have suggested that the INR is 

not appropriate for use in other clinical 

situations (eg, liver disease, hereditary 

factor deficiencies, routine screening, preoperative 

testing, and detecting vitamin K 

deficiency). There is little or no information 

available on the use of the INR reporting 

of drug-induced coagulation defects in 

subjects on OAT. Does a single coagulation 

factor deficiency, such as a factor 

FVII deficiency, have a significant effect 

on the INR? 9 This could present problems 

in clinical settings where the INR only is 

reported. 

Fairweather and colleagues 9 presented 

a further argument against the use of reporting 

INRs only. The presence of a 

mildly prolonged PT may be the only clue 

to a clinically significant coagulopathy. 

However, the upper range of normal is 

obscured by the exponential nature of the 

INR calculation. The example they used 

discussed the upper limit of normal for 2 

reagents, which correspond to a PT ratio 

of 1.2. This would correspond to an INR 

of 1.2 for a reagent with an ISI of 1.0 and 

an INR of 1.4 for a reagent with an ISI of 

2.0. The problem would then be in interpreting 

the INR values in the range of 1.3 

to 1.4. One local hospital in our area went 

to INR value reporting because the surgeons 

would misinterpret what they perceived 

to be mildly prolonged PTs. 

Consequently, they would order freshfrozen 

plasma for surgeries unnecessarily. 

Final Notes 

The accuracy and precision of the INR 

is dependent on the PT assay and the ISI of 

thromboplastin. Other researchers have 

noted that since the ISI is the exponent of 

the INR equation, the higher the ISI 

assigned to thromboplastins the greater the 

imprecision of the INR as a result of the 

mathematical outcome. 20 In support of this 

information we discovered, in a study, that 

when the INR approaches 3.0 or greater 

the discrepancy in the INR value was between 

different reagent/instrument systems. 

Therefore the large difference in assigned 

ISI values is probably the most important 

variable that influences the poor correlation 

seen in different laboratories reagent/instrument 

combinations. Thromboplastins with 

an ISI less than 1.2 produce a wider range 

of values in the PT and PT ratio. Consequently, 

the precision of the INR is similarly 

improved. Since the calculation of the 

INR requires using the ISI exponentially, 

the farther the ISI value is from 1.0, the 

less accurate the INR values will be. 


© 

Manufacturer assigned ISIs, not specific to 

the local reagent/instrument set-up, may 

introduce even more inaccuracy. 

Instrumentation can also greatly influence 

the INR values. Because manufacturers 

provide limited guidelines for instrument 

assigned ISIs, the laboratory should validate 

its coumadin influenced INR values 

by performing local on-site ISI calibration. 

If the laboratory in Pennsylvania had a protocol 

for locally calibrating their ISI values, 

the disaster that occurred with the inaccurate 

ISI being used may have been averted. 

1. Adverse events and deaths associated with laboratory 

errors at a hospital-Pennsylvania, 2001. MMWR. 

2001:710-711. 

2. McCullough, Marie. Lab error deaths may now total 

five. The Inquirer (Philadelphia, PA), August 3, 2001. 

3. McGlasson DL. A review of variables affecting 

PTs/INRs. Clin Lab Sci. 1999;12:353-358. 

4. Cunningham MT, Johnson GF, Pennell BJ, et al. The 

reliability of manufacturer-determined, instrumentspecific 

international sensitivity index values for 

calculating the international normalized ratio. AJCP. 

1994;102:128-133. 

5. Ts’ao C, Swedlund J, Neofotistos D. Implications of 

use of low international sensitivity index 

thromboplastins in prothrombin testing. Arch Pathol 

Lab Med. 1994;118:1183-1187. 

6. Duncan EM, Casey CR, Duncan BM, et al. Effect of 

concentration of trisodium citrate anticoagulant on 

calculation of the international normalized ratio and 

the international sensitivity index of thromboplastin. 

Thromb Haemost. 1994;72:84-88. 

7. Adcock JM, Kressen DC, Marlar RA. Effect of 3.2% 

vs. 3.8% sodium citrate on routine coagulation 

testing. Am J Clin Pathol. 1997;107:105-110. 

8. Dwyre AL, Giles AR, Key LA, et al. The effects of 

sodium citrate anticoagulant concentration, storage on 

or off cellular matrix, and specimen age on 

prothrombin time INR using a low ISI (1.06) rabbit 

brain thromboplastin. Thromb Haemost. 1995;73:1237. 

9. Fairweather RB, Ansell J, Anton M, et al. College of 

American Pathologists Conference XXXI on 

laboratory monitoring of anticoagulant therapy: 

Laboratory monitoring of oral anticoagulant therapy. 

Arch Pathol Med. 1998;122:768-781. 

10. NCCLS H21-A3. Collection, transport, and 

processing of blood specimens for coagulation 

testing and general performance of coagulation 

assays; approved guideline-3rd ed. 1998;18:20. 

11. Van den Besselaar AMHP, Halem-Visser LP, 

Loeliger EA. The use of evacuated tubes for blood 

collection in oral anticoagulant control. Thromb 

Haemost. 1983;50:676-677. 

12. Raskob GE, Durica SS, Owen WL, et al. Monitoring 

low-dose warfarin therapy be a central laboratory 

and implications for clinical trials and patient care: 

the coumadin aspirin reinfarction (CARS) pilot study 

group. Am J Cardiol. 1996;78:1074-1076. 

13. Baglin T, Luddington R. Reliability of delayed INR 

determination: Implication for decentralized 

anticoagulant care with off-site blood sampling. Br J. 

Haematol. 1997;96:431-434. 

14. Foubister Vida. Quick on the draw-coagulation tube 

response. CAP Today. 2002;16:38-42.

15. McGlasson DL, Hickman JR, More LE, et al. 

Discrepancies in international normalized ratios 

(INR) in swine and humans. Clin Lab Sci. 

1998;11:156-160. 

16. McGlasson DL. A Comparison of international 

normalized ratios after local calibration of thromboplastin 

international sensitivity indexes. Accepted for 

Publication in Clinical Laboratory Science. 

17. Adcock DM, Johnston M. Evaluation of frozen 

plasma calibrants for enhanced standardization of the 

international (INR): A multi-center study. Thromb 

Hemost. 2002;87:74-79. 

18. Mant MJ, Stang L, Etches WS. Warfarin monitoring 

in patients with anticardiolipin antibodies, but 

without lupus anticoagulants. Thrombosis Research. 

2000;99:477-482. 

19. Bijsterveld NR, Middeldorp S, Berends F, et al. 

Monitoring therapy with vitamin K antagonists in 

patients with lupus anticoagulant: effect on different 

tests for INR determination. J Thrombosis 

Thrombolysis. 2000;9:263-269. 

20. Van den Besselaar AMHP. Field study for 

lyophilized plasmas for local prothrombin time 

calibration in the Netherlands. J Clin Pathol. 

1997;50:371-374.

Laboratory Variables That May Affect Test Results in Prothrombin ...

Create successful ePaper yourself

Delete template?

Save as template?