COAGUCHEK & INTERNATIONAL

NORMALIZATION RATIO (INR)

FIBRIN

PLT
RBC

Speaker
MAHENDRA
NORMAL HEMOSTASIS
There is 5 component of normal hemostasis

• Blood vessels

• Platelets

• Plasma coagulation factor

• Antithrombotic factor

• Fibrinolytic system
 COAGULATION CASCADE

Activated
partial Prothrombin
thromboplastin Time
Time
(APTT)
 PROTHROMBIN TIME
PRINCIPLE
• Tissue thromboplastin in presence of Ca++ activated
the Ext. pathway of coagulation mechanism. When it
is added to normal citrated plasma, clotting
mechanism initiated, forming a solid gel clot within a
specified period of time. The time required for clot
formation would be prolonged if there is alteration in
Ext. pathway or common pathway
REAGENTS
• Patient’s platelets poor plasma
• Control’s platelets poor plasma
• Thromboplastin
– It is tissue extract obtained from different species and different
organ containing tissue factor and phopsholipid e.g. uniplastin
which is used in most of the institution.
– It derived from rabbit brain
– Recently there is introduction of recombinant thromboplastin,
having ISI value close to 1.
– It is highly sensitive to factor deficiency and anticoagulant treated
patient plasma sample
• CaCl2
– 0.025 mol/L
– Now a days it comes mixed with thromboplastin e.g. uniplastin 
liquid calcified thromboplastin reagent
METHODOLOGY
Blood collected from appropriate site (more preferentially from anticubital vein)

Mixed with anticoagulant in the ratio of 9:1
e.g. 1.8 ml of sampel of blood.
0.2 ml of 3.2% Tri. Sod. citrate

Centrifuge mixture at 3000 rpm for 10 min (10-15 min)

Take 0.1 ml of plasma in test tube and place tube in water bath for 3-5 min at 37 0C

Now fercibly add 0.2 ml of reagent which is prewarmed at 37 0C for at least 3 min
and start stopwatch

As soon as fibrin strand is visible and the gel/clot formation begins, stop the
watch, and note the time in second

 These tests should be done in duplicate

EXPRESSION OF RESULTS
• Three forms
– Seconds : mean of the duplicate reading in seconds
– Ratio of mean time of patient to controls
– INR
NORMAL RANGE: 11-16 seconds
INTERPRETATION
– PT measures the quality of extrinsic pathway (as well as
common pathway) of coagulation
– Causes of prolonged PT
• Oral anticoagulant drug
• Deficiency of vitamin K – malabsorption, lack of
colonization of bacteria e.g. newborn
• Liver disease (poor synthesis of VII factor)
• DIC (because of increased consumption)
• Rarely factor VII, X, V or prothrombin deficiency or defect
 INTERNATIONAL
NORMALIZATION RATIO
• Because there is difference between different
batches and manufacturer of tissue factor
(thromboplastin), WHO and the International
Committee on thrombosis and hemostasis make
an attempt to standardize the PT across different
reagent of varying sensitivity (i.e. varying ISI) and
established a system for reporting the result of
blood coagulation which is termed as I.N.R.
INTERNATIONAL SENSITIVITY INDEX (I.S.I.)

• The I.S.I. value indicate how the particular batch

of tissue factor compares to an internationally
standardized sample
• It characterizes the sensitivity of thromboplastin,
which can variably effect the P.T.
• ISI depends on instrument and reagent
• So each manufacturer gives an ISI for any tissue
factor they make
• ISI usually between 1.0 to 1.4
• Some different thromboplastin and their ISI value are
given-

Thromboplastin ISI
Thrombotest 1.03
Thromborel 1.23
Dade FS 1.35
Simplastin 2.0
Boehringer 2.1
Ortho 2.3
Uniplastin ~1
• With the help of ISI and ratio of test and control
PT, we can calculate the INR by
PT (test) ISI

INR = ---------------
PT (normal)
 In most of institution INR calculated by using INR conversion table -

•First we calculate ratio

of PT test / PT normal
and see the calculated
value in vertical table
and then determine the
INR for the respective
ISI which is given in
horizontal top line
• Satisfactory INR results are within 10% of the mean
certified of the IRP (International reference preparation)

• An important use of INR is to standardized the dose of

anticoagulant drugs

• By measuring the INR of the patient who is on oral

anticoagulants, the level of anticoagulant in all plasma
sample can be compared and meaningful therapeutic
range established regardless of the thromboplastin used
• Different therapeutic range of INR are recommended for different
conditions
Recommended therapeutic range for oral anticoagulant therapy
Indication INR
Treatment of venous thrombosis 2.0-3.0
Treatment of pulmonary embolism 2.0-3.0
Prophylaxis of venous thrombosis (high-risk surgery) 2.0-3.0
Prevention of systemic embolism 2.0-3.0
Tissue heart valves 2.0-3.0
AMI (to prevent systemic embolism) 2.0-3.0
Valvular heart disease 2.0-3.0
Atrial fibrillation 2.0-3.0
Mechanical prosthetic valves (high risk) 2.5-3.5
Systemic recurrent emboli 2.5-3.5
 COAGULATION ANALYZER
• Because of wide utility of PT and INR specially in
patients on oral anticoagulant and because of need of
rapid result, follow up and increase workload various
coagulation analyzer are invented such as
– Semiautomated coagulant analyzer
– Automated coagulant analyzer
– Self monitoring analyzer
• Semiautomated and automated analyzer measure most
of coagulant test while self monitoring analyzer
measure only PT and INR
SELF MONITORING ANALYZER

• Coaguchek and coaguchek ‘S’

• Avosure
• Coagucare
• INR ratio (hemosense)
• Protime microcoagulation system
Out of these coaguchek is popular, FDA approved and
commercially used. But still not popular in our country
COAGUCHEK SYSTEM
• It has been specifically developed for healthcare
professionals and their patient to enable to near patient
testing of coagulation level (PT/INR) within their
general practice, at home, during mobile emergency
treatment or for routine follow up in a hospital clinics.
• Coaguchek system are easy to use of reflectance
photometer portable and battery powered device for
rapid measurement of PT and INR for monitoring of
oral anticoagulant
• In 2006 Roche Diagnostics launched two brands
– The Coagucheck XS system
– The Coagucheck XS plus system
• Coagucheck XS system
– It is mainly for patient purpose
– It is CE marketed and FDA approved
since Feb 2007
• Coaguchek XS Plus system
– Mainly for healthcare professionals
– It is same as coaguchek XS system,
but with extended quality control
and data management options and
connectivity feature
– It is CE marketed and FDA approved
since Feb 2007
– It can store upto 500 test results
with date and time
• Principle
– Both have the same technology – electrochemical
detection system
• Components
– Coaguchek meter
– Batteries
– PT strips- 2 vials of 24 strip each with a code chip
– *1 printed manual in English
– *2 CD-Rom with other languages e.g. German,
French
 PROCEDURE
• Put a test strip in coaguchek
system. The code number of chip
inserted in the monitor flashes in the
display
• Be sure that this number is identical
with the code printed on the test
strip
• The blood drop symbol and the
application area lash to indicate that
the monitor is ready to test
• Within 120 sec of flashing we must
have applied the drop
• Prick the finger of patient with
seftclix device
• And place a drop of blood on strip. Apply the
blood directly from the finger to the
semicircular transparent sample application
area of the test strip
• Alternately, we can touch the blood drop
against the side of the sample application area
• Blood drop should apply within 15 sec of
pricking the finger tip
• After about one minute, read the result on
display.
• Result can display in following units
– INR
– Seconds
– % quick
• Measuring range of INR : 0.8-8.0
 CORRELATION
• The results obtained form both instruments in the study
are equivalent and fulfill all acceptance criteria based on
the draft ISO standard
ADVANTAGE
• More comfort
– For professionals – hand held, portable, can done at offsite
visit 500 memory status
– For patient
• Only one drop / capillary blood needed (10 ml)
• No need for venous sampling
• Immediate results, no need for second visit
• More independence
• Safety by counting on an board integrated system
control
– It displays results only after several quality control
steps have been passed
– Reagent is sensitive (ISI close to 1) and compares
very well with reference laboratory result
– There is automatic internal system which checks
integrity of every strip
– Reagent is insensitive to heparin
• 500 test results can be stored in memory
• Better clinical outcome with more frequent testing
NEGATIVE ASPECT

• Strips are very costly

• Results are comparable to laboratory

results yet laboratory results are more
accurate

• Patient should be trained properly

 SUMMARY
• PT is test which evaluate efficiency of extrinsic and
common pathway of coagulation
• INR is calculated in an attempt to standardize the PT
across different reagent of varying sensitivity
• PT and INR is used in the dose monitoring of oral
anticoagulant
• PT and INR is calculated by laboratory method in most
setup and is more accurate but require more technical
specification, setup and are time consuming. So many
automated devices have been invented out of which
coaguchek is more popular and more convenient for
both patient and professionals.