ROUTINE COAGULATION AND INTEPRETATION

DR EHRAM HJ JAMIANHEMATOLOGY UNITPATHOLOGY DEPARTMENT

Objective

Monitor anticoagulant therapy Identify factor deficiencies Check coagulation status

Pre, during and post surgery or trauma

Routine Coagulation Tests

Normal PT , APTT and Mixing test If PT and APTT normal,

No evidence of haemostatic problem

If PT and APTT not normal, Possible evidence of haemostatic

problem or haemostatic challenge

PROTHROMBIN TIME (PT) Prothrombin Time (PT) in contrast to

the APTT Measures the activity of the extrinsic and

common pathway of coagulation. The division of the clotting cascade into

the intrinsic, extrinsic and common pathways has little in vivo validity

But it remains a useful concept for interpreting the results of laboratory investigations.

PRINCIPLES

The PT measures the activity of the so-called extrinsic and common pathways of coagulation

Therefore dependent on the functional activity of factors VII, X, V, II (Prothrombin) and fibrinogen.

REFERENCE RANGES

Each laboratory should establish its own normal range

BUT in general, the prothrombin time lies between 13-15 seconds.

INTERPRETATION

The PT is usually performed as part of a series of tests which will include the APTT and sometimes the measurement of fibrinogen levels and possibly a thrombin time is based on:1) Isolated prolonged PT

Factor VII deficiency

2) Prolonged PT in association with other coagulation abnormalities

Vitamin K deficiency Vitamin K antagonists; Eg Warfarin,Phenindione,

Rodenticides Liver disease Malabsorption (Leading to Vit.K deficiency) High concentrations of unfractionated heparin Afibrinogenaemia and dysfibrinogenaemia Dilutional coagulopathy Eg Massive blood

transfusion Multiple clotting factor deficiencies; Eg FV and

FVIII deficiency

3) Shortened PT Following the use of rVIIa (NovoSeven®) The PT is often shortened

COMMENTS The prothrombin time forms the basis for

the assaying Factors VII, V, X, II and I. However the PT can be relatively

insensitive to minor reductions in some clotting factors.

Normal PT does not exclude a significant underlying coagulopathy Eg: The PT is normal in severe

haemophilia A, B and Factor XI deficiency

What Next?? In case in which there is an isolated prolongation of

the PT and the remainder of the screening tests (APTT, TT and Fibrinogen) ARE NORMAL…… The next most logical test is a Factor VII assay

Factor VII deficiency is rare It’s more common to find a prolonged PT in

combination with other abnormalities of the screen; Eg Prolonged APTT

In these case consult the possible differential diagnose The history including a drugs history and the examination are VITALLY important.

REMEMBER Warfarin & oral Vit.K antagonists

Will significantly prolonged the PT, but may prolong the APTT by only a few seconds

(except in overdose)

APTT - Introducton The APTT in contrast to the PT measures

the activity of the intrinsic and common pathways of coagulation.

The division of the clotting cascade into the intrinsic, extrinsic and common pathways has little in vivo validity but remains a useful concept for interpreting the results of laboratory investigations.

REFERENCE RANGES

The clotting time for the APTT lies between 27 – 35 seconds.

However, this varies widely between laboratories and is dependent upon a number of variables including whether Automated or manual Type of surface activator Incubation time

COMMENTS

The APTT is frequently used to monitor patients receiving unfractionated heparin (UFH).

PRINCIPLES

The APTT forms the basis for a number of factor assays including: Factors VIII, IX, XI and XII. Factors II, V and X

The APTT is used to screen for the presence of a number of clotting factors inhibitors including FVIII and FIX.

What Test NEXT??? Mixing Studied A mixing study in which

patient plasma is mixed with normal plasma [ratio 1:1] may help to distinguish between a clotting factor deficiency and an inhibitor.

If the mixture fails to correct the APTT with 3–4sec, this is strongly suggestive of:

1) A coagulation factor inhibitor Acquired FVIII Antibody

2) An anti-phospholipid antibody Lupus Anticoagulant

INTERPRETATION

1) ISOLATED PROLONGED APTT Deficiencies of Factor XII, XI, IX, VIII, V, II

and Fibrinogen. Contact factor deficiencies

Pre-kallikrein Multiple factor deficiencies

The factor level loss deficiencies Acquired inhibitor clotting factor

FVIII or FV

2) PROLONGED PT and APTT

Vitamin K deficiencies Liver disease due to: Malabsorbtion of Vit.K Decreased synthesis of clotting factor Dysfibrinogenaemia

Direct thrombin inhibitors Hirudin Argatroban

DIC – due to consumption of clotting factor. Massive blood transfusion Patient receive Thrombolytic Therapy

Due to reduction of fibrinogen

Multiple clotting factor deficiencies

3) Short APTT

An acute phase response leading to high FVIII levels

MIXING STUDIES

Involve repeat performance of abnormal tests as a mixed plasma

Normal plasma + Test plasma Many possible mix volumes Usual 1:1

Interpretation of mixing tests

Many people have difficulty No hard and fast rules General principles: Factor def may or may not be

significant (eg: FVIII vs FXII def ) Inhibitor may or may not be

significant (FVIII inhibitor vs LA vs heparin)

SUMMARY FOR ROUTINE COAGULATION TEST

TEST EXCLUSIVE COMMON

PT VII I, II, V and X

APTT XII, XI, IX and VIII I, II, V and X

TT - I

NORMAL PLASMA

TEST PLASMA

MIX (1:1) PLASMA

Inter-pretation

PT: NRR(10-18) 12 13 NR

APTT: (NRR:24-36) 30 38 37

TT: (NRR:12-18) 15 14 NR

EXERCISE 1

ANSWER 1

NORMAL PLASMA

TEST PLASMA

MIX (1:1) PLASMA

Inter-pretation

PT: NRR(10-18) 12 13 NR

APTT: (NRR:24-36) 30 38 37

Non correction (partial)

TT: (NRR:12-18) 15 14 NR

**Weak inhibitor; Eg LA, FVIII (check hx), perform additional tests if hx indicated.

EXERCISE 2

NORMAL PLASMA

TEST PLASMA

MIX (1:1) PLASMA

Inter-pretation

PT: NRR(10-18) 12 13 NR

APTT: (NRR:24-36) 30 38 31

TT: (NRR:12-18) 15 14 NR

ANSWER 2

NORMAL PLASMA

TEST PLASMA

MIX (1:1) PLASMA

Inter-pretation

PT: NRR(10-18) 12 13 NR

APTT: (NRR:24-36) 30 38 31 Correction

TT: (NRR:12-18) 15 14 NR

Mild factor deficiency eg FVIII, IX etc.

EXERCISE 3

NORMAL PLASMA

TEST PLASMA

MIX (1:1) PLASMA

Inter-pretation

PT: NRR(10-18) 12 13 NR

APTT: (NRR:24-36) 30 58 32

TT: (NRR:12-18) 15 14 NR

ANSWER 3

NORMAL PLASMA

TEST PLASMA

MIX (1:1) PLASMA

Inter-pretation

PT: NRR(10-18) 12 13 NR

APTT: (NRR:24-36) 30 58 32 Correction

TT: (NRR:12-18) 15 14 NR

Factor deficiency …eg FVIII, IX etc…

EXERCISE 4

NORMAL PLASMA

TEST PLASMA

MIX (1:1) PLASMA

Inter-pretation

PT: NRR(10-18) 12 13 NR

APTT: (NRR:24-36) 30 58 42

TT: (NRR:12-18) 15 14 NR

ANSWER 4

NORMAL PLASMA

TEST PLASMA

MIX (1:1) PLASMA

Inter-pretation

PT: NRR(10-18) 12 13 NR

APTT: (NRR:24-36) 30 58 42

Non correction (partial)

TT: (NRR:12-18) 15 14 NR

Moderate or strong inhibitor….eg..LA

EXERCISE 5

NORMAL PLASMA

TEST PLASMA

MIX (1:1) PLASMA

Inter-pretation

PT: NRR(10-18) 12 >120 >120

APTT: (NRR:24-36) 30 >120 >120

TT: (NRR:12-18) 15 >120 >120

ANSWER 5

NORMAL PLASMA

TEST PLASMA

MIX (1:1) PLASMA

Inter-pretation

PT: NRR(10-18) 12 >120 >120

Non correction (partial)

APTT: (NRR:24-36) 30 >120 >120

Non correction (partial)

TT: (NRR:12-18) 15 >120 >120

Non correction (partial)

Gross heparin contamination

EXERCISE 6

NORMAL PLASMA

TEST PLASMA

MIX (1:1) PLASMA

Inter-pretation

PT: NRR(10-18) 12 60 15

APTT: (NRR:24-36) 30 35 NR

TT: (NRR:12-18) 15 16 NR

ANSWER 6

NORMAL PLASMA

TEST PLASMA

MIX (1:1) PLASMA

Inter-pretation

PT: NRR(10-18) 12 60 15 Correction

APTT: (NRR:24-36) 30 35 NR

TT: (NRR:12-18) 15 16 NR

Thank You