ROUTINE COAGULATION AND INTEPRETATION

DR EHRAM HJ JAMIAN HEMATOLOGY UNIT PATHOLOGY 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 Its 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 34sec, 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
PT APTT

EXCLUSIVE
VII XII, XI, IX and VIII

COMMON
I, II, V and X I, II, V and X

TT

EXERCISE 1
NORMAL PLASMA PT: NRR (10-18) APTT: (NRR:24-36) TT: (NRR:1218) TEST PLASMA MIX (1:1) PLASMA NR 37 Interpretation

12 30

13 38

15

14

NR

ANSWER 1
NORMAL PLASMA PT: NRR (10-18) APTT: (NRR:24-36) TT: (NRR:12-18) TEST PLASMA MIX (1:1) PLASMA NR Interpretation

12

13

30

38

37

Non correction (partial)

15

14

NR

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

EXERCISE 2
NORMAL PLASMA PT: NRR (10-18) APTT: (NRR:24-36) TT: (NRR:12-18) TEST PLASMA MIX (1:1) PLASMA NR 31 NR Interpretation

12 30 15

13 38 14

ANSWER 2
NORMAL PLASMA PT: NRR (10-18) APTT: (NRR:24-36) TT: (NRR:1218) TEST PLASMA MIX (1:1) PLASMA NR 31 NR Correction Interpretation

12 30 15

13 38 14

Mild factor deficiency eg FVIII, IX etc.

EXERCISE 3
NORMAL PLASMA PT: NRR (10-18) APTT: (NRR:24-36) TT: (NRR:12-18) TEST PLASMA MIX (1:1) PLASMA NR 32 NR Interpretation

12 30 15

13 58 14

ANSWER 3
NORMAL PLASMA PT: NRR (10-18) APTT: (NRR:24-36) TT: (NRR:1218) TEST PLASMA MIX (1:1) PLASMA NR 32 NR Correction Interpretation

12 30 15

13 58 14

Factor deficiency eg FVIII, IX etc

EXERCISE 4
NORMAL PLASMA PT: NRR (10-18) APTT: (NRR:24-36) TT: (NRR:1218) TEST PLASMA MIX (1:1) PLASMA NR 42 NR Interpretation

12 30 15

13 58 14

ANSWER 4
NORMAL PLASMA PT: NRR (10-18) APTT: (NRR:24-36) TT: (NRR:1218) TEST PLASMA MIX (1:1) PLASMA NR 42 Non correction (partial) Interpretation

12 30

13 58

15

14

NR

Moderate or strong inhibitor.eg..LA

EXERCISE 5
NORMAL PLASMA PT: NRR (10-18) APTT: (NRR:24-36) TT: (NRR:1218) TEST PLASMA MIX (1:1) PLASMA >120 >120 >120 Interpretation

12 30 15

>120 >120 >120

ANSWER 5
NORMAL PLASMA PT: NRR (10-18) TEST PLASMA MIX (1:1) PLASMA >120 Interpretation
Non correction (partial)

12

>120

APTT: (NRR:24-36)
TT: (NRR:12-18)

30 15

>120 >120

>120 >120

Non correction (partial)

Non correction (partial)

Gross heparin contamination

EXERCISE 6
NORMAL PLASMA PT: NRR (10-18) APTT: (NRR:24-36) TT: (NRR:12-18) TEST PLASMA MIX (1:1) PLASMA 15 Interpretation

12

60

30 15

35 16

NR NR

ANSWER 6
NORMAL PLASMA PT: NRR (10-18) APTT: (NRR:24-36) TT: (NRR:1218) TEST PLASMA MIX (1:1) PLASMA 15 Interpretation

12

60

Correction

30 15

35 16

NR NR

Thank You