pt timp de protrombina

8/13/2019 PT Timp de Protrombina

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Prothrombin Time [PT]

Introduction

The prothrombin time was described by Quick in 1935 and the test was

often referred to as 'Quick's Prothrombin Time.' The prothrombin time

was developed to measure Prothrombin (Factor II) and hence its name.

However, it subsequently became clear that it was sensitive to

abnormalities of factors VII, X, V, II and fibrinogen.

The Prothrombin Time (PT) in contrast to the APTT measures the

activity of the so-called extrinsic and common pathways of coagulation.The division of the clotting cascade into the intrinsic, extrinsic and

common pathways is medieval and has little in vivo validity but

nevertheless remains a useful concept for interpreting the results of

laboratory investigations.

The prothrombin time is a one-stage test based upon on the time

required for a fibrin clot to form after the addition of Tissue Factor (TF)

(historically known as tissue thromboplastin), phospholipid and calcium

to decalcified, platelet poor plasma.The term 'Thromboplastin' was originally used to describe a substance

in plasma that converted prothrombin to thrombin. Historically

thromboplastins were extracted from brain and other organs and these

contained significant amounts of tissue factor [TF] and phospholipid

[Pl]. TF is species specific and most laboratories now use a

recombinant human TF with anISI close to 1 and which is relipidated to

provide a source of phospholipid. Animal thromboplastins are usually

derived from rabbit brain.

TF was originally designated Factor III when the nomenclature of theclotting proteins was undertaken.

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

pathways of coagulation and therefore, is dependent on the functional

activity of factors VII, X, V, II (Prothrombin) and fibrinogen. The

diagram below shows the clotting cascade and the factors that affect the

prothrombin time.

Method

Platelet poor plasma [PPP] is mixed with Tissue Factor (TF)

(containing phospholipid) at 37C and an excess of calcium chloride

(25mM) is added to initiate coagulation. In the manual technique at the

same time as the calcium is added, a stopwatch is started and stopped

when the clot forms. The time taken from the addition of calcium to the


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formation of the fibrin clot is known as the Prothrombin Time or PT. In

an automated system the formation of the clot is detected electronically

but the principles are identical.

Reagent ExplanationPlatelet Poor Plasma (PPP) Seepre-analytical variables

Tissue Factor [containing

hospholipid]

Tissue Factor binds to FVII and initiates

coagulation.

Exogenous phospholipid is used to replace

latelet phospholipid

Calcium Required for re-calcification

I nterpretation

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.

Abnormality Interpretation

Isolated Prolonged PT Factor VII deficiency

Prolonged PT inassociation with other

coagulation

abnormalities

Vitamin K deficiencyVitamin K antagonists e.g. warfarin,

henindione, rodenticides

Liver disease

alabsorption (leading to vitamin K

deficiency)

High concentrations of unfractionated heparin

Direct thrombin inhibitors e.g. Lepirudin,

argatroban

fibrinogenaemia and dysfibrinogenemia

Dilutional coagulopathy e.g. massive blood

transfusion

ultiple clotting factor deficiencies e.g. FV and

FVIII deficiency
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bnormalities of the vitamin K cycle e.g.

mutations within the VKORC1 gene

Chromosomal aberrations - the F7 and F10

genes are located on the long arm of

chromosome 13 - deletions of which areassociated with reduced FVII and FX levels.

Shortened PT Following treatment with rVIIa

Reference Ranges

The reference range depends upon a number of variables including:

- Source of Tissue Factor e.g. human, rabbit etc

- The exact technique used e.g. manual or automated- Method of end-point determination e.g. optical or mechanical

Each laboratory should establish its own normal range but in general

the prothrombin time for a normal plasma sample, lies between 13-15

seconds.

What Test Next

In cases in which there is an isolated prolongation of the PT and theremainder 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 and it is more common to find a prolonged

PT in combination with other abnormalities of the screen e.g. a

prolonged APTT. In these cases - consult the table above for the possible

differential diagnoses and therefore, how to proceed. The history

including a drug history and the examination are of fundamental

importance

Remember - Warfarin and other oral Vitamin K antagonists will

significantly prolong the PT but may prolong the APTT by only a fewseconds (except in overdose)

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