COGULATION

PROFILE
Bleeding time, clotting time,
PT, and PTT
Presented By

HUSSAIN AKHTAR

WHAT IS COAGULATION?
Coagulation is a complex process by which blood forms clots. Blood

must be remain fluid with in the vasculature and yet clot quickly when
expose to non endothelial surface at a site of vascular injury.
It is an important part of haemostasis (the cessation of blood loss from
a damaged vessel), where in a damaged blood vessel wall is covered
by a platelet and fibrin-containing clot to stop bleeding and begin
repair of the damaged vessel.
Disorders of coagulation can lead to an increased risk of bleeding
(hemorrhage) or clotting (thrombosis).

Hemostasis is maintained in the body

via three mechanisms:
Vascular spasm - Damaged blood vessels.

constrict
Platelet plug formation - Platelats adhere
to damaged endothelium to form platelet
plug (primary hemostasis) and then
degranulate.
Blood Coagulation - Clots form upon the
conversion of fibrinogen to Fibrin, and its
addition to the platelet plug (secondary
hemostasis).

Factor I

Fibrinogen

Factor VIII

Antihemophilic
globulin

Factor II

Prothrombin

Factor IX

Partial
thromboplastin
component

Factor III

Thromboplastin Factor X

Stuart-Prower
factor

Factor IV

Calcium

Factor XI

Plasma
thromboplastin
antecedent

Factor V

Labile or
proaccelerin

Factor XII

Hageman factor

Factor VII

Stable factor or
proconvertin

Factor XIII

Fibrinstabilizing factor

THE CLOTTING MECHANISM

INTRINSIC
Collagen

EXTRINSC
Tisue Thromboplastin

XII
XI
IX
VIII

VII

X
FIBRINOGEN
(I)

V
PROTHROMBIN
(II)

THROMBIN
(III)

FIBRIN

FIBRINOLYTIC PHASE
ANTICLOTTING MECHANISMS ARE

ACTIVATED TO ALLOW CLOT

DISINTEGRATION AND REPAIR OF THE
DAMAGED VESSEL.

HEMOSTASIS
DEPENDENT UPON:

Vessel Wall Integrity

Adequate Numbers of Platelets
Proper Functioning Platelets
Adequate Levels of Clotting Factors
Proper Function of Fibrinolytic Pathway

So What Causes Bleeding Disorders?

VESSEL DEFECTS
PLATELET DISORDERS
FACTOR DEFICIENCIES

VESSEL DEFECTS
VITAMIN C DEFICIENCY
BACTERIAL & VIRAL INFECTIONS
ACQUIRED

PLATELET DISORDERS
THROMBOCYTOPENIA
(INADEQUATE NUMBER OF PLATELETS)

Causes

DRUG INDUCED
BONE MARROW FAILURE
HYPERSPLENISM
OTHER CAUSES

THROMBOCYTOPATHY
) ADEQUATE NUMBER BUT ABNORMAL FUNCTION
)

causes
UREMIA
INHERITED DISORDERS
MYELOPROLIFERATIVE DISORDERS
DRUG INDUCED(ASPIRIN,

NSAIDS)

FACTOR
DEFICIENCIES
Acquired:
Inherited:
1.

HEMHHHHOPHILIA A

1. Anticoagulant

therapy
2.

HEMOPHILIA B

2. Liver diseases
3.

VON WILLEBRANDS
DISEASE

3. DIC

LABORATORY EVALUATION
PLATELET COUNT
BLEEDING TIME (BT)
Clotting time (CT)
PROTHROMBIN TIME (PT)
Activated PARTIAL THROMBOPLASTIN TIME
(APTT)

PLATELET COUNT (CBC)

NORMAL

100,000 - 400,000 CELLS/MM3

< 100,000

Thrombocytopenia

50,000 - 100,000

Mild Thrombocytopenia

< 50,000 Sever Thrombocytopenia

BLEEDING TIME
PROVIDES ASSESSMENT OF PLATELET COUNT
AND FUNCTION
NORMAL VALUE
2-8 MINUTES

Clotting time - capillary method

Material
1.
2.
3.
4.
5.
6.

Sterile disposable pricking needle or lancet.

Stop watch
Dry glass capillary tube (narrow diameter 1 top 2 mm,
minimum 10 cm long.)
Cotton Swab of absorbent cotton.
Spirit wetted, cotton swab.
70 % v/v ethyl alcohol

Clotting time of whole blood

Clotting Time - Slide Method

The surface of the glass tube

initiates the clotting process.
This test is sensitive to the
factors involved in the intrinsic
pathway
The expected range for clotting
time is 4-10 min.

PROTHROMBIN TIME
Measures Effectiveness of the Extrinsic
Pathway
NORMAL VALUE
10-15 SECS

PT
The prothrombin time: is therefore the time required for the plasma

to clot after an excess of thromboplastin and an optimal concentration

of calcium have been added.

Measures the function of the Extrinsic Pathway.

Sensitive to Factors I, II, V, VII, X.
The PT evaluates patients suspected of having an inherited or

acquired deficiency in these pathways.

THE CLOTTING MECHANISM

INTRINSIC
Collagen

EXTRINSC
Tisue Thromboplastin

XII
XI
IX
VIII

VII

X
FIBRINOGEN
(I)

V
PROTHROMBIN
(II)

THROMBIN
(III)

FIBRIN

When is it ordered?
Used to monitor oral anticoagulant therapy (Warfarin /

Coumadin).
When a patient who is not taking anti-coagulant drugs

has signs or symptoms of a bleeding disorder.

When a patient is to undergo an invasive medical

procedure, such as surgery, to ensure normal clotting

ability.

An elevated prothrombin
time may indicate the
Vitamin K deficiency
presence
of:

(Vitamin K is needed to make prothrombin and other clotting factors)

DIC
liver disease
a deficiency in one or more of the following factors:

I, II, V, VII, X.
Anticoagulant (warfarin)

INR
A PT test may also be called an INR test.
INR (international normalized ratio) stands for a way of

standardizing the results of prothrombin time tests, no

matter the testing method.
So your doctor can understand results in the same way
even when they come from different labs and different
test methods.
Using the INR system, treatment with (anticoagulant
therapy) will be the same. In some labs, only the INR is
reported and the PT is not reported

An INR of 1.0 means that the patient PT is normal.

An INR greater than 1.0 means the clotting time is

elevated.
INR of greater than 5 or 5.5 = unacceptable high risk of
bleeding,whereas if the INR=0.5 then there is a high
chance of having a clot.
Normal range for a healthy person is 0.91.3, and for
people on warfarin therapy, 2.03.0, although the target
INR may be higher in particular situations, such as for
those with a mechanical heart valve.

PARTIAL THROMBOPLASTIN TIME

Measures Effectiveness of the Intrinsic
Pathway

NORMAL VALUE
25-40 SECS

PTT
The partial thromboplastin time (PTT) or activated partial

thromboplastin time (aPTT or APTT( is a performance

indicator measuring the efficacy of both the "intrinsic" and
the common coagulation pathways.
It is also used to monitor the treatment effects with

heparin a major anticoagulant.

Kaolin cephalin clotting time (KccT) is a historic name for

the activated partial thromboplastin time

THE CLOTTING MECHANISM

INTRINSIC
Collagen

EXTRINSC
Tisue Thromboplastin

XII
XI
IX
VIII

VII

X
FIBRINOGEN
(I)

V
PROTHROMBIN
(II)

THROMBIN
(III)

FIBRIN

Normal PTT times require the presence of

the following coagulation factors:

I, II, III, IV, V, VI, VIII, IX, X, XI, & XII

When is it ordered?
When a patient presents with unexplained bleeding or

bruising,
It may be ordered as part of a pre-surgical evaluation for

bleeding tendencies,
When a patient is on intravenous (IV) or injection heparin

therapy, the APTT is ordered at regular intervals to

monitor the degree of anticoagulation.

Prolonged APTT may

indicate:
Use of heparin.
antiphospholipid antibody:especially lupus anticoagulant,

which paradoxically increases propensity to thrombosis

coagulation factor deficiency ,

e.g hemophilia
DIC
Liver disease

FACTOR DEFICIENCIES
Inherited:
1.

HEMOPHILIA A

Acquired:
1. Anticoagulant

therapy

2. HEMOPHILIA B

2. Liver
3. VON
WILLEBRANDS
DISEASE

diseases
3. DIC

 HEMOPHILIA A (Classic Hemophilia)

80-85% of all Hemophiliacs

Deficiency of Factor VIII
Lab Results - Prolonged PTT

HEMOPHILIA B (Christmas

Disease)

10-15% of all Hemophiliacs

Deficiency of Factor IX
Lab Test - Prolonged PTT

VON WILLEBRANDS DISEASE

Deficiency of VWF & amount of Factor VIII
Factor VIII is bound to vWF while inactive in
circulation; Factor VIII degrades rapidly when not
bound to vWF
Lab Results - Prolonged BT, PTT

ANTICOAGULANTS

An anticoagulant is a substance that prevents

coagulation; that is, it stops blood from clotting
This prevents deep vein thrombosis, pulmonar
embolism, myocardial infarction and stroke.

ANTICOAGULANTS
1. Coumadins (Vitamin K antagonists)
2. Heparin

Coumadin's
These oral anticoagulants that antagonize the

effects of vitamin K.
Examples include warfarin. It takes at least 48 to
72 hours for the anticoagulant effect to develop.
Where an immediate effect is required, heparin
must be given concomitantly.
Monitored by PT times
These anticoagulants are used to treat patients
with deep-vein thrombosis (DVT), pulmonary
embolism (PE), atrial fibrillation (AF), and
mechanical prosthetic heart valves.

Heparin
Heparin is a biological substance.
It works by activating antithrombin III, which

blocks thrombin from clotting blood.

Heparin Therapy is Monitored by PTT times
Low molecular weight heparin is a more highly
processed product that is useful as it does not
require monitoring of the APTT coagulation
parameter (it has more predictable plasma levels)
and has fewer side effects.

Liver Disease
Liver Disease can Result in Reduced

Production of Coagulation
Factors
(I,II,V,VII,IX,X).

DIC
Disseminated intravascular coagulation (DIC is a

pathological activation of coagulation) blood

clotting) mechanisms that happens in response to
a variety of diseases
DIC leads to the formation of small blood clots
inside the blood vessels throughout the body
The small clots also disrupt normal blood flow to
organs (such as the kidneys), which may
malfunction as a result

As the small clots consume coagulation proteins

and platelets, normal coagulation is disrupted and

abnormal bleeding occurs from the skin the
gastrointestinal tract, the respiratory tract and
surgical wounds.
The PT and APTT are usually very prolonged and
the fibrinogen level markedly reduced
High levels of fibrin degradation products,
including D-dimer, are found owing to the intense
fibrinolytic activity stimulated by the presence of
fibrin in the circulation.

Definitive diagnosis depends on the result of

DIC:
Thrombocytopenia) prolonged bleeding time)
Prolongation of prothrombin time and activated

partial thromboplastin time

A low fibrinogen concentration
Increased levels of fibrin degradation products

Pre-analytic
errors
Problems with blue-top tube
Partial fill tubes
Vacuum leak and citrate

evaporation

Problems with phlebotomy

Heparin contamination
Wrong label
Slow fill
Underfill
Vigorous shaking

Biological effects

Hct 55 or 15
Lipemia, hyperbilirubinemia,
hemolysis

Laboratory errors
Delay in testing
Prolonged incubation at 37C
Freeze/thaw deterioration