hematology: blood coagulation

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Medical Laboratory

Scientist

HematologyPart 4 of 4: Blood coagulation

Brief overview

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Hemostasis

Normal hemostasis is the responsibility of a complex system of three

individual components:

Platelets - in the circulation

Endothelial cells – line the wall of the blood vessel

Blood-clotting proteins – circulate in the blood

The process of hemostasis occurs in three phases:

1. Vascular platelet phase: primary hemostasis

2. Activation of the coagulation cascade: formation of the clot

3. Activation of a series of control mechanisms: stop the

propagation of the clot and limit activation of the coagulation

cascade to the region of endothelial rupture3


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Mechanisms of Blood Coagulation

Primary hemostasis:

1. Vasoconstriction: When injury occurs, vessel walls constrict,

causing reduced blood flow to the site of injury.

2. Platelet plug: Platelets aggregate to the site of the injury. They

stick together acting as a "plug."

Secondary hemostasis

3. Platelets activate the process which causes a fibrin clot to form.

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Clotting Cascade

Extrinsic Pathway

The extrinsic pathway is activated by external trauma that

causes blood to escape from the vascular system. This

pathway is quicker than the intrinsic pathway. It involves factor

VII.

Intrinsic Pathway

The intrinsic pathway is activated by trauma inside the vascular

system, and is activated by platelets, exposed endothelium,

chemicals, or collagen. This pathway is slower than the extrinsic

pathway, but more important. It involves factors XII, XI, IX, VIII.

Common Pathway

Both pathways meet and finish the pathway of clot production in

what is known as the common pathway. The common pathway

involves factors I, II, V, and X.

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Coagulation Cascade

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Damaged vessel

Intrinsic systemActivated by chemicals, collagen,

exposed endothelium, platelets

Extrinsic systemBlood escapes from

vascular system

Contact damaged tissues

Release phospholipoproteins

and organelle membrane

Derives tissue thromboplastin

or

Tissue Factor

Factor XII Factor XIIa

XI XIa

X

IXaVIIIa

PL

Ca++

VIIa

VIIIX

Xa

Prothrombin Thrombin

XIII

FibrinogenSoluble fibrin

monomer

Ca++

VIIIa

PL

Ca++

Va

PL

Ca++

XIIIa

Fibrin clot

PL = Platelet Phospholipids


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Activated Partial Thromboplastin

Time (aPTT)

aPTT measures the time necessary to generate

fibrin from initiation of the intrinsic pathway.

Activation of factor XII is accomplished with an

external agent (e.g., kaolin) capable of activating

factor XII without activating factor VII.

The normal time is usually reported as less than

30 to 35 seconds (25 to 35 seconds), and

decreased values ("short") may be abnormal.

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Prothrombin Time (PT)

PT measures the time necessary to generate

fibrin after activation of factor VII.

It measures the integrity of the "extrinsic"

and "common" pathways (factors VII, V, X,

prothrombin, and fibrinogen).

A prolonged PT may reflect either factor

deficiency or a circulating inhibitor of

coagulation.

The test is more sensitive than the aPTT for

deficient levels of factors, and a relatively

small drop in factor VII levels may prolong

the PT.

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Thrombin Time (TT)

TT is the time to drive the reaction of fibrinogen to

fibrin in the presence of thrombin

It measures the integrity of this reaction and

isolates an abnormality to either a decrease in

normal fibrinogen or an inhibitor to its activation.

Abnormalities can be: deficient fibrinogen (< 100

mg/dl), abnormal fibrinogen, or an inhibitor to the

reaction.

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Coagulation Cascade

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Damaged vessel

Intrinsic systemActivated by chemicals, collagen,

exposed endothelium, platelets

Extrinsic systemBlood escapes from

vascular system

Contact damaged tissues

Release phospholipoproteins

and organelle membrane

Derives tissue thromboplastin

or

Tissue Factor

Factor XII Factor XIIa

XI XIa

X

IXaVIIIa

PL

Ca++

VIIa

VIIIX

Xa

Prothrombin Thrombin

XIII

FibrinogenSoluble fibrin

monomer

Ca++

VIIIa

PL

Ca++

Va

PL

Ca++

XIIIa

Fibrin clot

PL = Platelet Phospholipids

aPTT

PT

TT


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Antithrombin III Test

This test is done if repeated blood clots oocur or if blood

thinning medicine does not work.

Lower-than-normal AT III can have an increased risk of clotting.

Lower than normal AT III may be due to:

Bone marrow transplant

DIC (disseminated intravascular coagulation)

AT III deficiency, an inherited condition causing lower blood

clotting protein levels

Liver cirrhosis

Nephrotic syndrome

Higher than normal AT III may be due to:

Use of anabolic steroids

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Factor VIII assay

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This test is used to find the cause of too much bleeding (decreased

blood clotting), or if a family member is known to have hemophilia A

A normal value is 50 - 200% of the laboratory control or reference value.

Decreased levels may be due to:

Disseminated intravascular coagulation (DIC)

Hemophilia A

Presence of a Factor VIII inhibitor (antibody)

Von Willebrand's disease

Increased levels may be due to:

Advanced age

Diabetes

Liver disease

Inflammation

Pregnancy

Obesity

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