Human Physiology, 14th edition (2016)

Blood, Heart, and Circulation 415

in laboratories by allowing blood to clot in a test tube and then

centrifuging the tube so that the clot and blood cells become

packed at the bottom of the tube.)

The conversion of fibrinogen into fibrin may occur via

either of two pathways. Blood left in a test tube will clot with-

out the addition of any external chemicals. Because all of the

components are present in the blood, this clotting pathway

is called the intrinsic pathway. Damaged tissues, however,

release a chemical that initiates a “shortcut” to the formation

of fibrin. Because this chemical is not part of blood, the shorter

pathway is called the extrinsic pathway.

The intrinsic pathway is initiated by exposure to hydro-

philic surfaces in vitro (such as the glass of a test tube) or

to negatively charged structures such as collagen, polyphos-

phates, and neutrophil extracellular traps (NETS; chapter 15,

section 15.1) in the exposed tissues of a wound in vivo. This

contact pathway activates a plasma protein called factor XII

( table 13.4 ), which is a protein-digesting enzyme (a protease).

Active factor XII in turn activates another clotting factor, which

activates yet another. The plasma clotting factors are numbered

in order of their discovery, which does not reflect the actual

sequence of reactions.

The next steps in the sequence require the presence of

Ca^2 1 and phospholipids, the latter provided by platelets. These

(clots formed in arteries, where the blood flow is more rapid,
generally lack red blood cells and thus appear gray). Finally,
contraction of the platelet mass in the process of clot retraction
forms a more compact and effective plug. Fluid squeezed from
the clot as it retracts is called serum, which is plasma without
fibrinogen, the soluble precursor of fibrin. (Serum is obtained

TxA 2

ADP

ADP

Activated

platelets

(b) (c)

Fibrin

Inactive

platelets

ADP

PGI 2

NO

AMP

VWF CD39

(a)

Endothelial cell Collagen

Figure 13.7 Platelet aggregation.

( a ) Platelet aggregation is prevented in an intact

endothelium because it separates the blood

from collagen, a potential platelet activator. Also,

the endothelium secretes nitric oxide ( NO ) and

prostaglandin I2 ( PGI2 ), which inhibit platelet

aggregation. An enzyme called CD39 breaks down

ADP in the blood, which would otherwise promote

platelet aggregation. ( b ) When the endothelium is

broken, platelets adhere to collagen and to von

Willebrand’s factor ( V WF ), which helps anchor the

platelets that are activated by this process and by

the secretion of ADP and thromboxane A2 ( Tx A2 ),

a prostaglandin. ( c ) A platelet plug is formed and

reinforced with fibrin proteins.

Figure 13.8 Colorized scanning electron micro-
graph of a blood clot. The threads of fibrin have trapped red
blood cells in this image.

Fibrin

Red blood

cells