Physiology of Coagulation and Clotting

T/F: Leukocytes and RBCs drive most blood-mediated inflammatory responses

FALSE

___________ drive most blood-coagulation responses

Platelets

What is the buffy coat portion of blood composed of and what
percentage of whole blood does it take up?

Leukocytes and platelets <1%

List cells in the blood that have a nucleus

Monocytes Neutrophils Lymphocytes

T/F: Platelets have no nucleus, actin, or myosin and therefore cannot
proliferate/synthesize proteins

FALSE

What is the purpose of contractile proteins in platelets?

Clot retraction / platelet aggregation

List 7 things platelets have/produce:

Actin and myosin Contractile ptns ER and
Golgi Mitochondria Eiconsanoids and eiconsanoid
production enzymes Cell surface receptors
Granules

What is the function of the ER and golgi in platelets?

Contain enzymes/ptns and store calcium

What is the function of the mitochondria in platelets?

Forms ADP/ATP

What is an example of an eiconsanoid and eiconsanoid enzymes in platelets?

Thromboxane (TXA1) Thromboxane synthase,
cyclooxygenase

T/F: TXA1 is a very potent vasodilator

FALSE

List examples of cell surface receptors on platelets

GP receptor Serotonin receptor
Protease-activated receptor (PAR) Purinergic
receptor

What is the function of granules in platelets?

Contain serotonin, Ca, enzymes, ADP, and PDGF

What is the overall function of platelets?

Form platelet plug that helps seal breaks in blood vessels

How are circulating platelets kept inactive and mobile?

Endothelium creates slick surface by continuous production of NO and
prostacyclin inhibiting the platelets from sticking

During hemostasis (stopping bleeding), platelets adhere to
____________ and release chemicals that act as ___________ to change
the physical properties of nearby platelets

Collagen fibers; autocoids

Defined as fast series of rxns to stop bleeding

Hemostasis

List the 3 main steps in hemostasis

Vascular spasm Platelet plug formation
Coagulation (blood clotting)

List the triggers for vasoconstriction

Direct injury to vascular smooth muscle Chemicals
released by endothelial cells and platelets Pain
reflexes

T/F: Vasoconstriction is most effective in the aorta and pulmonary arteries

FALSE

Platelet plug formation is a _____________ (positive/negative)
feedback cycle.

Positive

Describe how the platelet plug formation occurs

Damaged endothelium exposes collagen fibers Platelets
stick to collagen via von willebrand factor (by binding to GP
receptor on platelets) Platelets swell, become
spiked/sticky, and release chemical messengers to make nearby
platelets sticky Platelet plug forms

What process reinforces platelet plug formation by initiating the
formation of fibrin threads?

Coagulation

T/F: In platelet plug formation, the blood is transformed from liquid
to gel

FALSE

Which clotting factors need vitamin K in order to be synthesized?

II, VII, IX, and X

During coagulation, ________ forms a mesh that traps red blood cells
and platelets forming the clot

Fibrin

List the important components of platelet activation:

Formation of Thromboxane (through activity of COX)
Release of platelet granules Expression of GPIIb/IIIa
via various receptor activation (i.e. ADP)

List the drugs that inhibit cyclooxygenase

Aspirin

List the important agonists for platelet activation

Thrombin TXA2 ADP

An important transducing mechanism in platelet activation is enhanced
_______ in the platelet

Ca

Glycoprotein receptors are also called:

Integrin receptors

How does PGH2 inhibit aggregation and cause vasodilation through the
epithelial cells?

PGH2 activates PS which synthesizes PGI2

How does PGH2 cause aggregation and vasoconstriction in platelets?

PGH2 activates TS which synthesizes TxA2

How does aspirin decrease aggregation and vasoconstriction of platelets?

Inhibits COX1 = no PGH2 = no TS = no TxA2

List the important contents of the ? granules

Fibrinogen von Willebrand factor (VWF)

List the important contents of the dense granules

ADP ATP Ca

List the PDE inhibitors

Dipyridamole Cilostazol
Aspirin/Dipyridamole

List the inhibitors of ADP-mediated Platelet aggregation

Ticlopidine Clopidogrel Presurgrel
Ticagrelor Cangrelor

List the GPIIb/IIIa inhibitors

Abciximab Eptifibatide Tirofiban

T/F: Inhibition of PDE means cAMP does not get broken down which
leads to an increased level of Ca within the platelet = release
granules, express GPIIb/IIIa, and platelet changes shape increasing SA

FALSE

T/F: Activation of both P2Y1 and P2Y12 is
required for ADP-mediated platelet aggregation to occur

TRUE

P2Y1 is _____ coupled

Gq

P2Y12 is _____ coupled

Gi