primary hemostasis

what are the three steps of hemostasis?

1. primary hemostasis

2. secondary hemostasis

3. tertiary hemostasis

what characterizes primary hemostasis?

Formation of platelet plug and vascular spasm

what characterizes secondary hemostasis?

Formation of blood clot

what characterizes tertiary hemostasis?

Degradation of the blood clot or fibrinolysis (also known as thrombolysis)

why do we want to degrade the blood clot?

Blood wants laminar flow but with blood clot we have tubular flow, remove blood clot to get blood flow back to what vessels want

Define the cell-based model of hemostasis

Based on the principle that all hemostatic reactions occur exclusively on the surface of activated platelets NOT directly on damaged cell walls

thrombocytopenia

decrease in the number of platelets

hemophilia

the blood doesn't clot in the typical way because it doesn't have enough blood-clotting proteins (clotting factors)

hyperfibrinolysis

uncontrolled production of activating factors; common in Greyhounds

what is the goal of vasospasm?

vasoconstrict to make platelets have an easier job

what is the composition of the vessel wall?

composed of endothelial cells in the lumen

what constitutes the subendothelial area of vessels?

collagen fibers, smooth muscle cells, and fibroblasts

what are the vessels like in normal conditions?

blood not in contact with fibroblasts and collagen, only in contact if we destroy endothelial

what does it mean when we say that smooth muscle cells = autonomic “multi-type”

• No gap junctions between smooth muscle cells allowing for:fast contraction of smooth muscle cells

• regulation of cells

• localized response of cells

where does hemostasis occur?

• cell surfaces of primarily platelets, endothelial cells, and fibroblasts; can also have leukocytes and erythrocytes

what is important to know about where hemostasis occurs?

Only in DAMAGED WALL of blood vessels NOT fluid phase of blood

what does DIC stand for?

desseminated intravascular coagulation

what system is causing autonomic innervation of smooth muscle endothelial cells and what is being released to cause this?

1. sympathetic division

2. norepinephrine

what do endothelial cells release as anti-thrombotic molecules?

nitric oxide and prostacyclin to prevent formation of thrombocytes after being stimulated by moving through blood vessels

when will vasospasm occur?

immediately when vessel injury occurs to reduce blood flow and blood loss (want to create as small of a hole in injury as possible) → myogenic contraction of smooth muscle cells

what is vasospasm caused by?

1. Sympathetic stimulation: norepinephrine

2. Immediate release of endothelin from damaged endothelial cells

3. Release of thromboxane A2, ADP, and serotonin from activated platelets

when is platelet plug formation appropriate?

Only for small ruptures to blood vessels, not strong enough to take care of larger injuries or bigger vessels and will need coagulation to reinforce the clot

what stimulates the release of von Willebrand Factor (vWF)?

exposed collagen fibers and damaged endothelial cells

what happens when vWF and collagen bind to receptors on surface of neighboring platelets?

platelets change in shape and become activated once they bind to this (located on surface of activated platelet)

glycoprotein 1B

glycoprotein receptor on surface of activated platelets that helps other platelets bind to damaged vascular wall; will lead to change in platelet shape

resting platelet shape

big and round

activated platelet shape

star-like or like fried egg

platelet degradation releases

1. ADP

2. Platelet activating factor (PAF) → activates other platelets to come and join injury site

3. Thromboxane A2 (TXA2)

4. Coagulation factors and calcium in preparation for secondary hemostasis

platelet adhesion

bound to vWF platelets undergo a configurational change and exposes receptors for resting platelets → loose binding

platelet aggregation

• binding of and to fibrinogen (plasma protein) enables adhesion of platelets to each other to be stronger

Platelets bind to other platelets through

fibrinogen

platelet activation implies

1. shape change

2. cytoskeletal reorganization (Allows to extend pseudopodia (finger like projections) to adhere better to the damaged vessel wall)

3. granule release

4. Expression of surface receptors

5. Production of TXA2

what specific receptors are expressed on activated platelets?

GP 2b/3a and P-selectin

what does production of TXA2 allow for?

Leads to conversion of arachidonic acid to TXA2 through action of COX-1 to further enhance hemostatic response

why is it good that platelets are not "normally sticky"?

they can go through blood and not attach to endothelial cells; these platelets are known as platelets in a “resting state” → not reactive

describe platelet morphology

• Round to oval → half the size of RBC

• Do not have nucleus in mammals

what do the granules of platelets contain?

calcium

what are platelets derived from?

bone marrow megakaryocytes

where is throbopoeitin produced and what is its function?

Thrombopoeitin from kidneys and liver stimulate myeloid stem cells in bone marrow to produce megakaryocyte

what is the function of megakaryocytes?

extend cytoplasmic extensions through the walls of bone marrow capillaries and release thousands of cytoplasmic fragments → these fragments are called platelets or thrombocytes

what is the lifespan of platelets?

super short since they cannot produce new proteins

what are some similarities between platelets and RBC?

produced in bone marrow and they are also anucleated (besides reptiles)

what is the cause of Rickettsial Disease?

microorganisms of the genera Ehrlichia and Anaplasma

what is the effect of Rickettsial Disease?

platelet destruction in the spleen and reduce adhesion ability of platelets

what acts as a carrier for Ricketts disease?

ticks

what are the signs for Rickettsial Disease?

1. no signs

2. nosebleeds (epistaxis)

3. bleeding in the bowels (resulting in black stools)

4. bleeding of gums

5. prolonged bleeding after surgery

what is the cause for Von Willebrand Disease?

defective or deficient von Willebrand factor

what is the effect of Von Willebrand Disease?

VwF circulates as a complex with coagulation factor 8, mediating platelet adhesion to subendothelial surfaces = first step in clot formation; no vWF= no clot formation

what is the most commonly inherited bleeding disorder in dogs?

Von Willebrand Disease

what breeds are associated with Von Willebrand Disease?

Doberman pinschers, German Shepherds, and mixed breeds

what are the signs of Von Willebrand Disease?

1. gingival bleeding

2. epistaxis

3. mucosal bleeding and hematuria

4. some puppies may bleed excessively only after bleeding trigger

what do activated endothelial cells release?

vWF, tPA, and endothelin-1

describe receptors on platelets

The receptors (constitute surface where blood clot will happen) allow for hemostatic process to take place only in site of the injury on the surface of the platelet cells

describe Intracellular vesicles in platelets

secretory products contain different granules that have dozens of different molecules that will help hemostasis

what do activated endothelial cells favor?

favor the formation of thrombin, a key enzyme that stimulates blood clotting (secondary hemostasis)

antithrombic molecules

Nitric oxide and prostacyclin

what mechanism describes how platelets bind to the injured vessel?

platelets bind to damaged endothelium via vWF receptors on their surface

what mechanism best describes the role of fibrinogen in the formation of a platelet plug?

fibrinogen acts as a bridge between platelets, factilitating their aggregation

how does fibrinogen acts as a bridge between activated platelets?

fibrinogen binds to GP2b/3a receptors on the surface of platelets, facilitating platelet aggregation and formation of platelet plug

what is the proper platelet plug sequence order?

vWf secreted from endothelial cellsplatelet activationplatelet aggregation

what cellular process mainly associates primary and secondary hemostasis?

platelet degranulation

what process of hemostasis is mainly affected by a reduction or defective vWF molecule?

platelet binding

what molecules prevent platelets from binding to healthy endothelium?

prostacyclin and nitric oxide

what are the bleeding triggers for von Willebrand disease in dogs?

1. injection

2. venipuncture

3. surgery

where are endothelial cells located?

in walls of arteries, veins, smaller vessels (including capillaries)

what does an intact endothelium prevent?

adhesion of platelets through the release of nitric oxide and prostacyclin

what do platelets release that stimulate vasoconstriction?

serotonin and thromboxane A2