meichner 3 hemostasis

hemostasis is the

highly balanced interaction btwn blood vessels, platelets, coagulation factors, fibrinolytic factors in the formation/dissolution of blood clots to stop hemorrhage w/o obstructing blood flow

hemostasis is the balance btwn what 2 processes

fibrin clot formation and fibrin clot degradation

3 parts of hemostasis

primary hemostasis, secondary hemostasis, fibrinolysis

primary hemostasis is the

formation of primary platelet plug

secondary hemostasis is the

stabilization of the plug w/cross-linked fibrin

what are the 7 categories of things that can initiate a hemostatic cascade

complete vessel injury, injury to the blood vessel endothelium, abnormal blood flow, diseases that cause release of large amt of tissue factor, conditions that cause unbalanced or excessive coagulation, conditions that cause a decrease in anticoagulant factors

name 2 causes of endothelial injury that initiate hemostatic cascade

inflammation, abnormal blood vessel formation

name 2 types of abnormal blood flow that initiate hemostatic cascade

turbulent blood flow, blood stasis

Name 2 conditions that release large amounts of tissue factor

extensive tissue necrosis and envenomation

name 5 conditions that cause unbalanced or excessive coagulation

neoplasia, heat stroke, pancreatitis, sepsis, IMHA

name 3 disease that decrease anticoagulant factors

liver, intestinal, and renal diseases

What happens immediately after vessel injury to limit blood loss?

vasoconstriction

What do platelets adhere to after vessel injury?

exposed subendothelial collagen

After adhering, what do platelets release, and why?

granule contents, which attract and activate more platelets

name 3 granule products released by platelets

serotonin, ADP, thromboxane A

platelets adhere and aggregate to form the

primary hemostatic plug

extrinsic pathway flow starts from

factor 3, Ca, factor 7, to factor x

intrinsic pathway flow starts from

factor 12, factor 11, to factor x

factor x activation leads to

production of thrombin

thrombin is essential for

conversion of fibrinogen to fibrin within the primary hemostatic plug and forms the secondary hemostatic plug

secondary hemostatic plug seals

vessel injury and maintains blood flow

key participants of hemostasis

blood vessels, platelets, coagulation factors

what parts of the blood vessels are important for hemostasis

endothelium, intact endothelium, damaged endothelium

endothelium is the

site of procoagulant and anticoagulant interactions

intact endothelium prevents

coagulation

damaged endothelium initiates

coagulation

3 hemostatic functions of platelets

prevent hemorrhage by forming primary hemostatic plug, facilitate assembly of coagulation factors to form more secondary hemostatic plugs, repair of vascular damage

2 non-hemostatic functions of platelets

interaction w/WBCs, promotion of inflammation and wound healing

clotting factors are

sequentially generated

4 fxns of thrombin

amplifies coagulation, converts fibrinogen to fibrin, activates coagulation control pathways, is potent so needs to be kept in check

cross-linked fibrin forms the

definitive stable hemostatic plug (secondary hemostasis)

flow of formation

primary platelet plug, definitive insoluble fibrin plug, clot retraction by platelets, fibrinolysis

Is the primary platelet plug reversible or irreversible?

reversible

primary hemostatic plug is not strong enough for

large vessels

primary hemostatic plug can only seal

small vessel damage

what is step 1 of primary hemostasis

platelet adhesion, platelets contact collagen and arrest via Von Willebrand Factor (vWF)

vWF is the

glue

2 types of adhesion vWF is responsible for

platelet-platelet adhesion, platelet-collagen adhesion

vWF is stored in

endothelial cells, only exposed after endothelial injury

step 2 of primary hemostasis

platelets change their shape (pseudopodia) and become activated

step 3 of primary hemostasis

platelets release granule contents

released granule agonists further

promote coagulation and recruits additional platelets to the plug

platelet aggregation occurs via

vWF and fibrinogen

final result of primary hemostasis

formation of platelet mass called the primary hemostatic plug (loose seal)

secondary hemostasis produces a

stable clot

secondary hemostasis is made up of

platelets + cross-linked fibrin + red cells

key participants in secondary hemostasis

coagulation factors in the coagulation cascade

coagulation cascade is a

series of enzymatic rxns where each factor activates the next factor in the cascade

2 different models of coagulation

classic cascade, cell-based model

classic cascade model contains

extrinsic, intrinsic, common

Where are most coagulation factors synthesized?

in the liver

Why is liver disease a risk factor for bleeding?

most coagulation factors are made in the liver

How are coagulation factors numbered?

in order of discovery, not their order in the cascade

what factor number doesn’t exist?

factor 6

factor 3 =

tissue factor

factor 4 =

calcium

factor 2 =

thrombin

factor 1 =

fibrinogen

in what form do most factors circulate?

inactive, they’re activated w/platelet activation at sites of vascular injury

how is an activated factor written

with a lowercase “a”

Which coagulation factors are vitamin K–dependent?

2, 7, 9, 10

Which anticoagulant factors are vitamin K–dependent?

proteins C, S, X

Why is vitamin K needed for these factors?

A vitamin K–dependent enzyme is essential for synthesizing them in the liver

Vitamin K is fat soluble, so what diseases can cause deficiency?

malabsorption/maldigestion diseases

what toxins target vitamin K-dependent factors?

anticoagulant rodenticides

What is the general half-life of vitamin K–dependent factors?

1-2 days

Which vitamin K–dependent factor has the shortest half-life, and how long is it?

factor 7, at 4-6 hours

Which factors make up the intrinsic pathway?

12, 11, 9, 8

Which factors make up the extrinsic pathway?

TF3 and 7

Which factors make up the common pathway?

10, 5, 2, 1

What initiates the extrinsic pathway?

tissue factor 3

where is tissue factor released from

injured endothelium or tissue

where is tissue factor found?

vessels, skin, mucosa, connective tissue

What cells synthesize tissue factor?

endothelial cells and monocytes

what are the 2 steps of the extrinsic pathway?

TF activates 7 to 7a, 7a then activates 10 to 10a

What 2 things help the extrinsic pathway?

calcium and phospholipids

what are the intrinsic pathway factors?

12, 11, 9, 8

what activates factor 12?

contact w/exposed collagen (a negatively charged surface)

steps of the intrinsic pathway

factor 12 is activated to 12a, 12a activates 11 to 11a, 11a activates 9 to 9a, 9a complexes with 8a, 9a and 8a activate 10

what does factor 8 circulate with and why

vWF, which protects 8

what activates factor 8 to 8a

thrombin

what is the common pathway?

divide by 2
10 → 5, → 2 → 1 (1=fibrin)

which pathways can activate factor 10

either extrinsic or the intrinsic

what does 10a activate

5 to 5a

what does thrombin convert fibrinogen into

fibrin, 1a

what does 10a/5a complex do

activate prothrombin (2) to thrombin (2a)

what are 2 properties of fibrin before cross-linking

it polymerizes into strands and is weak and relatively soluble

what does factor 13 do

forms cross-links that make fibrin strands stable

what ion assists the common pathway

calcium

thrombin generation is initiated by

extrinsic pathway

thrombin amplification and propagation is done by

intrinsic pathway

Does thrombin have procoagulant or anticoagulant functions?

both

What are thrombin’s procoagulant functions?

activates platelets, converts fibrinogen to fibrin, activates 11, 8, 5, 13

What is thrombin’s anticoagulant function?

activates protein C, which inactivates 5a and 8a and promotes fibrinolysis

what is critical to the cell-based model of coagulation

thrombin

cell-based model plays out

in vivo

Why are fibrinolysis and regulation needed?

cleanup is required after clot formation, clotting can’t go on unchecked

what does fibrinolysis do?

removes the fibrin clot, counteracts coagulation, restores normal vessel architecture and patency

when does fibrinolysis start

once the fibrin clot forms

what enzyme primarily mediates fibrinolysis

plasmin