Hemostasis and Related disorders

what is the overall goal of hemostasis?

to form a blood clot that prevents or limits bleeding

what are the 4 major steps of normal hemostasis in order?

1. arteriolar vasoconstriction

2. primary hemostasis (platelet plug)

3. secondary hemostasis (fibrin deposition)

4. clot stabilization and resorption

which step forms the initial platelet plug?

primary hemostasis

which step strengthens the platelet plug with fibrin?

secondary hemostasis

what is the immediate response after vascular injury?

arteriolar vasoconstriction

what is the purpose of vasoconstriction after injury?

reduce blood flow to injured area

what mediates arteriolar vasoconstriction?

Endothelin

endothelin

endothelium derived vasoconstrictor

is vasoconstriction enough by itself to permanently stop bleeding ?

No. it is transient; bleeding would resume without the proper steps of hemostasis

what is the main event of primary hemostasis?

formation of the platelet plug

What becomes exposed when the endothelium is distrupted?

vWF and collagen

what do exposed vWF and collagen promote?

platelet adherence and activation

what happens to platelets after they become activated?

• change shape: increase surface area

• release secretory granules → (platelet recruitment and aggregation)

what two important mediators (secretory granules) are released by activated platelets?

ADP and thromboxane A2

what is the function of ADP and TXA2 in primary hemostasis?

promote platelet recruitment and aggregation

in primary hemostasis platelets go through which three steps?

adhesion

activation

aggregation

What platelet receptor is involved in adhesion?

GpIb

(glycoprotein Ib)

GpIb binds to what?

von willebrand factor (vWF)

Platelets adhere to the ____ through binding of _________ receptor to ____ exposed on endothelium

ECM;

glycoprotein Ib;

vWF

what 3 events happen during platelet activation?

1. change shape (increase SA)

2. increased affinity for fibrinogen

3. secretion of granule contents

what platelet receptor is involved in aggregation?

Glycoprotein IIb/IIIa

what binds GpIIb/IIIa during platelet aggregation?

fibrinogen

how does fibrinogen promote platelet aggregation?

it links platelets together by binding GpIIb/IIIa receptors

what is the major purpose of secondary hemostasis?

to consolidate/stabilize the initial platelet plug with fibrin

what is exposed at the site of injury that initiates coagulation?

tissue factor (TF)

what is the membrane-bound procoagulant glycoprotein that binds and activates factor VII

tissue factor

TF binds and activates which coagulation factor?

Factor VII

what major enzyme is generated through the coagulation cascade?

thrombin

what does thrombin do to fibrinogen?

cleaves fibrinogen→ fibrin

what does fibrin form?

fibrin meshwork that stabilizes the platelet plug

what happens to fibrin and platelet aggregates during clot stabilization?

Fibrin and platelet aggregates contract to form permanent platelet plug

What is t-PA and where is it produced?

tissue plasminogen activator, produced by endothelial cells

what is the overall role of t-PA?

helps limit clotting at the site of injury and allows clot resorption/repair

________ are the regulators of hemostasis

Endothelial cells

what enzyme breaks down fibrin?

plasmin

what is plasminogen?

precursor of plasmin

what activates plasminogen?

t-PA

What initiates the intrinsic pathway?

blood contacting negatively charged surfaces such as exposed collagen from damaged blood vessels

what are the key factors of the intrinsic pathway?

factor XII

factor XI

factor IX
factor VIII

what initiates the extrinsic pathway?

exposure of tissue factor during injury

what are the key players in the extrinsic pathway?

Tissue factor + Factor VII

what is the common pathway?

convergence of intrinsic and extrinsic pathways

what are the major players of the common pathway?

factor X
prothrombin

thrombin

fibrinogen

fibrin

what happens to prothrombin in the common pathway?

it is converted to thrombin

what happens to fibrinogen?

converted to fibrin by thrombin

what pathway does prothrombin time evaluate

extrinsic pathway

what factors are assessed by Prothrombin time?

factors VII

factor X

factor V

prothrombin

fibrinogen

what is measured during a PT test?

time until a fibrin clot forms

what is the international normalized ratio? (INR)

“corrected” prothrombin time

Why is international normalized ratio needed?

prothrombin time results vary depending on the manufacturer/reagents, so INR accounts for reagent differences

what pathway does partial thromboplastin time (PTT) assess?

assesses the intrinsic pathway

what factors are assessed by PTT (partial thromboplastin time)?

XII,

XI,

IX,

VIII,

X,

V,

prothrombin,

fibrinogen

what is ultimately measured during PTT?

time to fibrin clot formation

What does thrombin time test and identify?

test the last step of coagulation

Fibrinogen → Fibrin → clot

identifies problem with fibrinogen or thrombin inhibitor issue ( something blocking thrombin)

Patient has a defect in the intrinsic pathway. Which test should be prolonged?

partial thromboplastintime

Patient has a defect in the extrinsic pathway. Which test should be prolonged?

prothrombin time

Factor VIII deficiency should affect which test?

partial thromboplastin time

Factor IX deficiency should affect which test?

Factor VII belongs to which pathway and therefore affects which test?

what is thrombins major action?

converts fibrinogen → fibrin

what coagulation factor does thrombin activate to help stabilize the clot?

Factor XIII

What effect does thrombin have on platelets

promotes platelet activation and aggregation

does thrombin only promote coagulation?

No. it becomes an Anticoagulant when it contacts normal endothelium

besides coagulation what process does thrombin promote?

inflammation;

Angiogenesis(new BV form from preexisting);

Repair

what factors that limit coagulation ?

1. dilution

2. fibrinolytic cascade

how does dilution limit coagulation?

blood flowing past site of injury washes out activated coagulation factors

what is the fibrinolytic cascade?

plasminogen is activated to Plasmin by t-PA (tissue plasminogen activator);

Plasmin breaks down fibrin

what is the normal platelet count ?

150,000- 450,000 uL

what is the platelet count in thrombocytopenia ?

<150,000 uL