Principles of Hemostasis

Question 1

define hemostasis

Answer 1

a complex physiological process that balances forces of coagulation and anticoagulation to protect the vasculature from uncontrolled bleeding or excessive clotting

Question 2

what are the three phases of hemostasis?

Answer 2

primary= formation of platelet plug
secondary= coagulation
tertiary= fibrinolysis (vascular repair)

Question 3

what are the three steps of forming a platelet plug?

Answer 3

platelet adhesion
platelet activation
platelet aggregation

Question 4

what is von Willebrand factor?

Answer 4

large, heterogeneous multimeric glycoprotein.

Question 5

what does von Willebrand factor do?

Answer 5

• protects coagulation factor VIII from rapid inactivation

- binds platelets via the glycoprotein receptor complex (causes platelets to adhere to injured part of wall)

Question 6

what makes vWF bind to platelets?

Answer 6

change in shear rate (blood flow)

Question 7

what happens to the conformation of vWF when the sheer rate changes?

Answer 7

it unravels

Question 8

how do vWF and collagen bind platelets?

Answer 8

vWF via glycoprotein Ib receptor

collagen via the glycoprotein VI receptor and a2b1 integrin

Question 9

what is the most common congenital bleeding disorder?

Answer 9

von Willebrand disease

Question 10

what is von Willebrand disease?

Answer 10

deficiency in vWF
manifests as impaired platelet function
-bruise easily
-bleeding gums
-epistaxis

Question 11

how can von Willebrand disease be treated?

Answer 11

transfusion of FFP, cryo, DDAVP or vWF/FVIII concentrate

Question 12

how are platelets activated?

Answer 12

by agonists at the site of injury -collagen, thrombin, ADP and epinephrine

Question 13

what happens when platelets are activated?

Answer 13

1. change morphology
2. Release the contents of their alpha granules and dense granules – ADP, serotinin, factor V, factor VIII, vWF, fibrinogen
3. Release substances synthesized in the cytosol (thromboxane A2) into the environment
4. **Express new negatively-charged receptors on their surface membrane

Question 14

why does aspirin inhibit platelet aggregation?

Answer 14

it's a "cox blocker"
blocks cyclooxygenase (COX)

Question 15

what are the three main platelet surface receptors?

Answer 15

thrombin
ADP
Fibrinogen

Question 16

what are the primary platelet aggregation adhesive molecules?

Answer 16

fibrinogen and vWF

Question 17

platelet aggregation is mediated by….

Answer 17

the surface receptor-glycoprotein IIb/IIIa receptor

Question 18

what is the fibrin stabilizing factor?

Answer 18

Factor VIII

Question 19

what are the direct effects of aspirin on fibrinogen and FXIII?

Answer 19

aspirin acetylates fibrinogen-clot structure is looser and easier to lyse

Question 20

the proper interaction of coagulation factors requires the presence of what?

Answer 20

a negatively charged phospholipid membrane

Question 21

where are most coagulation factors synthesized?

Answer 21

the liver

Question 22

which factor is the only one with extra-hepatic origin?

Answer 22

Factor VIII

Question 23

what is the principle function of vitamin K?

Answer 23

catalyzes the carboxylation of glutamic acid

Question 24

what does coumadin do?

Answer 24

inhibits carboxylation of the vitamin K dependent factors by vitamin K

Question 25

which has the shortest half life of the vitamin K dependent factors?

Answer 25

FVII

Question 26

hemophilia A is a deficiency of _____ | hemophilia B is a deficiency of _____

Answer 26

``` A = FVIII B = FIX ```

Question 27

what is also known as "Christmas disease?"

Answer 27

Hemophilia B

Question 28

of the two models of coagulation, which is considered to be the older model?

Answer 28

coagulation cascade

Question 29

what is the main objective of the coagulation cascade?

Answer 29

essence is to create thrombin

Question 30

what are the three pathways of the coagulation cascade?

Answer 30

common, intrinsic, extrinsic

Question 31

name some of the hemostatic actions of thrombin

Answer 31

cleavage of fibrinogen to fibrin activates platelets activates F V, VII, VIII, IX, XIII

Question 32

what are the three overlapping stages in the cell-based model of coagulation?

Answer 32

initiation, amplification and propagation

Question 33

in the cell-based model of coagulation, what is initiation?

Answer 33

a procoagulant stimulus generates enough thrombin to initiate coagulation process

Question 34

in the cell-based model of coagulation, what is amplification?

Answer 34

platelets and coagulation factors are activated

Question 35

in the cell-based model of coagulation, what is propagation?

Answer 35

large amounts of thrombin are generated on the activated platelet surface

Question 36

prothrombin is converted to thrombin in which step of the cell-based model of coagulation?

Answer 36

initiation

Question 37

name three regulators of coagulation

Answer 37

Tissue Factor Pathway Inhibitor (TFPI) Antithrombin (AT): biggest inhibitor of thrombin in adults Protein C (PC)

Question 38

what is the primary anticoagulant action of heparin?

Answer 38

its ability to inhibit thrombin activity

Question 39

what are some of the effects heparin on AT?

Answer 39

binds to AT and causes a conformational change in the molecular structure of AT (need ~ 80% to be effective) transforms AT from a slow to a rapid inhibitor of thrombin

Question 40

neonates have low levels of what?

Answer 40

procoagulant and anticoagulant factors

Question 41

neonatal platelet counts are what percent of adults?

Answer 41

100%...they're the same

Question 42

what is the relationship between vWF and age?

Answer 42

decreases with age

Question 43

the FDA has approved the use of recombinant activated factor VII for what uses?

Answer 43

patients with hemophilia A and B with developed inhibitors against FVIII and FIX patients with FVII deficiency

Question 44

rFVIIa has a huge affinity for what?

Answer 44

Tissue factor