anti coagulants

Question 1

what is a haemostatic plug formed from

Answer 1

aggregated platelets within a fibrin mesh

Question 2

how does body respond to ruptured blood vessels

Answer 2

vasoconstriction + formation of haemostatic plug

Question 3

what does thrombomodulin do

Answer 3

thromobomodulin on endothelial cells reversibly binds thrombin

when bound thrombin no longer activates fibrin formation, however it does activate protein C

protein C inhibits coagulation factors 5a and 7a and stimulates fibrinolysis

Question 4

what factors prevent spontaneous coagulation

Answer 4

thrombomodulin, antithrombin 3 and heparin cofactor 2

Question 5

what does antithrombin 2

Answer 5

an alpha 2 globulin

neutralises serine proteases: factors: 2a, 9a, 10a, 11a and 12a

Question 6

what does heparin cofactor 2 do

Answer 6

inhibits factor 2a (thrombin)

Question 7

what are the 2 pathways of the blood coagulation cascade and how are they caused

Answer 7

intrinsic pathway: surface contact

extrinsic pathway: tissue damage, may also be activated by factor 12a

Question 8

describe intrinsic pathway of blood coagulation cascade

Answer 8

surface contact causes factor 12 to convert to 12a

12 a causes factor 11 to go to 11a

11a causes factor 9 to go to 9a

9a converts 8 to 8a and platelet factor 3

9a also converts 10 to 10a

10a converts 2 to 2a

2a converts 13 to 13a which along with calcium converts fibrin to inslouble fibrin

2a also converts fibrinogen into fibrin

2 a also acts on platelets

Question 9

how does extrinsic pathway of blood coagulation cascade happen

Answer 9

tissue damage leads to formation of tissue factor

tissue factor along with 7a causes 10 to convert to 10 a which then follows intrinsic pathway

tissue damage also gives rise to platelet factor 3 (platelets also give rise to platelet factor 3)

Question 10

what are targets of drugs of haemostasis

Answer 10

fibrin formation, platelet adhesion and activation and fibrin removal/fibrinolysis

Question 11

what agents promote blood coagulation

Answer 11

vitamin k; acts as cofactor for the g-carboxylation of glutamic acid residues on N terminals of precursor glycoproteins, this process yields zymogens (inactive precursors of active factors), zymogens: factors 2,7,9 and 10

vitamin k difficiency is normally acquired through liver disease or excessive use of oral anticoagulants

factor 8 is used for treatment of type A haemophilia

factor 9 is used for treatment of type B haemophillia

Question 12

which agents decrease blood coagulation

Answer 12

injectable anticoagulants : heparin

oral anticoagulants: warfarin

direct thrombin inhibitors: dabigatran

Question 13

where is heparin found endogenously

Answer 13

in mast cells and plasma

Question 14

what does heparin do

Answer 14

inactivates thrombin (factor 2a) and factors 9a-12a

anticoagulant effect due to pentasaccharide sequence that promotes action of antithrombin 3

it does this by combining with antithrombin 3 and accelerates its action

antithrombin 3 is physiological inhibitor of these factors

high molecular weight comes from bovine sources, not commonly used

low molecular weight is depolymersied and is synthetic

Question 15

what happens with prolonged use of heparin

Answer 15

prolonged use can deplete stores of antithrombin 3 and diminish effects of heparin

Question 16

how is heparin administered, how long is it active

Answer 16

it is not active orally, given via IV injection

active for 2-4 hours

Question 17

when is heparin given

Answer 17

low dose is given subcutaneously peri-operatively to reduce risk of deep venous thrombosis and pulmonary embolism

Question 18

how is dose of heparin calculated

Answer 18

since it binds plasma proteins; determined by bioassay and biological standardisation; dose is controlled by measuring partial thromboplastin time

Question 19

what are other injectable anticoagulants that do not involve antithrombin 3

Answer 19

thrombin inhibitors: such as lepirudin, useful for patients who develop immune response to heparin

ancrod: acts on fibrinogen to produce unstable fibrin fibrils leading to depletion of fibrinogen

Question 20

how does warfarin act

Answer 20

interferes with reduction of viatmin K, prevents vitamin K from acting as cofactor in gamma carboxylation of glutamate residues at N terminal ends of factors 2,7,9 and 10

if these residues are not carboxylated they are non functional and so inactive

Question 21

what is adverse affect of warfarin

Answer 21

excessive bleeding, counteracted with increasing vitamin k intake but it takes some time to produce active factors

Question 22

describe warfarin pharmacokinetics

Answer 22

administered orally, half life is 40 hours, drug is only effective when existing pool of factors is depleted which takes 12-16 hours

maximum effect at 36-48 hours

duration of action is 4-5 days

rate of exhaustion of active coagulation factors is increased when metabolic is increased

dose does not need to be monitored continuously

Question 23

what benefits do direct thrombin inhibitors have

Answer 23

actions are more predictable than warfarin

easier to use because actions are more predictable so lab monitoring is not necessary

reacts with less other drugs than warfarind

however does not seem to have better protective efficacy (e.g against strokes) than warfarin

Question 24

what are drug interactions with oral anticoagulants (warfarin)

Answer 24

response of oral anticoagulants is decreased by:
prior administration of drugs which cause induction of liver microsomal e.g barbiturates

oral contraceptives

response to oral anticoagulatns is increased by:

drugs which displace plasma protein binding of the anticoagulant e.g aspirin

agents which impair platelet aggregation e.g aspirin

Question 25

what is thrombosis

Answer 25

pathological formation of haemostatic plug, factors that contribute to likelihood are ;

injury to vessel wall, altered blood flow, altered coagulability of blood

Question 26

what are white clots

Answer 26

aggregated platelets

Question 27

what causes platelet activation and what causes platelet aggregation

Answer 27

platelets are either activated by thrombin or adhesion to thrombogenic surface

platelet activation:

arachidonic acid generation leads to cyclic endoperoxidase which causes synthesis of TXA2

TXA2 causes expression of glycoprotein 1ib/3a receptors which leads to platelet linkage by fibrinogen binding to glycoprotein receptors

Question 28

what are the most commonly used drugs in atherosclerotic disease

Answer 28

aspirin: irreversible COX2 inhibitor

ADP (P2Y12) inhibitors: clopidogrel

in acute coronary syndrome low molecular weight heparins are used

Question 29

what is the fibrinolytic cascade

Answer 29

initiated by coagulation cascade

results in formation of plasmin from plasminogen which digests fibrin by tissue plasminogen activators such as streptokinase

drugs may work to promote formation of plasmin

Question 30

what is a red clot

Answer 30

the fibrin mesh