Drugs affecting haemostasis

Question 1

what is virchow’s triad?

Answer 1

endothelial injury, change in pattern of blood flow and hypercoagulability

Question 2

why are these drugs needed?

Answer 2

bleeding patients e.g. clotting disorders, surgical bleeding

patients prone to clotting e.g. cats with heart disease (saddle thrombus)

Question 3

what is primary haemostasis?

Answer 3

affects blood vessels and platelets. causes petechiae. 
vascular response = vasoconstriction and exposure of collagen 
platelet response = degranulation. adherence to exposed collagen, activated platelets produce chemotactic granules to attract further platelets and also trigger the clotting cascade

Question 4

what is secondary haemostasis?

Answer 4

the coagulation cascade. clinical sign if problem - cavitary bleeds e.g. rodenticide poisoning.
activation of thrombin which converts fibrinogen to fibrin (cross-links platelet plug to strengthen it)

Question 5

describe the clotting cascade

Answer 5

intrinsic and extrinsic pathways. both end by activating factor 10. this converts prothrombin to thrombin which then cleaves fibrinogen to fibrin. this is cross linked by factor 13 to form stable thrombus

Question 6

why is vitamin K important in haemostasis?

Answer 6

(= fat soluble vitamin so needs solubilisation in bile salts for absorption)
aids production of many clotting factors - 2,7, 9, 10.
used to treat rodenticide poisoning and poor coagulation due to lack of absorption of vit K.

Question 7

how does vit K produce clotting factors?

Answer 7

active form involved in carboxylation of glutamyl residues to activate clotting factors
vit K is activated by epoxide reductase reaction. rodenticides prevent this from happening

Question 8

give examples of vitamin K antagonist rodenticides (coumarins)
explain how they work

Answer 8

1st gen = warfarin - less potent
2nd gen = brodifacoum - more potent
work by blocking activation of vit K by preventing the epoxide reductase reaction
cats/ dogs may eat rodent killed my these and show clinical signs

Question 9

how is rodenticide poisoning treated?

Answer 9

phytomenadione - vit K1. SC then orally with fatty meal. don’t give IV (anaphylaxis) or IM (bleeding)

50mg tablets

Question 10

how are haemostatic drugs used topically?

Answer 10

assist in the control of persistent capillary bleeding,
ideally provide good haemostasis, minimal tissue reactivity, and be easy to sterilise and handle
only work if no haemostatic/ fibrinolytic defects
e.g. in surgery

Question 11

give some examples of topical haemostatic drugs/ products

Answer 11

adrenaline/ NA - cause vasoconstriction
misc e.g. silver nitrate - precipitate proteins, seal off blood vessel
haemostatic sponges - act as a scaffold e.g. oxidised cellulose
thrombogenic coils - fibres which induce fibrosis

Question 12

systemic - blood and blood products

Answer 12

not useful to replace platelets, very useful for clotting factors - vary in amount depending on formulation

Question 13

how is ddAVP used?

Answer 13

synthetic analogue of ADH, injectable/ nasal spray/ tablets. used to increase levels of vWF (clotting)

Question 14

how is protamine used?

Answer 14

inactivates heparin

Question 15

list 2 features of a good anticoagulant

Answer 15

preservative effect and maintains function of individual components of blood
contained in blood collection bags

Question 16

describe the use of anticoagulants in diagnostic samples

Answer 16

sodium oxalate - yellow - glucose
sodium citrate - purple - clotting times
EDTA - pink - haematology
heparin - orange - urgent biochem

Question 17

what patients have increased risk of clotting?

Answer 17

cats with heart disease at risk of saddle thrombi

D/C with heartworm, immune-mediated haemolytic anaemia, disseminated intravascular coagulation

Question 18

name 2 types of drugs that reduce clotting and give examples

Answer 18

antiplatelet drugs - aspirin

anticoagulants - heparin (warfarin)

Question 19

describe the use of aspirin as an antiplatelet

Answer 19

tablet. NSAID causes irreversible inhibition of platelet COX. therefore reduced production of eicosanoids needed for clotting
no GI signs at doses used for this effect

Question 20

describe the use of clopidogrel as an antiplatelet

Answer 20

tablet prodrug (slow onset of action), prevents platelet aggregation. reduces saddle thrombus risk in cats with heart disease

Question 21

describe the use of heparin as an anticoagulant

Answer 21

reversibly binds to antithrombin 3, increased inhibition of thrombin
IV/ SC
SE = haemorrhage
controversial use

Question 22

what is tertiary haemostasis?

Answer 22

fibrinolysis. tendency to clot if problem with this. liver produces plasminogen which is cleaved to plasmin. breaks up the clot

Question 23

name 2 fibrinolytic agents

Answer 23

streptokinase and tissue plasminogen activator

Question 24

how is streptokinase used?

Answer 24

converts plasminogen to plasmin.
topical/ parenteral use (care - sytemic fibrinolysis)
not licensed

Question 25

how is tissue plasminogen activator used?

Answer 25

selectively acts on plasminogen in fibrin clots. less likely to induce systemic fibrinolysis.
not licensed