Blood Coagulation

Question 1

What is thrombosis associated with in the arteries and in the veins?

Answer 1

Arterial: atherosclerosis
Venous: DVT

Question 2

Describe the extrinsic pathway of blood coagulation.

Answer 2

Utilises pre-formed factors hence, is rapid and short-lasting. In vivo pathway including tissue factor and factor VIIa.

Question 3

Describe the intrinsic pathway of blood coagulation.

Answer 3

Longer to activate compared to the extrinsic pathway, longer lasting. Includes factors XII and XI.

Question 4

Release of which mediators assists in platelet aggregation?

Answer 4

ADP, TXA2, PAF.

Question 5

What is the major endogenous inhibitor of blood coagulation?

Answer 5

Antithrombin III

Question 6

Where does ATIII act in the thrombosis pathway?

Answer 6

Factors XIIa, XIa, iXa, Xa, IIa and thrombin.

Question 7

Which factors released by the vascular endothelial cell layer inhibit player aggregation?

Answer 7

PGi2 and NO

Question 8

What is the route of administration of heparin?

Answer 8

I.v. or s.c.

Question 9

What is the molecular weight of heparin?

Answer 9

Daltons

Question 10

Can heparin be used in vitro or in vivo?

Answer 10

Both, in vitro and in vivo

Question 11

What is the endogenous form or haparin?

Answer 11

Heparan sulfate in endothelium.

Question 12

What is the mode of action of heparin?

Answer 12

Binds to ATIII as ATIII binds to serine site of clotting factors IIa (thrombin), IXa, Xa, XIa and XIIa to inhibit clotting.

Question 13

List two examples of LMWH.

Answer 13

Dalteparin and enoxaparin.

Question 14

What is the molecular weight of LMWH and heparin?

Answer 14

LMWH: 4000-15000
Heparin: 3000-40000

Question 15

What are the advantages of LMWH over heparin?

Answer 15

Greater bioavailability, longer 1/2 life, lower effect on platelet function.

Question 16

Which clotting factors does LMWH most affect?

Answer 16

Factor Xa, does not reach others.

Question 17

List the indications for heparin.

Answer 17

Surgery, IV device patency, unstable angina, prevention of arterial thrombosis in coronary angioplasty.

Question 18

List the common side effects of heparin.

Answer 18

Haemorrhage, bruising, pain
Thrombocytopaenia (reduce platelet count, reduced with LMWH) - can be transient-severe in 25% of patients or severe rarely, involving Ab formation.

Question 19

What is the antidote to heparin?

Answer 19

Protamine - basic protein that forms inactive complex with heparin.

Question 20

What is the route of administration of warfarin?

Answer 20

Oral

Question 21

How is vitamin K involved in thrombosis?

Answer 21

Its oxidation clotting factors are activated into gamma-carboxyglutamic acid residue forms.

Question 22

What is the mechanism of action of warfarin?

Answer 22

Vitamin K antagonist

Question 23

Regarding warfarin, what contributes to drug interactions, what is the 1/2-life and onset time and can it be used in vivo or in vitro?

Answer 23

Binds to plasma proteins
Variable 1/2-life, days for onset as clotting factors degrade
In vivo only

Question 24

List the indications for warfarin.

Answer 24

Treatment/prophylaxis of throboembolic disorders and cardiac complications:
PE, DVT, unstable angina, atrial fibrillation caused stroke

Question 25

What are the adverse effects of warfarin?

Answer 25

Bleeding, haemorrhage, (nose, urine, faeces) | Dose-monitoring required.

Question 26

What is the antidote for warfarin?

Answer 26

Oral or i.v. vitK, slow onset

Question 27

Why is dose monitoring important in warfarin use?

Answer 27

Large variability in response due to variable onset, long 1/2-life, drug interactions, diet.

Question 28

What is the normal INR range for warfarin?

Answer 28

0.9-1.3

Question 29

List factors that increase and decrease the response to warfarin.

Answer 29

Increase: vitK deficiency, liver disease, ageing. Decrease: pregnancy (avoid in early and late stages), poor patient compliance, vitK (green leafy vegetables), alcohol.

Question 30

List drugs that decrease the effect of warfarin.

Answer 30

Barbituates, rifampicin, carbamazepine (anti-epileptic), alcohol, vitK

Question 31

List drugs that increase the effect of warfarin.

Answer 31

Cimetidine (anti-ulcer), amiodarone | Salicylates (NSAID aspirin) due to displacement and anti-platelet effect.

Question 32

When are anticoagulant drugs used?

Answer 32

Surgery, DVT, atrial fibrillation, prosthetic heart valves, unstable angina.

Question 33

What is the mechanism of action of dabigatran?

Answer 33

Direct inhibition of thrombin

Question 34

Compare dabigatran to warfarin.

Answer 34

Increased stroke reduction, similar/reduced bleeding, no need for INR or dose monitoring, no/minimal drug and diet interactions, potentially hidden side ADRs and deaths.

Question 35

List classes of anti-platelet agents.

Answer 35

COX inhibitors, phosphodiesterase inhibitors, inhibitors of platelet binding/adhesion.

Question 36

List the adverse events of aspirin.

Answer 36

GI: dyspepsia, nausea, vomiting, bleeding | Gout (uncommon)

Question 37

What are the indications for low-dose aspirin therapy?

Answer 37

Prevention of stroke and MI, high-risk patients, unstable angina, post-MI, post-surgery

Question 38

List "other" anti-platelet compounds

Answer 38

Adenosine P2Y12 receptor blockers on platelents, inhibit ADP-induced aggreagtion (clopidogrel, ticlopidine) Abciximab - glycoprotein IIb/IIIa receptor antagonist on platelets, prevents binding of fibrinogen to platelets Phosphodiesterase inhibitors, increase cAMP, inhibit thromboxane A2 synthesis, vasodilate (dipyridamole)

Question 39

What are the indications for antiplatelet drugs?

Answer 39

Thromboembolic disorders, cardiac complications.

Question 40

List the ADRs of antiplatelet drugs?

Answer 40

Bleeding (severe - clopidogrel), headache, nausea (dipyridamole), antibody development, thrombocytopenia (low platelets) (abciximab).

Question 41

What is the mechanism of action of fibrinolytic drugs, such as tPA?

Answer 41

Converts plasminogen to plasmin.

Question 42

What factor gives tPA some selectivity?

Answer 42

Targets plasminogen adsorbed to fibrin.

Question 43

What are the indications for fibrinolytic agents?

Answer 43

AMI <12 hours PE Acute thrombotic stroke <4.5 hours