Anticoagulaiton drugs

Question 1

indications for antiocoagulants?

Answer 1

venous thrombosis
Afib

Question 2

MofA- anticoagulants?

Answer 2

target formation of fibrin clot

Question 3

naturally occuring anticoagulants?

Answer 3

-serine protease inhibitors
-Protein C and Protein S

Question 4

mofa heparin?

Answer 4

-activates antithrombin

Unfractioned heparin:
-antithrombin binds to thrombin + Xa

LMWH:
-antithrombin binds to Xa

Question 5

how long does it take for heparin to work?

Answer 5

immediate effect

Question 6

2 forms of heparin?

Answer 6

1. unfractioned
2. LMWH

Question 7

mofa unfractioned heparin?

Answer 7

Activates antithrombin and predominantly inhibits thrombin (but also works on Xa )

Question 8

mofa LMWH heparin?

Answer 8

Activates antithrombin (binds to it) and inhibits Xa

Question 9

how to monitor unfractioned heparin?

Answer 9

Activated partial thromboplastin time (APTT) for unfractionated

Question 10

how to monitor LMWH?

Answer 10

Anti-Xa assay for LMWH – but usually no monitoring of LMWH required

As factor 10a is in centre of haemostasis – will affect PT and APTT, but much more sensitive to APTT

Question 11

why use unfracitionated over LMWH?

Answer 11

unfractionated easier to reverse so may use if patient is more prone to bleeding

Question 12

complications of heparin?

Answer 12

Bleeding – as more anticoagulated

Heparin induced thrombocytopenia (with thrombosis) - monitor FBC in patients on heparin (more common in unfractionated)

Osteoporosis with long term use

Question 13

what to do if patient is on heparin and starts bleeding?

Answer 13

Stop heparin – has short half life (will take longer to disappear in LMWH)

If severe bleeding:
-Protamine sulphate (antidote)
-Reverses antithrombin effect, complete reversal for unfractionated and partial reversal for LMWH

Question 14

examples of coumarin anticoagulants?

Answer 14

warfarin, phenindione, acenocoumarin, phenprocoumon

Question 15

where are clotting factors made?

Answer 15

usually in liver

Question 16

Role of Vitamin K?

Answer 16

-Fat soluble vitamin, absorbed in jejeunum + ileum of intestine, requires bile salts for absorption

Final carboxylation of clotting factors 2 (prothrombin), 7, 9, 10 – all key components in secondary haemostasis

-also affect protein C and protein S (natural anticoagulants)– these drop initially on warfarin therapy, so always give heparin initially too

-Synthesised in liver

Question 17

MofA of warfarin?

Answer 17

inhibition of vitamin K:
-vitamin K helps make clotting factors 2 (prothrombin), 7, 9, 20
-also affect protein C and protein S (natural anticoagulants)

Question 18

what should be done in the initiation of warfarin?

Answer 18

should give heparin too
-as Warfarin also affect protein C and protein S (natural anticoagulants)– these drop initially on warfarin therapy, so always give heparin initially too

rapid- acute thrombosis
slow- in community, so not big affect on protein C or S

Question 19

how is warfarin monitored?

Answer 19

-INR
-PT and APTT prolonged (due to factor 2, 7, 9 and 10 being affected)
-clotting factor 7 has shortest has life and so PT prolonged the most

Question 20

what clotting factor has the shortest half life and what effect does that have?

Answer 20

o Shortest half-life is factor 7, so PT prolonged the most

Question 21

calculation for INR?

Answer 21

Question 22

Complications of Warfarin?

Answer 22

Haemorrhage

Bleeding complications:
Mild – skin bruising, epistaxis, haematuria
Severe – GI, intracerebral, significant drop in Hb

Question 23

risk factors for complications of a haemorrhage when on warfarin?

Answer 23

Risk factors – intensity of anticoagulation, concomitant clinical disorders, concomitant use of other medications, drug interactions, quality of management

Question 24

management of bleeding when patient is on warfarin?

Answer 24

Management depends on severity of bleeding and INR

Omit warfarin doses – hopefully bring INR down

If not, administer oral vitamin K – 6 hours to work

If severe :
-Give prothrombin complex concentrate (PTCC)
-If no PTCC available give FFP (takes longer to thaw so not first line)

Question 25

examples of new anticoagulants?

Answer 25

thrombin and Xa inhibitors

Question 26

examples of Xa inhibitors?

Answer 26

E.g. edoxaban, rivaroxaban, apixaban

Question 27

examples of thrombin inhibitors?

Answer 27

dabigatran

Question 28

MofA- dabigatran?

Answer 28

thrombin inhibitrs
-target thrombin

Question 29

CI thrombin inhibitors e.g. dabigatran?

Answer 29

caution - predominantly renally excreted so can accumulate and lead to bleeding complications if any renal co-morbidities/UTI

Question 30

advantages of thrombin inhibitors?

Answer 30

less drug interactions

Question 31

MofA edoxaban, rivaroxaban and apixaban?

Answer 31

Target factor 10a
Xa inhibitors

Question 32

advantages of edoxaban, rivaroxaban and apixaban?

Answer 32

less drug interactions

Question 33

what is heparin induced thrombocyotpenia?

Answer 33

-development of antibodies against platelets in response to heparin exposure causing platelet destruction (thrombocyopenia) and blood clots

Question 34

PATHOPHYSIOLOGY- heparin induced thrombocytopenia?

Answer 34

Development of antibodies against platelets in response to exposure to heparin

Anti-PF4/ heparin antibodies:
-Antibodies target platelet factor 4 (PF4) on platelets
- Bind to platelets and activate clotting mechanisms, causing hypercoagulable state leading to thrombosis
-Also break down platelets causing thrombocytopenia

Question 35

investigations- heparin induced thrombocytopenia?

Answer 35

HIT antibodies:
-Anti PF4
-anti heparin

Low platelets (thrombocytopenia)
Blood clots