Week 10- coagulation

Question 1

what is coagulation and its role?

Answer 1

the formation of a fibrin clot or thrombus 
-Reinforces platelet plug
- May trap blood cells
 white thrombus
 red thrombus

Question 2

what is the coagulation cascade?

Answer 2

there’s 2 Intrinsic or contact pathway
– all components present in blood, something exposed to it like glass
Extrinsic or in vivo pathway
– some components from outside blood, tissue damage
-after many stages thrombin changes to fibrinogen, to insoluble fibrin eventually leading to clot

Question 3

what is role of thrombin?

Answer 3

 Thrombin cleaves fibrinogen, producing fragments
that polymerise to form insoluble fibrin
 Activated Factor XIII(13) – strengthens fibrin links
 Platelet aggregation
 Cell proliferation
 Regulates smooth muscle contraction

Question 4

what is the role of the liver in coagulation?

Answer 4

-it synthesis clotting factors
- Vitamin K (phytomenadione)  “Koagulation” vitamin  Lipid soluble
 Required for synthesis of Factors II, VII, IX, X
Dietary source
Synthesis in GIT
 Synthesises bile salts
 Vitamin K absorption

Question 5

what are some anticoagulant durgs?

Answer 5

• warfarin

- heparin

Question 6

how do we prevent thrombosis using different drugs??

Answer 6

-Main drugs used for platelet-rich white thrombi
 Anti-platelet drugs - aspirin
 Main drugs to prevent or treat red thrombi
 Injectable anticoagulants (heparin and newer thrombin
inhibitors) – act immediately
 Oral anticoagulants (warfarin and related compounds)
- take several days
 Patients with venous thrombosis given injectable
anticoagulant until effects of warfarin established

Question 7

what is heparins and how does it work?

Answer 7

Mechanism of action - Activates antithrombin III
 inactivates thrombin and Xa(10a) and other ser proteases
 changes conformation of ATIII
 accelerates rate of action of ATIII
 Inhibiting a single molecule of Xa helps prevent
the formation of hundreds of thrombin molecules.

Question 8

what are the 2 different types of heparin?

Answer 8

 Unfractionated(UFH)
 Low molecular weight heparins (LMWH)
 Unfractionated heparin inhibits both thrombin and Xa, however,
LMWH inhibits mainly Xa and therefore its effect is more predictable.
 Unfractionated Heparin - hospitals only

Question 9

what are the pharmocokinetics of heparin?

Answer 9

 Not absorbed orally
 large size
 degradation
 Partially metabolised in the liver by heparinase to
uroheparin
 20-50% is excreted unchanged
 Parenteral administration
 IV or SC
 t 1/2 40-90 mins short
-acts immediately

Question 10

what are the LMWH over Heparin?

Answer 10

 LMWH bind less to endothelium and plasma proteins
 hence have a greater bioavailability and plasma half
life than unfractionated heparin
 Predictable dose response (only affect Xa)
 laboratory monitoring is rarely required
 Reduced frequency of dosing
 Less side effects
 Can be used at home! - Convenience/Cost

Question 11

what is the main oral coagulant?

Answer 11

warfarin

Question 12

what are some of the effects of vitamin k inhibiton?

Answer 12

 inhibits hepatic vitamin K dependent synthesis of
factors II(2), VII(7), IX(9) and X(10) and of anticoagulation protein C and it cofactor protein S
 since warfarin acts indirectly, it has no effect on existing clots
 takes at least 48-72 hours to achieve an
antithrombolytic effect

Question 13

what are the pharmocokinetics?

Answer 13

- Readily absorbed through the GIT
 quite lipophillic
 placenta
 breast milk
- Extensively bound to plasma proteins (99%)
- Plasma half life of ~37 hours (variable)
- Metabolised by cytochrome P450
- Difficult drug to control

Question 14

what are the pharmocokinetics?

Answer 14

 Readily absorbed through the GIT
 quite lipophillic
 placenta
 breast milk