clotting

Question 1

define embolus

Answer 1

object from another part of the body that obstruct the blood flow – most typically a blood clot (thrombus) that becomes an embolus

Question 2

where are common sites for embolus formation?

Answer 2

brain, heart, lungs

Question 3

how does a thrombus become an embolus?

Answer 3

it starts to break down and then lodges in other vessels

Question 4

what does an insoluble clot do?

Answer 4

plugs leak in vascular wall and can occlude vessel

Question 5

what do healthy vessels secrete to inhibit clot formation?

Answer 5

vasodilators - prostaglandins I2, NO

Question 6

how do smooth muscles in vessel walls respond to damage?

Answer 6

vasoconstriction

Question 7

how does damage in vascular wall result in leaking and clotting?

Answer 7

• Damage results in exposure of basement membrane – blood exposed to collagen, subendothelial tissue factor
• Damage causes exposure to vessel wall – blood now exposed to platelet activating factor
• Damage leads to exposure in lysed epithelial cells – blood exposed to ADP (adenosine diphosphate which causes fibrinogen bridge formation)
• Break in bottom of vessel will cause leakage – vessel responds immediately (vasoconstriction)

Question 8

what happens during vitamin C deficiency?

Answer 8

reduced produced of collagen - decreased clotting
scurvy - excessive bleeding

Question 9

what does NO and nitrates do?

Answer 9

vasodilation - therapeutic and recreational

Question 10

how does corticosteroid effect collagen production?

Answer 10

reduced collagen production when in excess

Question 11

what does ehlers danlos syndrome result in?

Answer 11

genetic defect producing a reduction in collagen production

Question 12

what is the function of platelets?

Answer 12

secrete factors to activate other platelets (ADP), allow adhesion (vWF), vasoconstriction
early plug to maintain homeostasis

Question 13

where are platelets produced?

Answer 13

mega carrier site within bone marrow

Question 14

what do cancers in bone marrow do to cell types?

Answer 14

expansion of some and then squish others - discrepancies indicate pathology

Question 15

how many pathways are there within clotting factors?

Answer 15

2 (intrinsic and extrinsic) and they converge into one common one

Question 16

what are key components within the clotting factor cascade?

Answer 16

calcium
- Centres on prothrombin to thrombin which then allows fibrinogen to convert to fibrin which essentially causes the clot by cross linking

Question 17

why is regulation of coagulation vital?

Answer 17

there is enough clotting potential within 1ml of blood to clot all the fibrinogen in the body in 10 to 15s

Question 18

what is the role of anti-thrombin?

Answer 18

serpin SERine protease inhibitor (heparin facilitates anti-thrombin action

Question 19

what is vitamin K deficiency usually seen with?

Answer 19

short bowel syndrome

Question 20

what is coumains role within VitK deficiency?

Answer 20

• Coumain prevents the reduction of vitamin K epoxides in liver microsomes and induces a state of analogous to vitamin K defiency

Question 21

what are commonly inherited haemophilias?

Answer 21

mutation in factor V gene and mutation within prothrombin gene

Question 22

what are fibrin clots degraded by?

Answer 22

serine proteases , plasmin

Question 23

how does plasmin degrade fibrin clots?

Answer 23

• Plasmin circulates in plasma as inert precursor (zymogen) plasminogen
• Plasminogen is converted to plasmin by two serine proteases – tPa and uPA
• Plasminogen activator inhibitor inhibits tPA causing fibrin to be degraded

Question 24

name some thrombolytic drugs

Answer 24

streptokinase, tPA, uPA
they promote dissolution of thrombi and activate plasminogen to plasmin

Question 25

when are anticoagulation drugs indicated?

Answer 25

• Atrial fibrillation
• Mechanical heart valve replacement
• Adjunct treatment of ACD
• Endocarditis
• Mitral stenosis – narrowing of valve- doesn’t fully open
• Joint replacement surgery
• Certain type of blood disorders that affect blood clots – inherited thrombophilia and antiphospholipid syndrome (sticky platelet syndrome or Hughes disease)

Question 26

what are type of anticoagulation drugs?

Answer 26

vit K antagonists (warfarin)
DOACs
heparin - unfractionated and LMWH
fondaparinux

Question 27

what is the drug action of warfarin?

Answer 27

synthesis of vitK dependent clotting factors are impaired - early stages of clotting

Question 28

what is a heparin bridge?

Answer 28

use heparin while warfarin starts to work as warfarin takes 2-3 days

Question 29

where is warfarin absorbed and what does it bind to?

Answer 29

almost all in the gut and binds to albumin

Question 30

when should you take warfarin?

Answer 30

same time each day - usually at night
do not double dose

Question 31

what is contra-indicated within warfarin?

Answer 31

pregnancy - tetragenic and can cause intercranial haemorrhage to baby during delivery if taken during last trimester
breastfeeding - found in breast milk

Question 32

what is warfarin metabolised by?

Answer 32

cytochrome P450 - long half life

Question 33

what do you need test before anticoag therapy comences?

Answer 33

prothrombin time - 10-15s is normal time

Question 34

what INR is preferred to prevent DVT?

Answer 34

2-2.5

Question 35

what INR is targeted for thromboprophylaxis following hip surgery?

Answer 35

2-3

Question 36

what INR is ideal to prevent recurring DVT and prevent of thrombosis following prosthetic mechanical heart valves?

Answer 36

3-4.5

Question 37

what is coagulatopathies?

Answer 37

conditions that affect how blood clots - can result in more bleeding duirng surgery, injury, delivery of baby, menstruation

Question 38

what is the most common acquired coagulopathy?

Answer 38

von willebrand disease - affects clotting factors