Intro to Haemostasis

Question 1

what is haemostasis?

Answer 1

arrest of bleeding and maintenance of vascular patency

Question 2

requirements of haemostasis?

Answer 2

permanent state of readiness
prompt response
localised response
protection against unwanted thrombosis

Question 3

components of normal haemostatic system?

Answer 3

formation of platelet plug (primary haemostasis)
formation of fibrin clot (2ndary haemostasis)
fibrinolysis
anticoagulant defences (once body recognises you’ve stopped bleeding)

Question 4

how are platelets formed?

Answer 4

in the bone marrow via budding from megakaryocytes

Question 5

where are megakaryocytes found?

Answer 5

only in the bone marrow

Question 6

do platelets have a nucleus?

Answer 6

no

Question 7

lifespan of platelets?

Answer 7

7-10 days

therefore told to stop anti-platelets a week before surgery etc

Question 8

how do platelets aggregate at site of injury?

Answer 8

endothelial damage exposes collagen and releases von Willebrand factor and other proteins to which platelets have receptors
platelet adhesion then takes place at site of injury
there is then secretion of various chemicals from the platelets which signal to other platelets and surface receptors causing aggregation of platelets at site of injury (platelet plug)

Question 9

what can cause the formation of a platelet plug?

Answer 9

vascular (lack of collagen in vessels - age, scurvy etc)
platelets (reduced number or reduced function - aspirin, NSAIDs ets)
von Willebrand factor (inherited deficiency)

Question 10

senile purpura?

Answer 10

easy bruising in elderly due to fragile vessel walls which rupture easily

Question 11

consequences of failure to form a platelet plug?

Answer 11

spontaneous bruising and purpura
mucosal bleeding
intracranial haemorrhage
retinal haemorrhages

Question 12

purpura is most visible on lower limb, why?

Answer 12

more pressure in vessels in lower limbs from walking around due to gravity

Question 13

does purpura blanche?

Answer 13

no

Question 14

presentations of mucosal bleeding?

Answer 14

epistaxis
GI
conjunctival
menorrhagia

Question 15

screening for primary haemostasis?

Answer 15

platelet count

no simple screening test for other components of primary haemostasis

Question 16

where does a fibrin clot occur?

Answer 16

on top of platelet plug

Question 17

platelets full of phospholipids which are what?

Answer 17

-ve charge

granules released from platelets are +ve so bind to -ve phospholipids

Question 18

what are the 3 parts of the sequence of fibrin clot formation?

Answer 18

initiation
propagation
amplification

Question 19

describe initiation phase of fibrin clot formation?

Answer 19

endothelial damage > Tissue factor (TF) released > Clotting factor (CF) 7 activated > activates CF 5 and 10

Question 20

describe propagation phase of fibrin clot formation?

Answer 20

activated CF5 and CF10 activates CF2 (prothrombin) to form CF2A (thrombin) > thrombin cleaves fibrinogen to form fibrin clot

Question 21

describe the amplification phase of fibrin clot formation?

Answer 21

once thrombin is generated, some feeds back and activates CF8 and 9
CF8 and CF9 activate more CF5 and CF10 which produces more thrombin therefore amplifying the system and producing a lot of fibrin from small damage

Question 22

cause of a single clotting factor deficiency?

Answer 22

usually CF 8 or 9 (lose amplification part so little thrombin formed)
= haemophilia
A = CF8
B = CF9 missing

Question 23

causes of multiple clotting factor deficiency?

Answer 23

usually acquired 
(tissue damage from trauma/ wrong blood/liver damage > lots of TF > lots of clots > lots of clot breakdown > CFs all used up)
disseminated intravascular coagulation
(CFs broken down as soon as their made so used up)

Question 24

causes of increased fibrinolysis?

Answer 24

usually part of complex coagulopathy

Question 25

fibrinolysis?

Answer 25

breakdown of fibrin to FDPs (fibrin degeneration products)

Question 26

how does fibrinolysis occur?

Answer 26

tissue plasminogen activator (tPA) converts plasminogen > plasmin
plasmin breaks down fibrin > FDPs

Question 27

how can fibrinolysis be measured?

Answer 27

measure FDPs in blood
(D-Dimer test)
- can help in diagnosis of disseminated intravascular coagulation, DVT/PE etc

Question 28

consequences of failure of fibrin clot formation?

Answer 28

no characteristic clinical syndrome
may be combined primary/secondary haemostatic failure
pattern of bleeding depends on whether single/multiple abnormalities and the clotting factors involved

Question 29

screening test for fibrin clot formation via CF 7?

Answer 29

FBC collected in citrate (contains specific amount of anticoagulant)
fill blood to the line so anticoagulant is correct
blood is spun and platelets removed (containing phospholipids)
citrate neutralised with calcium and start haemostasis in left over plasma via TF and phospholipids (thromboplastin) and time how long it takes to clot
= prothrombin time

Question 30

how are CFs 8 and 9 measured?

Answer 30

activated partial thromboplastin test

contact activator rather than thromboplastin added which activates 8 and 9 and time to clot is measured

Question 31

naturally occurring anticoagulants?

Answer 31

anti-thrombin (serine protease inhibitors?)
protein C (and its cofactor protein S)
- bind to and inactivate CF 5 and 8

Question 32

what is thrombophilia?

Answer 32

deficiency of naturally occurring anticoagulants
can be hereditary
increased tendency to develop DVT/PE