Haemostasis Physiology

Question 1

what is haemostasis?

Answer 1

arrest of bleeding and maintenance of vascular patency

Question 2

what is primary haemostasis?

Answer 2

formation of the platelet plug (in severe bleeding can be washed away)

Question 3

what is secondary haemostasis?

Answer 3

formation of the fibrin clot

Question 4

what is fibrinolysis

Answer 4

maintaining vascular patency and switching haemostasis off

Question 5

what are platelets?

Answer 5

small anucleate discs with a lifespan of 7-10 days

Question 6

what does endothelial wall damage cause?

Answer 6

exposes collagen and releases VWF

Question 7

what does VWF do?

Answer 7

platelets have receptors to VWF leading to platelet adhesion at the site of the injury
also carries factor VIII

Question 8

what do the bound platelets secrete?

Answer 8

ADP

thromboxane A2

Question 9

what does the secretion of ADP and thromboxane A2 from the platelets cause?

Answer 9

further aggregation

Question 10

what do platelets bind to at the site of injury?

Answer 10

subendothelial collagen via:

• VWF
• glycoprotein 1b

Question 11

what allows platelets to attach to one and other?

Answer 11

GPIIbIIIa

fibrinogen

Question 12

causes of failure of formation of the platelet plug

Answer 12

vascular
thrombocytopenia
VWF deficiency

Question 13

what are vascular causes of failure of formation of the platelet plug?

Answer 13

lack of collagen leads to weakened endothelial walls e.g. ageing and scurvy

Question 14

three causes of thrombocytopenia

Answer 14

1. reduced production
2. increased destruction
3. functional defects

Question 15

what causes reduced production thrombocytopenia?

Answer 15

bone marrow failure

Question 16

what causes increased destruction thrombocytopenia?

Answer 16

coagulopathy (DIC)
AI (ITP)
hypersplenism

Question 17

how does alcohol cause hypersplenism and thrombocytopenia?

Answer 17

alcohol causes portal hypertension and cirrhosis backs up to the spleen causing hypersplenism that traps platelets reducing count
alcohol can also have a toxic effect on the spleen

Question 18

functional defects causes of thrombocytopenia

Answer 18

drugs (aspirin, NSAIDs)

renal failure

Question 19

inheritance of VWF deficiency

Answer 19

AD

Question 20

presentation of failure of primary haemostasis

Answer 20

easy bruising/ purpura/ petechiae
mucosal bleeding (epistaxis, conjunctival haemorrhage)
menorrhagia

Question 21

diagnosis of failure of primary haemostasis

Answer 21

FBC for platelet count

Question 22

causes of failure of formation of the fibrin clot

Answer 22

single clotting factor deficiency
multiple clotting factor deficiencies
increased fibrinolysis

Question 23

what is a single clotting factor deficiency?

Answer 23

haemophilia

Question 24

causes of multiple clotting factor deficiencies

Answer 24

DIC
liver failure
vitamin K deficiency/ warfarin therapy

Question 25

presentation of failure of secondary haemostasis

Answer 25

bleeding into muscles and joints (ankles and knees)

Question 26

diagnosis of failure of secondary haemostasis

Answer 26

PT (TF/VIIa) | APTT (VIII/IXa)

Question 27

where are all coagulation factors synthesised?

Answer 27

hepatocytes

Question 28

which coagulation factors are carboxylated by vitamin K?

Answer 28

II VII IX X

Question 29

what does the addition of vitamin K to coagulation factors II, VII, IX and X cause?

Answer 29

gives them a negative charge to bind to Ca2+ on phospholipids

Question 30

what does vitamin K require for absorption?

Answer 30

bile salts

Question 31

causes of vitamin K deficiency?

Answer 31

``` poor dietary intake malabsorption obstructive jaundice head of pancreas cancer lack of bile salts vitamin K antagonists e.g. warfarin HDFN ```

Question 32

what are some naturally occurring anticoagulants?

Answer 32

serine protease inhibitors (anti-thrombin) protein C protein S

Question 33

what is thrombophilia?

Answer 33

deficiency of naturally occurring anticoagulants leading to an increased tendency to develop venous thrombosis

Question 34

action of anti-thrombin

Answer 34

binds to thrombin to switch haemostasis off

Question 35

action of protein S and C

Answer 35

bound by thrombomodulin which switches off clotting factors V/Xa and VIII/IXa

Question 36

two pathways in the coagulation cascade

Answer 36

1. extrinsic | 2. intrinsic

Question 37

what is the extrinsic pathway of the coagulation cascade?

Answer 37

TF and VIIa initiates haemostasis act on Va/Xa which act on prothrombin (factor II) of the common pathway this is cleaved to form thrombin (IIa) acts on fibrinogen (factor I) > fibrin (Ia)

Question 38

what is the intrinsic pathway of the coagulation cascade?

Answer 38

activated by IIa (thrombin) are VIIIa/IXa | these are also activated by XI and XII

Question 39

which pathway does PT measure?

Answer 39

extrinsic / factor VII

Question 40

how is the PT carried out

Answer 40

thromboplastin is added to the blood sample and timed how long it takes to clot

Question 41

normal PT

Answer 41

10-12 seconds

Question 42

what pathway does APTT measure?

Answer 42

intrinsic/ factor VIII IX

Question 43

how is the APTT test carried out?

Answer 43

a contact activator with calcium and phospholipid is added to blood and timed how long it takes to clot

Question 44

normal APTT

Answer 44

30-40 seconds

Question 45

what does a prolonged APTT indicate?

Answer 45

single clotting factor deficiency

Question 46

causes of a single clotting factor deficiency

Answer 46

``` haemophilia A or B (X-linked) XI or XII deficiency heparin VWF deficiency APLS ```

Question 47

how VWF deficiency prolong APTT?

Answer 47

VWF carries VIII so if deficient can prolong APTT

Question 48

what does a prolonged PT and APTT indicate?

Answer 48

multiple clotting factor deficiency

Question 49

causes of multiple clotting factor deficiency

Answer 49

``` heparin warfarin vitamin K deficiency liver disease DIC ```

Question 50

what is tested to distinguish DIC from liver disease?

Answer 50

D-dimers