haemostasis

Question 1

what is haemostasis

Answer 1

consequence of a tightly regulated process
- maintains fluid status in normal vessels whilst permitting rapid formation of haemostatic clot at a site of vascular injury

Question 2

basic principles of haemostasis

Answer 2

1) contraction of vessel wall
2) formation of platelet plug at site
3) formation of fibrillation clot to stabilise

Question 3

what happens when a vessel is injured

Answer 3

1) adhesion- following damage to vessel and exposure of underlying tissue, platelet adheres to collagen via von willebrand factor (vWF receptor)
2) platelets secrete granules containing substances(e.g ADP &thromboxane) to come activated and activate other platelets. platelets themselves have some coagulation factors
3) cross linking of platelets to form platelet plug. provides stability but friable.

Question 4

What are the mediating factors of haemostasis

Answer 4

platelet receptors 
Von Willebrand factor 
fibrinogen- links platelets 
collagen-binds platelets
ADP & thromboxane- cause interaction of platelets to make plug
thrombin- converts fibrinogen to fibrin

Question 5

what are the coagulation factors

Answer 5

fibrinogen
prothrombin
factor 5, 7, 8,9,10,11,12,13
tissue factor- exposed on blood vessels

Question 6

what are some natural anticoagulants

Answer 6

protein c
protein s
antithrombin
tissue factor pathway inhibitor

Question 7

tests for clotting defects (just name them )

Answer 7

activated partial thromboplastin time (APTT)
prothrombin time (PT)
thrombin clotting time

Question 8

what does APTT measure and what does it mean if its prolonged

Answer 8

measures intrinsic pathway

if prolonged suggests a deficiency in one of :factors 8(haemophilia A), 9(haemophilia B),11,12

Question 9

what does PT measure and what does it mean if its prolonged

Answer 9

extrinsic pathway
most commonly due to factor 7
defeicney in factor 5, 10, thrombin and fibrinogen can prolong both PT and APTT

Question 10

what does thrombin clotting time measure

Answer 10

measures conversion of fibrinogen to fibrin via the action of thrombin

Question 11

what initiates activation of clotting factors

Answer 11

exposure of collagen and tissue factor

Question 12

how protein C is a natural anticoagulant

Answer 12

thrombin binds to an endothelial cell receptor called thrombomodulin which activate protein C. this then inactivates factors 8a and 5a.
protein S is a cofactor for activated protein C

Question 13

how is antithrombin iii a natural anticoagulant

Answer 13

its a plasma protein that inactivates thrombin and several other clotting factors
its activated by heparin on the surface of endothelial cells.
the inactivated coating factors are carried away by the flowing blood

Question 14

what doe tissue factor pathway inhibitor do

Answer 14

• acts in the initiation phase of clotting
• secreted mainly by endothelial cells
• binds two tissue factor-factor 7a complexes and inhibits the ability of these complexes to generate factor 10a

Question 15

how does fibrinolysis occur

Answer 15

plasminogen produced in liver and taken in circulation to site.
plasminogen activator activates it to make plasmin which degrades the clot

Question 16

what’s thrombocytopenia and how does it present

Answer 16

def in platelets resulting in bleeding into the tissues , bruising and slow blood clotting after injury. 
presents with purpura, petechiae, mucosal bleeding , epistaxis, menorrhagia

Question 17

what is immune thrombocytopenia purpura

Answer 17

immune increased consumption of platelets

isolated low platelet count with a normal BM in the absence of other causes of low platelets

Question 18

what is thrombotic thrombocytopenia purpura

Answer 18

immune increased consumption of platelets
bloods clots form in small vessel throughout the body resulting in consumption of platelets and RBC due to their breakdown

Question 19

what is haemolytic-uraemic syndrome and symptoms

Answer 19

non immune increase in platelet consumption
low RBCs, plackets and acuter kidney injury
bloody diarrhoea , fever, vomitting and weakness, kidney failure and low platelets
more common in children

Question 20

what is hypersplenism

Answer 20

non immune increase in platelet consumption
enlargement in spleen
reduction in number of circulating cells
compensatory proliferative response in the BM

Question 21

what can happen to patients with haemophilia

Answer 21

muscle haematomas- bleed into muscles
recurrent haemarthroses- bleed into joints
join pain and deformity
prolonged bleeding posts dental extraction
intracerebral haemorrhage

Question 22

what causes haemophilia A and how will APTT and PT look, how is it treated

Answer 22

congenital lack of factor 8
x linked recessive- males only
prolonged APTT and normal PT because PT measures extrinsic pathway and factor 8 is part of intrinsic pathway
treated with recombinant factor 8 or DDAVP

Question 23

what causes haemophilia B , how does APTT and PT look and how is it treated

Answer 23

congenital reduction in factor 9
x linked recessive -males only
prolonged APTT and normal PT
treat with infusions of recombinant factor 9

Question 24

what is von willebrand’s disease

Answer 24

normally vWF carries factor 8 and mediates platelet adhesion to the endothelium but for patients with the disease there is abnormal platelet adhesion to vessel wall and reduced factor 8 amount/activity.
can cause spontaneous bleeding from mucous membranes, excessive bleeding from wounds e.g dental
menorrhagia
prolonged bleeding time in the presence of normal platelet count.

Question 25

what is disseminated intravascular coagulopathy (DIC)

Answer 25

type of microangiopathic haemolytic anaemia
-pathological activation of coagulation forming numerous micro thrombi in circulation leading to the consumption of clotting factors and platelets and a haemolytic anaemia.
failure of haemostasis can cause haemorrhage.
raised APTT and PT

Question 26

what causes DIC

Answer 26

must always be a trigger like:
malignancy 
massive tissue injury-burns 
infection 
massive haemorrhage and transfusion

Question 27

name some anticoagulants and how od they work

Answer 27

vitamin k inhibitors(warfarin)-affect vitamin k dependent factors such as 2,7, 9,10, protein c & s
direct oral anticoagulants (dabigatran, rivaroxaban, apixaban)-inhibit thrombin /factor 10a
low molecular weight heparins - potentiates action of anti-thrombin
heparin

Question 28

name some antiplatelet drugs

Answer 28

inhibit platelet aggregation and clot formation
aspirin - block formation of thromboxane A2 in platelets
clopidogrel/ticagrelor - block platelet ADP