Haemostasis and thrombosis Flashcards
What is appropriate coagulation?
Haemostasis:
primary haemostasis
secondary haemostasis
What is inappropriate coagulation?
Thrombosis:
arterial
venous
What happens when you have an injury?
Vessel injury -platelet adhesion platelet aggregation -activation of coagulation cascade fibrin formation *haemostatic plug fibrinolytic activity repair of vessel damage
What occurs in primary haemostasis?
when vessel wall is injured- exposes collagen
platelets stick to the collagen via von Willebrand factors
Types of platelet bleeding disorder and treatment used
- Due to a reduced number of platelets- inherited of acquired
- Due to abnormal function- can be inherited or acquire d (antiplatelet drugs used for thrombosis etc)
- tretament= platelet transfusion
What is Von Willebrand disease and what are its symptoms?
VWFs are missing- a common bleeding disorder
autosomal dominant
3 subtypes
milder bleeding than in haemophilia
main symptom= heavy periods
also:
bruising, cuts, gum bleeding, nose bleeds, post operative bleeding
How do you treat Von Willebrand disease?
- Intermediate purity factor 8 (plasma derived)
2. Desmopressin- makes the body release VWF from endothelial cells
Examples of coagulation factor disorders
Haemophilia a= factor 8 deficiency
Haemophilia b= factor 9 deficiency
-others- deficiency of fibrinogen, factor 2,5,7,10
*just giving plasma isnt ideal- need a more precise treatment
What are the symptoms of heamophilia?
clinical features of a & b is the same
sites of bleeding: joints, muscles, post trauma, postoperative
bleed into joint= hemarthrosis- lots of bleeds- erodes cartilage- bone on bone
How do we make clotting factor concentrates?
Plasma derived
Made using recombinant technology
-not enough demand to make all the clotting factors via recombinant technology (factor 5 etc.)
What are the treatments for primary haemostasis?
Platelet transfusion
demsopressin
VWF concentrate
What are the treatments for secondary haemostasis?
Specific clotting factors
What are the 2 types of thrombosis and what are their characteristics? What are their clinical presentations?
Arterial -high-pressure system -platelet rich myocardial infarction, thrombotic stroke Venous -low pressure -fibrin rich- problem on coagulation cascade DVT, pulmonary embolism
How are the 2 types of thrombosis treated?
Arterial- antiplatelet drugs
Venous- anticoagulant drugs
Examples of antiplatelet drugs
used to be: aspirin and clopidogrel
prasugrel, ticagrelor, cangrelor
What are the 3 types of anticoagulant drugs, examples of each type
Intravenous- unfractionated heparin
subcutaneous- low MW heparin
oral- warfarin
direct oral anticoagulants- dabigatran, rivaroxaban, apixaban, edoxaban
How does heparin work?
Binds to and activates antithrombin-
inhibits the coagulation cascade more efficiently
How is glycosaminoglycan antithrombotic?
Indirectly inhibits thrombin
effects anti thrombin
monitored with APTT test
given by continuous infusion
What is low molecular weight heparin, when is it used?
Smaller molecule made from heparin- easier for body to take
given subcutaneously
renally excreted
weight based
given once daily
-can be used as a treatment or in preventing thrombosis
-in hospital, over 45 years old, thrombosis risk high enough= put on this drug
What the pharmacology of warfarin?
Completely and rapidly absorbed inhibits vitamin K dependent clotting factors slow on and off action warfarin inhibits factors: 2,7,9 and 10 side fx: bleeding and embryopathy
How is warfarin monitored?
test used to monitor the effect of warfarin= international normalized ration
dose based on INR
frequency of monitoring depends on INR
blood test every week/ 8 weeks for rest of life
NO single dose for every person= personalised medicine
dose you need is genetically controlled
What is the cyclin involving s-warfarin, VKOR and GGCX?
Hypofunctional factors need to be carboxylated by the enzyme GGCX
GGCX requires vitamin k- when vitamin k is activated it is oxidized
VKOR recycles reduced vitamin K
S-warfarin inhibits VKOR- GGCX doesn’t work- clothing factors remain hypofunctional
CYP2C9 breaks down warfarin
Which 3 enzymes control your warfarin dose?
VKOR
GGCX
CYP2C9
How do people differ in warfarin digestion?
Some people break down warfarin rapidly, others dont
if we could identify the polymorphisms in the enzymes-
could work out the dose youd need
