haemostasis Flashcards
what is haemostasis?
the arrest of bleeding and maintenance of vascular patency
what are the 4 stages?
platelet plug formation (primary)
fibrin clot formation (secondary)
fibrinolysis
anticoagulant defences
what is primary haemostasis?
platelet plug formation
damage to endothelium = collagen + VWF -> platelet adhesion at site of injury
secretion of various chemicals -> platelet aggregation at site of injury
what is secondary haemostasis?
formation of fibrin clot
platelets are negatively charged
platelets release calcium when activated (positive charge)
blood clotting factors (negatively charged) are attracted to sit on phospholipid surface sue to positive calcium
what is fibrinolysis?
fibrin clot broken down by plasmin
what are the anticoagulant defences?
anti-thrombin, protein C and protein S
what factors are involved in the intrinsic pathway?
8, 9, 11, 12
what does the intrinsic pathway increase?
activated partial thromboplastin time (APTT)
what clotting factors are involved in extrinsic pathway?
7 (activated)
what increases in the extrinsic pathway?
partial thrombin time (PTT)
what factors are involved in the common pathway?
5, 10, 2, 1
what is increased in the common pathway?
APTT and PTT
what factors are affected by heparin?
2, 9, 10, 11
what clotting factors are affected by warfarin?
2, 7, 9, 10 (1972)
what clotting factors are affected in DIC?
1, 2, 5, 8, 11
what factors are affected in liver disease?
1, 2, 5, 7, 9, 10, 11
what factor is affected in von willebrands?
8
what does VWF increase?
APTT
what is increased in haemophilia?
APTT
what is increases in von willebrands?
APTT and bleeding time
what is increased in vitamin K deficiency?
APTT and PTT
what type of drug is heparin?
anticoagulant
what is unfractionated heparin MOA?
antithrombin agonist leading to inhibition of factor 2a and 10a
when in UFH used over LMWH and why?
in patients with higher risk of bleeding or renal impairment
due to shorter half-life
what are some examples of low molecular weight heparin?
dalteparin, enoxaparin
what is LMWH MOA?
targets factor 10a and inhibits it -> stops formation of thrombin and prevents conversion of fibrinogen to fibrin = stops clotting process
what is warfarin MOA?
vitamin K antagonist - inhibits synthesis of vitamin K dependent clotting factors (1972) as well as protein C and protein S
what type of medication is warfarin?
anticoagulant
when is warfarin indicated?
mechanical heart valves
a fib
recurrent VTE or not suitable for DOAC
what needs monitored in patients on warfarin?
INR - international normalised ratio
what is target INR for patients with conditions such as VTE, AF and MI?
2.5
what is warfarin metabolised by?
CYP450 enzymes
what is an example of a CYP450 inducer and what does it do?
carbamazepine, primidone
reduce efficacy of warfarin
what is an example of a CYP450 inhibitor and what does it do?
macrolides and metronidazole
increase INR levels
what drugs does warfarin interact with and what is the risk?
NSAIDS and SSRIs
inc risk of bleeding
how does a patient with a primary haemostatic disorder usually present?
menorrhagia, easy bruising, mucosal blood loss (epistaxis - nosebleeds), retinal haemorrhages
what are the causes of primary haemostatic disorders?
vascular - elderly, CTD, vit C deficiency, vasculitis
thrombocytopenia
- dec production = marrow failure
- inc production = DIC, autoimmune ITP, liver failure
VWF deficiency
what are secondary haemostatic disorders due to?
clotting factor deficiencies
