Haemostasis Flashcards
principles of haemostasis
normal number and function of platelets
functional coagulation cascade
normal vascular endothelium
what are the 3 stages of formation of a platelet rich thrombus
platelet adhesion
platelet activation/secretion
platelet aggregation
what converts fibrinogen to fibrin
thrombin
what stabilises the platelet thrombus
polymerisation of fibrin
what do platelet and vessel wall defects give rise to
prolonged bleeding time
causes of thrombocytopenia
bone marrow failure
peripheral consumption
causes of abnormal platelet function
most commonly drugs - aspirin, clopidogrel
renal failure - uraemia causes platelet dysfunction
causes of abnormal vessel walls
scurvy
ehlers danlos syndrome
henoch schonlein purpura
hereditary haemorrhagic telangiectasia
causes of abnormal interaction between platelets and vessel wall
von willebrand disease
drugs inhibiting platelet function
aspirin and COX inhibitors
reversible COX inhibitors - e.g. NSAIDs
dipyridamole
thienopyridines
integrin GP2b/3a receptor antagonists
coagulation pathways - intrinsic pathway
12 > 12a
11> 11a
9 > 9a, 8a
coagulation pathways - extrinsic pathway
10 > 10a, 5a
coagulation pathways - common pathway
2 > 2a
fibrinogen > fibrin
factor 12 deficiency
dont bleed
factor 7 deficiency
bleed abnormally
factor 8 and 9 deficiency
severe haemorrhagic diathesis despite normal extrinsic coagulation pathway
factor 11 deficiency
variable and mild bleeding diathesis
overlapping steps leading to coagulation
initiation
amplification
propagation
termination
what prevents over activity of coagulation cascade
natural inhibitors
what does tissue factor pathway inhibitor inhibit
TF-7a complex/f10a inhibited by TFPI
what does antithrombin inhibit
thrombin and f10a activity
what does protein c pathway inhibit
f5a and f8a
prothrombin time
measured in seconds
reflects extrinsic pathway and common pathway
activated partial thromboplastin time
measured in seconds
reflects intrinsic pathway and common pathway
fibrinogen lab measurement
measured in grams/L
reflects functional activity of fibrinogen protein
f12 defect inheritance
autosomal
f11 defect inheritance
autosomal
f9 defect - haemophilia B inheritance
x-linked recessive
f8 defect - haemophilia A inheritance
x-linked recessive
von willebrand disease inheritance
autosomal dominant
f7 defect inheritance
autosomal recessive
f10, 5, 2, 1 and 13 defect inheritance
autosomal recessive
haemophilia A
x linked recessive - typically expressed in males and carried in females
deficiency/dysfunction of f8
traditional management of haemophilia
supportive measures - ice, immobilisation, rest
replacement of missing clotting protein
antifibrinolytic agents
congenital haemophilia
haemarthroses
muscle bleeds
soft tissue bleeds
acquired haemophilia
large haematomas
gross haematuria
retropharyngeal and retroperitoneal haematomas
cerebral haemorrhages
compartment syndromes
roles of von willebrand factor
promote platelet adhesion to subendothelium at high shear rates
carrier molecule for f8
von willebrand disease
mainly autosomal dominant inheritance
men and women affected
associated with defective primary haemostasis
variable reduction in f8 levels - mucocutaneous bleeding including menorrhagia, post-op/post partum bleeding
von willebrand management
antifibrinolytics
DDAVP
factor concentrates containing vWf
contraceptive pill for menorrhagia
acquired coagulation disorders
underproduction of coagulation factors - liver failure, vit K deficiency
anticoagulants - warfarin, direct oral anticoagulants
immune - acquired haemophilia, acquired VWD
consumption of coagulation factors
effect of liver disease of haemostasis
reduced hepatic synthesis of clotting factors
thrombycytopaenia secondary to hypersplenism
reduced vit K absorption due to cholestatic jaundice causing deficiencies of f2, 7, 9 and 10 - warfirin
treated with plasma products and platelets to cover procedures, and vit K
disseminated intravascular coagulation (DIC)
acquired syndrome - systemic intravascular activation of coagulation - thrombin explosion
widespread deposition of fibrin in circulation
tissue ischaemia and multi-organ failure
consumption of platelets and coagulation factors to generate thrombin - may induce severe bleeding
excess plasmin generated to maintain vascular patency, leads to fibrinogenolysis
DIC coagulation parameters
prolonged prothrombin time
prolonged activated partial thromboplastin time
low fibrinogen
raised d-dimers - marker of increased fibrinolysis
