haemostasis + thrombophilia Flashcards
decreased haptoglobin can indicate
intravascular haemolysis
haemostasis
arrest of bleeding + maintenance of vascular patency
components of normal haemostatic system
- formation of platelet plug - primary haemostasis
- formation of fibrin clot - secondary
- fibrinolysis
- anticoagulant defences
formation of platelet plug
damage to blood vessel exposes collagen, von willebrand factor binds to collagen acting as an anchor for platelets to join
- platelets adhere via vWF - they activate + degranulate, shape changes + release chemicals that keeps vessel constricted + draw more platelets in
following formation of platelet plug, coagulation is activated to form a fibrin mesh which stabilises the platelet plug (secodary haemostasis)
causes of failure of platelet plug
vascular
platelets - reduced (thrombocytopenia), reduced function
von willebrand factor
consequences of failure of platelet plug
easy brusing, purpura
epistaxis, GI, conjuctival
menorrhagia
intracranial haemorrhages
retinal haemorrhages
screening tests for primary haemostasis
platelet count
causes of failed fibrin clot formation
single clotting factor deficiency - usally hereditary (haemophilia)
multiple clotting factor deficiencies - usually acquired (DIC)
increased fibrinolysis - usually part of complex coagulopathy
naturally occuring anticoagulants
- serine protease inhibitors
- protein C + protein S - switch off factor 5 + factor 8
thrombophilia
where there is increased risk of vvenous thrombosis due to dysregulation of coagulation system
can be hereditary or acquired
causes of hereditary thrombophilias
Factor V Leiden = commonest
prothrombin 20210 mutation
antithrombin deficiency
protein C / S deficiency (normally inactivates V+VIII, south east asian population)
when should hereditary thrombophilia screening be considered?
venous thrombosis <45y/o
recurrent venous thrombosis
unusual benous thrombosis
fam history of venous thrombosis
fam history of thrombophilia
factor V leiden (activated protein C resistence)
commonest inherited thrombophilia
autosomal dominant (but incomplete penetrance - not all with mutation are affected)
missense mutation where activated factor V is inactivated 10 times more slowly by activated protein C than normal (becomes resistanct to inactivation by protein C)
heterozygotes - 4-5 risk of VTW
homo - 10 fold risk
causes of acquired thrombophilias
antiphospholipid syndrome
drugs - COCP
antiphopholipid syndrome
acquired disorder with predisposition to venous + arterial thromboses, recurrent fetal loss + thrombocytopenia
can be primary or secondary to SLE
antiphospholipid investigations
anticardiolipin antibodies, anti-beta2-GPI antibodies or positive lupus anticoagulant assay
thromobocytopenia
prolonged aPPT
features of antiphospholipid syndrome
venous/arterial thromboses
recurrent fetal loss
livedo reticularis - lace appearance of skin
thrombocytopenia
preeclmapsia, pulmonary hypertension
management of antiphospholipid syndrome
low dose aspirin
warfarin INR 2-3 - teratogenic
pregnancy - LMWH + aspirin
antiphospholipid pathophysio
antibodies lead to a conformational change in beta2 glycoprotein 1 (unknown function in health) which leads to activation of both primary + secondary haemostasis + vessel wall abnormalities
causes of thrombocytopenia
reduced production (marrow problem)
- sepsis
- b12 or folic acid def
- liver failure - reduced thrombopoietin in liver
- leukaemia
- myelodysplastic syndrome
increased destruction
- coagulopathy -> DIC
- autoimmune -> ITP
- hypersplenism
platelet functional defects
- drugs - aspirin, NSAIDs
- renal failure
Von Willebrands disease
commonest inherited bleeding disorder
autosomal dominant, variable severity
behaves like platelet disorder - epistaxis+menorrhagia common, haemoarthroses rare
role of von Willebrand factor
large glycoprotein synthesised by megakaryocytes + vascular endothelial cells
exists as multimers
promotes platelet adhesion to damaged endothelium
carrier moleucule for factor VIII - stabilises it
features of von willebrands disease
excess/prolonged bleeding from minor wounds/post-op
easy bruising
menorrhagia
epistaxis
GI bleeding
(in contrast to haemophilia A or B, bleeding into joints or muscles is uncommon)
von willebrand disease investigations
prolonged bleeding time
aPPT prolonged
factor VIII actively reduced -> PT time normal
(defective platelet aggregation with ristocetin)
management of von willebrands disease
trnaexamic acid for mild bleeding
desmopressin - raises levels of vWF by inducing release of vWF from Weibel-palde bodies
factor VIII concentrate
commonest cause of primary haemostatic failure
thrombocytopenia
- usually acquired - hypersplenism, ITP, marrow failure
causes of failed fibrin clot
multiple clotting factor deficiencies
- generally acquired -> DIC, liver failure, vit K def/warfarin therapy
single clotting factor def
- generally hereditary -> haemophilia
coagulation factor synthesis
all coagulation factors are syntesised in hepatocytes - reduced in liver function
factors II, VII, IX + X are carboxylated by vit K which is essential for function
which factors are carboxylated by vit K ?
II, VII, IX + X
vit K absorption
absorbed upper/small intestine
*requires bile salts for absorption
causes of vit K deficiency
poor dietary intake, malabsorption
obstructive jaundic - lack of bile acids
vit K antagonist - warfarin
haemorrhagic disease of newborn
vit K deficiency
common for newborns - esp if exclusively breast fed
feature = easy bruising, internal bleeding if bad
complication = haemorrhagic disease of newborn
