haemostasis + thrombophilia

Question 1

decreased haptoglobin can indicate

Answer 1

intravascular haemolysis

Question 2

haemostasis

Answer 2

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

Question 3

formation of platelet plug

Answer 3

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)

Question 4

causes of failure of platelet plug

Answer 4

vascular
platelets - reduced (thrombocytopenia), reduced function

von willebrand factor

Question 5

consequences of failure of platelet plug

Answer 5

easy brusing, purpura
epistaxis, GI, conjuctival
menorrhagia
intracranial haemorrhages
retinal haemorrhages

Question 6

screening tests for primary haemostasis

Answer 6

platelet count

Question 7

causes of failed fibrin clot formation

Answer 7

single clotting factor deficiency - usally hereditary (haemophilia)

multiple clotting factor deficiencies - usually acquired (DIC)

increased fibrinolysis - usually part of complex coagulopathy

Question 8

naturally occuring anticoagulants

Answer 8

1. serine protease inhibitors
2. protein C + protein S - switch off factor 5 + factor 8

Question 9

thrombophilia

Answer 9

where there is increased risk of vvenous thrombosis due to dysregulation of coagulation system

can be hereditary or acquired

Question 10

causes of hereditary thrombophilias

Answer 10

Factor V Leiden = commonest
prothrombin 20210 mutation
antithrombin deficiency

protein C / S deficiency (normally inactivates V+VIII, south east asian population)

Question 11

when should hereditary thrombophilia screening be considered?

Answer 11

venous thrombosis <45y/o
recurrent venous thrombosis
unusual benous thrombosis
fam history of venous thrombosis
fam history of thrombophilia

Question 12

factor V leiden (activated protein C resistence)

Answer 12

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

Question 13

causes of acquired thrombophilias

Answer 13

antiphospholipid syndrome
drugs - COCP

Question 14

antiphopholipid syndrome

Answer 14

acquired disorder with predisposition to venous + arterial thromboses, recurrent fetal loss + thrombocytopenia
can be primary or secondary to SLE

Question 15

antiphospholipid investigations

Answer 15

anticardiolipin antibodies, anti-beta2-GPI antibodies or positive lupus anticoagulant assay

thromobocytopenia
prolonged aPPT

Question 16

features of antiphospholipid syndrome

Answer 16

venous/arterial thromboses
recurrent fetal loss
livedo reticularis - lace appearance of skin
thrombocytopenia
preeclmapsia, pulmonary hypertension

Question 17

management of antiphospholipid syndrome

Answer 17

low dose aspirin
warfarin INR 2-3 - teratogenic

pregnancy - LMWH + aspirin

Question 18

antiphospholipid pathophysio

Answer 18

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

Question 19

causes of thrombocytopenia

Answer 19

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

Question 20

Von Willebrands disease

Answer 20

commonest inherited bleeding disorder
autosomal dominant, variable severity

behaves like platelet disorder - epistaxis+menorrhagia common, haemoarthroses rare

Question 21

role of von Willebrand factor

Answer 21

large glycoprotein synthesised by megakaryocytes + vascular endothelial cells
exists as multimers
promotes platelet adhesion to damaged endothelium

carrier moleucule for factor VIII - stabilises it

Question 22

features of von willebrands disease

Answer 22

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)

Question 23

von willebrand disease investigations

Answer 23

prolonged bleeding time
aPPT prolonged
factor VIII actively reduced -> PT time normal

(defective platelet aggregation with ristocetin)

Question 24

management of von willebrands disease

Answer 24

trnaexamic acid for mild bleeding
desmopressin - raises levels of vWF by inducing release of vWF from Weibel-palde bodies

factor VIII concentrate

Question 25

commonest cause of primary haemostatic failure

Answer 25

thrombocytopenia
- usually acquired - hypersplenism, ITP, marrow failure

Question 26

causes of failed fibrin clot

Answer 26

multiple clotting factor deficiencies
- generally acquired -> DIC, liver failure, vit K def/warfarin therapy

single clotting factor def
- generally hereditary -> haemophilia

Question 27

coagulation factor synthesis

Answer 27

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

Question 28

which factors are carboxylated by vit K ?

Answer 28

II, VII, IX + X

Question 29

vit K absorption

Answer 29

absorbed upper/small intestine

*requires bile salts for absorption

Question 30

causes of vit K deficiency

Answer 30

poor dietary intake, malabsorption
obstructive jaundic - lack of bile acids
vit K antagonist - warfarin
haemorrhagic disease of newborn

Question 31

vit K deficiency

Answer 31

common for newborns - esp if exclusively breast fed
feature = easy bruising, internal bleeding if bad

complication = haemorrhagic disease of newborn