Haematology 3

Question 0

Clotting as a dynamic process

Answer 0

Normal blood doesn’t clot-> intersection of prothrombin and anitcoagulant factors within blood and epithelium
Thrombosis occurs when balance is tipped towards clotting
Abnormal bleeding occurs when balance is tipped away from clotting

Question 1

Virchows triad

Answer 1

Reduction in blood flow
Disturbance of blood vessels
Disturbance of blood properties

Question 2

Different sorts of clot

Answer 2

Arterial-> platelet based-> inhibited using aspirin

Venous-> fibrinogen based-> inhibited using warfarin

Question 3

Coagulation cascade requires

Answer 3

An initiating protease
Lipoprotein surface-> platlets
Calcium
Fresh supply of zymogen proteins

Question 4

Prothrombin time test

Answer 4

Usually 9-12 secs
Measures activity of extrinsic pathway-> thrombin burst
Use to monitor effects of warfarin
Vitamin K-> essential factor to a hepatic gamma-glutamyl carboxylate that adds a carboxyl group to gluts mic acids residues on factors II,VII,IX and X and protein S,C and Z
Vit K deficiency-> increased prothrombin time
Pathologically prolonged in liver disease, DIC

Question 5

Activated partial thromboplastin time

Answer 5

Usually 22-32 secs
Measures activity of intrinsic pathway
Asses effect of infact ironed heparin, hirudin
Kaolin clotting time is an altnative
Pathologically prolonged-> haemophlla A and B, von willebrands, lupus anticoagulant liver disease, DIC

Question 6

Thrombin time

Answer 6

Usually 13-20 secs
Measures final common pathway
Prolonged by any heparin
Pathologically prolonged-> liver disease, dysfibrinogenaemia, DIC

Question 7

Mixing studies

Answer 7

Prolonged PT/INR or APTT
Factor deficiency or factor inhibitor?
Mix patient serum and normal serum 50:50
Factor deficiency will be corrected
Factor inhibitor still present 
Variations can then identify factors effected and strength of inhibitor

Question 8

Fibrinogen, plasmin and D-dimmers

Answer 8

Fibrinogen= clotting factor 1
Converted to fibrin in final step
FXIII than cross links fibrin
Plasmin is activated wherever clotting occurs-> breaks down fibrin in to degradation products-> D dimer fragment

Question 9

Using D-dimers

Answer 9

Can be used to exclude thrombosis
Normally thrombosis, infection, inflammation, cancer, pregnancy
Don’t do it on any one who looks ill!

Question 10

Cell based model of haemostatsis

Answer 10

Alternative explanation of clotting-> very complicate

Clotting cascade is useful model for relating to blood tests

Question 11

Template bleeding time

Answer 11

All other tests are test tube tests
Bleeding time measures coagulation in vivo
Venous pressure increased to 40mmHg using a cuff
Template razor cuts two 5 mm cuts in skin
Excess blood is removed with filter paper
Time to stop bleeding is measured
Normal 2-8 mins

Question 12

Causes of abnormal bleeding

Answer 12

Dysfunctional clotting factors 
Insufficient clotting factors
Abnormal biochemical environment 
Dysfunctional platelets 
Insufficient platelets
Dysfunctional vascular endothelium
Dysfunctional vessel constriction

Question 13

Haemophilia A and B

Answer 13

Haem A-> reduced clotting factors 8
Haem B-> reduced clotting factor 9
Both X chromosome
Varied severity depending on factor levels
Serve less than 1%

Question 14

Haemophilia presentation

Answer 14

Boys
Joint bleeding as baby starts to walk
Prolonged APTT
Treat with factor replacement

Question 15

Disseminated intravascular coagulation

Answer 15

Microscopic clots form in the circulation
May be triggered by infection, malignancy, pregnancy complications, massive bleeding
When platelets and clotting factors run out-> massive bleeding
Identify cause and remove it
Use platelet and plasma transfusion

Question 16

Transfusion coagulopathy

Answer 16

Occurs under situations of massive transfusion
Platelets and clotting factors depleted and diluted
-> acidotic and hypothermic-> clotting factors no longer work

Question 17

Dysfunctional platelets

Answer 17

Most commonly due to drug use-> aspirin, clopidogrel, abciximab
Secondary to liver disease
Rarely congenital
Predispose to bleeding form mucosal surfaces
Remove cause

Question 18

Low platelets

Answer 18

Liver disease
Sometimes marrow failure
Rarely immune thrombocytopenia purpura
Mucosal bleeding
Treat with platelet transfusions and procoagulant drugs

Question 19

Vascular bleeding problems

Answer 19

Scury-> collagen dysfunction due to vit C deficiency
Bleeding mucosa, skin petechiael bleeding, curly hairs
Ehlers-danlos and other congenital collagen disordered
Surgery!

Question 20

Risk factors for arterial clots

Answer 20

Risk factors for Atheroma
Age
Hypertension
Diabetes
Smoking
High cholesterol
Personal history of stroke/heart attack
Family history of stroke/heart attack 
Additional risks when blood becomes more prone to coagulation-> infection, inflammation, cancer

Question 21

Managing arterial clots

Answer 21

Thrombolysis:
Acute clot
Within hours of onset
tPA activates plasmin to accelerate clot decay
Heparin used after for short term prevention
Prevention:
Platelet inhibition-> aspirin etc
Reduce Atheroma-> stains to lower cholesterol! treat diabetes, BP, smoking

Question 22

Risk factors for venous clots

Answer 22

Causes of venous stasis:
Increasing ages
Immobility
Surgery, casts
Hospitalisation, long plane flights
Pregnancy
Causes of increase coagulation:
Cancers inflammation, infection 
Pregnancy 
History of DVT or PE

Question 23

Managing venous clots

Answer 23

Prevention:
Keep patients mobile
Elastic stockings to maintain venous return
Prophylactic heparin to reduce active clotting
Treatment:
Immediately using high does heparin
Medium term, warfarin (vit K antagonist)

Question 24

Inherited thrombophillia

Answer 24

Not clinically common
Predisposes to DVT and PE but not MI or CVA
Anti thrombin deficiency 
Protein C deficiency 
Protein S deficiency 
Factor 5 Leiden weak cause of clots
Prothrombin gene mutation 
Lupus anticoagulant is not inherited but is often tested-> an antibody that predisposes to arterial and venous thrombosis, miscarriage

Question 25

Heparins

Answer 25

Increase activity of anti thrombin in its deactivation of factor X and II
Low molecular weight heparinise are produced by enzymatic cleavage of unfractionated heparin
LMWH give more consistent anticoagulation but UFH is easily reversible

Question 26

Warfarin

Answer 26

Antagonises vit K
Prevents factor II,VII,IX,X production in the liver
Oral
Loads of interactions

Question 27

International normalised ratio

Answer 27

Prothrombin time adjusted for international comparison
Used for measuring warfarin effect
Monster acute liver damage