Haematology 3 Flashcards
Clotting as a dynamic process
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
Virchows triad
Reduction in blood flow
Disturbance of blood vessels
Disturbance of blood properties
Different sorts of clot
Arterial-> platelet based-> inhibited using aspirin
Venous-> fibrinogen based-> inhibited using warfarin
Coagulation cascade requires
An initiating protease
Lipoprotein surface-> platlets
Calcium
Fresh supply of zymogen proteins
Prothrombin time test
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
Activated partial thromboplastin time
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
Thrombin time
Usually 13-20 secs
Measures final common pathway
Prolonged by any heparin
Pathologically prolonged-> liver disease, dysfibrinogenaemia, DIC
Mixing studies
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
Fibrinogen, plasmin and D-dimmers
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
Using D-dimers
Can be used to exclude thrombosis
Normally thrombosis, infection, inflammation, cancer, pregnancy
Don’t do it on any one who looks ill!
Cell based model of haemostatsis
Alternative explanation of clotting-> very complicate
Clotting cascade is useful model for relating to blood tests
Template bleeding time
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
Causes of abnormal bleeding
Dysfunctional clotting factors Insufficient clotting factors Abnormal biochemical environment Dysfunctional platelets Insufficient platelets Dysfunctional vascular endothelium Dysfunctional vessel constriction
Haemophilia A and B
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%
Haemophilia presentation
Boys
Joint bleeding as baby starts to walk
Prolonged APTT
Treat with factor replacement
Disseminated intravascular coagulation
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
Transfusion coagulopathy
Occurs under situations of massive transfusion
Platelets and clotting factors depleted and diluted
-> acidotic and hypothermic-> clotting factors no longer work
Dysfunctional platelets
Most commonly due to drug use-> aspirin, clopidogrel, abciximab
Secondary to liver disease
Rarely congenital
Predispose to bleeding form mucosal surfaces
Remove cause
Low platelets
Liver disease Sometimes marrow failure Rarely immune thrombocytopenia purpura Mucosal bleeding Treat with platelet transfusions and procoagulant drugs
Vascular bleeding problems
Scury-> collagen dysfunction due to vit C deficiency
Bleeding mucosa, skin petechiael bleeding, curly hairs
Ehlers-danlos and other congenital collagen disordered
Surgery!
Risk factors for arterial clots
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
Managing arterial clots
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
Risk factors for venous clots
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
Managing venous clots
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)
Inherited thrombophillia
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
Heparins
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
Warfarin
Antagonises vit K
Prevents factor II,VII,IX,X production in the liver
Oral
Loads of interactions
International normalised ratio
Prothrombin time adjusted for international comparison
Used for measuring warfarin effect
Monster acute liver damage
