Co-agulation 1 Flashcards
• What is the point of the whole coagulation cascade
to activate thrombin
• What does thrombin do?
- Activates fibrin from fibrinogen
- Fully activates platelets
1+2 allow formation of stable clots
• What are the different steps in the formation of clots do we need to know?
Trigger
Primary haemostasis
Thrombin generation
Fibrin clot formation
Trigger
- trauma
- collagen and tissue factor are exposed
- von willebrand factor binds to collagen
Primary Haemostasis
- platelets bind to vWF
- activates platelets + aggregate + stick to one another
- forms primary platelet plug
Thrombin generation
- tissue factor activates coagulation cascade w/ clotting factors
- cascade generates thrombin
Fibrin clot formation
- thrombin activates more platelets
+ converts fibrinogen -> fibrin
= stable clot
• In what three important ways is this clot formation regulated?
ADAMTS 13
Antithrombin activated protein C
Plasmin
ADAMTS 13 An enzyme that prevents vWF getting too big and sticky
Prevents the generation of too much thrombin, which limits how big the clots get
Plasmin cleaves fibrin and so breaks down fibrin clot
• How do we classify clinical disorders of haemostasis?
Primary haemostasis disorder (platelets, vWF and collagen)
Coagulation pathway disorder (coagulation pathway problem )
• What sort of bleeds do patients characteristically get in:
- primary haemostasis disorder?
- Coagulation pathway disorder
- example conditions for each?
You get smacked in the leg. How will your bleeding be if you have the above types of disorders?
Abnormal bruising - Ecchymoses/petechiae
Purpura (skin bleeding in small vessels in skin)
Joint bleeds
Deep soft tissue bleeds
Primary haemostasis
(e.g. thrombocytopaenia)
Coagulation pathway
(e.g. Haemophilia)
o Primary haemostasis = you will get immediate bleeding because you don’t have the primary haemostasis mechanism to form the mechanical platelet plug and stop bleeding
o Coagulation disorder = you will get delayed bleeding 2-3 days later. This is because your primary haemostasis mechanism is functioning and so you can make a platelet plug and stop the bleeding, but this is never reinforced by fibrin depositio
• What laboratory investigations of bleeding do you do?
first line?
platelet count + blood film (will tell you if you have thrombocytopenia)
coagulation screen (PT + aPTT) tell you if there is problem with coagulation cascade
• How do PT and aPTT tests differ?
therefore:
Long PT; long aPTT?
Long PT; normal aPTT?
Normal PT; long aPTT?
PT
- detects abnormal FVII (extrinsic pathway)
- common pathway (2, 5, 10 , fibrinogen)
aPTT
- detects abnormal (8,9,11) intrinsic pathway
- common pathway (2,5,10, fibrinogen)
Common pathway
FVII (extrinsic pathway)
FVIII, FIX, FXI (intrinsic pathway)
remember e before i
(PT before aPTT)
What is wrong in the following genetic clotting factor disorders?
Von Willebrand disease?
(most common of them all!)
Haemophilia A?
Haemophilia B?
vWF (so it’s a primary haemostasis problem)
FVIII (so it’s a coagulation pathway problem)
Defect in F8 gene, a sex linked recessive mutation
FIX (so it’s a coagulation pathway problem)
Defect in F9 gene, a sex linked recessive mutation
Haemophilia
• What are the clinical features of Haemophilia (we alluded to it before)?
o If factor level is <1%, ?
if factor level is >5%, ?
o Soft tissue and joint bleeds
o CNS/GI bleeds
o Chronic arthropathy (due to the chronic synovitis that is caused by the bleeding)
o If factor level is <1%, you can get spontaneous bleeding; if factor level is >5%, you can get bleeding from low impact.
• What does the level of factor depend on in a Haemophiliac?
The level of factor depends on how severe the mutation
• How do we manage haemophiliacs?
Recombinant factor concentrate. This is given prophylactically to ensure factor levels never drop to extremely low levels
Von Willebrand Disease
• What happens in mild and severe Von Willebrand disease?
o Mild disease = defective primary haemostasis only with mild mucocutaneous bleeding symptoms.
o Severe disease = the above PLUS additional coagulation pathway defect due to low FVIII in the plasma
severe mucocutaneous + joint bleeds
• How will the PT and aPTT be in someone with Von Willebrand disease?
(mild + severe)
Normal, because vWF is not a roman numeral factor and so is not testes in the PT/aPTT.
However, in severe Von Willebrand disease, the aPTT will be long because of the low FVIII levels.
• How do we treat Von Willebrand disease?
- to reduce clot breakdown?
- to release endogenous FVIII?
- LAST LINE therapy? (or before surgery)
- Tranexamic acid – reduces clot breakdown (a.k.a. an anti-fibrinolytic)
- DDAVP/Desmopressin – this releases endogenous FVIII and vWF. This is good for if you need a short term boost.
- vWF/FVIII concentrate – very expensive so is a last line therapy, but has to be used before things like surgery.
