Lecture 12: coagulation in the lab + bleeding disorders Flashcards
APPT test measure the?
INTRINSIC PATHWAY
- Starts with the contact factors that aren’t normally used in the body but if they are triggered then they can cause a clot
- Activation of XII then activates XI and then IX through to VIII and V before prothrombin is converted to thrombin
- Doesn’t require VII or TF
- APPT is thus prolonged by XI, IX and VIII all causing clotting disorders (XII will prolonge but not cause disorder)
How is APPT performed?
- Venous blood sample collected into citrate that stops clotting by soaking up all the calcium
- It is spun down to collect plasma
- Add phospholipid and an activator to activate XII
- Add calcium and time length for clot formation.
Prothrombin time? Looks for deficiencies in? Ratio?
Uses the extrinsic pathway
You add a lot of TF so that the intrinsic pathway is bypassed and rather it just produces thrombin from TF converting X -> Xa and Xa converting prothrombin to thrombin with V as its cofactor.
- Looks at deficiencies in factor VII, X and V as well as prothrombin and fibrinogen
- Doesn’t look for VIII or IX and so you may have a severe clotting disorder from a deficiency in one of these but have a normal Prothrombin time
- PR : prothrombin ratio looks at the time compared to 20 or so normal people using the exact same equipment
Thrombin Clotting time?
Used to measure fibrinogen and looks at the inhibitors of it such as: Heparin and dibigatran
Adding a variable quantity of thrombin to plasma and looking at time. If you however, just add a small amount then you can look at the effect of the inhibitors
Mixing studies?
1:1 mixing with normal plasma + incubation-(looks for rare factors)
- sample corrects to normal and remains normal = factor deficiency (APPT only needs 30-40%)
- If sample doesn’t fully correct then an inhibitor must be present
Inhibitors in lab coagulation tests? Prolonged APTT 1+1?
Lupus anticoagulant
- antibody mediated - doesn’t cause bleeding just increases APTT
- Binds phospholipid and in a lab this causes increased time
Heparin
- confirmed by the addition of protamine (binds and reverses effects)
- upregulates antithrombin by a LARGE amount
- commonly used to ‘lock’ central lines - contamination common
- thrombin clotting time increased
Dibigatran
- Used to treat AF and directly binds thrombin and increased APTT and 1+1
- Thrombin clotting time increased
- Protamine does nothing
Aquired factor inhibitor (Rare)
- autoimmune antibodies usually against VIII
- Increase bleeding and bruising (can be life threatening)
Interpretation of Prolonged APTT with normal PT?
Interpretation of Prolonged PT with normal APTT?
BOTH prolonged?
APTT prolonged with normal PT:
- Factor deficiency in VIII, IX, XI, XII (intrinsic)
- XII is asymptomatic and XI is mild
- VIII and IX are more serious
Prolonged PT with normal APTT
- Deficiency of Factor VII (extrinsic)
- occasionally mild deficiency of II, V, X and I
Both
- Multiple factor deficiency
Common scenarios resulting from multiple factor deficiencies?
- Warfarin or Vitamin L deficiency (II, VII, IX, X)
- Mssive blood loss: loss of coagulation factors and dilution with fluids
- Disseminated Intravascular coagulation (DIC)
- widespread activation of coagulation causing thrombosis followed by bleeding as clotting factors and platelets used up. Low fibrinogen often seen.
- Liver disease: lack of production of factors and inhibitors (except VIII made by endothelial cells)
Prolonged PT DD?
EXTTRINSIC and COMMON pathways
- Warfarin (low II, VII, IX, X)
- Vitamin K def
- Liver disease
- Low factor VII (APTT would be normal)
How does Warfarin work?
Inhibits recycling of Vitamin K leading to a lack of carboxylating factors (II, VII, IX and X)
Dose adjustments need to be made by monitoring the INR
Reversed by vitamin K (or more rapidly by replacing clotting factors)
Used in AF, venous thromboembolism and other thrombotic disorders
23 y/o man knocked off his bike
APPT and PR high with LOW fibrinogen?
Consumptive coagulopathy = DIC
We make sure that we give a unit of plasma with each unit of blood to stop this from happening
Haemophilia?
Severe disease - X linked
- spontaneous joint bleeds lead to chronic arthropathy, joint destruction, deformity and arthritis
- soft tissue bleeds lead to tissue and nerve damage as wekk as deformity
Haemophilia A? B? Treatment?
A = Factor VIII deficiency - most common heriditary disease with serious bleeding (1 in 5000 men) - mild, moderate and severe
B = Factor IX deficiency - 1 in 30000 with identical clinical features to Haemophilia A
We can give recombinant missing factors - and give propylaxis in children and teenagers
Von Willebrand Factor?
Plasma glycoprotein synthesised in megakaryocytes and endothelial cells - promotes platelet adhesion at vessel wall.
Serves as a carrier for factor VIII
- Deficiency leads to platelets not binding and can lead to lack of VIII
- Bleeding disorder in 1-3% of population of varying amounts - not everyones APTT is prolonged
