Lecture 12: Coagulation System Flashcards
Draw out the flow diagram of the blood coagulation in vivo
What are the 3 roles of thrombin?
1) The initial thrombin formation (from Xa activity) is to produce more thrombin
2) But it’s main job is to convert fibrin from fibrinogen which is the net that cross-links platelets to form a clot.
3) convert XIII to XIIIa which stabilises the fibin net by cross linking it.
What is the role of XIIIa?
stabilises the fibrin net by cross linking it.
Extrinsic pathway is ______ important
Extremely important (has the tissue factor in it)
What does the APTT test measure?
It measures the factors of the intrinisic pathway (so all factors except VII)
- Activated partial thromboplastin time (aPTT or APTT) is a medical test that characterizes blood coagulation, also known as clotting.*
- Apart from detecting abnormalities in blood clotting,[2] partial thromboplastin time is also used to monitor the treatment effects with heparin, a widely prescribed drug that reduces blood’s tendency to clot.*
The key clotting factors that is affected by APTT (so if APTT is prolongued you wonde about it), are f_actor 8, 9. 11 and 12._
(Deficient factor 12 does not cause you to bleed)
The intrinsic pathway does not include ______
Tissue factor/VIIa
What factors does the APTT measure?
All factors except VII
XII
XI
IX
VIII
Describe the steps to measure the activated Partial Thromboplastin time
APTT is performed by adding an activator (e.g. kaolin, micronised silica, ellagic acid) to platelet poor plasma in the presence of phospholipid and calcium.
- Venous blood sample collected into citrate (blue lid)
- Citrate stops blood from clotting in the tube because it removes calcium (chelation)
- Spin the sample down to collect the plasma
- Add phospholipid and an activator to plasma
- Add calcium to overcome the citrate
- Measure length of time to clot formation.
The normal clotting time is ~24-37 seconds, although this will vary depending on reagents and assay kits.
APTT is performed by adding an ______ (e.g. kaolin, micronised silica, ellagic acid) to _____________ in the presence of _______________________.
APTT is performed by adding an activator (e.g. kaolin, micronised silica, ellagic acid) to platelet poor plasma in the presence of phospholipid and calcium.
If you put blood in a glass or plastic tube, it coagulates because_______
Because of the Silica in the glass/plastic. (contact factor)
What is needed to test the APTT? (3)
1) Contact factor (e.g. kaolin, silica, ellagic acid)
2) Source of phospholipid
3) Calcium
What test can test the factors of the intrinsic pathway?
APTT
APTT measures all factors with the exception of ________\_
It is most sensitive to reductions in _________________
It is commonly prolonged in the haemophilias due to reduced levels of _______\_
This test measures all factors with the exception of factor VII.
- It is most sensitive to reductions in contact factors (XII and XI)
It is commonly prolonged in the haemophilias due to reduced levels of VIII and IX.
Why is the Prothrombin time NOT physiological?
Why?
In vivo, the tissue factor pathway is switched off quickly, and we need the IXa and XIIIa to act as an amplifer.
In PR/vitro, we add so much tissue factor that the amplification is by-passed/ this is not necessary.
Prothrombin time is prolonged in people with VII deficiency, X, V, Prothrombin or lacking in fibrinogen.- but is not prolonged in people who lack VIII or IX
Therefore this test is not physiological, as if you lack VIII or IX, you will have a severe bleeding disorder, but will have a normal Prothrombin ratio.
What drug can the Prothrombin time monitor?
Drug Monitoring
It is used to monitor therapy with oral anticoagulant drug warfarin. When prothrombin ratio is used to measure the effect of warfarin a correction factor is introduced, to account for different thromboplastin sensitivity to warfarin.
- Corrected PR used for warfarin monitoring is called international normalised ratio (INR).
- INR is therefore an adjusted PR facilitating interpretation of warfarin control by removing an important laboratory variable.
Prothrombin time is prolonged in people with_________________
but is not prolonged in people who lack______
Prothrombin time is prolonged in people with
1) VII deficiency,
2) X,
3) V,
4) Prothrombin
5) lacking in fibrinogen.
But is not prolonged in people who lack
1) VIII
2) IX
the Prothrombin time/ratio is sensitive to defects in …..
The test is sensitive to defects in three of four vitamin K dependent factors in extrinsic pathway, includes II (prothrombin), VII, X.
It is also sensitive to V, fibrinogen.
How do you calculate the prothrombin ratio from time?
The Prothrombin time (in sec) is often converted to the prothrombin ratio
This standardises the test to account for the diff lab methods and different normal ranges for the prothrombin time
= Prothrombin time (patient) / Prothrombin time (normal plasma)
The normal ratio is usually around 1.0 (0.9-1.2)
The Thrombin Clotting Time is used to measure _______________
The test is sensitive to abnormalities of fibrinogen.
It is also sensitive to inhibitory effects of heparin and FDP (fibrin degradation products).