L14 Coagulation in the lab and other disorders Flashcards
What is the steps of APTT test - Activated Partial Thromboplastin time
Blue tube
(The citrate anticoagulation can be overcome by adding a known amount of ca2+)
- Venous blood collected into tube w citrate to bind calcium and prevent clotting.
- Sample is spun to collect plasma
- Activator - contact factor - and phospholipid added to trigger 12 to activate 12a –> intrinsic coagulation pathway
- Add calcium to overcome citrate
- Then measure the time it takes to form a crosslinking fibrin clot.
- In what situations is APTT prolonged? and why
2. Which factor does APTT not test
1a). Factor deficiency
- contact factors 12, 11,
- hemophilias: 8 or 9 only.
-Von Willebrand Factor
Other tests would be normal because of the common pathway.
b) Presence of inhibitor
- Unfractionated heparin
- Dabigatran
- Acquired inhibitors: eg. lupus anticoagulant
- or rare autoimmune single factor deficiency to 8.
APTT doesn’t test 7 - intrinsic pathway
What is the Prothrombin time and why can it be long.
Activation of the extrinsic pathway by adding lots of tissue factor.
Long PT is due to
- deficiency in 7
- deficiency in the common pathway 10, 5, Prothrombin, Fibrinogen.
What is Prothrombin ratio
Prothrombin time of patient (s)/ prothrombin time of normal plasma (s)
This helps to standardise different labs ‘normal plasma’
The normal ratio is around 1.0
What is Thrombin Clotting time and what is it used to measure
Adding Thrombin to platelet poor plasma to get fibrinogen to clot.
This is used to
- measure quantity of fibrinogen in the blood using a standard curve.
- diluted TCT to makes the reaction sensitive to presence of certain inhibitors of clotting.
eg. - Heparin, dabigatran,
lupus anticoagulant or rare autoimmune single factor deficiency to 8.
What is a mixing study and what does correction and non correction mean
Prolonged APTT and Prolonged mixing study = 1+1
It is done if APTT is prolonged. It adds the normal plasma to the patient plasma in equal volume .
- Corrected to normal + remains: factor deficiency
- Uncorrected: inhibitor of clotting present.
- these are not natural inhibitors such as Protein C, antithrombin and protein S because they don’t affect APTT.
What is INR - international normalised ratio
Corrected Prothrombin ratio used for warfarin monitoring to account for different thromboplastin sensitivity to warfarin
This is because warfarin reduces vit k dependent factors 2,7,9 and 10. (APTT is prolonged also)
Which of the inhibitors of clotting doesn’t cause bleeding but prolongs APTT
Lupus anticoagulant which may be part of antiphospholipid syndrome: leads to excessive clotting.
-or present transiently in unwell patients
How does heparin work and how to differentiate it from other 1+1 prolonged APTTs
(lupus a., heparin, dabigatran but not factor 8 autoimmune antibody)
Heparin may contaminate the sample if its taken from the central line
Heparin activates anti-thrombin to inhibit thrombin in a way that is greater than normal inhibition.
Dabigatran directly inhibits thrombin and therefore formation of fibrin.
Both Heparin and dabigatran will have extremely long TCT
whereas lupus will not. Lupus will also not have bleeding.
Heparins TCT can be corrected by protamine whereas
Dabigatran is not
What are the 4 causes for acquired Factor deficiency,
what factors do they affect specifically
and which ones will have more abnormalities in PR, and show low fibrinogen
- Warfarin use or Vit K deficiency (sensitive to PR): affects
F2, 7, 9 and 10 - Massive blood loss, transfusion without replacement of plasma: causes loss of all coagulation factors, and dropping fibrinogen and dilution with fluids
- Disseminated Intravascular coagulation: sepsis or malignancy causes all coagulation factors and platelets used up being activated with clotting then bleeding follows. shows low fibrinogen
- Liver failure/disease: Sensitive PR. = lack of production of all coagulation factors and inhibitors (except 8 made in bv lining)
How does Warfarin work and how can it be reversed
Inhibits the recycling of Vit K. Vit-K dependent factors are produced but are not carboxylated so they are inactive.
Can be reversed slowly 12-24 hrs by giving excess Vit K
or fast with replacement of clotting factors 2, 9 and 10 via Prothrombinex
What is Haemophilia and the 2 types.
Presentation - in severe (1%> factor present, identical in both types), and treatment
Investigation can include gene sequencing of factor gene.
- Haemophilia is an X-linked recessive disorder in
- Factor 8 (Type A- more common)
- Factor 9 (Type B) - Presents untreated as
- Spontaneous joint bleeds –> chronic arthropathy and joint destruction.
- Soft tissue bleeds–> intracranial haemorrhage, muscle, renal, GI, nerve damage.
Treatment is by recombinant factor replacement, with prophylactic treatment given in childhood to prevent joint damage.
What is Von Willebrand disease mechanism and tested for
- common inherited bleeding - mostly mild quantitative abnormality,
What are the tests
- Autosomal dominant inherited reduced/abnormal Von Willebrand factor which is used for promoting platelet adhesion at vessel wall and stabilising F8 as a complex.
- Don’t have to have a prolonged APTT bc F8 has to have significant <40%
- Tested for with platelet function screen, low factor 8 and low level/function of VW f.
What are the symptoms and treatments of Von Willebrand disease
- Symptoms are due to lack of platelet tethering.
- Mucosal bleeding, epistaxis, GI blood loss,
- Bruising, menorrhagia, PPH, Perioperative bleeding - Treatment: DDAVP = desmopressin triggering release of VWf and f8. Otherwise purified plasma 8/VWf (biostate)
What is an explanation for abnormal APTT, corrected with mixing and no bleeding history
Deficiencies in factor 12. Hereditary deficiency is common with no bleed sequelae
