Haemophilia Flashcards
when assessing bleeding disorders, what are some important features on history?
previous response to haemostatic challenges (such as surgery)
family history?
drug history?
type of bleeding - joint, spont, mucosal?
age when bleeding started?
what is ecarin time?
this is a test to determine whether a prolonged PT is due to Vitamin K deficiency or liver disease (leading to generalised factor deficiency)
Ecarin is the same as Echis time and is named for the Echis snake, whose venom is used for the test.
In this test, the venom activates prothrombin (to thrombin) without vitamin K.
- What is a reptilase time (RT) and how is it used?
If heparin is suspected as the cause of a prolonged thrombin time (TT), heparin assays or reptilase time (RT) can be used to confirm heparin presence. RT measures the time it takes for a clot to form after reptilase has been added to plasma. TT may be ordered with an RT to investigate a prolonged clotting time.
Since TT, but not RT, is affected by the anticoagulant heparin, prolongation of both TT and RT indicates decreased fibrinogen level and/or abnormal function of fibrinogen. If TT is prolonged but RT is normal, heparin contamination is likely the cause.
The clotting-based functional fibrinogen assay is now routinely available in clinical laboratories and has largely replaced the need for TT and RT for evaluation of fibrinogen.
What are the assays that can be used in the NOACs?
With the direct-IIa inhibitors
(dabigatran - note the ending T-ran - the T stands for thrombin (in the naming convention))
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Ecarin Clotting Time is the best, and can be used to quantitatively measure the activity.
PT is relatively insensitive, APTT is relatively SENSITIVE.
Thrombin time is TOO SENS
The Xa-inhibitors (ravaroXaBAN and apiXaBAN (note the Xa BAN suffix to identify Xa binding))
PT is SENS at high concentration
APTT is relatively INSENS
TT is not useful
ECT is not useful
Anti-Xa is the best, and how we quantitatively measure the effect of the drug.
what is senile purpura?
this is the process whereby vessels get very rigid and friable. they are easily damaged and can cause purpura.
not related to coagulation or platelet disorder (although can always have co-existant disease)
What factor level is altered when vWF level is altered?
plasma vWF carries factor VIII around the body, to prevent it from being broken down.
this means that with vWD you can get a prolonged APTT.
(but it is often only a small decrease in FVIII, and so the APTT can be normal)
what sort of bleeding patterns do we get with vWD? (what surfaces)
it tends to be mucosal surfaces, such as epistaxis and menorrhagia.
what are the 3 types of vWD?
type 1: partial quantitative deficiency (decreased level and therefore functional ability)
type 2: qualitative - normal level, but works badly
type 3: severe deficiency
if you have a female with low factor VIII, what is a possible cause?
there is a subtype of vWD, type 2N, which has normal vWF but decreased binding of factor VIII!
isn’t that ridic!?
basically, you see a woman with haemophilia A, but that can’t be, because it’s X-linked. so then you should think of this ridiculousness…
what sort of test do we do to prove vWD?
we use a VWF:Ag which binds vWF and tells us the amount.
On a separate vial, we then use a VWF:RCo which binds vWF and tells us the function of the vWF
finally we check the level of factor VIII
if the total level of vWF is very low, then we have type 3
if the vWF:RCo is significantly higher than the vWF:Ag level, then the function is okay, but the level is low –> this is type 1!
if the vWF:RCo (functional assay) is much lower than the vWF:Ag, then this is type 2!
What are the levels of factor with different severities of haemophilia?
normal range of clotting factors is wide, from 50 - 150%
mild haemophilia is 5 - 49% of normal levels
moderate is 1 - 5% (this has to occur with trauma, even if it is very minor)
severe is <1% (this is associated with spontaneous bleed)
what do we use for haemophilia A and B?
synthetically derived factor VIII and IX
if the patient has inhibitors, then we have to by-pass those, and give factor VII
What do we use for VWF?
for milder cases of VWF or mild haemophilia A, DDAVP causes an acute release of VWF and FVIII
if the patient needs factor VIII we have to use plasma derived concentrate
why would you use tranexamic acid in a haemophilia or VWD case?
tranexamic acid is an anti-fibrinolytic.
that is, it works against fibrinolysis.
that is, it stabilises clot
So, it can be used after surgery or bleeding to help the body heal.
why do haemophiliacs get inhibitors?
how common is it?
if the patient has very low titres of a factor, then the body isn’t familiar with them. as such, with repeated administrations, the body creates antibodies to these factors.
the risk in severe Haemophilia A is about 30%
Haem B is less common (1-2%)
