Alfred Saturday course Haem 1 Flashcards
biggest risk factor for a recurrent VTE
previous idiopathic DVT/PE
(20% of idiopathic VTE will have another event after stopping the anticoagulant)
continuation of anticoagulant longer does not reduce this risk
highest risk in the first 12 months, then 3-5%/year
what is the most common hereditary thrombophilia
factor 5 leiden/Activated protein C resistance (2-10%)
what hereditary thrombophilias would change management
deficiencies of natural anticoagulants:
- Protein C, S and antithrombin
management of periop anticoagulation with surgery in antithrombin deficiency
replace antithrombin
which DOACs have been used for long term treatment of VTE
apixaban, rivaroxaban low dose (after the first 6 months of full dose anticoagulation)
duration of anticoagulation
provoked 3-6 mo
unprovoked at least 6 months
correlation between initial type of thrombotic event in APLS and the recurrence type
Arterial -> another arterial
Venous -> another venous
most common aetiology of antiphospholipid syndrome
primary antiphospholipid syndrome (>50%)
SLE next most common
lupus anticoagulant coagulation testing results
APTT prolonged that doesn’t correct w mixing
normal TVT
prolonged reptilase time
doesn’t correct with heparinase or protamine
what is the definition of “correction” of APTT with mixing
correction to 4-5 secs of the lab APTT normal range
how does TCT work
add thrombin and see how long it takes for blood to clot
which immunoglobulin for anticardiolipin is more associated with thrombosis
IgG > IgM
which test confers the lowest risk of APLS/thrombosis (e.g. LAC, aCL, beta2-GPI)
anti-cardiolipin
manageemnt of antiphospholipid antibody and no previous thrombosis or pregnancy complications (e.g. found incidentally)
- close clinical surveillance antepartum
- post-partum prophylaxis for 6/52
what postpartum risk factor confers the greated risk for the pregnancy associated VTE?
post-partum OR 4-21
placental abruption OR 2-16
post-partum haemorrhage OR 1.3-21
(but overall the greatest rist factor is a previous VTE OR 24.8)
what does anti-thrombin act on?
inhibits thrombin and anti-Xa
what is the clinical utilisation of fondaparinux
HIITS
which DOAC is a pro-drug
dabigatran
what DOAC is most dependent on renal function for excretion?
dabigatran (80% renal excretion)
dabigatran coagulation testing results
- linear relationship with APTT
- dilute TCT can be used to provide quantification (TCT exquisitely sensitive and normal result can almost disprove dabigatran in system)
- INR/PT insensitive
what is the dilute TCT (or haemaclot) used for?
quantification of dabigatran
MOA of andexanet alfa
decoy Xa molecule that has no anticoagulating activity
can reverse all direct and indirect Xa inhibitors (including LMWH)
what is involved in the initiation of coagulation?
tissue damage and tissue factor activates VIIa
that activates Xa and Va
that creates a small amount of thrombin
which creates fibrin
clinical epistaxis and recurrent GI bleeding - what kind of bleeding disorder is this most likely to indicate
platelet/vWF defect
why does the INR not reflect the anticoagulation at the initiation of warfarin
factor VII drops first because of its shorter half life. Factor X and IX drops slower.
Moreover, there is a decrease of protein C and S and there is a theoretical prothrombic state at the initiation of warfarin
a delayed failure to correct APTT - cause?
autoimmune inhibitor phenomenon (rather than haemophillia assoc inhibitor)
but haemophilia inhibitor can still be time dependent
what does thrombin clottig time reflect and what are the causes
the action of thrombin on fibrinogen
causes:
- abnormal fibrinogen/fibrinogen degradation product
- heparin
- paraprotein esp IgM
- dabigatran
haemophiia patient without family history (known family tree)
novel mutational events
1/3 of patients don’t have a family history
severity classification of FVIII or FIX (factor levels)
severe <1%
mod 1-5%
mild >5%
timing of post op bleeding (immediate vs delayed) and likely bleeding defect
platelets = immediate
coagulation factor def = delayed
what HIV agents are assos with renal stones (significant especially in haemophilia)
protease inhibitors
what does cryprecipitate contain?
- fibrinogen
- Factor VIII (the protein missing in patients with haemophilia A)
- Factor XIII
- von Willebrand factor (helps the platelets stick together)
MOA tranexamic acid
blocks lysin residues and plasminogen cannot attach and break down fibrin
route of liver biopsy for haemophilliacs
transjugular liver biopsy as bleeding is intravascular
how to quantite factor inhibitors
bethesda assay
Emicizumab MOA
factor VIII inhibitor bypassing fraction
monoclonal antibody overcomes the lack of factor VIII by bridging factors IX and X to restore haemostasis.
what type of vWD can DDAVP be used in
only type I
should not be used in pregnancy
what is bernard-soulier syndrome
abnormality of glycoprotein Ib-IX-V
actsl like vWFD
large platelets
MOA romiplostin
genetically engineered protein which binds to the thrombopoietin receptor even though its structure differs from that of human thrombopoietin. Activation of the receptor increases platelet production
stimulates bone marrow production of platelets
only available in australia for patients who relapsed for splenectomy or cannot have one
treatment of ITP platelets >30
observe
treatment of ITP with platelets <30
steroids - 1st line
then IVIG, anti-D
role of splenectomy in ITP
consider for:
-adults who have a relapse ot have not had a response to corticosteroids, IVIG, anti-D
differences in ITP vs gestational thrombocytopenia
- <70 more likely ITP
- 1st trimester more likely ITP
- history of ITP prior pregnancy
when to treat ITP in pregnancy
plt <80, trial of steroids with gradual taper or IVIG
what thrombotic microangiopathies are amendable to plasma exchange
TTP
catastrophic antiphospholipid syndrome
pathogenesis of HITTS
formation of neoepitopes that occurs when heparin binds to PF4, resulting in conformational changes
the pathogenic HIT antibodies are directed against neoepitopes on a self protein
what chromosome codes ABO blood group
9
most common blood group in australia
O+
what is the process of cross matching
donor red cells against patient serum/plasma
what is the purpose of the direct antiglobulin test
looking for antibody bound/complement bound RBC in the circulation
(cf IAT where the antibody is in the serum/plasma and is added to reagent RBC and add AHG
what is the commonest transfusion problem
TACO - transfusion associated circulatory overload
what type of transfusion reaction is extravascular
delayed haemolytic transfusion reaction
due to an antibody stimulated by previous pregnancy or transfusions. IgG antidboy that bind to Fc receptors of splenic macrophages and gradually reduce them
what antibody is involved in acute haemolytic transfusion reaction?
IgM antibodies which activates comlement and the membrane attack complex and rapidly destroys red cells
definition of febrile non-haemolytic transfusion reactions
>1 degree increase in temperature and no other likely explanation
most common cause of febrile non-haemolytic transfusion reactions
cytokine storm
(used to be antibodies against donor leukocytes before widespread leukophoresis)
what blood product is most likely to cause TRALI
plasma
most common cause of non-haemolytic transfusion reaction
interaction between donor granu
