Alfred Saturday course Haem 1

Question 1

biggest risk factor for a recurrent VTE

Answer 1

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

Question 2

what is the most common hereditary thrombophilia

Answer 2

factor 5 leiden/Activated protein C resistance (2-10%)

Question 3

what hereditary thrombophilias would change management

Answer 3

deficiencies of natural anticoagulants:

• Protein C, S and antithrombin

Question 4

management of periop anticoagulation with surgery in antithrombin deficiency

Answer 4

replace antithrombin

Question 5

which DOACs have been used for long term treatment of VTE

Answer 5

apixaban, rivaroxaban low dose (after the first 6 months of full dose anticoagulation)

Question 6

duration of anticoagulation

Answer 6

provoked 3-6 mo

unprovoked at least 6 months

Question 7

correlation between initial type of thrombotic event in APLS and the recurrence type

Answer 7

Arterial -> another arterial

Venous -> another venous

Question 8

most common aetiology of antiphospholipid syndrome

Answer 8

primary antiphospholipid syndrome (>50%)

SLE next most common

Question 9

lupus anticoagulant coagulation testing results

Answer 9

APTT prolonged that doesn’t correct w mixing

normal TVT

prolonged reptilase time

doesn’t correct with heparinase or protamine

Question 10

what is the definition of “correction” of APTT with mixing

Answer 10

correction to 4-5 secs of the lab APTT normal range

Question 11

how does TCT work

Answer 11

add thrombin and see how long it takes for blood to clot

Question 12

which immunoglobulin for anticardiolipin is more associated with thrombosis

Answer 12

IgG > IgM

Question 13

which test confers the lowest risk of APLS/thrombosis (e.g. LAC, aCL, beta2-GPI)

Answer 13

anti-cardiolipin

Question 14

manageemnt of antiphospholipid antibody and no previous thrombosis or pregnancy complications (e.g. found incidentally)

Answer 14

1. close clinical surveillance antepartum
2. post-partum prophylaxis for 6/52

Question 15

what postpartum risk factor confers the greated risk for the pregnancy associated VTE?

Answer 15

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)

Question 16

Answer 16

Question 17

what does anti-thrombin act on?

Answer 17

inhibits thrombin and anti-Xa

Question 18

what is the clinical utilisation of fondaparinux

Answer 18

HIITS

Question 19

which DOAC is a pro-drug

Answer 19

dabigatran

Question 20

what DOAC is most dependent on renal function for excretion?

Answer 20

dabigatran (80% renal excretion)

Question 21

dabigatran coagulation testing results

Answer 21

• 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

Question 22

what is the dilute TCT (or haemaclot) used for?

Answer 22

quantification of dabigatran

Question 23

MOA of andexanet alfa

Answer 23

decoy Xa molecule that has no anticoagulating activity

can reverse all direct and indirect Xa inhibitors (including LMWH)

Question 24

what is involved in the initiation of coagulation?

Answer 24

tissue damage and tissue factor activates VIIa

that activates Xa and Va

that creates a small amount of thrombin

which creates fibrin

Question 25

clinical epistaxis and recurrent GI bleeding - what kind of bleeding disorder is this most likely to indicate

Answer 25

platelet/vWF defect

Question 26

why does the INR not reflect the anticoagulation at the initiation of warfarin

Answer 26

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

Question 27

a delayed failure to correct APTT - cause?

Answer 27

autoimmune inhibitor phenomenon (rather than haemophillia assoc inhibitor) but haemophilia inhibitor can still be time dependent

Question 28

what does thrombin clottig time reflect and what are the causes

Answer 28

the action of thrombin on fibrinogen causes: - abnormal fibrinogen/fibrinogen degradation product - heparin - paraprotein esp IgM - dabigatran

Question 29

haemophiia patient without family history (known family tree)

Answer 29

novel mutational events 1/3 of patients don't have a family history

Question 30

severity classification of FVIII or FIX (factor levels)

Answer 30

severe \<1% mod 1-5% mild \>5%

Question 31

timing of post op bleeding (immediate vs delayed) and likely bleeding defect

Answer 31

platelets = immediate coagulation factor def = delayed

Question 32

what HIV agents are assos with renal stones (significant especially in haemophilia)

Answer 32

protease inhibitors

Question 33

what does cryprecipitate contain?

Answer 33

* fibrinogen * Factor VIII (the protein missing in patients with haemophilia A) * Factor XIII * von Willebrand factor (helps the platelets stick together)

Question 34

MOA tranexamic acid

Answer 34

blocks lysin residues and plasminogen cannot attach and break down fibrin

Question 35

route of liver biopsy for haemophilliacs

Answer 35

transjugular liver biopsy as bleeding is intravascular

Question 36

how to quantite factor inhibitors

Answer 36

bethesda assay

Question 37

Emicizumab MOA

Answer 37

factor VIII inhibitor bypassing fraction monoclonal antibody overcomes the lack of factor VIII by bridging factors IX and X to restore haemostasis.

Question 38

what type of vWD can DDAVP be used in

Answer 38

only type I should not be used in pregnancy

Question 39

what is bernard-soulier syndrome

Answer 39

abnormality of glycoprotein Ib-IX-V actsl like vWFD large platelets

Question 40

MOA romiplostin

Answer 40

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

Question 41

treatment of ITP platelets \>30

Answer 41

observe

Question 42

treatment of ITP with platelets \<30

Answer 42

steroids - 1st line then IVIG, anti-D

Question 43

role of splenectomy in ITP

Answer 43

consider for: -adults who have a relapse ot have not had a response to corticosteroids, IVIG, anti-D

Question 44

differences in ITP vs gestational thrombocytopenia

Answer 44

- \<70 more likely ITP - 1st trimester more likely ITP - history of ITP prior pregnancy

Question 45

when to treat ITP in pregnancy

Answer 45

plt \<80, trial of steroids with gradual taper or IVIG

Question 46

what thrombotic microangiopathies are amendable to plasma exchange

Answer 46

TTP catastrophic antiphospholipid syndrome

Question 47

pathogenesis of HITTS

Answer 47

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

Question 48

what chromosome codes ABO blood group

Answer 48

9

Question 49

most common blood group in australia

Answer 49

O+

Question 50

what is the process of cross matching

Answer 50

donor red cells against patient serum/plasma

Question 51

what is the purpose of the direct antiglobulin test

Answer 51

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

Question 52

what is the commonest transfusion problem

Answer 52

TACO - transfusion associated circulatory overload

Question 53

what type of transfusion reaction is extravascular

Answer 53

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

Question 54

what antibody is involved in acute haemolytic transfusion reaction?

Answer 54

IgM antibodies which activates comlement and the membrane attack complex and rapidly destroys red cells

Question 55

definition of febrile non-haemolytic transfusion reactions

Answer 55

\>1 degree increase in temperature and no other likely explanation

Question 56

most common cause of febrile non-haemolytic transfusion reactions

Answer 56

cytokine storm (used to be antibodies against donor leukocytes before widespread leukophoresis)

Question 57

what blood product is most likely to cause TRALI

Answer 57

plasma

Question 58

most common cause of non-haemolytic transfusion reaction

Answer 58

interaction between donor granu