Anticoagulant & inhibitor

Question 1

How can one differentiate factor inhibitors from factor deficiency? (1)

Answer 1

Mixing study, prolong APTT should be corrected after mix patient’s plasma with normal plasma in 1:1 ratio

Question 2

Why is warfarin not given to pregnant & lactating women? (1)

Answer 2

It is associated with spontaneous abortion

Question 3

State the relationship between protein C, protein S, and factor 5&8 (2)

Answer 3

Thrombin activate factor 5&8
Thrombin–thrombomodulin complex activate protein C
Protein S is a cofactor of protein C
Protein C inactivate factor 5&8

Question 4

APS is diagnosed by both clinical (2) and lab result (3)

Answer 4

Clinical:
Thrombosis
spontaneous abortion

Lab result:
LA
Anti - beta2-glycoprotein 1
Anti - cardiolipin
Presence twice with 12weeks interval

Question 5

Why is APTT named APTT? (2)

Answer 5

Activated
Ellagic acid is added to activate factor 12

PT
Thromboplastin (TF+PL)
Partial Thromboplastin (PL only)

Question 6

Factor V Leiden is a common cause of inherited thrombosis, explain how it leads to thrombosis. (2) Describe the screening test for APCR, can LA+ patients be screened? (2) How about Prothrombin G20210A? (1)

Answer 6

Factor V Leiden is a point mutated factor 5 which is resistant to protein C inactivation, so it is a condition of Activated protein C resistance (APCR).

APCR screening test is based on APTT ratio with and without APC addition. LA+ patient has prolong APTT rendering the ratio invalid.

Prothrombin G20210A is the second common cause of inherited thrombosis. It leads to prothrombin overexpression.

Question 7

Why is TT abnormal but Fibrinogen normal in patients taking heparin? (1)

Answer 7

Heparin acts with antithrombin to inactivate thrombin activity, so TT is prolonged.

Fibrinogen concentration is not affected because it is the activity of converting fibrinogen to fibrin that is being affected.

Question 8

If APTT is 110, but the patient is taking heparin, do you think the result is normal? (1)

Answer 8

Generally abnormal, therapeutic range of APTT should be within 2.5X UL, which is around 100.

Question 9

If INR is 3.6, but the patient is taking warfarin, do you think the result is normal? (1)

Answer 9

Generally abnormal, therapeutic range of INR is 2~3, even for patient with mechanical heart valves, INR should be 3.5 to be regarded as therapeutic level.

Question 10

Suggest a thrombolytic drug for treating MI (1)

Answer 10

tPA or streptokinase

Question 11

Why can platelet neutralization tests be used in LA diagnosis? (1)

Answer 11

PL is abundant on PLT surface, LA is an anti-PL, so it is cleared by binding PLT surface (neutralized) & thus APTT would be corrected.

Question 12

Why do some people have APS? (1) LA can prolong APTT, why do people with APS develop thrombosis instead of a tendency to bleed? (1)

Answer 12

APS can be caused by an underlying Autoimmune disorder such as SLE / RA.

LA prolong APTT because it binds PL required in coagulation cascade in vitro.
LA causes thrombosis in vivo because LA is Anti-PL, it binds PL on PLT to facilitate PLT aggregation

Question 13

When would a physician consider thrombophilia study? (3) What is included in the study? (3)

Answer 13

Young person / Pregnancy women with thrombosis
thrombosis with related Family history

Protein C , Protein S and Antithrombin should be included.
Additional panel can include Factor V Leiden & Prothrombin G20210A

Question 14

How common is the existence of Anti-PL in the general population? (1)

Answer 14

2%

Question 15

Why does some patient with factor 8 deficiency develops factor 8 inhibitor? (1)

Answer 15

They are treated with factor 8 replacement.
frequency is 10~20%

Question 16

Why is Recombinant factor 7 used to treat patients with factor 8 inhibitors? (1)

Answer 16

factor 7 activate factor 10, bypassing factor 8.
If factor 8 is given, it would just be inhibited by factor 8 inhibitor.

Question 17

What is the use of Bethesda assay? (1) Why is incubation for 2 hours at 37°C? (1)

Answer 17

It is an assay for factor 8 inhibitor.
different dilution of patient’s plasma mixed with normal plasma, the residual activity would be inversely proportional to the inhibitor activity in patient sample.
Incubation for 2 hours is for necessary because factor 8 inhibitor is time-dependent.

Question 18

Suggest a condition and a drug that is related to risk of thrombosis (2)

Answer 18

homocystinemia due to B12/Folate deficiency
Oral contraceptive

Question 19

What is Argatroban? (1) How to monitor its level? (1)

Answer 19

It is a thrombin inhibitor drug to replace heparin for patient with HIT.

APTT, within 3X UL = therapeutic level

Question 20

Describe 2 anti-PLT (2) Should you give anti-PLT to a patient of Hb = 5 & PLT = 40? (1)

Answer 20

Aspirin (COX I, TXA2 decrease)
Clopidogrel (ADPR I)

No, anti-PLT should not be given to anemic & thrombocytopenic patient

Question 21

For a patient with HIT, just change to warfarin, why is this a bad idea? (2)

Answer 21

Warfarin causes thrombosis initially, so overlapping with heparin is necessary. Heparin is stopped in HIT, so the transition is not possible & warfarin should not be prescribed as well.

Question 22

We monitor heparin with APTT, name a POCT test that is used in surgery that is faster than APTT (1)

Answer 22

activated clotting time (ACT), used in cardiac surgery.
It is accurate in heparin monitoring when high dose heparin is prescribed.

Question 23

LMWH therapy will be fine without monitoring, except in child, pregnant, renal, obese. Describe the assay for LMWH monitoring (3)

Answer 23

anti-factor Xa heparin assay
AT-heparin-Xa formed, free Xa cleaves chromogenic substrate and releases a yellow product
Color intensity of the product is inversely proportional to plasma heparin concentration