Exam 3- antiplatelets and anti-coagulants

Question 1

What are the functions of von-Willebrand Factor? (2)

Answer 1

Substance releases from damaged endothelium which induces platelet adhesion; also stabilizes Factor VIII

Question 2

Main factor complexes involved in the

a) extrinsic
b) intrinsic
c) central clotting pathways?

Answer 2

a) Tissue Factor / VIIa complex
b) Factor XIII/VI complex
c) V / Xa

Question 3

How is thrombin activated from prothrombin?

Answer 3

Cleavage by the factor V/Xa complex

Question 4

How is fibrin activated from fibrinogen?

Answer 4

Cleavage by thrombin

Question 5

How does thrombin positively feed back and enhance the clotting response?

Answer 5

Further activates the intrinsic pathway (factor VIII/IX)

Question 6

Which lab tests assess:

a) the extrinsic pathway
b) the intrinsic pathway?

Answer 6

a) prothrombin time (PT)(and INR)

b) activated partial thromboplastin time (APTT)

Question 7

Bleeding pattern in a failure of a) primary and b) secondary haemostasis?

Answer 7

a) Mucosal bleeding (e.g. GI, retina, epistaxis)

b) Large haematomas e.g. haemarthroses, intracranial

Question 8

IgA-mediated vasculitis causing polyarthritis and a palpable purpuric rash over buttocks/extensirs?

Answer 8

Henoch-Schonlein purpura

Question 9

What is the commonest inherited bleeding disorder and what is its inheritance pattern?

Answer 9

von Willebrand disease; usually autosomal dominant

Question 10

How does von Willebrand disease presennt?

Answer 10

Presents like a platelet disorder- bruising, mucosal bleeding (e.g. post tooth extraction)

Question 11

Causes of platelet disorders:

a) decreased production (3)
b) excessive destruction/use (2)
c) poor functioning (2)

Answer 11

a) marrow failure, aplastic anaemia, megaloblastic anaemia
b) immune thrombocytopenic purpura, DIC
c) antiplatelet drugs, uraemia

Question 12

Causes of multiple clotting factor deficiencies (3)

Answer 12

Liver failure
Vit K deficiency/warfarin
DIC

Question 13

What does an elevated D-dimer suggest?

Answer 13

Active clotting somewhere in the body; feature of DVT/PE and DIC

Question 14

X-linked inherited conditions with recurrent haemarthroses and soft tissue bleeds

Answer 14

Haemophilias A (factor XIII deficiency) and B (factor IX deficiency)

Question 15

Why is APTT deranged in the haemophilias?

Answer 15

APTT measures the intrinsic pathway; which is mediated by factors VIII and IX

Question 16

What is Virchow’s triad?

Answer 16

Stasis
Hypercoagulability
Endothelial injury/dysfunction

Question 17

Give examples of hereditary thrombophilias? (5)

Answer 17

Factor V Leiden 
Antithrombin deficiency
Protein C deficiency
Protein S deficiency
Prothrombin 20210

Question 18

How should hereditary thrombophilias be managed? (3)

Answer 18

Risk minimization
Short term prophylaxis to cover times of known risk e.g. pregnancy, surgery
Long-term anticoagulation if recurrent thromboses

Question 19

What is interesting about antiphospholipid syndrome?

Answer 19

Predisposes to both arterial and venous thromboses

Question 20

Risk factors for venous thrombosis (6)

Answer 20

Surgery
Immobility
Pregnancy, oral contraceptive pill, HRT
Age
Obesity
Varicose veins/venous insufficiency

Question 21

Main risk factors for arterial thrombosis (4)

Answer 21

Hypertension
Smoking
High cholesterol
Diabetes

Question 22

Mechanism of action of asprin?

Answer 22

Inhibits COX-1, thereby inhibiting production of thromboxane 2

Question 23

Mechanism of action of clopidogrel?

Answer 23

ADP receptor antagonists

Question 24

How long prior to surgery should antiplatelets be stopped?

Answer 24

7-10 days

Question 25

What are the main indications for anti-coagulant drugs? (3)

Answer 25

Venous thrombosis
Atrial fibrillation
Mechanical heart valves

Question 26

What are the two types of heparin? What is the difference between these?

Answer 26

Unfractioned (“standard”) heparin
Low molecular weight heparin.
LMWH only inhibits Factor Xa

Question 27

How does heparin work?

Answer 27

Potentiates anti-thrombin binding to clotting factors

Question 28

Monitoring of heparin:

a) unfractionated
b) LMWH

Answer 28

a) APTT

b) anti factor Xa assay, but routine monitoring not required

Question 29

What is the advantage of using standard heparin over LMWH?

Answer 29

Standard heparin can be quickly reversed with protamine sulfate; this only works partially for LMWH

Question 30

In coagulation what is Vitamin K required for?

Answer 30

The reduced form of Vitamin K is required as a co-factor for the carboxylation of the clotting factors 2, 7, 8 and 9

Question 31

How does warfarin cause anti-coagulation?

Answer 31

Inhibits the reduction of vitamin K

Question 32

Why is there a transient pro-coagulant state when warfarin is administered and how is this overcome?

Answer 32

Because levels of protein C and S also drop; heparin is used as bridging anticoagulation until the INR is at least 2.0

Question 33

Drugs which inhibit factor Xa?

Answer 33

NOACs such as rivaroxoban, apixiban

Question 34

How is warfarin reversed?

Answer 34

VitK and clotting factors

Question 35

What complication can be caused by long-term heparin?

Answer 35

Osteoporosis

Question 36

What is the target INR for recurrent PE?

Answer 36

3.5

Question 37

Why is prescription of rivaroxoban/dabigatran inappropriate for VTE prophylaxis in patients with artificial heart valves?

Answer 37

Not licensed for this indication

Question 38

Investigations in von-Willebrand disease? (2)

Answer 38

Prolonged bleeding time

APTT may be prolonged

Question 39

Intrinsic clotting pathway is mediated by which complex of clotting factors?

Answer 39

VIII/IXa

Question 40

Extrinsic clotting pathway is mediated by which clotting factors?

Answer 40

TF/VIIa

Question 41

What is the basis of the thrombophilia in Factor V Leiden?

Answer 41

Protein C is unable to break down this mutant version of Factor V

Question 42

Prothrombin is otherwise known as…

Answer 42

Factor II