bleeding and anti-coagulants

Question 1

what is the main role of the extrinsic pathway

Answer 1

initiation

Question 2

what is the main role of the intrinsic pathway

Answer 2

propogation

Question 3

name the different regulators of coagulation

Answer 3

• Thrombin itself stimulates anti-thrombin, its own regulator
o Degrades thrombin, FIXa, FXa, FXIa, and FXIIa
• TFPI – tissue factor pathway inhibitor

• Protein C is activated by thrombin into APC. This begins with thrombin and protein C binding to thrombomodulin allowing the change into APC
o Degrades factors Va and VIIIa

Question 4

what does the prothrombin time simulate

Answer 4

stimulates activation via the extrinsic pathway

Question 5

how is prothrombin time expressed?

Answer 5

INR

Question 6

what does an activated partial thromboplastin time simulate?

Answer 6

activation via the intrinsic pathway.

use contact factor to mimic collagen.

Question 7

what does thrombin clotting time measure

Answer 7

the conversion of fibrinogen to a fibrin clot

gives an indication of the amount of fibrin present in a patient’s blood and how well it functions

Question 8

what could prolong the thrombin clotting time

Answer 8

inhibitors of thrombin, fibrin degradation products, inhibitors of fibrin polymerisation

Question 9

what factors does warfarin impact

Answer 9

II, VII, IX and X
inhibits vitamin K oxide reductase, stopping the recycling of oxidised vitamin K. This stops the activity of the carboxylase enzyme necessary for coagulation factors to bind to phospholipid surfaces

Question 10

how do the heparins work

Answer 10

they augment the effect of antithrombin (up to 1000-2000x)

Particularly affects factors IIa and Xa

Question 11

what might unfractionated heparin be used for nowadays ?

Answer 11

treatment of mild to moderate pulmonary embolism, unstable angina and acute peripheral arterial occlusion.

Question 12

when would you use heparin

Answer 12

o Provides immediate but short acting anticoagulant effect
 Acute DVT or PE [sub cut LMWH]
 During cardiac bypass surgery [iv UFH]
 Acute coronary syndromes [along with anti-platelet agents]
 Medium term after VTE in cancer patients
o Prophylaxis against VTE patients
 Medical and post-op patients [low dose LMWH]
 Obstetric patients – used here as warfarin will cross the placenta

Question 13

what is the target INR on warfarin

Answer 13

2-3

Question 14

what is used to reverse warfarin

Answer 14

prothrombin complex concentrate

Question 15

which factor does dabigatran inhibit

Answer 15

factor IIa

Question 16

which DOACs inhibit factor Xa?

Answer 16

o rivaroxaban [Xarelto]
o apixaban [Eliquis]
o edoxaban [Lixiana]

Question 17

name some contra-indications of the DOACs

Answer 17

o pregnancy and breast feeding
o liver disease with cirrhosis +/- coagulopathy
o some drugs

Question 18

who may not be able to receive a DOAC or would need their dose adjusted?

Answer 18

those with renal impairment or a reduced CrCl

Question 19

name two tissue plasminogen activators

Answer 19

alteplase, tenectplase, reteplase

Question 20

which kinase is antigenic

Answer 20

streptokinase

Question 21

name three issues with the kinases

Answer 21

bleeding risk
streptokinase is antigenic
cell derivatives (urokinase) not acceptable to all patients

Question 22

in what way are the tissue plasminogen activators selective

Answer 22

relatively selective for clot bound plasminogen

Question 23

when might you use catheter directed thrombolysis ?

Answer 23

o Acute limb ischaemia (clot in an arterial vessel in say the leg)
o Massive DVT
o Blocked CVC

Question 24

how does clopidogrel work?

Answer 24

Anti-platelet drug. Inhibits ADP-mediated platelet aggregation via irreversible blockage of the ADP receptor.

Question 25

what are abciximab and tirofiban?

Answer 25

MAbs that antagonise the IIb/IIa receptors on platelets reducing their aggregation and reducing the binding of fibrinogen. used in setting of PCI to prevent ischaemic heart complications

Question 26

how does dipyridamole work

Answer 26

o Increased platelet concentration of cAMP via inhibition of phosphodiesterase enzymes that normally break it down o These increased levels block the platelet aggregation response to ADP o Reduced platelet aggregation

Question 27

name some causes of DIC

Answer 27

sepsis, malignancy, massive haemorrhage, severe trauma, complications of pregnancy e.g. pre-eclampsia, placental abruption, aminotic fluid embolism

Question 28

how would you treat DIC

Answer 28

find the underlying cause. | Give FFP +/- platelets if they are bleeding or at high risk of bleeding

Question 29

how can you reverse the effects of warfarin in someone with a high INR?

Answer 29

Give vitamin K (works within hours) | Give coagulation factors (II, VII, IX, X). These are given as prothrombin complex concentrates

Question 30

which factors are implicated in haemophilia A and B

Answer 30

VIII | IX

Question 31

what coag test will be prolonged in haemophiliacs

Answer 31

APTT

Question 32

how would you treat a coagulation factor deficiency?

Answer 32

• Education - patients and doctor • Desmopressin [DDAVP] • Replacement therapy o FFP / Cryoprecipitate o Plasma derived factor concentrate o Recombinant produced factor concentrate • Gene therapy (potential future therapy)

Question 33

what is the role of VWF?

Answer 33

* Facilitates platelet adhesion and aggregation in primary haemostasis * Binds FVIII and prolongs its half-life in the plasma – will influence secondary haemostasis

Question 34

what is the most common mild bleeding disorder

Answer 34

Von willebrand disease

Question 35

what sort of bleeding do you get in Von willebrand disease

Answer 35

mucosal type bleeding pattern

Question 36

what is the parthenogenesis of VW disease

Answer 36

you have reduced VWF which can led to reduced platelet aggregation and reduced factor 8/ 3 types with type three being a complete deficiency while type 1 is a partial quantitative deficiency of VWF

Question 37

why would you give transexamic acid or desmopressin in a bleeding disorder

Answer 37

it causes platelets and cells lining the vasculature to release more VWF

Question 38

what condition is lupus anti-coagulant associated with

Answer 38

anti-phospholipid syndrome

Question 39

what are conta-indications for thrombolysis

Answer 39

o Haemorrhagic stroke or stroke of unknown origin o Ischaemic stroke in preceeding 6 months o CNS damage

Question 40

what is an acquired haemophilia | How do you treat it?

Answer 40

This is the spontaneous development of auto-antibodies. These Abs interfere with factor VII. Result - prolonged APTT. Steroids