haemostasis and thrombosis

Question 1

initial stages of thrombosis- INITIATION

Answer 1

small scale production- TF activate factor 10 and 5 to form PROTHROMBINASE COMPLEX

this complex activates F2 into F2Aa (prothrombin= thrombin)

antithrombin (AT3) inactivates f2a and f10 to prevent further thrombin production

Question 2

types of anticoagulants

Answer 2

DABIGATRAN inhibits factor 2a ie behaves like antithrombin- ORAL

RIVAROXABAN- inhibits F10- ORAL

HEPARIN or low molecular weight heparin- activates antithrombin- IV

warfarin- vitK antagonist (F2,7,9,10)- ORAL

Question 3

use of drugs and comparison

Answer 3

used for DVT

low molecular weight heparin used initially as fast acting (IV), then oral drug (riv/war) used later as maintenance (ORAL)

digabatran unpopular as causes GI bleeding

Question 4

PE

Answer 4

in DVT, may dislodge and become embolism, which goes up to lungs

treatment same, except heparin may be used as well (ie maybe not low molecular weight)

Question 5

virchows triad components and importance

Answer 5

assesses risk of thrombosis

blood flow rate eg someone immobie

consistency of blood ie balance between pro/anti-coagulants

blood vessel wall- injury (often due to high BP) increases risk

Question 6

white vs red thrombus with treatment

Answer 6

red thrombus occurs in veins ie DVT- RBC rich

white thrombus occurs within artery ie atherosclerosis- not around vessel wall, but WITHIN vessel wall ie foam cells

red thrombi need anticoagulants, white need antiplatelets

Question 7

NSTEMI vs STEM with treatment

Answer 7

non st elevated MI is a PARTIAL occluded coronary artery- antiplatelets

STEMI is fully occluded- antiplatelets+ thrombolytics

treatment is antiplatelets,

Question 8

next stage of thrombosis- amplification

Answer 8

activated thrombin activates platelets, which change SHAPE, become sticky and attach to other platelets ie aggregation

Question 9

how platelets are activates

Answer 9

thrombin binds to protease-activated receptor on surface of platelets (PAR)= intracellular rise in Ca2+= release of ADP

ADP activates P2Y12 receptor (ADP receptor) on platelet to cause activation/aggregation

PAR activation causes arachidonic acid liberation, so COX generates TXA2, which causes expression of GP11B/111a receptor, needed for platelet aggregation

Question 10

antiplatelet drugs and how given

Answer 10

CLOPIDOGREL- inhibits ADP receptor- ORAL

low dose ASPIRIN- irreversible COX 1 inhibitor- ORAL

ABCIXIMAB- limited use but inhibits GP11B/3A receptor- IV

Question 11

final stage of thrombosis- propagation

Answer 11

activated platelets lead to LOTS of thrombin, which causes it to convert fibrinogen into fibrin strands

Question 12

thrombolytics ie clot busters- mechanism, use, example, and problem

Answer 12

TPA- convert plasminogen into plasmin, which degrades fibrin, breaking clot

used for emergencies eg STEMI/stroke, as anticoagulants/antiplatelets prevent growing of clot rather than breaking down of it

ALTEPLASE

not used for long term treatment as causes too much bleeding, only emergencies