Lecture 13 - Thrombosis

Question 1

Virchow’s Triad?

Answer 1

stasis flow of blood, vascular injury, hypercoagulability components of blood

Question 2

Risks of vascular injury?

Answer 2

trauma, surgical manipulation, prior thrombosis, arthlerosclerosis

Question 3

Risks of stasis?

Answer 3

immobility (post-op, coma), pressure (cathedar, coma), increased viscosity (EPO, dehydration, polycythaemia)

Question 4

Risks of Blood Hypercoagulability?

Answer 4

increased procoagulations, decrease in inhibitors, impired fibrinolysis (rare)

Question 5

Differentiating deep vein thrombosis and pulmonary embolism?

Answer 5

DVT: oedema, leg pain and swelling; PE: shortness of breath, chest pain, tachycardia, tachypnoea

Question 6

Method of reducing need for imaging?

Answer 6

algorithms of symptoms and clinical presentations, 2 or more is high risk requiring imaging, d-dimer blood test can indicate low risk still having requirement for imaging

Question 7

D-dimer?

Answer 7

positive in nearly all DVT and PE, alos positive in patients without DVT, high negative viability over positive,

Question 8

Screening methods for PE?

Answer 8

d-dimer, CT angiography, V/Q scan

Question 9

Massive PE?

Answer 9

sudden death (15%), mortality (>50%), hypotension, sever right heart strain due to back pressure from pulmonary arteries

Question 10

Thrombophilia?

Answer 10

tendency to develop thrombosis, can be acquired (cancer), inherited or both, manifested as venous thromboembolism

Question 11

Causes of VTE?

Answer 11

30-40% spontaneous (half of these are hereditary thrombophilia), remainder are provoked events: surgery, trauma, immobility, hospitalisation, malignancy, HRT/OCP/pregnancy

Question 12

Inherited thrombophilia - abnormal inhibitor function?

Answer 12

resistance to activated protein C (Factor V Leiden)

Question 13

Inherited thrombophilia - deficiency of inhibitors?

Answer 13

antithrombin, protein C or protein S deficiency - these ae rare BUT antithrombin deficiency is high risk for future thrombosis

Question 14

Inherited thrombophilia - increased factor levels?

Answer 14

prothrombin gene mutation 20210A, elevated factor VIII

Question 15

Factor V Leiden?

Answer 15

point mutation of arginine into glutamine at position 506 of factor V - the most common hereditary cause of thrombophilia

Question 16

Factor V Leiden physiology?

Answer 16

Activated protein C has decreased ability to inhibit the mutated factor V, leading to higher active levels and higher risk of thrombosis

Question 17

Why test for factor V leiden/activated protein C resistance?

Answer 17

heterozygotes carry 3-7x risk of thrombosis, homozygotes carry 50-100x, combined risk factor with OCP

Question 18

Heparin?

Answer 18

immediate effect on thrombosis, requires anti-thrombin, iinactivates X and II, APPT 1+ 1 prolonged, TCT prolonged, reversed with protamine

Question 19

Low Molecular weight Heparin?

Answer 19

subcutaneous rather than intravenous, higher bioavailabilty, weight based dose, e.g. enoxaparin

Question 20

Warfarin?

Answer 20

needs monitoring (INR), risks of interaction with antibioics, anticonvulsants & citalopram, high INR increases bleeding further, takes time to lower vitK derived clotting factors

Question 21

Reversal of bleeding on Warfarin?

Answer 21

VitK (slow), prothrombinex, II, IX and X (immediate)

Question 22

Direct Acting Oral Anticoagulants (DAOAC)?

Answer 22

Rivaroxaban (Xa) and Dabigatran (thrombin/IIa) - both ame as Warfarin for treating VTE but superior in treating atrial fibrillation

Question 23

DAOACs - advantages?

Answer 23

no monitoring needed, fixed dose, less intracranial haemmorhage (compared to warfarin)

Question 24

DAOACs - disadvantages?

Answer 24

renal excretion (esp. dabigatran) retained w renal impairment

Question 25

Clotting tests and DAOACs - Dabigatran?

Answer 25

TCT extremely sensitive, APTT prolonged at therapeutic windows, PR prolonged at very high levels

Question 26

Clotting tests and DAOACs - Rivaroxaban?

Answer 26

PR prolonged to some extent, APTT less so

Question 27

Antidote for dabigatran?

Answer 27

idarucizumab - direct immediate binding, subsides at high levels or renal failure

Question 28

Antidote for Xa inhibitor/rivaroxaban?

Answer 28

in development, prothrombinex may have some benefit

Question 29

Progression into morbidities?

Answer 29

30% DVT develop into post throbotic syndrome, untreatable put managed with compression stockings; 2% PE develop chronic thromboembolic pulmonary hypertension (shortness of breathe of exertion, dizziness and fatigue)