Lecture 13 - Thrombosis Flashcards
Virchow’s Triad?
stasis flow of blood, vascular injury, hypercoagulability components of blood
Risks of vascular injury?
trauma, surgical manipulation, prior thrombosis, arthlerosclerosis
Risks of stasis?
immobility (post-op, coma), pressure (cathedar, coma), increased viscosity (EPO, dehydration, polycythaemia)
Risks of Blood Hypercoagulability?
increased procoagulations, decrease in inhibitors, impired fibrinolysis (rare)
Differentiating deep vein thrombosis and pulmonary embolism?
DVT: oedema, leg pain and swelling; PE: shortness of breath, chest pain, tachycardia, tachypnoea
Method of reducing need for imaging?
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
D-dimer?
positive in nearly all DVT and PE, alos positive in patients without DVT, high negative viability over positive,
Screening methods for PE?
d-dimer, CT angiography, V/Q scan
Massive PE?
sudden death (15%), mortality (>50%), hypotension, sever right heart strain due to back pressure from pulmonary arteries
Thrombophilia?
tendency to develop thrombosis, can be acquired (cancer), inherited or both, manifested as venous thromboembolism
Causes of VTE?
30-40% spontaneous (half of these are hereditary thrombophilia), remainder are provoked events: surgery, trauma, immobility, hospitalisation, malignancy, HRT/OCP/pregnancy
Inherited thrombophilia - abnormal inhibitor function?
resistance to activated protein C (Factor V Leiden)
Inherited thrombophilia - deficiency of inhibitors?
antithrombin, protein C or protein S deficiency - these ae rare BUT antithrombin deficiency is high risk for future thrombosis
Inherited thrombophilia - increased factor levels?
prothrombin gene mutation 20210A, elevated factor VIII
Factor V Leiden?
point mutation of arginine into glutamine at position 506 of factor V - the most common hereditary cause of thrombophilia
Factor V Leiden physiology?
Activated protein C has decreased ability to inhibit the mutated factor V, leading to higher active levels and higher risk of thrombosis
Why test for factor V leiden/activated protein C resistance?
heterozygotes carry 3-7x risk of thrombosis, homozygotes carry 50-100x, combined risk factor with OCP
Heparin?
immediate effect on thrombosis, requires anti-thrombin, iinactivates X and II, APPT 1+ 1 prolonged, TCT prolonged, reversed with protamine
Low Molecular weight Heparin?
subcutaneous rather than intravenous, higher bioavailabilty, weight based dose, e.g. enoxaparin
Warfarin?
needs monitoring (INR), risks of interaction with antibioics, anticonvulsants & citalopram, high INR increases bleeding further, takes time to lower vitK derived clotting factors
Reversal of bleeding on Warfarin?
VitK (slow), prothrombinex, II, IX and X (immediate)
Direct Acting Oral Anticoagulants (DAOAC)?
Rivaroxaban (Xa) and Dabigatran (thrombin/IIa) - both ame as Warfarin for treating VTE but superior in treating atrial fibrillation
DAOACs - advantages?
no monitoring needed, fixed dose, less intracranial haemmorhage (compared to warfarin)
DAOACs - disadvantages?
renal excretion (esp. dabigatran) retained w renal impairment
Clotting tests and DAOACs - Dabigatran?
TCT extremely sensitive, APTT prolonged at therapeutic windows, PR prolonged at very high levels
Clotting tests and DAOACs - Rivaroxaban?
PR prolonged to some extent, APTT less so
Antidote for dabigatran?
idarucizumab - direct immediate binding, subsides at high levels or renal failure
Antidote for Xa inhibitor/rivaroxaban?
in development, prothrombinex may have some benefit
Progression into morbidities?
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)
