vascular system Flashcards
thrombosis: explain how a thrombus can form within a vein and identify the drugs used to treat deep vein thrombosis and pulmonary embolism
3 initial stages of thrombosis (small-scale thrombin production)
tissue factor -> prothrombinase complex -> antithrombin (AT-III)
initial stages of thrombosis (coagulation): tissue factor
tissue factor bearing cells activate factors X and V, forming a prothrombinase complex (fVa and fXa)
initial stages of thrombosis (coagulation): prothrombinase complex
prothrombinase complex activates factor II (prothrombin), creating factor IIa (thrombin); initiation stage of coagulation cascade
initial stages of thrombosis (anticoagulation): antithrombin (AT-III)
AT-III inactivates fIIa and fXa, regulating thrombin levels
4 mechanisms anticoagulants use to treat initial stages of thrombosis (first line of treatment); anticoagulants is generic term for drugs treating thrombosis, and specific term which targets coagulation factors
inhibit fIIa (same as antithrombin in body), inhibit fXa, increase activity of AT-III, reduce levels of other factors
example of fIIa inhibitor, and administration
dabigatran (direct-acting oral; causes GI bleeding)
example of fXa inhibitor, and administration
rivaroxaban (oral; maintenance treatment for DVT and PE)
2 classes of anticoagulants that increase activity of AT-III (fast onset of action, but not orally available)
heparin, low-molecular weight heparins
heparin administration and effects
IV, SC; activates AT-III and decreases fIIa and fXa (given for initial PE interim treatment - more effective than dalteparin so used in PE vs DVT)
low-molecular weight heparins example and effects
dalteparin (given initially as DVT or PE interim treatment, as work quickly); activate AT-III and decrease fXa
what factors is vitamin K required for
II, VII, IX, X
name a vitamin K antagonist, which therefore reduces levels of other factors, and administration and time of onset
warfarin (indirectly-acting oral, so slow onset of action (5-7 days) - maintenance treatment for DVT and PE)
in physiology, what are anti-coagulants balanced with, and how does change in thrombogenic conditions e.g. DVT/pulmonary embolism
balanced with pro-coagulants, but in thrombogenic conditions, pro-coagulants are higher than anti-coagulants
3 risk factors of Virchow’s triad (increase likelihood of thrombus formation)
rate of blood flow, consistency of blood, blood vessel wall integrity
in DVT/pulmonary embolism, describe rate of blood flow
slow/stagnating (e.g. due to immobility), with no replenishment of anti-coagulant factors and balance adjusted in favour of coagulation
in DVT/pulmonary embolism, describe consistency of blood
(not viscosity); natural imbalance between procoagulation (II, VII, IX, X) and anticoagulation factors; typically genetic
in DVT/pulmonary embolism, describe blood vessel wall integrity, and how hypertension increases risk of damage
damaged endothelia, so blood exposed to procoagulation factors; common in hypertension as blood hits endothelial cells more regularly, so more likely to get damaged
presentation of DVT and pulmonary embolism
swollen leg with pitting oedema and local tenderness (DVT) e.g. following immobility -> if embolises in lung (PE), chest pain, dyspnoea and tachypnoea
investigations of DVT
2-level Wells score (survey out of 10; higher the score, more likely the DVT); D-dimer test (tests for fibrin degradation products in blood); vein scan; confirmed by US
investigations for PE
CTPA (computed tomographic pulmonary angiography)
amplification stage of thrombosis: what does fIIa (thrombin) do
activates platelets
amplification stage of thrombosis: what do activated platelets do
change shape and attach to other platelets, forming occlusion
amplification stage of thrombosis: what does thrombin (fIIa) bind to on platelets
binds to protease-activated receptor (PAR) on platelet surface; PAR antagonists exist but not widely used
amplification stage of thrombosis: what does PAR activation of platelets lead to
rise in IC Ca2+ from internal stores, causing shape change (contraction, forming stellate appearance)
amplification stage of thrombosis: what does IC Ca2+ rise result in
exocytosis of ADP (paracrine and autocrine effect) from dense granules
amplification stage of thrombosis: what does ADP do in platelets (autocrine effect)
activates P2Y12 receptors, which cause platelet activation and aggregation
amplification stage of thrombosis: what does PAR activation in platelets liberate
arachidonic acid (AA)
amplification stage of thrombosis: what does cyclo-oxygenase (COX) convert arachidonic acid (AA) into
thromboxane A2 (TXA2)
amplification stage of thrombosis: what does TXA2 activation lead to being expressed on platelet surface
GPIIb/IIIa integrin receptors
amplification stage of thrombosis: what are GPIIb/IIIa integrin receptors involved in
platelet aggregation
what drug prevents platelet activation/aggregation by antagonising ADP (P2Y12) receptor, and administration
clopidogrel (oral; example of antiplatelet therapy given to treat NSTEMI as partially blocked)
what drug inhibits production of TXA2 by being an irreversible inhibitor of COX-1, and administration
low dose aspirin (oral: high doses are no more effective but cause more side effects; example of antiplatelet therapy given to treat NSTEMI as partially blocked)
what drug prevents platelet aggregation by antagonising GPIIb/IIIa integrin receptors, and administration
abciximab (IV, SC: limited use and only by specialists - monoclonal antibody)
presentation of (N)STEMI
chest pain, SOB, sweating, dizziness and chest pain
investigation of (N)STEMI
(no) change in ECG, increased troponin (breakdown of cardiac tissue, indicating MI)
collective term of anticoagulants and antiplatelets
blood thinners
propogation stage of thrombosis: what is generated
fibrin strands
propogation stage of thrombosis: what do activated platelets cause
large-scale thrombin production
propogation stage of thrombosis: how are fibrin strands created
fIIa binds to fibrinogen and converts it to fibrin strands
what drugs do not remove pre-formed clots (only prevent clot formation, so not useful in MI or stroke)
anticoagulants, antiplatelets
what drug class does remove pre-formed clots, and when are they used
thrombolytics (clot-busters), given if ischaemic stroke (occlusion due to thrombis formation in atria e.g. due to atrial fibrillation and embolised to cerebral arteries, but not category of white or red thrombus as in lumen of artery)
how do thrombolytics work
convert plasminogen to plasmin, which is a protease that degrades fibrin
example of a recombinant tissue type plasminogen activator (rt-PA), and administration
alteplase (IV), given as thrombolytic therapy for ischaemic stroke and STEMI (first line treatment to bust clot, then treat with antiplatelets and anticoagulants)
presentation of stroke
headache, dizziness, loss of coordination and numbness in face, arms and legs
invesitgation for stroke
serum glucose and electrolytes (normal range), CT scan (eliminate possibility of haemorrhagic stroke to diagnose ischaemic stroke)
initiation, amplification and propagation conditions
all 3 stages occur in all conditions (DVT, PE, MI, stroke)
DVT and PE general treatment
anticoagulants
NSTEMI and atherosclerosis general treatment
antiplatelets
stroke and subsequent rupture of atherosclerotic plaque general treatment
thrombolytics
haemostasis vs thrombosis
physiological formation of blood clot vs pathological formation of blood clot
side effect profile of anticoagulants, antiplatelets and thrombolytics
excessive bleeding
