thrombosis Flashcards
What is Thrombosis?
Solid mass of blood formed within the cardiovascular system involving the interaction of endothelial cells, platelets and the coagulation cascade that
impedes blood flow
what is haemostasis?
Haemostasis is the normal physiological process of coagulation to prevent bleeding
where does thrombosis occur?
Arterial & venous thrombosis
arterial thrombosis
what do they mostly result from?
are they platelet-rich? colour?
block which arteries?
what are they mostly due to? what does this lead to?
Mostly result from atheroma rupture (MI, stroke)
Platelet-rich “white” thrombosis
Block downstream arteries
Mostly due to atheroscelrosis hence plaques build up within interior of the vessel which rupture + thrombosis can occur which can block or impede blood flow
Venous thrombosis
what does it result from?
are they platelet rich? colour?
where could it go?
Result from stasis or a hypercoagulant state (DVT)
Platelet-poor “red” thrombus
May move to lungs
What makes blood clot?
the 4 key components
Four key components: Endothelium Platelets Coagulation Fibrinolysis (to resolve clot)
What is normal hameostasis?
what does it respond to?
what happens? 2 different main processes? what happens in the end?
Response to injury
Vessel constriction
↓
Formation of unstable platelet plug
(primary haemostasis) platelet adhesion
platelet aggregation
↓
Stabilisation of the plug with fibrin
(secondary haemostasis) blood coagulation
↓
Dissolution of clot and vessel repair
fibrinolysis
Platelets + coagulation
what causes this? (2)
what is primary haemostasis? (3)
what is secondary haemostasis? (2)
Tissue damage OR inflammation
primary hameostasis
platelet -> activated platelet (adhere, activate + aggeregate)
secondary haemostasis
fibrinogen -> fibrin (coagulation)
Both process happen together for clot
Importance of charged phospholipds on platelets
to allow coagulation to occur hence will lead to fibrin formation
coagulation + fibrinolysis
what do endothelila cells release? to what? what does this convert? what does this do?
endothelial cell will release tPA to plasminogen which is converted to potent plasmin -> breaks down fibrin into fibrin fragments + D-dimers
Blood coagulation inhibitors
name 2 different inhibitors and what they inactivate
Antithrombin III -> switch off the X to XA and thrombin’s activity
Protein c + s leads to activated protein C -> inactivates VIIIa and VA hence no amplification process
Deep vein thrombosis (DVT)
symptoms (5)
What do they all reflect?
Pain & tenderness of veins Limb swelling Superficial venous distension Increased skin temperature Skin discoloration
All reflect obstruction to the venous drainage
Involvement of valves in clot formation
what do valves do in veins?
what do contraction of muscles do?
how do clots form in this situation?
Valves in veins prevent backflow of blood
Contraction of nearby muscles squashes veins, acting as a pump to return blood to the heart
Clot formation happens when instead of strong upsurge of blood to the heart, it can eddy around valves hence more stasis and more risk of clot formation therefore can cause thrombosis + obstruction of blood flow
Virchow’s Triad
3 things that develop a venous thrombus?
Development of a venous thrombus depends on:
Changes in normal blood flow (stasis)
Alterations in the constituents of the blood (hypercoagulability)
Damage to the endothelial layer (extrinsic pathway will activate thrombosis)
Stasis
different reasons? (7)
Prolonged immobility e.g. surgery, travel
Stroke
Cardiac failure
Pelvic obstruction
Dehydration
Hyperviscosity
Polycythaemia -> increased RBC hence increased viscoscity of the blood and decreased blood flow
Hypercoagulabilty
what does this mean? what is there less of and more of?
Alterations in the constituents of blood components
HENCE
LESS Fibrinolytic factors, anticoagulant proteins/activity
MORE Coagulation factors, platelets
LESS Fibrinolytic factors, anticoagulant proteins/activity example
what defiency? what mututaion is this? effect of this?
e.g. ATIII deficiency
Protein C and Protein S deficiencies
FV Leiden mutation is a thrombophilia (resistance to the anticoagulant complex - activated protein C APC)
hence as protein c can’t break it down, it leads to amplification process
MORE Coagulation factors, platelets
such as?
Malignancy increases clotting factors
e.g. tissue factor, FXa, thrombin
Fate of venous thrombosis: lungs
small? large?
if small thrombosis, can be asymptomatic
if large can lead to obstructuion + rapid death
Proximal DVT
where? what is there risk of?
above knee
Higher risk of pulmonary embolism and post-thrombotic syndrome (pain, swelling, maybe even ulcers)
Distal DVT
where?
risk of?
below knee
Rarely cause pulmonary embolism
Rarely cause post-thrombotic syndrome
Post thrombotic syndrome
results from? what does it reduce? what does it increase? how does risk increase? symtoms?
Chronic complication develops in 20-50% of DVT patients Results from venous hypertension Reduces calf muscle perfusion Increases tissue permeability Risk increases with obesity and age Pain, swelling, oedema Redness Thickening of skin Ulcers in 5-10%
Anti-coagulants
what do they do? examples?
prevent clots
e.g. warfarin, heparin, direct oral anticoagulants
Thrombolytics/Fibrinolytics reverse
what do they do? examples
break down clots
e.g. plasminogen activators, streptokinase
Treatment of VTE
Cardiovascularly stable with acute VTE
what do you do? what drugs do you give?
Anticoagulate
Immediate anticoagulant effect
Heparin then warfarin/DOAC or immediate DOAC - Rivaroxaban or apixaban
Treatment of VTE
Circulatory collapse due to PE
what do you do differently in this case? what drugs do you give?
Thrombolysis
Alteplase (tissue plasminogen activator)
Streptokinase
Followed by heparin and warfarin or other - prevent recurrence
Investigations pre-treatment
what other tests than clot test do you do?
what are the clot tests?
Clotting screen
Prothrombin time (INR)
Partial thromboplastin time
Thrombin time
Full blood count
Urea and electrolytes
usually part of routine screen – to know creatinine clearance
Liver function tests
If clinical suspicion of liver disease
New(ish) anticoagulants
3 drug types
name the drugs
Indirect Xa inhibitors - enhance antithrombin
Fondaparinux
Idraparinux
Direct Xa inhibitors ORAL
Rivaroxaban
Apixaban
Direct thrombin inhibitors ORAL
Dabigatran
Bleeding complications from anticoagulants (3)
occurs with which drugs?
eyes
arm
brain
can occur with older anti-coagulants like warfarin
