Thrombosis Flashcards
how does DVT cause the sx and a PE
Blood clot in leg – blood cant get back = painful swollen leg
can move into R side of heart – block pul circ – R heart cant cope with strain = pt death
why is DVT important
DVT and PE are common and preventable causes of death
difficult to reverse - need to get rid of clot and restore circulation
may be indication of underlying cancer
consequence of DVT
death
recurrence common
thrombophlebetic pain - recurrent pain, swelling and ulcers (ie still have impaired circ)
pulmonary HTN if clot in lung not cleared – circ pressure in lungs changes
what are the contributory factors to thrombosis
virchow’s triad:
* blood
* vessel wall
* blood flow - coagulation factors accumulate more easily
factors in the blood that lead to thrombosis
Viscosity
* Haematocrit - myeloproloferative, polycythaemia
* Protein/paraprotein
Platelet count high – important in coagulation = thrombosis risk
Coagulation system - Net excess of procoagulant activity
coagulation cascade
what are the procoagulant factors
V
VIII
XI
IX
X
II
Fibrinogen
Platelets
what are the anticoagulant factors
TFPI
Protein C
Protein S
Thrombomodulin
EPCR
Antithrombin
Fibrinolysis
how do deficiencies in different factors (or having factor 5 liden) alter liklihood of thrombosis freee survival
All these patients ahd family members with thrombophilic traits
Antithrombin def is the highest risk of thrombosis
Curves show for people with these conditions – steep decline – increased tendency to thrombosis
Even curve with no defect falls steeper than general pop – so probably other things involved in these families
Factor V leiden – procoag effect
Half pf thrombosis tend to be precipitated by another factor eg surgery/COCP
how is the vessel wall usually antithrombotic
Expresses anticoagulant molecules
* Thrombomodulin - change thrombin from procoag
* Endothelial protein C receptor
* Tissue factor pathway inhibitor
* Heparans
Does not express tissue factor (procoag)
Secretes antiplatelet factors
* Prostacyclin
* NO
collagen and TF are kept outsied of the blood vessel (they are procoag)
eg of stimuli that make the vessel wall prothrombotic
Infection – including COVID-19
Malignancy
Vasculitis
Trauma
prothrombotic changes to the vessel wall
Anticoagulant molecules (eg TM) are down regulated
TF may be expressed
Prostacyclin production decreased
Adhesion molecules upregulated
Von Willebrand factor release
* Platelet and neutrophil capture
* Neutrophil extracellular traps (NETS) form
Capture Neutrophils which undergo NETosis And spill out DNA – prothrombotic surface
Blood cells on endothelial surface stim clotting, capture plts and activate them and capture vWF
mechanism of how stasis -> thrombosis
Accumulation of activated factors
Promotes platelet adhesion
Promotes leukocyte adhesion (NET) and transmigration
Hypoxia produces inflammatory effect on endothelium
-> Adhesion, release of VWF
ie make it easy for neutrophils and plts to stick to surface
causes of stasis
Immobility -> Surgery, Paraparesis, Travel
Compression -> Tumour, pregnancy
Viscosity -> Polycythaemia, Paraprotein
Congenital -> Vascular abnormalities
how does risk of PE change with flight distance
as distance increases, so does risk of PE
can thrombotic risks interact
yes
Circumstantial – reason got it on that particular day – cross thrombotic threshold
Circumstance is something that you can remove
What are the immediate acting anticoagulant drugs
Heparin
* Unfractionated heparin
* Low molecular weight heparin
Direct acting anti-Xa and anti-IIa
what is teh delayed anticoagulant
Vitamin K antagonists- Warfarin takes 5 days
mechanism and route of indireect anticoagulants
Heparins:
* Unfractionated heparin - iv - Monitored
* Low molecular weight heparin - sub cut - No monitoring
* Pentasaccharide - sub cut - No monitoring
pentasaccharide is the active part - can make it artificially
all directly activate antithrombin antithrombin
immediate effect
disadvantage - injections, osteoporosis
variably depend on renal function (unfractionated doesnt, pentasaccharide depends greatly) - dont want anticoag effects accumulating
what are the direct anticoagulants
Direct acting anticoagulants
Anti-Xa - Rivaroxaban, apixaban, edoxaban
Anti-IIa - Dabigatran
Properties
* Oral
* Immediate acting –peak in approx. 3-4 hours (cf LMWH)
* Also useful in long term
* Short half-life
* No monitoring
* non-reversibal
rivaroxiban directly blocks factor 10 active site
indirect delayed anticoag
warfarin - vitamin K antagonist
oral
Indirect effect by preventing recycling of Vit K (becoem Vit K deficient) -> action is delayed
Levels of procoagulant factors II, VII, IX & X fall
Levels of anticoagulant protein C and protein S also fall
Used for long term anticoagulation only - heart valves, antiphospholipid syndrome
monitoring of warfarin
measure INR (international normalised ratio) - derived from prothrombin time
narrow therapeutic window
Difficult because numerous interactions
* Dietary Vitamin K (eat more will need more warfarin)
* Variable absorption
* Interactions with other drugs
* Protein binding, competition/induction of cytochromes
* Teratogenic – anticoag fetus, neuro and bone problems
compare the anticoagulants
which patients are at risk of thrombosis
Medical in patients
* Infection/inflammation, immobility (inc stroke), age
Patients with cancer
* Procoag molecules, inflammation, flow obstruction
Surgical patients
* Immobility, trauma, inflammation
Previous VTE, Family history, genetic traits
Obese
Elderly
