HAEM: Venous Thrombosis Flashcards
What % of hospital deaths does PE account for?
5-10%
25000 deaths per annum related to VTE, difficult to reverse but preventable
What is the recurrence rate of VTE?
20% within 2 years and 4% pa after
What is the death rate from VTE?
5% die
What is the occurence of pulmonary hypertension with VTE?
4% at 2 years
What is Virchow’s triad?
- blood - hypercoagulability
- vessel wall - damage
- blood flow - stasis
What factors in blood increase risk of VTE?
- Viscosity
- Haematocrit
- Protein/paraprotein
- Platelet count
- Coagulation system - net excess of procoagulant activity
List some procoagulant and anticoagulant factors.
Procoagulant - V, VIII, XI, IX, X, II, Fibrinogen, Platelets
Anticoagulant - TFPI, Protein C, Protein S, Thrombomodulin, EPCR, Antithrombin, Fibrinolysis
Reduced protein C
Is VTE preventable in thrombophilias?
In thrombophilias, VTE is precipitated in 50% of cases so these are still preventable e.g. Factor V leiden, Protein C/S deficiency, antithrombin deficiency
What factors in vessel wall increase risk of VTE?
- Expresses anticoagulant molecules
- Thrombomodulin
- Endothelial protein C receptor (ERCP) - helps protein C become activated
- Tissue factor pathway inhibitor - FT usually kept outside the circulation
- Heparans - co-factor for antithrombin
- Does not express tissue factor
- Secretes antiplatelet factors e.g. Prostacyclin, NO
How does inflammation make the endothelium prothrombotic?
Inflammaton/injury makes the vessel wall prothormbotic e.g. infection, malignancy, vasculitis, trauma
Effects:
- 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
Describe the role of neutrophils in ‘immunothrombosis’.
How neutrophils contribute to thrombosis has been termed “immunothrombosis” highlighting that inflammation is an important drive for thrombosis.
Neutrophils - under stimuli release DNA forming neutrophil extracellular traps which…
- captures vWD,
- releases histones which activates platelets,
- provides a surface for contact activation of coagulant pathways (FXII –> XIIa)
- contains neutrophil elastase which can break down TFPI
How does blood flow/stasis increase risk of thrombosis?
Stasis –> thrombosis because..
- Accumulation of activated factors
- Promotes platelet adhesion
- Promotes leukocyte adhesion and transmigration
- Hypoxia produces inflammatory effect on endothelium - adhesion, release of VWF
What are the causes of blood stasis?
How does flight distance/time affect PE occurrence?
The longer the flight the higher the risk of PE.
How does taking the OC and having FVL increase risk of thrombosis compared to the general population?
RR of VTE with FVL + OC = x35
OC alone = ~x5
FVL alone = ~x7
Which of the inherited thrombophilias has the highest risk of thrombosis?
Antithrombin deficiency
Antithrombin - decline in antithrombin curve was steepest for this out of all the thrombophilias
What is the difference between high and low dose anticoagulant regimens?
- high - therapeutic (to treat active clot)
- low - prophylactic
What are the “immediate” and “delayed” anticoagulant drugs?
Immediate
- Heparin - Unfractionated heparin OR Low molecular weight heparin
- Direct acting anti-Xa and anti-IIa
Delayed
- Vitamin K antagonists e.g. warfarin
What factors does warfarin act on?
2, 7 , 9 , 10
How do heparins act?
Increase activity of antithrombin
What are the different types of heparin and their routes of administration ? Is the action of each monitored?
- Unfractionated heparin = iv infusion, monitored
- Low molecular weight heparin = sub cut, no monitoring
- Pentasaccharide = sub cut, no monitoring
What are the advantages and disadvantages of heparin?
Advantages
- Immediate effect - can be used for treatment of thrombosis
Disadvantages
- injections
- risk of osteoporosis
- variable renal dependence
What are the main targets of DOACs? Give an example of each.
Direct acting anticoagulants:
- Anti-Xa - Rivaroxaban, apixaban, edoxaban
- Anti-IIa - Dabigatran
What are the advantages of DOACs?
Advantages:
- Oral administration
- Immediate acting + good for long-term use –peak in approx. 3-4 hours (cf LMWH)
- Short half-life
- No monitoring
What is the MOA of warfarin?
- Indirect effect by preventing recycling of Vit
- Levels of procoagulant factors II, VII, IX & X fall
BUT levels of anticoagulant protein C and protein S also fall
Can warfarin be used for treatment of VTE?
No - onset of action is delayed
How is warfarin monitored and what is this based on? Why can warfarin not be taken in pregnancy?
INR - this is derived from prothrombin time (PT)
Teratogenic in pregnancy
Summarise the advantages and disadvantages of warfarin.
Advantages:
- Orally administered
Disadvantages:
- Delayed onset of action
- Causes fall of some anticoagulant factors - protein C + S
- May interact with dietary vit K
- Variable absorption
- Interaction with other drugs - due to protein binding and competition/induction of cytochromes
- Teratogenic in pregnancy
Comapre and contrast heparin, warfarin and DOACs in terms of:
- administration
- action
- onset
- monitoring
- half-life effect
- reversal
- pregnancy
What is a safe INR a abalance of?
Balance between thrombosis (low INR) and bleeding (high INR) must be achieved
List some patient risk factors for VTE.
- Being a medical in patient - Infection/inflammation, immobility (inc stroke), age
- Being a surgical patient - immobility, trauma, inflammation
- Cancer - procoag molecules, inflammation, flow obstruction
- Previous VTE, FH, genetic traits
- Obese
- Elderly
Which hospital patients should be assessed for risk of VTE and how should they be managed?
“All admissions to hospital should be assessed for thrombotic risk and unless contraindication exists, receive heparin prophylaxis” - NICE
This is done with a standard risk assessment form which assesses for risk of VTE on one side, and risk of bleeding on the other.
What are the types of thromboprophylaxis?
- Low molecular weight heparin (LMWH) e.g: Tinzaparin 4500u/ Enoxaparin 40mg od, not monitored
- TED Stockings (for surgery or if heparin contraindicated)
- Intermittent pneumatic compression (increases flow)
- Sometimes DOAC +/- aspirin (orthopaedics)
What does a risk assessment for VTE entail?
Looks at patient and procedural factors which may increase risk of VTE.
Patient factors:
- Age > 60yrs
- Previous VTE
- Active cancer
- Acute or chronic lung disease
- Chronic heart failure
- Lower limb paralysis (excluding acute CVA)
- Acute infection
- BMI>30
Procedural factors:
- Hip or knee replacement
- Hip fracture
- Other major orthopaedic surgery
- Surgery > 30mins
- Plaster cast immobilisation of lower limb
What does a risk assessment for bleeding entail?
Looks at patient and procedural factors which may increase risk of bleeding.
Patient factors:
Bleeding diathesis (eg haemophilia, VWD)
- Platelets < 100
- Acute CVA in previous month (H’gge or thromb)
- BP > 200 syst or 120 dias
- Severe liver disease
- Severe renal disease
- Active bleeding
- Anticoag or anti-platelet therapy
Procedural factors:
- Neuro, spinal or eye surgery
- Other surgery with high bleeding risk
- Lumbar puncture/spinal/epidural in previous 4 hours
Do proximal or distal VTEs have higher rates of recurrence?
Proximal e.g. above knee, have higher rates of recurrence
What type of bleeding do DOACs reduce compared to warfarin?
Intracranial most reduced - this is generally what kills patients on warfarin
Need to balance the risk of bleeding with the risk of recurrence of thrombosis when assessing need for long term therapy.
Do males or females have higher recurrence rates of thrombosis?
Males - unknown reasons so they require long term anticoagulation in some cases
Man after a walk - 5 - he had no preventable risk
LMWH therapeutic dose
NB: aspirin may work quite quickly but it is not a good anticoagulant for thrombosis.
Abdo-pelvis CT
What is the risk of recurrence of VTE in these scenarios?
- Surgery
- Idiopathic
- COCP, flight, trauma
Very low after surgical precipitant - no need for long term anticoagulation
High after idiopathic VTE - consider long term anticoagulation – esp with DOAC
After minor precipitants (COCP, flights, trauma) - usually 3 months adequate; longer duration may be dictated by presence of other thrombotic and haemorrhagic risk factors
What is the risk of recurrence in 2years in idiopathic VTE?
10-20% in 2yrs = risk of recurrence in idiopathic VTE
