HAEM: Venous Thrombosis Flashcards by Kishan P

What % of hospital deaths does PE account for?

5-10%

25000 deaths per annum related to VTE, difficult to reverse but preventable

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What is the recurrence rate of VTE?

20% within 2 years and 4% pa after

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What is the death rate from VTE?

5% die

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What is the occurence of pulmonary hypertension with VTE?

4% at 2 years

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What is Virchow’s triad?

blood - hypercoagulability
vessel wall - damage
blood flow - stasis

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What factors in blood increase risk of VTE?

Viscosity
- Haematocrit
- Protein/paraprotein
Platelet count
Coagulation system - net excess of procoagulant activity

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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

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Reduced protein C

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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

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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

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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

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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

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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

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What are the causes of blood stasis?

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How does flight distance/time affect PE occurrence?

The longer the flight the higher the risk of PE.

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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

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Which of the inherited thrombophilias has the highest risk of thrombosis?

Antithrombin deficiency

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Antithrombin - decline in antithrombin curve was steepest for this out of all the thrombophilias

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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: 1. **Anti-Xa** - Rivaroxaban, apixaban, edoxaban 2. **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 ## Footnote *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.

1. Being a medical in patient - Infection/inflammation, immobility (inc stroke), age 2. Being a surgical patient - immobility, trauma, inflammation 3. Cancer - procoag molecules, inflammation, flow obstruction 4. Previous VTE, FH, genetic traits 5. Obese 6. 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 ## Footnote *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 ## Footnote *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 precipitan**t - 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