DVT and Pulmonary Embolism Flashcards
DVT and PE background (5)
blood clot/thrombus forming in the leg
dangerous when above the knee - 50% embolise
common : 1/1000
8/100 have it due to inherited thrombophilia
Multifactorial risk
process (4)
thrombus: deep vein or valves
multiple triggers: becomes unbalanced system
above knee - break off and lodge in pulmonary circ (smallest place) : Pulmonary embolus -fragmentation of proximal clot which travels in venous system until it
lodges in the pulmonary circulation
Consequences locally in source limb and/or in
heart or lungs after embolisation
Virchow’s triad – contributing factors to
thrombosis (3)
- endothelial injury
-stasis (sticky) - blood components (clot): Platelets, Coagulation factors, Coagulation inhibitors, Fibrinolytic factors
Thrombosis is multi-factorial genetic and acquired risk factors (3)
either end up above threshold naturally (genetics + aging) or via acquired risk
clot formation process (6)
1) vessel injury
2) platelets released
3) vasocon + coag cascade
4) platelet aggregation
5) platelet fusion
6) stable haemostatic plug
blood coag cascade (3)
intrinsic
extrinsic = most common
haemostatic balance
summarised clot from (4)
Response to injury
Vessel constriction
Formation of unstable platelet plug
- platelet adhesion
- platelet aggregation
Fibrin stabilisation of the plug with fibrin
- blood coagulation
Dissolution of clot and vessel repair
- fibrinolysis
Fibrinolysis
Plasminogen > plasmin by t-PA
plasmin: breaks fibrin > D-dimer
Clotting factors, fibrinolytic factors and inhibitors and monitoring (5)
- Synthesised in
– liver
– endothelium
– megakaryocytes
(platelets)
Measurements:
* Prothrombin time –
PT = PTR
* Partial thromboplastin
time – APTT =APTTR
* Thrombin time - TT
wrong = clot or bleed
Venous thrombosis
Risk factors (10)
- stasis
-coag abnormalties
-Age - Past history or family of VTE
- Obesity
-Sepsis - Nephrotic syndrome
-Paroxysmal nocturnal
haemoglobinuria
-Behçet’s disease
-COVID-19
stasis causes (8)
- Prolonged immobility eg surgery, travel
- Stroke
- Cardiac failure
- Pelvic obstruction
- Dehydration (more sticky)
- Hyperviscosity
- Polycythaemia
-flying to holidays
coag abnormality (8)
- Surgery or major trauma
- Pregnancy and puerperium
- Oestrogen medication
- Malignancy
- Antiphospholipid antibodies (more platelets)
- Hereditary or acquired
thrombophilia
-Thrombocytosis - Heparin induced
thrombocytopenia
Clinical Features of DVT (7)
- Pain, tenderness of veins
- Limb swelling
- Superficial venous distension
-Increased skin temperature - Skin discoloration
- All reflect obstruction to the venous drainage
- There are multiple differential diagnoses for
these presenting features
DVT diagnosis (5)
Risk assessment
Evidence based pre test probability score
D dimer for exclusion
Diagnostic tests
Compression ultrasonography
Venography
DVT risk assessment
Clinical risk
score – determines role
for diagnostic imaging vs use of blood test for exclusion
DVT + PE (2)
- > 50% above knee DVT embolise
- Hospital acquired
thrombosis 25000pa
PE symptoms (5)
Dyspnoea
Pleuritic chest pain
Cough and haemoptysis
Dizziness
Syncope
- patient either very unwell or very well
PE signs (6)
Tachypnoea, tachycardia
Hypoxia
Pyrexia
Elevated jugular venous
pressure
Hypotension
ECG changes
or very few symps
Physiology of PE Symptoms (3)
Symptoms and signs determined by thrombus size and burden
Multiple small peripheral thrombi produce a different clinical picture to large proximal thrombus
Pulmonary infarction is not common – remember the bronchial circulation
PE diagnosis (8)
Risk assessment and diagnostic algorithm
D – dimer for exclusion in low risk cases only
Mortality stratification - PESI score
Assessment of compromise - Pa02 + D dimer + ECG + troponin and BNP
Consider echo
Diagnostic tests
CT pulmonary arteries – CTPA
Ventilation Perfusion Scan
VTE Long term consequences (4)
10% of all hospital
deaths
30% recurrence at 10years
30% post phlebitic3
syndrome at 10 years
Chronic
thromboembolic pulmonary
hypertension (CTPHE)
hospital acquired thrombosis (4)
-top prority for NHS since 2010
- assessing the risks of VTE + bleeding
- reducing the risk of VTE
-patient information + planning for discharge - extended prophylaxis
prevention + Treatment of VTE (8)
best care is prevention
- risk assessemnt
- prophylatic dose anti-coag
-intermittend compression devices
-compression hosiery
treatment:
-anticoag
-thrombolysis
-surgery
-prevention + antic
Why and how do we treat? (4)
- correct if there is no bleed risk = dissolves all clots everywhere
Most treatment aims to prevent thrombus propagation and
formation of new thrombus
while allowing the body to
concentrate lysis in the place where it is required
- Risks are short term impact of thrombus burden and damage to vessels while thrombus
remains - Newer approach – catheter directed thrombolys
if cardiovascularly stable with acute VTE… (2)
Anticoagulate
* Immediate anticoagulant effect
- Heparin then warfarin/DOAC or immediate DOAC-
Rivaroxaban or apixaban
Circulatory collapse due to PE -Thrombolysis (2)
Alteplase (tissue plasminogen activator)
(Streptokinase)
- Followed by heparin and warfarin/DOAC or other –
prevent recurrence
Investigations pre treatment (3)
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
Heparin - 2 types (6)
- from dog liver
*Glycosaminoglycan - Irreversible
- Immediate action
- Parenteral administration, iv or sc
- Renal excretio
unfractionated (UFH):
t ½ 1-2 hours
* accelerates inhibition of
thrombin (IIa) and Xa
* Effect easy to measure with standard clotting screen
Lower molecular weight:
t ½ 4-12 hours
* accelerates inhibition
of Xa > thrombin (IIa)
* Measurement of effect
requires Xa level assay
Low molecular weight heparin (4)
Renally cleared
- Half life 12 hours, peak activity 3-4hours
- No monitoring required -Predictability means this is not routine
- No reversal agent
- Anti Xa monitoring performed under certain
circumstances - preg
- renal failure
- obesity
- peak 4 hours post injection
Side effects of heparin - 2 main (6)
- Bleeding
– LMWH vs UFH less major bleeding (more even control)
– stop heparin
– give protamine sulphate – LMWH is harder to reverse - Heparin induced thrombocytopenia (HIT)
– minor platelet drop at 5 days - transient
– HIT with thrombosis syndrome (HITTS):
* Thrombocytopenia -IgG antibody to heparin + platelet factor 4 complexes
* Thrombosis - venous and arterial and gangrene
* Timing - 4-5 days after starting heparin
* other cause for thrombocytopenia not found
Warfarin (7)
Wisconsin Alumni Research Foundation
- decaying sweet clover
- 1940s used as rodenticide
haemorrhagic death - 1950 and 60s used to treat
thromboembolic disease in
Presidents Eisenhower &
Nixon
Rapidly absorbed t½ 36 - 42 hours
* 97% albumin bound in plasma
– pharmacological effect due to unbound fraction
- Eliminated by liver
- Interindividual dose variation
– genetic factors - CYP2C9 – ↑ sensitivity
- VKORC1 – principal genetic modulator
- Intraindividual dose variation
– compliance / comprehension
– diet
– co-morbid conditions eg right heart failure
– numerous drug interaction
book for dosing = prevent interruptions in treatments with no knowledge
Warfarin MoA (2)
antagonist of vitamin K dependent clotting factors
- multiple sites in cag cas = unpredictable effects
Warfarin –side effects
skin necrosis: give heparin first for Rx of VTE
otherwise can cause clot because you lose inhib factors before coag
How is the INR tested? (2)
venous sample:
- labour intensive
– accurate
– cheap
Near patient testing (NPT0 finger prick:
-capillary whole blood
– quick
– patients prefer
– immediate advice
– 0.5 variation in INR
– expensive
Warfarin – Interactions and Bleeding Risk (5)
drugs:
-increased vit K absorpt
-compete for plasma protein binding sites
-hepatotoxic
-induce hepatic enzymes
-have antiplatelet activity
= increasing bleeding = fatal , life threatening or minor
Warfarin reversal
vit k admin (every few hrs or days)
or replace complexes
warfarin + pregnancy (4)
crosses placenta= coumarin
embryopathy
* 6-12 weeks
* doses > 5mg
– increased fetal wastage
* intracerebral haemorrhage
* antepartum haemorrhage
warfarin is good but… (7)
- Narrow therapeutic window
- Frequent monitoring (not always available)
- Risk of bleeding (especially intracranial haemorrhage)
- Many contraindications and food and drug interactions
- Lifestyle restrictions
- Poor compliance and persistence
- Consequence: many patients are not sufficiently
anticoagulatant
DOAC’s Advantages
- Oral anticoagulant
- Rapid onset/offset of action
- No need for bridging
- Short half life
- Easy to control anticoagulant effect
- Little or no food-drug interactions
- Limited drug-drug interactions
- Predictable anticoagulant effect
- No need routine monitoring
New(ish) anticoagulants (3)
> Indirect Xa inhibitors - enhance antithrombin
– Fondaparinux
– Idraparinux
> Direct Xa inhibitors ORAL
– Rivaroxaban
– Apixaban
- Direct thrombin inhibitors ORAL
Rivaroxaban (7)
Direct inhibitor of Xa
- Oral agent ,once daily dosing
- Rapid onset of action and half life 4-9 hours
- Monitoring not usually necessary
- Renal excretion
- Few food or drug interactions
- GI side effects
Apixaban
- Direct inhibitor of Xa
- Oral agent
- Twice daily dosing
- Rapid onset of action
- Half life 9-14hours
- Monitoring not usually necessary
- Biliary and renal excretion
- Few food or drug interactions
- GI side effect
Dabigatran etexilate
