DVT and PE Flashcards
Prevalence of DVT
1:1000 annual incidence DVT Importance is above knee DVT 8:100 Inherited thrombophilia Multifactorial risk
DVT is a thrombus in a vein
Thrombus in deep vein of calf or beyond – common problem – most are calf only but common and incidence of above knee is sig
20% of untreated calf dvt progress to prox veins – 50% risk of PE
Heritance plus external factors
Process of DVT and PE formation
Thrombus in deep vein around valves
Multiple triggers – finely balanced system is destabilised
50% of above knee DVTs will embolise
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
Stasis turbulence and reduced flow – key is fine balance between coagulation and lysis – trigger destabilises the equilibrium
What is Virchows triad- factors contributing to thrombosis
Endothelial injury
Stasis
Blood components Platelets Coagulation factors Coagulation inhibitors Fibrinolytic factors
Virchow’s triad of vessel wall injury, blood clotting components and blood flow remains accurate in describing the important factors involved. More is now understood about the interaction between the different elements. Importance of each factor varies depending on the site, eg vessel wall damage is important in arterial thrombosis whereas stasis plays an important part in the development of venous thrombosis.
Virchow 1856
Vessel wall is naturally antithrombotic and inhibits clotting – disturbance leads to clotting
Local accumulation of clotting factors is the mechanism in stasis - endothelial hypoxia impairs vascular antithrombotic mechanisms
Thrombosis is multi-factorialgenetic and acquired risk factors
ageing is a risk
throw in extra risk like long flight (stasis) or a new hip (endothelial injury
Impact of vessel injury on the clotting cascade
Vessel injury can go into 2 directions:
1) Collagen exposure– platelet release reaction– thromboxane A2, ADP, primary haemostatic plug, platelet fusion– stable haemostatic plug
2) vasoconstriction- reduced blood flow- primary haemostatic plug- platelet fusion, stable haemostatic plug
3) Tissue factor- coagulation cascade- thrombin- fibrin- stable haemostatic plug
The endothelial cell forms a barrier between platelets and plasma clotting factors and the sub- endothelial tissues. These connective tissues include collagen, basement membrane, von Willebrand factor, microfibrils, elastin, mucoploysaccharides and fibronectin. Endothelial cells produce substances which can initiate coagulation, cause vasodilatation, inhibit platelet aggregation or haemostasis and can activate fibrinolysis; such substances include, tissue factor, prostacyclin, nitric oxide, antithrombin, tissue factor pathway inhibitor , protein S and tissue plasminogen activator.
Vasoconstriction reduces flow, allows contact and the activation of platelets and coagulation factors
Thromboxane A2 leads to vasoconstriction and release of granules and thus ADP and increased aggregation
describe the cell based model of coagulation
Initiation of coagulation occurs when sub-endothelial tissue is exposed to the circulation at a site of injury. These tissues express tissue factor at their surface, which binds to endogenous activated FVII
This complex binds small amounts of FX and FV to the exposed endothelial surface, which produce small quantities of thrombin
The thrombin activates platelets that are attracted to the site by the process, as well as other plasma-borne clotting factors
The activated factors (among them FVIII and FIX) enable the binding of activated FX and FV to the surface of platelets whose activation has produce conformational changes in their surface membranes to expose the ‘reaction sites’ necessary for continuation of the process
This leads to the ‘thrombin burst’ that is necessary for the large-scale production of fibrin and so the development of an effective clot
These three stages are called the initiation, amplification and propagation phases of coagulation
Platelets adhere and aggregate and are activated on procoagulant surface
Thrombin fibrin plug
More granules and accelerate
2 roles for thrombin crosslinking of XIII and fibrinogen to fibrin
(search up coagulation cascade and draw)
Haemostatic plug formation
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
Describe fibrinolysis
tPA breaks down plasminogen into plasmin
Plasmin converts fibrin into D dimer
Plasmin breaks down clot
FDP binds fibrin and stops clot
D dimer tells us there is clot breakdown and by default that there is clot formation
thrombin time tells us the time converting from fibrinogen to fibrin
prothrombin time measures time from tissue factor activation all the way to fibrin (if you have an abnormal prothrombin time you don’t really know where the problem is on its own)
partial thromboplastin time- looking at intrinsic pathway
where are clotting factors synthesised and how are they measured
Synthesised in
liver
endothelium
megakaryocytes (platelets)
most synthesis is in the liver but some proteins produced in high local concentration in endothelium (eg vWF) in megakaryocyte (eg factor V)
Measurements
Prothrombin time – PT = PTR
Partial thromboplastin time – APTT =APTTR
Thrombin time - TT
The aPTT test is used to measure and evaluate all the clotting factors of the intrinsic and common pathways of the clotting cascade by measuring the time (in seconds) it takes a clot to form after adding calcium and phospholipid emulsion to a plasma sample
The prothrombin time is a measure of the integrity of the extrinsic and final common pathways of the coagulation cascade. This consists of tissue factor and factors VII, II (prothrombin), V, X, and fibrinogen.
Thrombin time (TT) measures fibrin formation caused by the action of thrombin—the last step in the coagulation cascade. The principle of the test is that a standardized concentration of thrombin is added to citrated plasma and time to fibrin clot formation recorded in seconds
Risk factors for venous thromboembolism
STASIS: Prolonged immobility eg surgery, travel Stroke Cardiac failure Pelvic obstruction Dehydration Hyperviscosity Polycythaemia
COAGULATION ABNORMALITY Surgery or major trauma Pregnancy and puerperium Oestrogen medication Malignancy Antiphospholipid antibodies Hereditary or acquired thrombophilia Thrombocytosis Heparin induced thrombocytopenia
OTHERS Age Past history or family history of VTE Obesity Sepsis Nephrotic syndrome Paroxysmal nocturnal haemoglobinuria Behçet's disease
What are some clinical features of DVT
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 and PE diagnosis
DVT: Risk assessment Evidence based pre test probability score D dimer for exclusion Diagnostic tests Compression ultrasonography Venography
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
Long term consequences of VTE
10% of all hospital deaths
30% recurrence at 10 years
30% post phlebitic syndrome at 10 years
Chronic thromboembolic pulmonary hypertension (CTEPH)
50% ileofemoral DVT if the tghrombus doesn't dissolve, further thrombus formation in lungs lose pulmonary capillary vascular bed pressure in lungs goes up
scarring, damage to venous system, hyperpigmentation
Hospital acquired thrombosis
Top priority for NHS since 2010 (NICE)
Assessing the risks of VTE and bleeding
Reducing the risk of VTE
Patient information and planning for discharge – extended prophylaxis
Treatment of VTE
Why and how do we treat?
Best care is prevention ! This is our aim
Anticoagulants
Thrombolysis
Surgery
Compression hosiery????? evidence
Problem is thrombus
Two approaches
Lyse the thrombus
Prevent further thrombus formation
What we do reflects a risk benefit analysis
Lysis has the problem that if given systemically it lyses all thrombus 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
If cardiovascularly stable with acute VTE – Anticoagulate
Immediate anticoagulant effect
Heparin then warfarin/DOAC or immediate DOAC- Rivaroxaban or apixaban
Circulatory collapse due to PE Thrombolysis Alteplase (tissue plasminogen activator) Streptokinase Followed by heparin and warfarin or other – prevent recurrence
Investigations needed pre-treatment
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
Extrinsic pathway – liver disease, warfarin and vitamin K deficiency
Time to clot after addition of tissue factor
